Note: Descriptions are shown in the official language in which they were submitted.
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CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
BIOMARKERS AND METHODS FOR DETERMINING SENSITIVITY TO
EPIDERMAL GROWTH FACTOR RECEPTOR MODULATORS
FIELD OF THE INVENTION
The present invention relates generally to the field of pharmacogenomics, and
more specifically to methods and procedures to determine sensitivity in
patients to
allow the development of individualized genetic profiles which aid in treating
diseases and disorders based on patient response at a molecular level.
BACKGROUND OF THE INVENTION:
Cancer is a disease with extensive histoclinical heterogeneity. Although
conventional histological and clinical features have been correlated to
prognosis, the
same apparent prognostic type of tumors varies widely in its responsiveness to
therapy and consequent survival of the patient.
New prognostic and predictive markers, which would facilitate an
individualization of therapy for each patient, are needed to accurately
predict patient
response to treatments, such as small molecule or biological molecule drugs,
in the
clinic. The problem may be solved by the identification of new parameters that
could
better predict the patient's sensitivity to treatment. The classification of
patient
samples is a crucial aspect of cancer diagnosis and treatment. The association
of a
patient's response to a treatment with molecular and genetic markers can open
up new
opportunities for treatment development in non-responding patients, or
distinguish a
treatment's indication among other treatment choices because of higher
confidence in
the efficacy. Further, the pre-selection of patients who are likely to respond
well to a
medicine, drug, or combination therapy may reduce the number of patients
needed in
a clinical study or accelerate the time needed to complete a clinical
development
program (M. Cockett et al., 2000, Current Opinion ifz Biotechnology, 11:602-
609).
The ability to predict drug sensitivity in patients is particularly
challenging
because drug responses reflect not only properties intrinsic to the target
cells, but also
a host's metabolic properties. Efforts to use genetic information to predict
drug
sensitivity have primarily focused on individual genes that have broad
effects, such as
the multidrug resistance genes, ~2drl and fnfpl (P. Sonneveld, 2000, J.
Intef°n. Med.,
247:521-534).
CA 02512536 2005-06-30
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The development of microarray technologies for large scale characterization
of gene mRNA expression pattern has made it possible to systematically search
for
molecular markers and to categorize cancers into distinct subgroups not
evident by
traditional histopathological methods (J. Khan et al., 1998, Cancer Res.,
58:5009-
5013; A.A. Alizadeh et al., 2000, Natui°e, 403:503-511; M. Bittner et
al., 2000,
Nature, 406:536-540; J. Khan et al., 2001, Nature Medicine, 7(6):673-679; and
T.R.
Golub et al., 1999, Science, 286:531-537; U. Alon et al., 1999, Proc. Natl.
Acad. Sci.
USA, 96:6745-6750). Such technologies and molecular tools have made it
possible to
monitor the expression level of a large number of transcripts within a cell
population
at any given time (see, e.g., Schena et al., 1995, Science, 270:467-470;
Lockhart et al.,
1996 Nature Biotechnology, 14:1675-1680; Blanchard et al., 1996,
Natuf°e
Biotechnology, 14:1649; U.S. Patent No. 5,569,588 to Ashby et al.).
Recent studies demonstrate that gene expression information generated by
microarray analysis of human tumors can predict clinical outcome (L.J. van't
Veer et
al., 2002, Nature, 415:530-536; M. West et al., 2001, Proc. Natl. Acad. Sci.
USA,
98:11462-11467; T. Sorlie et al., 2001, Proc. Natl. Acad. Sci. USA, 98:10869-
10874;
M. Shipp et al., 2002, Nature Medicine, 8(1):68-74). These findings bring hope
that
cancer treatment will be vastly improved by better predicting the response of
individual tumors to therapy.
Needed are new and alternative methods and procedures to determine drug
sensitivity in patients to allow the development of individualized genetic
profiles
which are necessary to treat diseases and disorders based on patient response
at a
molecular level.
SUMMARY OF THE INVENTION:
The invention provides methods and procedures for determining patient
sensitivity to one or more Epidermal Growth Factor Receptor (EGFR) modulators.
The invention also provides methods of determining or predicting whether an
individual requiring therapy for a disease state such as cancer will or will
not respond
to treatment, prior to administration of the treatment, wherein the treatment
comprises
one or more EGFR modulators. The one or more EGFR modulators are compounds
that can be selected from, for example, one or more EGFR specific ligands, one
or
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more small molecule EGFR inhibitors, or one or more EGFR binding monoclonal
antibodies.
In one aspect, the invention provides a method for identifying a mammal that
will respond therapeutically to a method of treating cancer comprising
administering
an EGFR modulator, wherein the method comprises: (a) measuring in the mammal
the level of at least one biomarker selected from the biomarkers of Table 4;
(b)
exposing the mammal to the EGFR modulator; (c) following the exposing of step
(b),
measuring in the mammal the level of the at least one biomarker, wherein a
difference
in the level of the at least one biomarker measured in step (c) compared to
the level of
the at least one biomarker measured in step (a) indicates that the mammal will
respond therapeutically to said method of treating cancer.
As used herein, respond therapeutically refers to the alleviation or
abrogation
of the cancer. This means that the life expectancy of an individual affected
with the
cancer will be increased or that one or more of the symptoms of the cancer
will be
reduced or ameliorated. The term encompasses a reduction in cancerous cell
growth
or tumor volume. Whether a mammal responds therapeutically can be measured by
many methods well known in the art, such as PET imaging.
The at least one biomarker can also be selected from the biomarkers of Table
5. The mammal can be, for example, a human, rat, mouse, dog rabbit, pig sheep,
cow,
horse, cat, primate, or monkey.
The method of the invention can be, for example, an in vitro method and
wherein the at least one biornarker is measured in at least one mammalian
biological
sample from the mammal. The biological sample can comprise, for example, at
least
one of whole fresh blood, peripheral blood mononuclear cells, frozen whole
blood,
fresh plasma, frozen plasma, urine, saliva, skin, hair follicle, or tumor
tissue.
In another aspect, the invention provides a method for identifying a mammal
that will respond therapeutically to a method of treating cancer comprising
administering an EGFR modulator, wherein the method comprises: (a) exposing
the
mammal to the EGFR modulator; (b) following the exposing of step (a),
measuring in
the mammal the level of the at least one biomarker selected from the
biomarkers of
Table 4, wherein a difference in the level of the at least one biomarker
measured in
step (b), compared to the level of the biomarker in a mammal that has not been
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exposed to said EGFR modulator, indicates that the mammal will respond
therapeutically to said method of treating cancer.
In yet another aspect, the invention provides a method for testing or
predicting
whether a mammal will respond therapeutically to a method of treating cancer
comprising administering an EGFR modulator, wherein the method comprises: (a)
measuring in the mammal the level of at least one biomarker selected from the
biomarkers of Table 4; (b) exposing the mammal to the EGFR modulator; (c)
following the exposing of step (b), measuring in the mammal the level of the
at least
one biomarker, wherein a difference in the level of the at least one biomarker
measured in step (c) compared to the level of the at least one biomarker
measured in
step (a) indicates that the mammal will respond therapeutically to said method
of
treating cancer.
In another aspect, the invention provides a method for determining whether a
compound inhibits EGFR activity in a mammal, comprising: (a) exposing the
mammal to the compound; and (b) following the exposing of step (a), measuring
in
the mammal the level of at least one biomarker selected from the biomarkers of
Table
4, wherein a difference in the level of said biomarker measured in step (b),
compared
to the level of the biomarker in a mammal that has not been exposed to said
compound, indicates that the compound inhibits EGFR activity in the mammal.
In yet another aspect, the invention provides a method for determining
whether a mammal has been exposed to a compound that inhibits EGFR activity,
comprising (a) exposing the mammal to the compound; and (b) following the
exposing of step (a), measuring in the mammal the level of at least one
biomarker
selected from the biomarkers of Table 4, wherein a difference in the level of
said
biomarker measured in step (b), compared to the level of the biomarker in a
mammal
that has not been exposed to said compound, indicates that the mammal has been
exposed to a compound that inhibits EGFR activity.
In another aspect, the invention provides a method for determining whether a
mammal is responding to a compound that inhibits EGFR activity, comprising (a)
exposing the mammal to the compound; and (b) following the exposing of step
(a),
measuring in the mammal the level of at least one biomarker selected from the
biomaxkers of Table 4, wherein a difference in the level of said biomarker
measured
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in step (b), compared to the level of the biomarker in a mammal that has not
been
exposed to said compound, indicates that the mammal is responding to the
compound
that inhibits EGFR activity.
As used herein, "responding" encompasses responding by way of a biological
and cellular response, as well as a clinical response (such as improved
symptoms, a
therapeutic effect, or an adverse event), in a mammal
The invention also provides an isolated biomarker selected from the
biomarkers of Table 4. The biomarkers of the invention comprise sequences
selected
from the nucleotide and amino acid sequences provided in Table 4 and the
Sequence
Listing, as well as fragments and variants thereof.
The invention also provides a biomarker set comprising two or more
biomarkers selected from the biomarkers of Table 4.
The invention also provides kits for determining or predicting whether a
patient would be susceptible or resistant to a treatment that comprises one or
more
EGFR modulators. The patient may have a cancer or tumor such as, for example,
a
colon cancer or tumor.
In one aspect, the kit comprises a suitable container that comprises one or
more specialized microarrays of the invention, one or more EGFR modulators for
use
in testing cells from patient tissue specimens or patient samples, and
instructions for
use. The kit may further comprise reagents or materials for monitoring the
expression
of a biomarker set at the level of mRNA or protein.
In another aspect, the invention provides a kit comprising two or more
biomarkers selected from the biomarkers of Table 4.
In yet another aspect, the invention provides a kit comprising at least one of
an
antibody and a nucleic acid for detecting the presence of at least one of the
biomarkers selected from the biomarkers of Table 4. In one aspect, the kit
further
comprises instructions for determining whether or not a mammal will respond
therapeutically to a method of treating cancer comprising administering a
compound
that inhibits EGFR activity. In another aspect, the instructions comprise the
steps of
(a) measuring in the mammal the level of at least one biomarker selected from
the
biomarkers of Table 4, (b) exposing the mammal to the compound, (c) following
the
exposing of step (b), measuring in the mammal the level of the at least one
biomarker,
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wherein a difference in the level of the at least one biomarker measured in
step (c)
compared to the level of the at least one biomarker measured in step (a)
indicates that
the mammal will respond therapeutically to said method of treating cancer.
The invention also provides screening assays for determining if a patient will
be susceptible or resistant to treatment with one or more EGFR modulators.
The invention also provides a method of monitoring the treatment of a patient
having a disease treatable by one or more EGFR modulators.
The invention also provides individualized genetic profiles which are
necessary to treat diseases and disorders based on patient response at a
molecular
level.
The invention also provides specialized microarrays, e.g., oligonucleotide
microarrays or cDNA microarrays, comprising one or more biomarkers having
expression profiles that correlate with either sensitivity or resistance to
one or more
EGFR modulators.
The invention also provides antibodies, including polyclonal or monoclonal,
directed against one or more biomarkers of the invention.
The invention will be better understood upon a reading of the detailed
description of the invention when considered in connection with the
accompanying
figures.
BRIEF DESCRIPTION OF THE FIGURES:
FIG. 1 illustrates a EGFR biomarker identification and prioritization
strategy.
FIG. 2A illustrates the RT-PCR results for EGFR in thirty one colon cancer
cell lines to identify cell lines which do not have significant mRNA
expression of
EGFR.
FIG. 2B illustrates the ICSO profile for twenty two colon cancer cell lines
with
an EGFR inhibitor compound, and determination of sensitive and resistant cell
lines.
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DETAILED DESCRIPTION OF THE INVENTION:
The invention provides biomarkers that respond to the modulation of a
specific signal transduction pathway and also correlate with EGFR modulator
sensitivity or resistance. These biomarkers can be employed for predicting
response
to one or more EGFR modulators. In one aspect, the biomarkers of the invention
are
those provided in Table 4 and the Sequence Listing, including both
polynucleotide
and polypeptide sequences.
The biomarkers were determined by an in vit~°o assay employing
microarray
technology to monitor simultaneously the expression pattern of thousands of
discrete
genes in untreated cells, whose response to the modulation of a signal
transduction
pathway, in particular the EGFR pathway, was tested on untreated cells whose
sensitivity to EGFR modulators was tested. The biomarkers have expression
levels in
the cells that are dependent on the activity of the EFGR signal transduction
pathway
and that are also highly correlated with EGFR modulator sensitivity exhibited
by the
cells. Biomarkers serve as useful molecular tools for predicting a response to
EGFR
modulators, preferably biological molecules, small molecules, and the like
that affect
EGFR kinase activity via direct or indirect inhibition or antagonism of EGFR
kinase
function or activity.
EGFR MODULATORS
As used herein, the term "EGFR modulator" is intended to mean a compound
or drug that is a biological molecule or a small molecule that directly or
indirectly
modulates EGFR activity or the EGFR signal transduction pathway. Thus,
compounds or drugs as used herein is intended to include both small molecules
and
biological molecules. Direct or indirect modulation includes activation or
inhibition
of EGFR activity or the EGFR signal transduction pathway. In one aspect,
inhibition
refers to inhibition of the binding of EGFR to an EGFR ligand such as, for
example,
EGF. In another aspect, inhibition refers to inhibition of the kinase activity
of EGFR.
EGFR modulators include, for example, EGFR specific ligands, small
molecule EGFR inhibitors, and EGFR monoclonal antibodies.. In one aspect, the
EGFR modulator inhibits EGFR activity and/or inhibits the EGFR signal
transduction
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pathway. Tn another aspect, the EGFR modulator is an EGFR antibody that
inhibits
EGFR activity and/or inhibits the EGFR signal transduction pathway.
EGFR modulators include biological molecules or small molecules.
Biological molecules include all lipids and polymers of monosaccharides, amino
acids, and nucleotides having a molecular weight greater than 450. Thus,
biological
molecules include, for example, oligosaccharides and polysaccharides;
oligopeptides,
polypeptides, peptides, and proteins; and oligonucleotides and
polynucleotides.
Oligonucleotides and polynucleotides include, for example, DNA and RNA.
Biological molecules further include derivatives of any of the molecules
described above. For example, derivatives of biological molecules include
lipid and
glycosylation derivatives of oligopeptides, polypeptides, peptides, and
proteins.
Derivatives of biological molecules further include lipid derivatives of
oligosaccharides and polysaccharides, e.g., lipopolysaccharides. Most
typically,
biological molecules are antibodies, or functional equivalents of antibodies.
Functional equivalents of antibodies have binding characteristics comparable
to those
of antibodies, and inhibit the growth of cells that express EGFR. Such
functional
equivalents include, for example, chimerized, humanized, and single chain
antibodies
as well as fragments thereof.
Functional equivalents of antibodies also include polypeptides with amino
acid sequences substantially the same as the amino acid sequence of the
variable or
hypervariable regions of the antibodies. An amino acid sequence that is
substantially
the same as another sequence, but that differs from the other sequence by
means of
one or more substitutions, additions, and/or deletions, is considered to be an
equivalent sequence. Preferably, less than 50%, more preferably less than 25%,
and
still more preferably less than 10%, of the number of amino acid residues in a
sequence are substituted for, added to, or deleted from the protein.
The functional equivalent of an antibody is preferably a chimerized or
humanized antibody. A chimerized antibody comprises the variable region of a
non-
human antibody and the constant region of a human antibody. A humanized
antibody
comprises the hypervariable region (CDRs) of a non-human antibody. The
variable
region other than the hypervariable region, e.g., the framework variable
region, and
the constant region of a humanized antibody are those of a human antibody.
_g_
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Suitable variable and hypervariable regions of non-human antibodies may be
derived from antibodies produced by any non-human mammal in which monoclonal
antibodies are made. Suitable examples of mammals other than humans include,
for
example, rabbits, rats, mice, horses, goats, or primates.
Functional equivalents further include fragments of antibodies that have
binding characteristics that are the same as, or are comparable to, those of
the whole
antibody. Suitable fragments of the antibody include any fragment that
comprises a
sufficient portion of the hypervariable (i.e., complementarity determining)
region to
bind specifically, and with sufficient affinity, to EGFR tyrosine kinase to
inhibit
growth of cells that express such receptors.
Such fragments may, for example, contain one or both Fab fragments or the
F(ab')2 fragment. Preferably, the antibody fragments contain all six
complementarity
determining regions of the whole antibody, although functional fragments
containing
fewer than all of such regions, such as three, four, or five CDRs, are also
included.
In one aspect, the fragments are single chain antibodies, or Fv fragments.
Single chain antibodies are polypeptides that comprise at least the variable
region of
the heavy chain of the antibody linked to the vaxiable region of the light
chain, with or
without an interconnecting linker. Thus, Fv fragment comprises the entire
antibody
combining site. These chains may be produced in bacteria or in eukaryotic
cells.
The antibodies and functional equivalents may be members of any class of
immunoglobulins, such as IgG, IgM, IgA, IgD, or IgE, and the subclasses
thereof.
In one aspect, the antibodies are members of the IgGl subclass. The functional
equivalents may also be equivalents of combinations of any of the above
classes and
subclasses.
In one aspect, EGFR antibodies can be selected from chimerized, humanized,
fully human, and single chain antibodies derived from the marine antibody 225
described in U.S. Patent No. 4,943,533 to Mendelsohn et al. In one aspect, the
225
derived antibodies have the following hypervariable (CDR) regions of the light
and
heavy chain, wherein the amino acid sequences are indicated below the
nucleotide
sequences:
HEAVY CHAIN HYPERVARIABLE REGIONS (VH):
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CDRl
AACTATGGTGTACAC (SEQ ID NO: 179)
N Y G V H (SEQ ID NO: 180)
CDR2
GTGATATGGAGTGGTGGAAACACAGACTATAATACACCTTTCACATCC
(SEQ ID NO: 181)
VIWSGGNTDYNTPFTS(SEQIDN0:182)
CDR3
GCCCTCACCTACTATGATTACGAGTTTGCTTAC (SEQ ID NO: 183)
ALTYYDYEFAY(SEQIDN0:184)
LIGHT CHAIN HYPERVARIABLE REGIONS (VL):
CDRl
AGGGCCAGTCAGAGTATTGGCACAAACATACAC (SEQ ID NO: 185)
RASQSIGTNIH(SEQIDN0:186)
CDR2
GCTTCTGAGTCTATCTCT (SEQ ID NO: 187)
A S E S I S (SEQ ID NO: 188)
CDR3
CAACAAAATAATAACTGGCCAACCACG (SEQ ID NO: 189)
Q Q N N N W P T T (SEQ ID NO: 190)
In another aspect, the EGFR antibody can be selected from the antibodies
described in
U.S. Patent No. 6,235,883 to Jakobovits et al., U.S. Patent No. 5,558,864 to
Bendi et
al., and U.S. Patent No. 5,891,996 to Mateo de Acosta del Rio et al.
In addition to the biological molecules discussed above, the EGFR modulators
useful in the invention may also be small molecules. Any molecule that is not
a
biological molecule is considered herein to be a small molecule. Some examples
of
small molecules include organic compounds, organometallic compounds, salts of
organic and organometallic compounds, saccharides, amino acids, and
nucleotides.
Small molecules further include molecules that would otherwise be considered
biological molecules, except their molecular weight is not greater than 450.
Thus,
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small molecules may be lipids, oligosaccharides, oligopeptides, and
oligonucleotides
and their derivatives, having a molecular weight of 450 or less.
It is emphasized that small molecules can have any molecular weight. They
are merely called small molecules because they typically have molecular
weights less
than 450. Small molecules include compounds that are found in nature as well
as
synthetic compounds. In one embodiment, the EGFR modulator is a small molecule
that inhibits the growth of tumor cells that express EGFR. In another
embodiment,
the EGFR modulator is a small molecule that inhibits the growth of refractory
tumor
cells that express EGFR.
Numerous small molecules have been described as being useful to inhibit
EGFR. For example, U.S. Patent No. 5,656,655 to Spada et al. discloses styryl
substituted heteroaryl compounds that inhibit EGFR. The heteroaryl group is a
monocyclic ring with one or two heteroatoms, or a bicyclic ring with 1 to
about 4
heteroatoms, the compound being optionally substituted or polysubstituted.
U.S. Patent No. 5,646,153 to Spada et al. discloses bis mono and/or bicyclic
aryl heteroaryl, carbocyclic, and heterocarbocyclic compounds that inhibit
EGFR.
U.S. Patent No. 5,679,683 to Bridges et al. discloses tricyclic pyrimidine
compounds that inhibit the EGFR. The compounds are fused heterocyclic
pyrimidine
derivatives described at column 3, line 35 to column 5, line 6.
U.S. Patent No. 5,616,582 to Barker discloses quinazoline derivatives that
have receptor tyrosine kinase inhibitory activity.
Fry et al., Science 265, 1093-1095 (1994) in Figure 1 discloses a compound
having a structure that inhibits EGFR.
Osherov et al. disclose tyrphostins that inhibit EGFR/HERl and HER 2,
particularly those in Tables I, II, III, and IV.
U.S. Patent No. 5,196,446 to Levitzki et al. discloses heteroarylethenediyl or
heteroarylethendeiylaryl compounds that inhibit EGFR, particularly from column
2,
line 42 to column 3, line 40.
Panek et al., Journal of Pharmacology and Experimental Therapeutics 283,
1433-1444 (1997) discloses a compound identified as PD166285 that inhibits the
EGFR, PDGFR, and FGFR families of receptors. PD166285 is identified as 6-(2,6-
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dichlorophenyl)-2-(4-(2-diethylamirioethyoxy)phenylamino)-8-methyl-8H-
pyrido(2,3-d)pyrimidin-7-one having the structure shown in Figure 1 on page
1436.
BIOMARI~ERS AND BIOMARI~ER SETS
The invention includes individual biomarkers and biomarker sets having both
diagnostic and prognostic value in disease areas in which signaling through
EGFR or
the EGFR pathway is of importance, e.g., in cancers or tumors, in
ixnmunological
disorders, conditions or dysfunction, or in disease states in which cell
signaling and/or
cellular proliferation controls are abnormal or aberrant. The biomarker sets
comprise
a plurality of biomarkers such as, for example, a plurality of the biomarkers
provided
in Table 4 below, that highly correlate with resistance or sensitivity to one
or more
EGFR modulators.
The biomarker sets of the invention enable one to predict or reasonably
foretell the likely effect of one or more EGFR modulators in different
biological
systems or for cellular responses. The biomarker sets can be used in i~ vitro
assays of
EGFR modulator response by test cells to predict ifs vivo outcome. In
accordance
with the invention, the various biomarker sets described herein, or the
combination of
these biomarker sets with other biomarkers or markers, can be used, for
example, to
predict how patients with cancer might respond to therapeutic intervention
with one or
more EGFR modulators.
A biomarker set of cellular gene expression patterns correlating with
sensitivity or resistance of cells following exposure of the cells to one or
more EGFR
modulators provides a useful tool for screening one or tumor samples before
treatment
with the EGFR modulator. The screening allows a prediction of cells of a tumor
sample exposed to one or more EGFR modulators, based on the expression results
of
the biomarker set, as to whether or not the tumor, and hence a patient
harboring the
' tumor, will or will not respond to treatment with the EGFR modulator.
The biomarker or biomarker set can also be used as described herein for
monitoring the progress of disease treatment or therapy in those patients
undergoing
treatment for a disease involving an EGFR modulator.
The biomarkers serve as targets for the development of therapies for disease
treatment. Such targets may be particularly applicable to treatment of breast
disease,
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such as breast cancers or tumors. Indeed, because these biomarkers are
differentially
expressed in sensitive and resistant cells, their expression patterns are
correlated with
relative intrinsic sensitivity of cells to treatment with EGFR modulators.
Accordingly, the biomarkers highly expressed in resistant cells may serve as
targets
for the development of new therapies for the tumors which are resistant to
EGFR
modulators, particularly EGFR inhibitors.
MICROARRAYS
The invention also includes specialized microarrays, e.g., oligonucleotide
microarrays or cDNA microarrays, comprising one or more biomarkers, showing
expression profiles that correlate with either sensitivity or resistance to
one or more
EGFR modulators. Such microarrays can be employed in in vitro assays for
assessing
the expression level of the biomarkers in the test cells from tumor biopsies,
and
determining whether these test cells are likely to be resistant or sensitive
to EGFR
modulators. For example, a specialized microarray can be prepared using all
the
biomarkers, or subsets thereof, as described herein and shown in Table 4.
Cells from
a tissue or organ biopsy can be isolated and exposed to one or more of the
EGFR
modulators. Following application of nucleic acids isolated from both
untreated and
treated cells to one or more of the specialized microarrays, the pattern of
gene
expression of the tested cells can be determined and compared with that of the
biomarker pattern from the control panel of cells used to create the biomarker
set on
the microarray. Based upon the gene expression pattern results from the cells
that
underwent testing, it can be determined if the cells show a resistant or a
sensitive
profile of gene expression. Whether or not the tested cells from a tissue or
organ
biopsy will respond to one or more of the EGFR modulators and the course of
treatment or therapy can then be determined or evaluated based on the
information
gleaned from the results of the specialized microarray analysis.
ANTIBODIES
The invention also includes antibodies, including polyclonal or monoclonal,
directed against one or more of the polypeptide biomarkers. Such antibodies
can be
used in a variety of ways, for example, to purify, detect, and target the
biomarkers of
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the invention, including both i~ vitro and ih vivo diagnostic, detection,
screening,
andlor therapeutic methods.
FITS
The invention also includes kits for determining or predicting whether a
patient would be susceptible or resistant to a treatment that comprises one or
more
EGFR modulators. The patient may have a cancer or tumor such as, for example,
a
breast cancer or tumor. Such kits would be useful in a clinical setting for
use in
testing a patient's biopsied tumor or cancer samples, for example, to
determine or
predict if the patient's tumor or cancer will be resistant or sensitive to a
given
treatment or therapy with an EGFR modulator. The kit comprises a suitable
container
that comprises: one or more microarrays, e.g., oligonucleotide microarrays or
cDNA
microarrays, that comprise those biomarkers that correlate with resistance and
sensitivity to EGFR modulators, particularly EGFR inhibitors; one or more EGFR
modulators for use in testing cells from patient tissue specimens or patient
samples;
and instructions for use. In addition, kits contemplated by the invention can
further
include, for example, reagents or materials for monitoring the expression of
biomarkers of the invention at the level of mRNA or protein, using other
techniques
and systems practiced in the art such as, for example, RT-PCR assays, which
employ
primers designed on the basis of one or more of the biomarkers described
herein,
immunoassays, such as enzyme linked immunosorbent assays (ELISAs),
immunoblotting, e.g., Western blots, or ifz situ hybridization, and the like,
as further
described herein.
APPLICATION OF BIOMARI~ERS AND BIOMARI~ER SETS
The biomarkers and biomarker sets may be used in different applications.
Biomarker sets can be built from any combination of biomarkers listed in Table
4 to
make predictions about the likely effect of any EGFR modulator in different
biological systems. The various biomarkers and biomarker sets described herein
can
be used, for example, as diagnostic or prognostic indicators in disease
management, to
predict how patients with cancer might respond to therapeutic intervention
with
compounds that modulate the EGFR, and to predict how patients might respond to
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therapeutic intervention that modulates signaling through the entire EGFR
regulatory
pathway.
While the data described herein were generated in cell lines that are
routinely
used to screen and identify compounds that have potential utility for cancer
therapy,
the biomarkers have both diagnostic and prognostic value in other diseases
areas in
which signaling through EGFR or the EGFR pathway is of importance, e.g., in
immunology, or in cancers or tumors in which cell signaling and/or
proliferation
controls have gone awry.
In the examples described below, the sensitivity and resistance
classifications
in the twenty two colon cell lines were similar for the two EGFR modulators
tested.
Therefore, the biomarkers of the invention are expected to have both
diagnostic and
prognostic value for other compounds that modulate EGFR or the EGFR signaling
pathways.
Those having skill in the pertinent art will appreciate that the EGFR
signaling
pathway is used and functional in cell types other than cell lines of colon
tissue.
Therefore, the described biomarkers are expected to have utility for
predicting drug
sensitivity or resistance to compounds that interact with or inhibit the EGFR
activity
in cells from other tissues or organs associated with a disease state, or
cancers or
tumors derived from other tissue types. Non-limiting examples of such cells,
tissues
and organs include breast, colon, lung, prostate, testes, ovaries, cervix,
esophagus,
pancreas, spleen, liver, kidney, stomach, lymphocytic and brain, thereby
providing a
broad and advantageous applicability to the biomarkers described herein. Cells
for
analysis can be obtained by conventional procedures as known in the art, for
example,
tissue biopsy, aspiration, sloughed cells, e.g., colonocytes, clinical
or.medical tissue or
cell sampling procedures.
In accordance with the invention, cells from a patient tissue sample, e.g., a
tumor or cancer biopsy, can be assayed to determine the expression pattern of
one or
more biomarkers prior to treatment with one or more EGFR modulators. Success
or
failure of a treatment can be determined based on the biomaxker expression
pattern of
the cells from the test tissue (test cells), e.g., tumor or cancer biopsy, as
being
relatively similar or different from the expression pattern of a control set
of the one or
more biomarkers. Thus, if the test cells show a biomarker expression profile
which
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corresponds to that of the biomarkers in the control panel of cells which are
sensitive
to the EGFR modulator, it is highly likely or predicted that the individual's
cancer or
tumor will respond favorably to treatment with the EGFR modulator. By
contrast, if
the test cells show a biomarker expression pattern corresponding to that of
the
biomarkers of the control panel of cells which are resistant to the EGFR
modulator, it
is highly likely or predicted that the individual's cancer or tumor will not
respond to
treatment with the EGFR modulator.
The invention also provides a method of monitoring the treatment of a patient
having a disease treatable by one or more EGFR modulators. The isolated test
cells
from the patient's tissue sample, e.g., a tumor biopsy or tumor sample, can be
assayed
to determine the expression pattern of one or more biomarkers before and after
exposure to an EGFR modulator wherein, preferably, the EGFR modulator is an
EGFR inhibitor. The resulting biomarker expression profile of the test cells
before
and after treatment is compared with that of one or more biomarkers as
described and
shown herein to be highly expressed in the control panel of cells that are
either
resistant or sensitive to an EGFR modulator. Thus, if a patient's response is
sensitive
to treatment by an EGFR modulator, based on correlation of the expression
profile of
the one or biomarkers, the patient's treatment prognosis can be qualified as
favorable
and treatment can continue. Also, if, after treatment with an EGFR modulator,
the
test cells don't show a change in the biomarker expression profile
corresponding to the
control panel of cells that are sensitive to the EGFR modulator, it can serve
as an
indicator that the current treatment should be modified, changed, or even
discontinued. Tlus monitoring process can indicate success or failure of a
patient's
treatment with an EGFR modulator and such monitoring processes can be repeated
as
necessary or desired.
The biomarkers of the invention can be used to predict an outcome prior to
having any knowledge about a biological system. Essentially, a biomarker can
be
considered to be a statistical tool. Biomarkers are useful primarily in
predicting the
phenotype that is used to classify the biological system. In an embodiment of
the
invention, the goal of the prediction is to classify cancer cells as having an
active or
inactive EGFR pathway. Cancer cells with an inactive EGFR pathway can be
considered resistant to treatment with an EGFR modulator. An inactive EGFR
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pathway is defined herein as a non-significant expression of the EGFR or by a
classification as "resistant" or "sensitive" based on the ICSO value of each
colon cell
line to a compound (EGFR inhibitor compound BMS-461453) exemplified herein.
A number of the biomarker described herein are known to be regulated by
EGFR, e.g., mucin 2 (J Biol Chem. 2002 Aug 30;277(35):32258-67). Another
biomarker, betacellulin, is know to be an EGFR ligand (Biochem Biophys Res
Commun. 2002 Jun 28;294(5):1040-6). A functional relationship of the top
biomarkers to the EGFR is expected, since biomarkers that contribute to high
biomarker accuracy are likely to play a functional role in the pathway that is
being
modulated. For example, Perception therapy (i.e., antibody that binds to the
Her2
receptor and prevents function via internalization) is indicated when the Her2
gene is
overexpressed. It is unlikely that a therapy will have any therapeutic effect
if the
target enzyme is not expressed.
However, although the complete function of all of the biomarkers are not
currently known, some of the biomarkers are likely to be directly or
indirectly
involved in the EGFR signaling pathway. In addition, some of the biomarkers
may
function in the metabolic or other resistance pathways specific to the EGFR
modulators tested. Notwithstanding, knowledge about the function of the
biomarkers
is not a requisite for determining the accuracy of a biomarker according to
the practice
of the invention.
DISCOVERY OF BIOMARKERS
An approach has been discovered in which biomarkers were identified whose
expression patterns, in a subset of cell lines, correlated to and can be used
as an ih
vitro marker of cellular response to treatment or therapy with one compound,
or with
a combination or series of compounds, that are known to inhibit or activate
the
function of a protein, enzyme, or molecule (e.g., a receptor) that is directly
or
indirectly involved in cell proliferation, cell responses to external stimuli,
(such as
ligand binding), or signal transduction, e.g., a receptor tyrosine kinase.
Preferred are
antagonists or inhibitors of the function of a given protein, e.g., a receptor
tyrosine
kinase.
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Two analytical strategies were deployed to discover biomarkers useful for
predicting the sensitivity or resistance of cancer cells to treatment with one
or more
EGFR modulators. FIG. 1 illustrates the EGFR biomarker identification and
prioritization strategy. In one strategy, the mRNA expression level of EGFR
was
used to identify six colon cancer cell lines with, inferred from the mRNA
expression
level, no significant presence of the EGFR protein and hence no significant
activity of
the EGFR pathway (FIG. 2A). In subsequent analyses, biomarkers were identified
that had no significant mRNA expression level in the six cell lines and no
inferred
presence of the EGFR protein. Further, it was required that these biomarkers
would
have a significant mRNA expression level in at least six other cell lines.
In a second strategy, an EGFR specific tyrosine kinase inhibitor compound
was used to determine compound sensitivity in a panel of twenty two colon
cancer
cell lines following exposure of the cells to the compound. Some of the cell
lines
were determined to be resistant to treatment with the inhibitor compound,
while
others were determined to be sensitive to the inhibitor (FIG. 2B). A subset of
the cell
lines examined provided an expression pattern or profile of biomarkers that
correlated
to a response by the cells to the EGFR inhibitor compound as well as the
absence of
significant EGFR expression as thus could serve as biomarkers.
By combining the use of EGFR co-regulation studies in tumor cells with
experimental studies in cultured cells as a model of i~ vivo effects, the
invention
advantageously focuses on cell-intrinsic properties that are exposed in cell
culture to
identify biomarkers that predict compound sensitivity and resistance. The
discovery
and identification of biomaxkers in tumor cells and cell lines assayed i~
vitr°o can be
used to predict responses to one or more EGFR modulators i~ vivo and, thus,
can be
extended to clinical situations in which the same biomarkers axe used to
predict
patients' responses to one or more EGFR modulators and treatments comprising
one
or more EGFR modulators.
As described in the examples below, oligonucleotide microarrays were used to
measure the expression levels of over 44,792 probe sets in a panel of thirty
one
untreated colon cancer cell lines for which the expression status of the EGFR
and the
drug sensitivity to EGFR inhibitor compounds was determined. This analysis was
performed to determine whether the gene expression signatures of untreated
cells
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were sufficient for the prediction of sensitivity of the disease to inhibition
of the
EGFR by small molecule or biological molecule compounds. Through data
analysis,
biomarkers were identified whose expression levels were found to be highly
counter-
correlated with the status of the EGFR and correlated with the drug
sensitivity. In
addition, the treatment of cells with a small molecule EGFR inhibitor also
provided
gene expression signatures predictive of sensitivity to the compound.
The means of performing the gene expression and biomarker identification
analyses embraced by the invention is described in further detail and without
limitation below.
ICSO Determination and Phenotype Classification Based on Sensitivity of Twenty-
two
Colon Cancer Cell lines to EGFR Inhibitor Compounds
Twenty two colon cell lines were treated with a small molecule EGFR
inhibitor (BMS-461453) to determine the individual ICSO value. The ICSO for
each cell
line was assessed by MTS assays. The average ICSO values along with standard
deviations were calculated from two to five individual determinations for each
cell
line. As shown in FIG. 2B, a 4-fold variation in the ICSO values was observed
for the
small molecule EGFR inhibitor among the 22 colon cancer cell lines. The ICSO
unit is
~M.
All cell lines with at least a 1.75 fold lower ICSO than the most resistant
cell
lines were considered to be sensitive to treatment with the small molecule
EGFR
inhibitor. FIG. 2B represents the resistance/sensitivity classifications of
the twenty-
two colon cell lines to the small molecule EGFR inhibitor. Five cell lines
were
classified as sensitive and seventeen cell lines as resistant.
Description of the Strategy for Identifying Biomarkers
Biomarkers were discovered based on two criteria: (i) the correlation of their
mRNA expression level to the expression of EGFR in cell lines with
insignificant
EGFR expression and (ii) the correlation of the ICSO values for the small
molecule
EGFR inhibitor BMS-461453 with gene expression levels.
For each of these two biomarker selection strategies, two independent
"discovery" probe set lists were established by using statistical filters with
different
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stringency levels to identify genes whose expression correlated with either
EGFR
status or ICSO value. These statistical methods are described below and
resulted in
four discovery probe set lists: EGFR-A and EGFR-B (correlation with no
significant
EGFR expression) and IC-50-A, IC-50-B (correlation with ICSO expression), the
A-
lists containing probe sets selected by more stringent conditions. To then
establish
two biomarker probe set lists, probe sets that appeared in both EGFR-A and IC-
50 B
were selected (Biomarker Probe Set List A, Table 2) and probe sets that
appeared in
both EGFR-B and IC-50-A were selected (Biomarker Probe Set List B, Table 3).
Identifying Genes that Significantly Correlate with EGFR status classification
RT-PCR expression data for EGFR were obtained from thirty one colon
cancer cell lines and six cell lines with a significantly lower expression
level of EGFR
compared to the other cell lines were identified as described in Example 1
below.
(FIG. 2A). Expression profiling data of 44,792 probe sets represented on the
HG-
U133 array set for all thirty one untreated colon cancer cell lines were
obtained and
analyzed for the identification of probe sets which would be correlated with
the above
described six cell lines with no significant mRNA expression of EGFR. For the
discovery probe set list EGFR-A, all probe sets which were judged to be absent
by the
Affymetrix Mas 5.0 software in six of the six colon cancer cell lines with
significantly
lower expression of EGFR were identified. Second, it was required that these
probe
sets would be judged to be present in at least six cell lines of the twenty
five cell lines
classified as having significant mRNA expression of the EGFR. This analytical
strategy resulted in the identification of 280 probe sets that could be
analyzed in
comparison to the discovery probe set list IC-50-B.
The discovery probe set list EGFR-B was generated by selecting all probe sets
which were judged to be absent by the Affymetrix Mas 5.0 software in five of
the six
colon cancer cell lines with significantly lower expression of EGFR and which
would
be present in at least six cell lines of the twenty five cell lines classified
as having
significant mRNA expression of the EGFR. Discovery probe set list EGR-B
contains
1,852 probe sets (LJ133A: 876; U133B: 976).
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Identifying Genes that Significantly Correlate with Drug
Resistance/Sensitivity
Classification
Expression profiling data of 44,792 probe sets represented on the HG-U133
array set far twenty two untreated colon cell lines were obtained and
preprocessed as
described in Example 1 below. These data were analyzed using the Student's
TTEST
to identify genes whose expression patterns were strongly correlated with the
drug
resistance/sensitivity classification. Table 1 provides the
resistance/sensitivity
phenotype classification of the twenty two colon cell lines for the EGFR
antagonist
BMS-461453 based on the ICSO results. The mean ICSO values along with standard
deviations (SD) were calculated from 2 to 5 individual determinations for each
cell
line as shown. The mean ICSO across the twenty two colon cell lines for BMS-
461453
was calculated and used to normalize the ICSO data for each cell line. A11
cell lines
with at least a 1.75 fold lower ICSO than the most resistant cell lines were
considered
to be sensitive to treatment with BMS-461453. The cell lines designated with
an
asterisk are defined as being sensitive to the drug treatment.
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TABLE 1 - Resistance/Sensitivity Phenotype Classification of Twenty Two Colon
Cell Lines
Cell lines ICso SD
CCD 33C0* 2 1.28
LOVO* 2.3 2.28
LSI 74T* 3.5 1.93
Caco2* 5.5 3.97
SW403 * 5.7 4.94
CCDIBCo 7.1 3.84
SW837 7.2 3.30
Sk-Co-1 9 2.02
MIP 9.7 0.52
SW1417 10 0.00
HT-29 10 0.00
T84 10 0.00
CX-1 10 0.00
Colo-205 10 0.00
Colo-201 10 0.00
Co1o320HSR 10 0.00
HCT8 10 0.00
Co1o320DM 10 0.00
SW480 10 0.00
HCT116 10 0.00
SW620 10 0.00
HCTl 165542 10 0.00
An "idealized expression pattern" corresponds to a gene that is uniformly high
in one
class (e.g., sensitive) and uniformly low in the other (e.g., resistant).
Initially, a
Student TTEST was performed in which a T value was obtained for each probe
set.
Once a T value was generated, its corresponding confidence value (P) was found
on a
standard table of significance. The confidence value is a measure of the
probability to
observe a certain mean expression difference between two groups by chance
alone
and is obtained using the following formula:
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T(g.C) _ (Xl - X2) / ( Varl/nl '+' Var2/n2)1l2
wherein,
T(g,c) represents the T value between expression for gene g and the
sensitivity/resistance classification c;
Xl represents mean gene expression level of samples in class 1;
X2 represents mean gene expression level of samples in class 2;
varl represents variance of gene expression for samples in class 1;
var,~ represents variance of gene expression for samples in class 2;
nl represents number of samples in class 1;
nz represents number of samples in class 2; and
corresponding confidence value (P) for T values are obtained from a standard
table of
significance.
To generate discovery probe set list IC-50-B, a confidence value of 0.05 or
lower was used as the cut off for probe sets to be included in the list.
Discovery probe
set list IC-50-B contains 5,050 probe sets (LT133A: 2,498; U133B: 2,552).
Discovery probe set list IC-50-A was generated using the Pearson correlation
coefficient (a dimensionless index that ranges from -1.0 to 1.0). This value
was
calculated by treating the IC50 data as continuous variables and by utilizing
a lineax
regression model to correlate gene expression levels with ICSO values for
twenty-two
colon cell lines. Probe sets with a correlation coefficient less than -0.5
were selected
(p <0.02), a total of 902 probe sets (LT133A: 467; U133B: 435).
Finally, two separate biomarker probe set lists were generated, biomarker
probe set lists A and B, by identifying probe sets which were present in EGFR-
A and
IC-50-B (Biomarker Probe Set List A) (Table 2) or were present in EGFR-B and
IC-
50-A (Biomarker Probe Set List B) (Table 3).
The biomarker probe set list A (Table 2) contains a total of 74 probe sets
(U133A: 43; U133B: 31) and provides the polynucleotides identified to be
biomarkers
of EGFR antagonist sensitivity employing strategy A. With strategy A,
polynucleotides were required to satisfy a stringent criteria for EGFR status
coregulation and a less stringent condition for correlation to IC$o values.
Namely, the
polynucleotides had to be called absent by the Affymetrix software in six out
of the
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six cell lines with lowest expression of EGFR and be differentially expressed
in the
sensitive and resistance cell lines with a P value equal to or less than 0.05.
TABLE 2 - Biomarker Probe Set List A
Unigene TitleAffymetrix Description Affymetrix
robe set
hemoglobin, gb:BC005931.1 /DEF=Homo Sapiens, 211745 x
at
alpha 1 hemoglobin, alpha 2, clone MGC:14541,
mRNA,
complete cds. /FEA=mRNA
/PROD=hemoglobin, alpha 2
/DB XREF= 1:13543547 /FL= b:BC005931.1
dipeptidylpeptidagb:M80536.1 /DEF=H.sapiens dipeptidyl203716 s_at
se IV (CD26, peptidase IV (DPP4) mRNA, complete
cds.
adenosine /FEA=mRNA /GEN=DPP4 /PROD=dipeptidyl
deaminase peptidase IV /DB XREF=gi:181569
complexing /IJG=Hs.44926 dipeptidylpeptidase
IV (CD26,
protein 2) adenosine deaminase complexing protein
2)
/FL= b:M80536.1 gb:NM 001935.1
spondin 1, Consensus includes gb:AI885290 /FEA=EST213994~s
(f at
spondin) /DB XREF=gi:5590454
extracellular/DB XREF=est:w192a04.x1
matrix protein/CLONE=IMAGE:2432334 /UG=Hs.5378
spondin 1, (f spondin) extracellular
matrix
protein
3-hydroxy-3- gb:NM 005518.1 /DEF=Homo sapiens 204607 at
3-
methylglutaryl-hydroxy-3-methylglutaryl-Coenzyme
A synthase
Coenzyme A 2 (mitochondrial) (HMGCS2), mRNA.
synthase 2 /FEA=mRNA /GEN=HMGCS2 /PROD=3-
(mitochondrial)hydroxy-3-methylglutaryl-Coenzyme
A synthase
2(mitochondrial) /DB XREF=gi:5031750
/LTG=Hs.59889 3-hydroxy-3-methylglutaryl-
Coenzyme A synthase 2 (mitochondrial)
/FL= b:NM 005518.1
mucin 2, gb:NM 002457.1 /DEF=Homo sapiens 204673 at
mucin 2,
intestinal/tracheaintestinaltracheal (MUC2), mRNA.1FEA=mRNA
1 /GEN=MUC2 /PROD=mucin 2, intestinaltracheal
/DB XREF=gi:4505284 /LTG=Hs.315
mucin 2,
intestinaltracheallFL=gb:NM 002457.1
gb:L21998.1
cystic fibrosisgb:NM_000492.2 /DEF=Homo Sapiens 205043 at
cystic
transmembranefibrosis transmembrane conductance
regulator,
conductance ATP-binding cassette (sub-family
C, member 7)
regulator, (CFTR), mRNA. /FEA=mRNA /GEN=CFTR
ATP-
binding cassette/PROD=cystic fibrosis transmembrane
(sub-family conductanceregulator, ATP-binding
C, cassette (sub-
member 7) family C, member 7) /DB XRFF= 1:6995995
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/LTG=Hs.663 cystic fibrosis transmembrane
conductance regulator, ATP-binding
cassette
(sub-family C, member 7) /FL=gb:NM
000492.2
CUG triplet Consensus includes gb:N36839 /FEA=EST202156 s_at
repeat, RNA- lDB XRFF=gi:1157981
i
binding proteinXREF=est:yy35~7.s1
2 /DB
/CLONE=IMAGE:273253 /UG=Hs.211610
CUG
triplet repeat, RNA-binding protein
2
!FL=gb:U69546.1 gb:AF036956.1
gb:AF090694.1 b:NM 006561.1
nuclear receptorgb:NM_000901.1 /DEF=Homo Sapiens 205259 at
nuclear
subfamily receptor subfamily 3, group C, member
3, 2
group C, member(NR3C2), mRNA. /FEA=mRNA /GEN NR3C2
2 /PROD=nuclear receptor subfamily
3, group C,
member 2 !DB XREF=gi:4505198 /LJG=Hs.1790
nuclear receptor subfamily 3, group
C, member 2
/FL=gb:M16801.1 gb:NM 000901.1
cystic fibrosisConsensus includes gb:W60595 /FEA=EST215702~s
at
transmembrane/DB XREF=gi:1367354
conductance /DB XREF=est:zc91b04.s1
regulator, /CLONE=IMAGE:338479 /LTG=Hs.663
ATP- cystic
binding cassettefibrosis transmembrane conductance
regulator,
(sub-family ATP-binding cassette (sub-family
C, C, member 7)
member 7)
cytochrome gb:NM 000775.1 /DEF=Homo Sapiens 205073 at
P450, subfamilycytochrome P450, subfamily IIJ (arachidonicd
aci
IIJ (arachidonicepoxygenase) polypeptide 2 (CYP2J2),
mRNA.
acid /FEA=mRNA IGEN=CYP2J2
epoxygenase) /PROD=cytochrome P450, subfamily
IIJ
polypeptide (arachidonic acidepoxygenase) polypeptide
2 2
/DB XREF=gi:4503226 /UG=Hs.152096
cytochrome P450, subfamily IIJ (arachidonic
acid
epoxygenase) polypeptide 2 /FL=gb:U37143.1
b:NM 000775.1
cystatin S gb:NM 001899.1 /DEF=Homo Sapiens 206994 at
cystatin S
(CST4), mRNA. /FEA=mRNA /GEN=CST 4
/PROD=cystatin S /DB XREF=gi:4503108
/LTG=Hs.56319 cystatin S /FL=gb:NM
001899.1
spondin 1, Consensus includes gb:AI885290 /FEA=EST213993 at
(f
spondin) lDB_XREF=gi:5590454
extracellularlDB XREF=est:w192a04.x1
matrix protein/CLONE=IMAGE:2432334 /UG=Hs.5378
spondin 1, (f spondin) extracellular
matrix
rotein
fibroblast 022969.1 /DEF=Homo sapiens fibroblast203638 s_at
growth gb:NM
factor receptor_ d
2 growth factor receptor 2 (bacteria-expresse
(bacteria- kinase, keratinocyte growth factor
receptor,
ex ressed craniofacial dysostosis 1, Crouzon
kinase, syndrome,
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keratinocyte Pfeiffer syndrome, Jackson-Weiss
syndrome)
growth factor(FGFR2), transcript variant 2, mRNA.
receptor, /FEA=mRNA /GEN=FGFR2 /PROD=fibroblast
craniofacial growth factor receptor 2, isoform
2precursor
dysostosis lDB_XREF=gi:131862521LJG=Hs.278581
l,
Crouton fibroblast growth factor receptor
2 (bacteria-
syndrome, expressed kinase, keratinocyte growth
factor
Pfeiffer receptor, craniofacial dysostosis
1, Crouton
syndrome, syndrome, Pfeiffer syndrome, Jackson-Weiss
Jackson-Weisssyndrome) /FL=gb:NM 022969.1 gb:M97193.1
syndrome) gb:M80634.1
mucin 3B Consensus includes gb:AB038783.1 214898 x
lDEF=Homo at
sapiens MUC3B mRNA for intestinal
mucin,
partial cds. /FEA=mRNA /GEN=MUC3B
JPROD=intestinal mucin !DB XREF=gi:9929917
/LJG=Hs.129782 mucin 3A, intestinal
AA Consensus includes gb:AV728958 /FEA=EST212703 at
/DB_~REF=gi:10838379
/DB XREF=est:AV728958
/CLONE=HTCBYF04 /LJG=Hs.150443
KIAA0320 rotein
CUG triplet gb:NM 006561.1 /DEF=Homo Sapiens 202158 s_at
CUG
repeat, RNA- triplet repeat, RNA-binding protein
2 (CUGBP2),
binding proteinmRNA. /FEA=mRNA /GEN=CUGBP2
2
/PROD=CUG triplet repeat, RNA-binding
protein
2 /DB XREF=gi:5729815 /UG=Hs.211610
CUG
triplet repeat, RNA-binding protein
2
/FL=gb:U69546.1 gb:AF036956.1
gb:AF090694.1 gb:NM 006561.1
spondin 1, gb:AB051390.1 /DEF=Homo Sapiens 209437_s_at
(f mRNA for
spondin) VSGPF-spondin, complete cds. IFEA=mRNA
extracellular/PROD=VSGPF-spondin
matrix protein/DB XREF=gi:l 1320819 /LJG=Hs.5378
spondin
1, (f spondin) extracellular matrix
protein
/FL= b:AB051390.1
mucin 3B Consensus includes gb:AF113616 /DEF=Homo214676 x
at
sapiens intestinal mucin 3 (MUC3)
gene, partial
cds /FEA=mRNA /DB_XREF=gi:6466800
/UG=Hs.129782 mucin 3A, intestinal
EphAl gb:NM 005232.1 /DEF=Homo Sapiens 205977 s_at
EphAl
(EPHA1), mRNA. /FEA=mRNA /GEN=EPHAl
/PROD=EphAl /DB_~REF=gi:4885208
/LJG=Hs.89839 EphAl /FL=gb:M18391.1
b:NM 005232.1
matrilin 3 gb:NM_002381.2 /DEF=Homo Sapiens 206091 at
matrilin 3
(MATN3) precursor, mRNA. /FEA=mRNA
/GEN=MATN3 /PROD=matrilin 3 precursor
/DB ~~REF= 1:13518040 /LTG=Hs.278461
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matrilin 3 /FL=gb:NM 002381.2
bone 001200.1 /DEF=Homo sapiens bone 205290 s_at
gb:NM
morphogenetic_
morphogenetic protein 2 (BMP2),
mRNA.
protein 2 /FEA=mRNA /GEN=BMP2 /PROD=bone
morphogenetic protein 2 precursor
/DB XREF=gi:4557368 /UG=Hs.73853
bone
mo hogenetic rotein 2 /FL=gb:NM
001200.1
interferon Consensus includes gb:A1073984 /FEA=EST204057 at
consensus /DB_~~REF=gi:3400628
sequence binding/DB XREF=est:oy66cO5.x1
protein 1 /CLONE=IMAGE:1670792 lUG=Hs.14453
interferon consensus sequence binding
protein 1
/FL= b:M91196.1 gb:NM 002163.1
retinoic acidConsensus includes gb:AI669229 /FEA=EST221872~at
receptor /DB XREF=gi:4834003
responder /DB XREF=est:wc13e06.x1
(tazarotene /CLONE=IMAGE:2315074 /LTG=Hs.82547
induced) 1 retinoic acid receptor responder
(tazarotene
induced) 1
cystic fibrosisConsensus includes gb:W60595 /FEA=EST215703 at
transmembranelDB_XREF=gi:1367354
conductance /DB XREF=est:zc91b04.s1
regulator, /CLONE=IMAGE:338479 /LTG=Hs.663
ATP- cystic
binding cassettefibrosis transmembrane conductance
regulator,
(sub-family ATP-binding cassette (sub-family
C, C, member 7)
member 7)
fibroblast gb:M87771.1 IDEF=Human secreted 208228 s
growth fibroblast at
factor receptorgrowth factor receptor (K-sam-III)
2 mRNA,
(bacteria- complete cds. /FEA=mRNA /GEN=K-sam-III
expressed /PROD=fibroblast growth factor receptor
kinase,
keratinocyte fDB_XREF=gi:1867811UG=Hs.278581
growth factorfibroblast growth factor receptor
2 (bacteria-
receptor, expressed kinase, keratinocyte growth
factor
craw ofacial receptor, craniofacial dysostosis
1, Crouzon
dysostosis syndrome, Pfeiffer syndrome, Jackson-Weiss
1,
Crouzon syndrome) /FL=gb:NM 022970.1 gb:M87771.1
syndrome,
Pfeiffer
syndrome,
Jackson-Weiss
syndrome)
myosin, heavygb:NM_003802.1 /DEF=Homo sapiens 208208 at
myosin,
polypeptide heavy polypeptide 13, skeletal muscle
13, (MYH13),
skeletal musclemRNA. /FEA=mRNA /GEN=MYH13
/PROD=myosin, heavy polypeptide
13, skeletal
muscle /DB XREF=gi:11321578
/LTG=Hs.278488 myosin, heavy polypeptide
13,
skeletal muscle /FL= b:NM 003802.1
-27-
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gb:AF 111782.2
ESTs, Weakly Consensus includes gb:AW675655 /FEA=EST222354 at
similar to /DB XREF=gi:7540890
138022
hypothetical /DB XREF=est:ba52e01.x1
protein /CLONE=IMAGE:2900184 /UG=Hs.314158
[H.sa iens ESTs
hypothetical gb:NM 017699.1 /DEF=Homo sapiens 219734 at
protein hypothetical protein FLJ20174 (FLJ20174),
FLJ20174 mRNA. /FEA=mRNA /GEN=FLJ20174
/PROD=hypothetical protein FLJ20174
/DB XREF=gi:8923170 /UG=Hs.114556
hypothetical protein FLJ20174
/FL=gb:NM 017699.1
PTPRF Consensus includes gb:AI692180 /FEA=EST212841 s_at
interacting /DB XREF=gi:4969520
protein, binding/DB XREF=est:Wd37fl76.x1
protein 2 /CLONE=IMAGE:2330339 /UG=Hs.12953
(liprin
beta 2) PTPRF interacting protein, binding
protein 2
(li rin beta 2)
ribonuclease,gb:NM 002933.1 IDEF=Homo sapiens 201785 at
RNase A family,ribonuclease, RNase A family, 1 )
(pancreatic
1 (pancreatic)(RNASE1), mRNA. /FEA=mRNA
/GEN=RNASE1 /PROD=ribonuclease,
RNase A
family, 1 (pancreatic) /DB XREF=gi:4506546
/LTG=Hs.78224 ribonuclease, RNase
A family, 1
(pancreatic) /FL=gb:BC005324.1
gb:NM 002933.1 gb:D26129.1
hairless (mouse)O18411.1 lDEF=Homo Sapiens hairless220163 s
gb:NM at
homolog _
protein (putative single zinc finger
transcription
factor protein, responsible for
autosomal
recessive universal congenital alopecia,
HR gene)
(HSA277165), mRNA. /FEA=mRNA
/GEN=HSA277165 /PROD=hairless protein
/DB XREF=gi:11036651 /UG=Hs.272367
hairless protein (putative single
zinc finger
transcription factor protein, responsible
for
autosomal recessive universal congenital
alopecia, HR ene) /FL=gb:NM 018411.1
nuclear receptorConsensus includes gb:AF228413.1 210174 at
/DEF=Homo
subfamily sapiens hepatocyte transcription
5, factor mRNA,
group A, 3UTR. /FEA=mRNA /DB XREF=gi:7677372
member 2 /UG=Hs.l 83123 nuclear receptor
subfamily 5,
group A, member 2 /FL=gb:U93553.1
b:AB019246.1 gb:AF124247.1
superoxide gb:NM 003102.1 /DEF=Homo Sapiens 205236 x
at
dismutase superoxide dismutase 3, extracellular
3, (SOD3),
extracellularmRNA. /FEA=mRNA /GEN=SOD3
/PROD=su eroxide dismutase 3, extracellular
-28-
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/DB XR.EF=gi:4507150 /UG=Hs.2420
superoxide dismutase 3, extracellular
/FL= b:J02947.1 b:NM 003102.1
zinc finger gb:NM 003438.1 /DEF=Homo sapiens 207394~at
zinc
protein 137 finger protein 137 (clone pHZ-30)
(ZNF137),
(clone pHZ-3 mRNA. /FEA=mRNA /GEN=ZNF 13 7
0)
/PROD=zinc finger protein 137 (clone
pHZ-30)
/DB XREF=gi:4507988 /LTG=Hs.151689
zinc
finger protein 137 (clone pHZ-30)
/FL=gb:NM 003438.1 gb:U09414.1
Homo Sapiens Consensus includes gb:AL049983.1 217288_at
/DEF=Homo
mRNA; cDNA sapiens mRNA; cDNA DKFZp564D042
(from
DKFZp564D042 clone DKFZp564D042). /FEA=mRNA
(from clone /DB XREF=gi:4884234 /UG=Hs.240136
Homo
DKFZp564D042 sapiens mRNA; cDNA DI~FZp564D042
(from
clone DI~FZ 564D042)
Hermansky- Consensus includes gb:AL022313 /DEF=Human217354 s
at
_
Pudlak syndromeDNA sequence from clone RPS-1119A7
on
chromosome 22q12.2-12.3 Contains
the TXN2
gene for mitochondria) thioredoxin,
a novel gene,
the EIF3S7 gene for eukaryotic translation
initiation factor 3 subunit 7 (zeta,
6667kD) (EIF3-
P66), the gene f... /FEA=CDS 3
/DB XREF=gi:4200326 /UG=Hs.272270
Human
DNA sequence from clone RPS-1119A7
on
chromosome 22q12.2-12.3 Contains
the TXN2
gene for mitochondria) thioredoxin,
a novel gene,
the EIF3S7 gene for eukaryotic translation
initiation factor 3 subunit 7 (zeta,
6667kD) (EIF3-
P66), the ene for a nov
peroxisomal 018441.1 /DEF=Homo sapiens 221142 s_at
gb:NM
traps 2-enoyl_
peroxisomal traps 2-enoyl CoA reductase;
CoA reductase;putative short chain alcohol dehydrogenase
putative short(HSA250303), mRNA. /FEA=mRNA
chain alcohol/GEN=HSA250303 /PROD~eroxisomal
traps 2-
dehydrogenaseenoyl CoA reductase;putative short
chain alcohol
dehydrogenase /DB XREF=gi:8923751
/UG=Hs.281680 peroxisomal traps
2-enoyl CoA
reductase; putative short chain
alcohol
dehydrogenase lFL=gb:NM 018441.1
BTG family gb:NM 006763.1 /DEF=Homo sapiens 201236 s
BTG at
, family, member 2 (BTG2), mRNA. /FEA=mRNA
member 2
/GEN=BTG2 (PROD=BTG family, member
2
/DB XREF=gi:5802987 /UG=Hs.75462
BTG
family, member 2 /FL=gb:U72649.1
gb:NM 006763.1
phosducin gb:M33478.1 /DEF=Human 33-kDa 211496 s_at
hototransducing rotein mRNA, com
lete cds.
_29_
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/FEA=mRNA /DB_XREF=gi:177186
/UG=Hs.550 phosducin /FL=gb:NM 022577.1
gb:M33478.1 gb:AF076465.1
Rho GTPase gb:NM_015366.1 /DEF=Homo Sapiens 205980 s
Rho at
activating GTPase activating protein 8 (ARHGAPB),
protein
g mRNA. /FEA=mRNA 1GEN=ARHGAP8
/PROD=Rho GTPase activating protein
8
/DB XREF=gi:7656903 /UG=Hs.102336
Rho
GTPase activating protein 8
/FL= b:NM 015366.1
Homo sapiens Consensus includes gb:AW593996 /FEA=EST213256~at
clone 24707 /DB XREF=gi:7281254
mRNA sequence/DB XREF=est:hg41g06.x1
/CLONE=IMAGE:2948218 /UG=Hs.124969
Homo sa iens clone 24707 mRNA se
uence
caspase 10, gb:NM 001230.1 /DEF=Homo sapiens 205467 at
caspase
apoptosis-related10, apoptosis-related cysteine protease
cysteine protease(CASP 10), mRNA. /FEA=mRNA
/GEN=CASP10 /PROD=caspase 10, apoptosis-
related cysteine protease /DB XREF=gi:4502568
/LTG=Hs.5353 caspase 10, apoptosis-related
cysteine protease 1FL=gb:U60519.1
gb:NM 001230.1
KIA.A0690 Consensus includes gb:AK000238.1 216360 x
/DEF=Homo at
protein Sapiens cDNA FLI20231 fis, clone
COLF5511,
highly similar to AB014590 Homo
sapiens
mRNA for I~IAA0690 protein. /FEA=mRNA
/DB XREF=gi:7020188 !UG=Hs.60103
KIAA0690 protein
Homo sapiens ; Consensus includes gb:AW001287 227676 at
/FEA=EST
Similar to /DB XREF=gi:5848203
RII~EN cDNA /DB XREF=est:wu27e06.x1
1810037020 /CLONE=IMAGE:2521282 /LTG=Hs.61265
gene, clone ESTs, Weakly similar to G786_HUMAN
MGC:21481 PROTEIN GS3786 H.sapiens
IMAGE:385206
2, mRNA,
com lete cds
ESTs Consensus includes gb:AA581439 /FEA=EST244650 at
-
/DB XREF=gi:2359211
/DB XREF=est:nh13c10.s1
/CLONE=IMAGE:952242 /UG=Hs.152328
ESTs
ESTs Consensus includes gb:AI739241 /FEA=EST238984 at
-
/DB XREF=gi:5101222
/DB XREF=est:wi14h02.x1
(CLONE=IMAGE:2390259 /LTG=Hs.171480
ESTs
-30-
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hypothetical Consensus includes gb:AB046810.1 232083~at
/I7EF=Homo
protein Sapiens mRNA for I~IAA1590 protein,
partial
FLJ23045 cds. /FEA=mRNA /GEN=I~IA.A1590
/PROD=KIAA1590 protein
/DB XREF=gi:100472541UG=Hs.101774
h othetical rotein FLJ23045
regenerating gb:AY007243.1 /DEF=Homo sapiens 223447 at
gene type regenerating gene type IV mRNA,
IV complete cds.
/FEA=mRNA (PROD=regenerating gene
type IV
/DB XREF=gi:12621025 /LTG=Hs.105484
Homo
sapiens regenerating gene type IV
mRNA,
com fete cds lFL=gb:AY007243.1
ESTs Consensus includes gb:AI139990 /FEA=EST231022 at
/DB XREF=gi:3647447
/DB XREF=est:qa47d03.x1
/CLONE=IMAGE:1689893 /LTG=Hs.134586
ESTs
ESTs Consensus includes gb:AI733801 /FEA=EST237923 at
/DB XREF=gi:5054914
/DB XREF=est:qk39c04.x5
(CLONE=IMAGE:1871334 IIJG=Hs.146186
ESTs
hypothetical Consensus includes gb:AI~002203.1 226992 at
/DEF=Homo
protein sapiens cDNA FLJ11341 fis, clone
MGC20702 PLACE1010786. /FEA=mRNA
/DB XREF=gi:7023932 /LJG=Hs.10260
Homo
Sapiens cDNA FLJ11341 fis, clone
PLACEl010786
ESTs, Weakly Consensus includes gb:AI457984 /FEA=EST243729 at
similar to /DB XREF=gi:4312002
ALU1_HUMAN /DB XREF=estaj66a04.x1
ALU /CLONE=IMAGE:2146446 /UG=Hs.165900
SUBFAMILY ESTs, Weakly similar to ALUC_HUMAN
J ! ! ! !
SEQUENCE ALU CLASS C WARNING ENTRY ! ! !
CONTAMINAT H.sapiens
ION WARNING
ENTRY
[H.sa iens]
Homo Sapiens Consensus includes gb:T86159 /FEA=EST227724 at
cDNA: lDB_xR.EF=gi:714511
FLJ22063 fis,/DB XREF=est:yd84h07.s1
clone HEP10326/CLONE=IMAGE:114973 /UG=Hs.10450
Homo sapiens cDNA: FLJ22063 fis,
clone
HEP 103 26
ESTs Consensus includes gb:AI806131 /FEA=EST231148 at
/DB XREF=gi:5392697
/DB XREF=est:wf06c06.x1
/CLONE=IMAGE:2349802 /UG=Hs.99376
-31-
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ESTs
_
anterior gradientConsensus includes gb:AI922323 /FEA=EST228969 at
2 (Xenepus lDB_~~REF=gi:5658287
laevis) homolog/DB XREF=est:wn90h03.x1
/CLONE=IMAGE:2453141 /UG=Hs.293380
ESTs
ESTs Consensus includes gb:AI493909 /FEA=EST235562 at
/DB XRFF=gi:4394912
!DB_~~REF=est:qz94e02.x1
/CLONE=IMAGE:2042234 /UG=Hs.6131
ESTs
hypothetical Consensus includes gb:AI339568 /FEA=EST222727 s
at
protein /DB_~~REF=gi:4076495
FLJ22233 /DB XREF=est:qk67e10.x1
/CLONE=IMAGE:1874058 /UG=Hs.286194
hypothetical protein FLJ22233
/FL=gb:NM 024959.1
GaINAc alpha-2,Consensus includes gb:Y11339.2 /DEF=Homo227725 at
6- sapiens mRNA for GaINAc alpha-2,
6-
sialyltransferasesialyltransferase I, long form.
/FEA=mRNA
I, long form /PROD=GaINAc alpha-2,6-sialyltransferase
I
/DB XREF=gi:75762751UG=Hs.105352
GaINAc al ha-2, 6-sialyltransferase
I, long form
ESTs Consensus includes gb:AI917390 /FEA=EST240964 at
/DB XREF=gi:5637245
IDB_XREF=estas79a05 .x 1
/CLONE=IMAGE:2237456 /UG=Hs.99415
ESTs
Homo Sapiens Consensus includes gb:AI~026404.1 232321 at
/DEF=Homo
cDNA: sapiens cDNA: FLJ22751 fis, clone
KAIA0483,
FLJ22751 fis,highly similar to AF016692 Homo
Sapiens small
clone intestinal mucin (MLTC3) mRNA. /FEA=mRNA
KAIA0483, /DB_~~REF=gi:10439257 /UG=Hs.271819
Homo
highly similarsapiens cDNA: FLJ22751 fis, clone
to I~AIA0483,
AF016692 Homohighly similar to AF016692 Homo
sapiens small
sapiens smallintestinal mucin (MUC3) mRNA
intestinal
mucin
(MLTC3) mRNA
Homo Sapiens Consensus includes gb:AK026984.1 229021 at
/DEF=Homo
cDNA: Sapiens cDNA: FLJ23331 fis, clone
HEP12664.
FLJ23331 fis,/FEA=mRNA /DB_XREF=gi:10439980
clone HEP12664/UG=Hs.50742 Homo Sapiens cDNA:
FLJ23331
fis, clone HEP 12664
ESTs Consensus includes gb:AA827649 /FEA=EST235515 at
/DB XR.EF=gi:2900090
/DB XREF=est:od01a12.s1
/CLONE=IMAGE:1357918 /UG=Hs.105317
ESTs
rostate cancerConsensus includes b:AA633076 /FEA=EST226167 at
-32-
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associated /DB XREF=gi:2556490
protein 7 /DB_~REF=est:nq38a06.s1
/CLONE=IMAGE:l 146130 /UG=Hs.27495
rostate cancer associated rotein
7
ESTs Consensus includes gb:N37023 /FEA=EST225407 at
/DB XREF=gi:1158165
/DB XREF=est:yy40d03.s1
(CLONE=IMAGE:273701 /UG=Hs.235883
ESTs
ESTs, Weakly Consensus includes gb:AI864053 /FEA=EST235678 at
similar to lDB XREF=gi:5528160
I38588
reverse /DB_XREF=est:wj S Shl0.x1
transcriptase/CLONE=IMAGE:2406787 /UG=Hs.39972
homolog ESTs, Weakly similar to I38588 reverse
[H.sa iens transcri tase homolog H.sa iens
ESTs, Weakly Consensus includes gb:AA557324 /FEA=EST227702 at
similar to /DB XREF=gi:2327801
JX03311aurate!DB XREF=est:n181a02.s1
omega- /CLONE=IMAGE:1057034 /UG=Hs.26040
hydroxylase ESTs, Weakly similar to fatty acid
omega-
[H.sa fens] hydroxylase H.sa iens
ESTs Consensus includes gb:BF594323 /FEA=EST238103 at
/DB X_RFF=gi:11686647
JDB XREF=est:7h79g07.x1
/CLONE=IMAGE:3322236 /LJG=Hs.158989
ESTs
ESTs, Weakly Consensus includes gb:AI827789 /FEA=EST228241 at
similar to /DB XREF=gi:5448449
JE0350 Anterior/DB XREF=est:wf33a07.x1
gradient-2 /CLONE=IMAGE:2357364 /UG=Hs.100686
[H.sapiens] ESTs, Weakly similar to JE0350 Anterior
adient-2 H.sa iens
ESTs Consensus includes gb:AI968097 /FEA=EST237835 at
/DB XREF=gi:5764915
/DB XREF=est:wu13a12.x1
/CLONE=IMAGE:2516830 /UG=Hs.131360
ESTs
ESTs Consensus includes gb:H05025 /FEA=EST241874 at
/DB XREF=gi:868577
/DB XREF=est:yl74g12.s1
/CLONE=IMAGE:43864 /UG=Hs.323767
ESTs
Homo sapiens,Consensus includes gb:AA524690 /FEA=EST226168 at
Similar to /DB XREF=gi:2265618
RII~EN cDNA /DB_~~REF=est:ng38e07.s1
1110060018 /CLONE=IMAGE:937092 /UG=Hs.294143
gene, clone ESTs, Weakly similar to predicted
using
MGC:17236 Genefinder C.elegans
IMAGE:3 86413
- 33 -
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7, mRNA,
com fete cds
ESTs Consensus includes gb:AI300126 /FEA=EST240830 at
/DB XREF=gi:3959472
/DB XREF=est:qn54IU2.x1
/CLONE=IMAGE:1902075 /UG=Hs.257858
ESTs
Homo sapiens Consensus includes gb:AA129774 /FEA=EST227019~at
cDNA FLJ13137/DB XREF=gi:1690185
fis, clone /DB XREF=est:z116h09.s1
NT2RP3003150 /CLONE=IMAGE:502145 /UG=Hs.288905
Homo sapiens cDNA FLJ13137 fis,
clone
NT2RP3003150
ESTs Consensus includes gb:AW024656 /FEA=EST242358 at
!DB XREF=gi:5878186
/DB XREF=est:wu78hO5.x1
/CLONE=IMAGE:2526201 /UG=Hs.233382
ESTs, Moderately similar to AF119917
62
PR02822 H.sapiens
The biomarker probe set list B (Table 3) contains 95 probe sets (U133A: 47;
U133B 48). The biomarker probe set list B contains polynucleotides identified
to be
biomarkers of EGFR antagonist sensitivity employing strategy B. In strategy B,
polynucleotides were required to satisfy a stringent criteria for correlation
to IC$o
values and a less stringent condition for EGFR status coregulation. Namely,
the
polynucleotides had to have a Pearsons correlation of -0.5 or less with
respect to ICS
and be called absent by the Affymetrix software in 5 out of the 6 cell lines
with lowest
expression of EGFR.
TABLE 3 - Biomarker Probe Set List B
Unigene TitleAffymetrix Description Affymetrix
robe set
dopa Consensus includes gb:AW772056 /FEA=EST214347 s-at
decarboxylase/DB XREF=gi:7704118
(aromatic /DB XREF=est:hn64g06.x1
L-
amino acid /CLONE=IMAGE:3032698 JUG=Hs.150403
decarboxylase)dopa decarboxylase (aromatic L-amino
acid
decarboxylase)
cystic fibrosisgb:NM 000492.2 IDEF=Homo Sapiens 205043 at
cystic
transmembranefibrosis transmembrane conductance
regulator,
conductance ATP-binding cassette (sub-family
C, member 7)
regulator, (CFTR), mRNA. /FEA=mRNA /GEN=CFTR
ATP-
binding cassette/PROD=cystic fibrosis transmembrane
-34-
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(sub-family conductanceregulator, ATP-binding
C, cassette
member 7) (sub-family C, member 7)
~
/DB XREF=gi:6995995 /UG=Hs.663
cystic
fibrosis transmembrane conductance
regulator,
ATP-binding cassette (sub-family
C, member 7)
/FL=gb:NM 000492.2
carcinoembryoiugb:BC005008.1 /DEF=Homo sapiens, 203757 s
at
c antigen-relatedcarcinoembryonic antigen-related
cell adhesion
cell adhesionmolecule 6 (non-specific cross
reacting antigen),
molecule 6 clone MGC:10467, mRNA, complete
(non- cds.
specific cross/FEA=mRNA /PROD=carcinoembryonic
reacting antigen)antigen-related cell adhesionmolecule
6 (non-
specific cross reacting antigen)
/DB XRFF=gi:13477106 /UG=Hs.73848
carcinoembryonic antigen-related
cell adhesion
molecule 6 (non-specific cross
reacting antigen)
/FL=gb:BC005008.1 gb:M18216.1 gb:M29541.1
gb:NM 002483.1
hypothetical gb:NM 017655.1 /DEF=Homo sapiens 219970 at
protein hypothetical protein FLJ20075 (FLJ20075),
FLJ20075 mRNA. /FEA=mRNA /GEN=FLJ20075
/PROD=hypothetical protein FLJ20075
/DB XREF=gi:8923083 /UG=Hs.205058
hypothetical protein FLJ20075
/FL= b:NM 017655.1
ATPase, ClassConsensus includes gb:AW006935 214070 s
IFEA=EST at
V, type 10B /DB XREF=gi:5855713
/DB XREF=est:wt08b11.x1
/CLONE=IMAGE:2506845 /UG=Hs.109358
ATPase, Class V, type lOB
cystic fibrosisConsensus includes gb:W60595 IFEA=EST215702 s_at
transmembrane/DB XREF=gi:1367354
conductance /DB XREF=est:zc91b04.s1
regulator, /CLONE=IMAGE:338479 /UG=Hs.663
ATP- cystic
binding cassettefibrosis transmembrane conductance
regulator,
(sub-family ATP-binding cassette (sub-family
C, C, member 7)
member 7)
HERV-H LTR- gb:NM 007072.1 /DEF=Homo Sapiens 220812 s_at
HERV-
associating H LTR-associating 2 (HHLA2), mRNA.
2
/FEA=mRNA IGEN=HHLA2 /PROD=HERV-H
LTR-associating 2 /DB XREF=gi:5901963
/UG=Hs.252351 HERV-H LTR-associating
2
/FL=gb:AF126162.1 gb:NM 007072.1
AA Consensus includes gb:AV728958 212703 at
/FEA=EST
/DB XREF=gi:10838379
/DB XREF=est:AV728958
/CLONE=HTCBYF04 /UG=Hs.150443
KIAA0320 protein
-35-
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hemoglobin, Consensus includes gb:T50399 /FEA=EST214414 x
at
alpha 2 /DB XREF=gi:652259
/DB XREF=est: yb3 Ob 11. s 1
/CLONE=IMAGE:72669 /UG=Hs.251577
hemo lobin, al ha 1
spondin 1, Consensus includes gb:AI885290 213993 at
(f /FEA=EST
spondin) /DB XREF=gi:5590454
extracellular/DB XREF=est:w192a04.x1
matrix protein/CLONE=IMAGE:2432334 /UG=Hs.5378
spondin 1, (f spondin) extracellular
matrix
rotein
hemoglobin, gb:BC005931.1 /DEF=Homo sapiens, 211745 x
at
alpha 1 hemoglobin, alpha 2, clone MGC:14541,
mRNA, complete cds. /FEA=mRNA
/PROD=hemoglobin, alpha 2
/DB XREF= 1:13543547 /FL= b:BC005931.1
serine (or gb:NM_002639.1 /DEF=Homo Sapiens 204855 at
serine
cysteine) (or cysteine) proteinase inhibitor,
Glade B
proteinase (ovalbumin), member 5 (SERPINBS),
mRNA.
inhibitor, /FEA=mRNA /GEN=SERPINBS /PROD=serine
Glade B
(ovalbumin), (or cysteine) proteinase inhibitor,
cladeB
member 5 (ovalbumin), member 5 /DB XREF=gi:4505788
/LTG=Hs.55279 serine (or cysteine)
proteinase
inhibitor, Glade B (ovalbumin),
member 5
/FL=gb:NM 002639.1 gb:U04313.1
3-hydroxy-3- gb:NM 005518.1 /DEF=Homo sapiens 204607 at
3-
methylglutaryl-hydroxy-3-methylglutaryl-Coenzyme
A synthase
Coenzyme A 2 (mitochondrial) (HMGCS2), mRNA.
synthase 2 /FEA=mRNA /GEN=HMGCS2 /PROD=3-
(mitochondrial)hydroxy-3-methylglutaryl-Coenzyme
A synthase
2(mitochondrial) /DB XREF=gi:5031750
/LJG=Hs.59889 3-hydroxy-3-methylglutaryl-
Coenzyme A synthase 2 (mitochondrial)
/FL=gb:NM_005518.1
anterior gradientgb:AF088867.1 /DEF=Homo Sapiens 209173 at
putative
2 (Xenepus secreted protein XAG mRNA, complete
Gds.
laevis) homolog/FEA=mRNA /PROD~utative secreted
protein
XAG /DB XREF=gi:6652811 /LTG=Hs.91011
anterior gradient 2 (Xenepus laevis)
homolog
/FL=gb:AF007791.1 gb:AF038451.1
b:NM 006408.1 b:AF088867.1
FXYD domain- gb:BC005238.1 /DEF=Homo Sapiens, 202489 s
FXYD at
containing domain-containing ion transport
ion regulator 3,
transport clone MGC:12265, mRNA, complete
Gds.
regulator /FEA=mRNA /PROD=FXYD domain-
3
containing ion transport regulator3
/DB XREF=gi:13528881 /LTG=Hs.301350
FXYD domain-containin ion trans
ort regulator
-36-
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3 /FL= b:NM 005971.2 gb:BC005238.1
dipeptidylpeptidagb:M80536.1 /DEF=H.sapiens dipeptidyl203716 s_at
se IV (CD26, peptidase IV (DPP4) mRNA, complete
cds.
adenosine /FEA=mRNA /GEN=DPP4 /PROD=dipeptidyl
deaminase peptidase IV lDB_~iREF=gi:181569
complexiiig /LTG=Hs.44926 dipeptidylpeptidase
IV (CD26,
protein 2) adenosine deaminase complexing
protein 2)
lFL=gb:M80536.1 gb:NM_001935.1
cystic fibrosisConsensus includes gb:W60595 /FEA=EST215703 at
transmembrane/DB XREF=gi:1367354
conductance /DB XREF=est:zc91b04.s1
regulator, /CLONE=IMAGE:338479 IUG=Hs.663
ATP- cystic
binding cassettefibrosis transmembrane conductance
regulator,
(sub-family ATP-binding cassette (sub-family
C, C, member 7)
member 7)
EphAl gb:NM 005232.1 /DEF=Homo Sapiens 205977 s_at
EphAl
(EPHA 1 ), mRNA. /FEA=mRNA /GEN=EPHA1
/PROD=EphAl !DB XREF=gi:4885208
/LTG=Hs.89839 EphAl /FL=gb:M18391.1
b:NM 005232.1
spondin l, Consensus includes gb:AI885290 213994_s_at
(f /FEA=EST
spondin) /DB XREF=gi:5590454
extracellular/DB XREF=est:w192a04.x1
matrix protein/CLONE=IMAGE:2432334 /UG=Hs.5378
spondin 1, (f spondin) extracellular
matrix
protein
CUG triplet gb:NM 006561.1 /DEF=Homo sapiens 202158 s_at
CUG
repeat, RNA- triplet repeat, RNA-binding protein
2
binding protein(CUGBP2), mRNA. /FEA--mRNA
2
/GEN=CUGBP2 /PROD=CUG triplet repeat,
RNA-binding protein 2 /DB XREF=gi:5729815
/LJG=Hs.211610 CUG triplet repeat,
RNA-
binding protein 2 /FL=gb:U69546.1
gb:AF036956.1 gb:AF090694.1
gb:NM 006561.1
DKFZP434C091 Consensus includes gb:AL080170.1 215047 at
protein /DEF=Homo Sapiens mRNA; cDNA
DKFZp434C091 (from clone DKFZp434C091);
partial cds. /FEA=mRNA
IGEN=DKFZp434C091 (PROD=hypothetical
protein /DB XREF=gi:5262639 /UG=Hs.51692
DKFZP434C091 protein
mucin 3B Consensus includes gb:AF113616 214676_x_at
/DEF=Homo
Sapiens intestinal mucin 3 (MUC3)
gene, partial
cds /FEA=mRNA /DB XREF=gi:6466800
/UG=Hs.129782 mucin 3A, intestinal
potassium gb:U90065.1 /DEF=Human potassium 204678 s_at
channel
channel, KCNO1 mRNA, com fete cds. /FEA=mRNA
-37-
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subfamily /PROD=potassium channel KCNO1
K,
member 1 IDB XREF=gi:1916294 /UG=Hs.79351
(TWIK-1) potassium channel, subfamily K,
member 1
(TWIK-1) /FL=gb:U33632.1 gb:U90065.1
gb:U76996.1 gb:NM 002245.1
nuclear receptorgb:NM 000901.1 /DEF=Homo Sapiens 205259 at
nuclear
subfamily receptor subfamily 3, group C,
3, member 2
group C, member(NR3 C2), mRNA. /FEA=mRNA /GEN--NR3
C2
2 /PROD=nucleax receptor subfamily
3, group C,
member 2 /DB XREF=gi:4505198
/UG=Hs.1790 nuclear receptor subfamily
3,
group C, member 2 /FL=gb:M16801.1
gb:NM 000901.1
BTG family, gb:NM 006763.1 /DEF=Homo Sapiens 201236 s
BTG at
member 2 family, member 2 (BTG2), mRNA.
/FEA=mRNA IGEN=BTG2 /PROD=BTG
family, member 2 /DB XREF=gi:5802987
/IJG=Hs.75462 BTG family, member
2
/FL=gb:U72649.1 b:NM 006763.1
G protein- gb:AF062006.1 /DEF=Homo Sapiens 210393 at
orphan G
coupled receptorprotein-coupled receptor HG38 mRNA,
49 complete cds. /FEA=mRNA /PROD=orphan
G
protein-coupled receptor HG3 8
/DB XREF=gi:3366801 /UG=Hs.285529
G
protein-coupled receptor 49 /FL=gb:AF062006.1
b:AF061444.1 gb:NM 003667.1
hypothetical gb:NM 017640.1 IDEF=Homo Sapiens 219573lat
protein hypothetical protein FLJ20048 (FLJ20048),
FLJ20048 mRNA. /FEA=mRNA /GEN=FLJ20048
/PROD=hypothetical protein FLJ20048
!DB_~REF=gi:8923056 /L1G=Hs.116470
hypothetical protein FLJ20048
/FL=gb:NM 017640.1
cytochrome gb:NM 000775.1 /DEF=Homo Sapiens 205073 at
P450, subfamilycytochrome P450, subfamily IIJ
(arachidonic
IIJ (arachidonicacid epoxygenase) polypeptide 2
(CYP2J2),
acid mRNA. /FEA=mRNA /GEN=CYP2J2
epoxygenase) /PROD=cytochrome P450, subfamily
IIJ
polypeptide (arachidonic acidepoxygenase) polypeptide
2 2
/DB XREF=gi:4503226 /UG=Hs.152096
cytochrome P450, subfamily IIJ
(arachidonic
acid epoxygenase) polypeptide 2
lFL= b:U37143.1 gb:NM 000775.1
brain-specificgb:NM 007030.1 /DEF=Homo sapiens 206179 s_at
brain-
protein p25 specific protein p25 alpha (p25),
alpha mRNA.
IFEA=mRNA JGEN=p25 /PROD=brain-specific
protein p25 alpha /DB XREF=gi:5902017
ICTG=Hs.29353 brain-s ecific rotein
25 al ha
-38-
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/FL=gb:AB017016.1 gb:NM 007030.1
mucin 2, gb:NM 002457.1 /DEF=Homo Sapiens 204673 at
mucin 2,
intestinal/tracheaintestinaltracheal (MUC2), mRNA.
1 /FEA=mRNA /GEN=MUC2 /PROD=mucin
2,
intestinaltracheal /DB XREF=gi:4505284
/LTG=Hs.315 mucin 2, intestinaltracheal
/FL=gb:NM 002457.1 gb:L21998.1
hypothetical gb:NM 017699.1 /DEF=Homo Sapiens 219734 at
protein hypothetical protein FLJ20174 (FLJ20174),
FLJ20174 mRNA. /FEA~nRNA /GEN=FLJ20174
(PROD=hypothetical protein FLJ20174
/DB XREF=gi:8923170 /LTG=Hs.114556
hypothetical protein FLJ20174
/FL=gb:NM 017699.1
metastasis- gb:NM 004739.1 lDEF=Homo sapiens 203444 s
at
associated metastasis-associated 1-like 1
1-like (MTA1L1),
1 mRNA. /FEA--mRNA /GEN=MTA 1 L 1
/PROD=metastasis-associated 1-like
1
/DB XR.EF=gi:4758739 /LJG=Hs.173043
metastasis-associated 1-like 1
/FL=gb:AB016591.1 gb:NM 004739.1
b:AF295807.1
bone gb:NM_001200.1 /DEF=Homo Sapiens 205290 s_at
bone
morphogeneticmorphogenetic protein 2 (BMP2),
mRNA.
protein 2 /FEA=mRNA /GEN=BMP2 /PROD=bone
morphogenetic protein 2 precursor
/DB XREF=gi:4557368 IIJG=Hs.73853
bane
morpho enetic protein 2 /FL=gb:NM
001200.1
heparanase gb:NM 006665.1 /DEF=Homo Sapiens 219403 s_at
heparanase (HPSE), mRNA. /FEA=mRNA
/GEN=HPSE /PROD=heparanase
/DB XREF=gi:5729872 /LTG=Hs.44227
heparanase /FL=gb:AF165154.1 gb:AF152376.1
gb:NM 006665.1 gb:AF084467.1
gb:AF155510.1
tumor necrosisgb:BC002794.1 IDEF=Homo Sapiens, 209354 at
tumor
factor receptornecrosis factor receptor superfamily,4
member 1
superfamily, (herpesvirus entry mediator), clone
MGC:3753,
member 14 mRNA, complete cds. /FEA=mRNA
(herpesvirus /PROD=tumor necrosis factor receptor
entry mediator)superfamily,member 14 (herpesvirus
entry
mediator) /DB XREF=gi:12803894
iUG=Hs.279899 tumor necrosis factor
receptor
superfamily, member 14 (herpesvirus
entry
mediator) /FL=gb:BC002794.1 gb:U70321.1
gb:U81232.1 gb:NM 003820.1 b:AF153978.1
CUG triplet Consensus includes gb:N36839 /FEA=EST202156 s_at
re eat, RNA- /DB ~~REF= 1:1157981
-39-
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binding protein/DB XREF=est:yy35f07.s1
2
/CLONE=IMAGE:273253 /UG=Hs.211610
CUG triplet repeat, RNA-binding
protein 2
/FL=gb:U69546.1 gb:AF036956.1
~gb:AF090694.1 gb:NM 006561.1
ESTs, Consensus includes gb:R06655 /FEA=EST217546 at
Moderately /DB XREF=gi:757275
similar to /DB XREF=est:yf10e02.r1
AF0788441 /CLONE=IMAGE:126458 /LTG=Hs.188518
hqp0376 proteinESTs, Moderately similar to AF078844
1
[H.sa iens h 0376 rotein H.sa iens
hairless (mouse)018411.1 /DEF=Homo sapiens hairless220163 s_at
gb:NM
homolog _
protein (putative single zinc finger
transcription
factor protein, responsible for
autosomal
recessive universal congenital
alopecia, HR
gene) (HSA277165), mRNA. /FEA=mRNA
/GEN=HSA277165 /PROD=hairless protein
lDB_XREF=gi:1103 6651 ILTG=Hs.2723
67
hairless protein (putative single
zinc finger
transcription factor protein, responsible
for
autosomal recessive universal congenital
alo ecia, HR ene) /FL=gb:NM 018411.1
branched chainConsensus includes gb:NM_005504.1 214452 at
aminotransferase/DEF=Homo Sapiens branched chain
1, cytosolic aminotransferase l, cytosolic (BCATl),
mRNA.
/FEA=CDS /GEN=BCATl /PROD=branched
chain aminotransferase 1, cytosolic
!DB XI2EF=gi:5031606 lLJG=Hs.157205
branched chain aminotransferase
1, cytosolic
/FL= b:U21551.1 b:NM 005504.1
pancreas- gb:NM 016341.1 /DEF=Homo Sapiens 205112 at
enriched pancreas-enriched phospholipase
C
phospholipase(LOC51196), mRNA. /FEA=mRNA
C
/GEN=LOC51196 IPROD~ancreas-enriched
phospholipase C /DB XREF=gi:7705940
/UG=Hs.6733 pancreas-enriched phospholipase
C /FL=gb:AF190642.2 gb:AF117948.1
b:NM 016341.1
prostaglandin-gb:NM 000963.1 /DEF=Homo Sapiens 204748 at
endoperoxide prostaglandin-endoperoxide synthase
2
synthase 2 (prostaglandin GH synthase and
(prostaglandincyclooxygenase) (PTGS2), mRNA.
G/H synthase /FEA=mRNA /GEN=PTGS2
and /PROD=prostaglandin-endoperoxide
synthase
cyclooxygenase)2(prostaglandin GH synthase and
cyclooxygenase) /DB XREF=gi:4506264
/UG=Hs.196384 prostaglandin-endoperoxide
synthase 2 ( rostaglandin GH synthase
and
-40-
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cyclooxygenase) /FL=gb:M90100.1
gb:L15326.1 gb:NM 00096
3.1
phosphatase _ 204054 at
and 000314.1 /DEF=Homo Sapiens
gb:NM
tensin homolog_
phosphatase and tensin homolog
(mutated in
(mutated in multiple advanced cancers 1) (PTEN),
mRNA.
multiple /FEA=mRNA /GEN=PTEN
advanced cancers/PROD=phosphatase and tensin homolog
1) (mutated inmultiple advanced cancers
1)
/DB XREF=gi:4506248 /UG=Hs.10712
phosphatase and tensin homolog
(mutated in
multiple advanced cancers 1) lFL=gb:U92436.1
gb:U93051.1 gb:U96180.1 gb:NM 000314.1
retinoic acidConsensus includes gb:AI669229 221872 at
/FEA=EST
receptor /DB XREF=gi:4834003
responder /DB XREF=est:WC13e06.x1
(tazarotene /CLONE=IMAGE:2315074 /UG=Hs.82547
induced) 1 retinoic acid receptor responder
(tazarotene
induced) 1
protease inhibitorgb:NM 002638.1 /DEF=Homo sapiens 203691 at
protease
3, skin-derivedinhibitor 3, skin-derived (SI~ALP)
(PI3), mRNA.
(SKALP) /FEA=mRNA /GEN=PI3 /PROD~rotease
inhibitor 3, skin-derived (SI~ALP)
/DB XREF=gi:4505786 /LTG=Hs.112341
protease inhibitor 3, skin-derived
(SKALP)
/FL= b:NM 002638.1
zinc finger gb:NM 003438.1 /DEF=Homo Sapiens 207394 at
zinc
protein 137 finger protein 137 (clone pHZ-30)
(ZNF137),
(clone pHZ-30)mRNA. /FEA=mRNA /GEN=ZNF137
/PROD=zinc finger protein 137 (clone
pHZ-30)
/DB XREF=gi:4507988 ILTG=Hs.151689
zinc
finger protein 137 (clone pHZ-30)
/FL=gb:NM_003438.1 gb:U09414.1
myosin, lightgb:NM 002477.1 /DEF=Homo sapiens 205145 s_at
myosin,
polypeptide light polypeptide 5, regulatory
5, (MYLS), mRNA.
regulatory /FEA=mRNA /GEN=MYLS /PROD=myosin,
light polypeptide 5, regulatory
JDB_XREF=gi:4505304 lUG=Hs.170482
myosin, light polypeptide 5, regulatory
/FL=gb:L03785.1 gb:NM 002477.1
tumor necrosis000043.1 /DEF=Homo sapiens tumor 204781 s
gb:NM at
factor receptor_ 6
necrosis factor receptor superfamily,
member
superfamily, (TNFRSF6), mRNA. /FEA=mRNA
member 6 /GEN=TNFRSF6 /PROD=apoptosis (APO-1)
antigen 1 /DB XREF=gi:4507582
/LTG=Hs.82359 tumor necrosis factor
receptor
superfamily, member 6 /FL=gb:M67454.1
gb:NM 000043.1
h othetical Consensus includes b:AI339568 /FEA=EST222727 s
at
-41-
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protein /DB XREF=gi:4076495
FLJ22233 /DB XREF=est:qk67e10.x1
/CLONE=IMAGE:1874058 lUG=Hs.286194
hypothetical protein FLJ22233
/FL=gb:NM 024959.1
regenerating gb:AY007243.1 /DEF=Homo Sapiens 223447 at
gene type regenerating gene type IV mRNA,
IV complete
cds. /FEA=mRNA /PROD=regenerating
gene
type IV /DB XREF=gi:12621025
/UG=Hs.105484 Homo sapiens regenerating
gene type IV mRNA, complete cds
/FL=gb:AY007243.1
Homo Sapiens Consensus includes gb:AK025615.1 225285 at
cDNA: /DEF=Homo sapiens cDNA: FLJ21962
fis,
FLJ21962 fis,clone HEP05564. IFEA=nlRNA
clone HEP05564/DB XREF=gi:10438186 /UG=Hs.7567
Homo
sa iens cDNA: FLJ21962 fis, clone
HEP05564
phosphoproteinConsensus includes gb:AK000680.1 225626 at
associated /DEF=Homo Sapiens cDNA FLJ20673
With fis,
glycosphingolipiclone KAIA4464. /FEA=mRNA
d-enriched /DB XREF=gi:7020924 lLTG=Hs.266175
microdomains phosphoprotein associated with
GEMs
/FL=gb:AF240634.1 gb:NM 018440.1
hypothetical Consensus includes gb:BF111925 226171 at
iFEA=EST
protein /DB XREF=gi:10941704
FLJ20209 /DB XREF=est:7138gO5.x1
/CLONE=IMAGE:3523784 lUG=Hs.3685
hypothetical protein FLJ20209
Homo sapiens Consensus includes gb:AA532640 226484 at
/FEA=EST
mRNA for /DB XREF=gi:2276894
KIAA1190 lDB_XREF=est:nj 17c04.s1
protein, partial/CLONE=IMAGE:986598 /LJG=Hs.206259
cds Homo sapiens mRNA for KIAA1190
protein,
artial cds
KIAA1543 Consensus includes gb:AB040976.1 226494 at
protein /DEF=Homo sapiens mRNA for KIAA1543
protein, partial cds. JFEA~mRNA
/GEN=KIAA1543 /PROD=KIAA1543 protein
/DB XREF=gi:7959352 /LTG=Hs.17686
KIAAl543 rotein
hypothetical Consensus includes gb:AW138767 227180 at
/FEA=EST
protein /DB XREF=gi:6143085 /DB XREF=est:UI-H-
FLJ23563 BI1-aep-a-12-0-ULsl
/CLONE=IMAGE:2719799 /UG=Hs.274256
hypothetical rotein FLJ23563
ESTs Consensus includes gb:AW264333 227320 at
/FEA=EST
/DB XREF=gi:6641075
/DB XREF=est:x 98e01.x1
-42-
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/CLONE=IMAGE:2758680 /UG=Hs.21835
ESTs
ESTs Consensus includes gb:BF589359 227354 at
/FEA=EST
/DB _X_RFF=gi:11681683
/DB XREF=est:nab25dOl.x1
/CLONE=IMAGE:3266737 /UG=Hs.13256
ESTs
Homo Sapiens,Consensus includes gb:AW001287 227676_at
/FEA=EST
Similar to /DB XREF=gi:5848203
RIKEN cDNA /DB XREF=est:wu27e06.x1
1810037020 /CLONE=IMAGE:2521282 /UG=Hs.61265
gene, clone ESTs, Weakly similar to G786_HCTMAN
MGC:21481 PROTEIN GS3786 H.sapiens
IMAGE:385206
2, mRNA,
com fete cds
Homo sapiens Consensus includes gb:T86159 /FEA=EST227724 at
cDNA: /DB XR.EF=gi:714511
FLJ22063 fis,/DB XREF=est:yd84h07.s1
clone HEP10326/CLONE=IMAGE:114973 /UG=Hs.10450
Homo sapiens cDNA: FLJ22063 fis,
clone
HEP 10326
ESTs Consensus includes gb:AI700341 228653 at
/FEA=EST
/DB XREF=gi:4988241
/DB XREF=est:wd06e1O.x1
/CLONE=IMAGE:2327370 /UG=Hs.110406
ESTs
ESTs Consensus includes gb:BG494007 228716 at
/FEA=EST
/DB XREF=gi:13455521
/DB XREF=est:602542289F1
!CLONE=IMAGE:4673182 /UG=Hs.203213
ESTs
ESTs Consensus includes gb:AI559300 229331 at
/FEA=EST
/DB XRFF=gi:4509505
/DB XREF=estaq43d03.,x1
/CLONE=IMAGE:2211557 /UG=Hs.294140
ESTs
hypothetical Consensus includes gb:AI830823 229439 s
/FEA=EST at
protein /DB XREF=gi:5451416
lDB_~R.EF=est:wj52b06.x1
/CLONE=IMAGE:2406419 /UG=Hs.95549
by othetical rotein
ESTs Consensus includes gb:BF431989 229657 at
/FEA=EST
IDB_XREF=gi:11444103
/DB XREF=est:nab84a05.x1
/CLONE=IMAGE:3274280 /UG=Hs.203213
ESTs
ESTs Consensus includes gb:BF589413 229893 at
/FEA=EST
- 43 -
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/DB XREF=gi:11681737
lDB_XREF=est:nab26b11.x1
/CLONE=IMAGE:3267020 /UG=Hs.55501
ESTs
brain-specificConsensus includes gb:BG055052 230104 s_at
/FEA=EST
protein p25 /DB XREF=gi:12512386
alpha
/DB XREF=est:nac94g06.x1
/CLONE=IMAGE:3441995 /UG=Hs.29353
brain-s ecific rotein 25 al ha
ESTs, Weakly Consensus includes gb:BF110588 230645 at
/FEA=EST
similar to /DB XREF=gi:10940278
MMHUE4 fDB_XREF=est:7n39e12.x1
erythrocyte /CLONE=IMAGE:3567071 /UG=Hs.150478
membrane ESTs, Weakly similar to KIAA0987
protein
protein 4.1, H.sapiens
parent splice
form [H.sa
iens
ESTs Consensus includes gb:BF592062 230760 at
/FEA=EST
/DB XREF=gi:11684386
/DB XREF=est:7n98h06.x1
/CLONE=IMAGE:3 572962 ILJG=Hs.23
3 890
ESTs
hepatocyte Consensus includes gb:AI032108 230914 at
/FEA=EST
nuclear factor/DB_~~REF=gi:3250320
4,
alpha /DB XREF=est:ow92dll.xl
/CLONE=IMAGE:1654293 /UG=Hs.54424
hepatocyte nuclear factor 4, alpha
ESTs Consensus includes gb:AW203959 230944 at
/FEA=EST
/DB XREF=gi:6503431 /DB XREF=est:UI-H-
BI 1-aeu-b-12-0-UI. s 1
!CLONE=IMAGE:2720590 /UG=Hs.149532
ESTs
ESTs Consensus includes gb:AI139990 231022~at
/FEA=EST
/DB XREF=gi:3647447
/DB XREF=est:qa47d03.x1
/CLONE=IMAGE:1689893 /UG=Hs.134586
ESTs
ESTs Consensus includes gb:AI806131 231148 at
/FEA=EST
/DB XREF=gi:5392697
lDB XREF=est:wf06c06.x1
/CLONE=IMAGE:2349802 /UG=Hs.99376
ESTs
hypothetical Consensus includes gb:AB046810.1 232083 at
protein /DEF=Homo Sapiens mRNA for KIAA1590
FLJ23045 protein, partial cds. /FEA=mRNA
/GEN=KIAA1590 /PROD=KIAA1590 protein
/DB_~REF=gi:10047254 /LTG=Hs.141774
by othetical rotein FLJ23045
-44-
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Homo Sapiens Consensus includes gb:AC004908 232641 at
/DEF=Homo
PAC clone Sapiens PAC clone RPS-855D21 /FEA=CDS
RPS- 3
855D2 1 /DB XREF=gi:4156179 /UG=Hs.249181
Homo sa iens PAC clone RPS-855D21
putative Consensus includes gb:AJ251708.1 234669 x
at
microtubule- /DEF=Homo Sapiens partial mRNA
for putative
binding proteinmicrotubule-binding protein. /FEA--mRNA
/PROD=putative microtubule-binding
protein
/DB XREF=gi:6491740 /UG=Hs.326544
utative microtubule-binding rotein
ESTs Consensus includes gb:AI741469 234970 at
/FEA=EST
/DB XREF=gi:5109757
/DB_~~REF=est:wgl lbOl.x1
/CLONE=IMAGE:2364745 /LJG=Hs.57787
ESTs
ESTs Consensus includes gb:AI417897 235444 at
/FEA=EST
/DB XRFF=gi:4261401
/DB XREF=estag55b06.x1
/CLONE=IMAGE:2112659 lUG=Hs.235860
ESTs
ESTs Consensus includes gb:AI493909 235562 at
/FEA=EST
/DB XR.EF=gi:4394912
/DB XREF=est:qz94e02.x1
/CLONE=IMAGE:2042234 /UG=Hs.6131
ESTs
ESTs Consensus includes gb:AV741130 235651 at
/FEA=EST
/DB XREF=gi:10858711
~
/DB
XREF=est:AV741130
/CLONE=CBCATB06 /UG=Hs.173704 ESTs,
Moderately similar to ALUB_HUMAN
ALU
SUBFAMILY SX SEQUENCE
CONTAMINATION WARNING ENTRY
H.sapiens
ESTs Consensus includes gb:AW339510 235866 at
/FEA=EST
/DB XREF=gi:6836136
/DB XREF=est:xz91h08.x1
/CLONE=IMAGE:2871615 /UG=Hs.42722
ESTs
ESTs Consensus includes gb:AI076192 236422 at
/FEA=EST
/DB XREF=gi:3405370
/DB XREF=est:oz01g07.x1
/CLONE=IMAGE:1674108 /UG=Hs.131933
ESTs
ESTs Consensus includes gb:AL044570 236548 at
/FEA=EST
/DB XREF=gi:5432785
/DB XREF=est:DKFZp434L082_s1
/CLONE=DKFZp434L082 fUG=Hs.147975
ESTs
- 45 -
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ESTs Consensus includes gb:AI733801 /FEA=EST237923 at
/DB XREF=gi:5054914
/DB XREF=est:qk39c04.x5
/CLONE=IMAGE:1871334 /UG=Hs.146186
ESTs
Homo Sapiens,Consensus includes gb:T69015 /FEA=EST238422 at
clone /DB XREF=gi:680163
MGC:16402 /DB XREF=est:yc31f04.s1
IMAGE:394036 /CLONE=IMAGE:82303 /UG=Hs.192728
0, mRNA, ESTs
com lete cds
ESTs Consensus includes gb:AA502384 /FEA=EST238956 at
_
/DB XREF=gi:2237351
/DB XREF=est:ne27fll.sl
/CLONE=IMAGE:898605 /UG=Hs.151.529
ESTs
ESTs Consensus includes gb:AI739241 /FEA=EST238984 at
_
/DB XREF=gi:5101222
/DB XREF=est:wi14h02.x1
/CLONE=IMAGE:2390259 /UG=Hs.171480
ESTs
ESTs Consensus includes gb:AA088446 /FEA=EST239065 at
_
/DB XREF=gi:1633958
/DB XREF=est:z189f04.s1
/CLONE=IMAGE:511807 /UG=Hs.170298
ESTs
ESTs Consensus includes gb:AI493046 /FEA=EST239148 at
_
/DB XREF=gi:4394049
/DB XREF=est:qz49b04.x1
/CLONE=IMAGE:2030191 /UG=Hs.146133
ESTs
ESTs Consensus includes gb:AI243098 /FEA=EST239966 at
/DB XREF=gi:3838495
/DB XREF=est:qh26e03.x1
/CLONE=IMAGE:1845820 /UG=Hs.178398
ESTs
Weakly Consensus includes gb:AI633523 /FEA=EST240106 at
ESTs, _
similar to /DB XREF=gi:4684853
A49175 Motch /DB XREF=estah68b11.x1
B
protein - (CLONE=IMAGE:2123805 /LJG=Hs.44705
mouse
M.musculus] ESTs
betacellulin Consensus includes gb:AI620677 /FEA=EST241412 at
_
/DB XREF=gi:4629803
lDB_XREF=estau85e09.x1
/CLONE=IMAGE:2257864 /UG=Hs.154191
ESTs
ESTs Consensus includes gb:BF696216 /FEA=EST242626 at
_
/DB XREF=gi:11981624
-46-
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/DB XREF=est:602124536F1
/CLONE=IMAGE:4281632 lUG=Hs.l 88724
ESTs
ESTs Consensus includes gb:N57929 /FEA=EST242978 x
at
lDB XRFF=gi:1201819
/DB XR.EF=est:yv61e06.s1
/CLONE=IMAGE:247234 /UG=Hs.48100
ESTs
ESTs, Weakly Consensus includes gb:AI457984 243729 at
/FEA=EST
similar to /DB XREF=gi:4312002
ALUl_HUMAN /DB XREF=estaj66a04.x1
ALU /CLONE=IMAGE:2146446 /UG=Hs.165900
SUBFAMILY ESTs, Weakly similar to ALUC_HUMAN
J ! ! ! !
SEQUENCE ALU CLASS C WARNING ENTRY ! ! !
CONTAMINAT H.sapiens
ION WARNING
ENTRY
[H.sapiens)
ESTs Consensus includes gb:AA581439 244650 at
/FEA=EST
/DB XREF=gi:2359211
/DB XREF=est:nh13c10.s1
/CLONE=IMAGE:952242 lUG=Hs.152328
ESTs
The two biomarker probe sets A and B were then combined, a total of 161
different probe sets, and the redundant polynucleotides were removed,
representing
125 unique polynucleotides which are provided below in Table 4. The Table 4
polynucleotides are biomarkers of the invention.
TABLE 4 - Biomarkers
Unigene Title Affymetrix Description Affymetrix
And SEQ ID robe set
NO:
3-hydroxy-3- gb:NM 005518.1 /DEF=Homo sapiens204607
3- at
methylglutaryl- hydroxy-3-methylglutaryl-Coenzyme~
A
Coenzyme A synthase 2 (mitochondrial) (HMGCS2),
synthase 2 mRNA. /FEA=mRNA /GEN=HMGCS2
(mitochondrial) /PROD=3-hydroxy-3-methylglutaryl-
Coenzyme A synthase 2(mitochondrial)
SEQ ID NOS: /DB XREF=gi:5031750 /UG=Hs.59889
1 3-
(DNA) and 126 hydroxy-3-methylglutaryl-Coenzyme
A
(amino acid) synthase 2 (mitochondrial)
/FL=gb:NM 005518.1
ATPase, Class Consensus includes gb:AW006935 214070 s at
V,
type lOB /FEA=EST /DB XREF=gi:5855713
/DB XREF=est:wt08bll.xl
_47_
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SEQ ID NO: 2 /CLONE=IMAGE:2506845 /UG=Hs.109358
(DNA) ATPase, Class V, a lOB
bone morphogeneticgb:NM 001200.1 /DEF=Homo sapiens 205290 s_at
bone
protein 2 morphogenetic protein 2 (BMP2),
mRNA.
/FEA=mRNA IGEN=BMP2 /PROD=bone
SEQ ID NOS: 3 morphogenetic protein 2 precursor
(DNA) and 127 /DB XREF=gi:4557368 /UG=Hs.73853
bone
(amino acid) morphogenetic protein 2
lFL=gb:NM 001200.1
brain-specific gb:NM 007030.1 /DEF=Homo sapiens 206179 s at
protein brain-
p25 alpha specific protein p25 alpha (p25),
mRNA.
IFEA=mRNA /GEN~25 !PROD=brain-
SEQ ID NOS: 4 specific protein p25 alpha
(DNA) and 128 /DB XREF=gi:5902017 /LTG=Hs.29353
(amino acid) brain-specific protein p25 alpha
/FL=gb:AB017016.1 gb:NM 007030.1
branched chain Consensus includes gb:NM 005504.1214452_at
aminotransferase/DEF=Homo sapiens branched chain
1,
cytosolic aminotransferase 1, cytosolic
(BCAT1),
mRNA. /FEA=CDS /GEN=BCAT1
SEQ ID NOS: 5 /PROD=branched chain aminotransferase
1,
(DNA) and 129 cytosolic /DB XREF=gi:5031606
(amino acid) /LJG=Hs.157205 branched chain
aminotransferase l, cytosolic
/FL=gb:U21551.1 b:NM 005504.1
BTG family, membergb:NM 006763.1 /DEF=Homo Sapiens 201236 s_at
BTG
2 family, member 2 (BTG2), mRNA.
/FEA=mRNA /GEN=BTG21PROD=BTG
SEQ ID NOS: 6 family, member 2 /DB XREF=gi:5802987
(DNA) and 130 /UG=Hs.75462 BTG family, member
2
(amino acid) /FL=gb:U72649.1 gb:NM 006763.1
Carcinoembryonicgb:BC005008.1 /DEF=Homo sapiens, 203757 s_at
antigen-related carcinoembryonic antigen-related
cell cel1
adhesion moleculeadhesion molecule 6 (non-specific
6 cross
(non-specific reacting antigen), clone MGC:10467,
cross mRNA,
reacting antigen)complete cds. /FEA=inRNA
/PROD=carcinoembryonic antigen-related
SEQ ID NOS: 7 cell adhesionmolecule 6 (non-specific
cross
(DNA) and 131 reacting antigen) /DB XREF=gi:13477106
(amino acid) /LTG=Hs.73848 carcinoembryonic
antigen-
related cell adhesion molecule
6 (non-specific
cross reacting antigen) /FL=gb:BC005008.1
gb:M18216.1 gb:M29541.1 gb:NM
002483.1
caspase 10, apoptosis-gb:NM 001230.1 /DEF=Homo sapiens 205467 at
related cysteinecaspase 10, apoptosis-related
cysteine
protease protease (CASP 10), mRNA. /FEA=mRNA
/GEN=CASP 10 /PROD=caspase 10,
SEQ ID NOS: 8 a o tosis-related cysteine protease
-48-
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(DNA) and 132 /DB XREF=gi:4502568 /UG=Hs.5353
(amino acid) caspase 10, apoptosis-related
cysteine
rotease /FL=gb:U60519.1 gb:NM
001230.1
CUG triplet repeat,gb:NM 006561.1 /DEF=Homo sapiens202158 s at
CUG
RNA-binding proteintriplet repeat, RNA-binding protein2
2 (CUGBP2), mRNA. /FEA=mRNA
/GEN=CUGBP2 /PROD=CUG triplet
repeat,
SEQ ID NOS: 9 RNA-binding protein 2
(DNA) and 133 /DB XREF=gi:5729815 lUG=Hs.211610
(amino acid) CUG triplet repeat, RNA-binding
protein 2
/FL=gb:U69546.1 gb:AF036956.1
gb:AF090694.1 gb:NM 006561.1
cystatin S gb:NM 001899.1 /DEF=Homo sapiens206994 at
cystatin S (CST4), mRNA. /FEA=mRNA
SEQ ID NOS: 10 /GEN=CST4 /PROD=cystatin S
(DNA) and 134 /DB XREF=gi:4503108 /LJG=Hs.56319
(amino acid) cystatin S /FL=gb:NM 001899.1
cystic fibrosis gb:NM 000492.2 JDEF=Homo sapiens205043 at
cystic
transmembrane fibrosis transmembrane conductance
conductance regulator, ATP-binding cassette
(sub-family
regulator, ATP- C, member 7) (CFTR), mRNA.
binding cassette/FEA=mRNA /GEN=CFTR /PROD=cystic
(sub-
family C, memberfibrosis transmembrane conductanceregulator,
7)
ATP-binding cassette (sub-family
C, member
SEQ ID NOS: 11 7) /DB XREF=gi:6995995 /UG=Hs.663
(DNA) and 135 cystic fibrosis transmembrane
conductance
(amino acid) regulator, ATP-binding cassette
(sub-family
C, member 7) /FL=gb:NM 000492.2
cytochrome P450,gb:NM 000775.1 /DEF=Homo sapiens205073 at
subfamily IIJ cytochrome P450, subfamily IIJ
(arachidonic
(arachidonic acid epoxygenase) polypeptide
acid 2 (CYP2J2),
epoxygenase) mRNA. /FEA=mRNA /GEN=CYP2J2
polypeptide 2 /PROD=cytochrome P450, subfamily
IIJ
(arachidonic acidepoxygenase)
polypeptide 2
SEQ ID NOS: 12 /DB XREF=gi:4503226 /LTG=Hs.152096
(DNA) and 136 cytochrome P450, subfamily IIJ
(arachidonic
(amino acid) acid epoxygenase) polypeptide
2
/FL=gb:U37143.1 b:NM 000775.1
dipeptidylpeptidasegb:M80536.1 /DEF=H.sapiens dipeptidyl203716 s at
IV (CD26, adenosinepeptidase IV (DPP4) mRNA, complete
cds.
deaminase /FEA=mRNA /GEN=DPP4
complexing protein/PROD=dipeptidyl peptidase IV
2)
IDB_XREF=gi:181569 iLTG=Hs.44926
SEQ ID NOS 13 dipeptidylpeptidase IV (CD26,
adenosine
(DNA) and 137 deaminase complexing protein
2)
(amino acid) /FL=gb:M80536.1 gb:NM 001935.1
DI~FZP434C091 Consensus includes gb:AL080170.1215047 at
rotein /DEF=Homo sa iens mRNA; cDNA
-49-
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DKFZp434C091 (from clone
SEQ ID NO: 14 DKFZp434C091); partial cds. /FEA=mRNA
(DNA) /GEN=DKFZp434C091 /PROD=hypothetical
protein /DB XREF=gi:5262639
/UG=Hs.51692 DKFZP434C091 rotein
dopa decarboxylaseConsensus includes gb:AW772056 214347 s at
(aromatic L-amino/FEA=EST /DB XREF=gi:7704118
acid decarboxylase)/DB XREF=est:hn64g06.x1
/CLONE=IMAGE:3032698 /LTG=Hs.150403
SEQ ID NO: 15 dopa decarboxylase (aromatic
L-amino acid
(DNA) decarboxylase)
EphAl gb:NM 005232.1 /DEF=Homo Sapiens205977 s_at
EphA 1 (EPHA 1 ), mRNA. /FEA=mRNA
SEQ ID NOS: 16 /GEN=EPHAl /PROD=EphAl
(DNA) and 138 /DB XREF=gi:4885208 /LTG=Hs.89839
(amino acid) E hAl /FL=gb:M18391.1 gb:NM 005232.1
ESTs, ModeratelyConsensus includes gb:R06655 217546_at
/FEA=EST
similar to AF078844/DB XREF=gi:757275
1 hqp0376 protein/DB XREF=est:yf10e02.r1
[H.sapiens] /CLONE=IMAGE:126458 /UG=Hs.188518
ESTs, Moderately similar to AF078844
1
SEQ ID NO: 17 hqp0376 protein H.sapiens
(DNA)
ESTs, Weakly Consensus includes gb:AW675655 222354 at
similar
to I38022 /FEA=EST /DB XREF=gi:7540890
hypothetical /DB XREF=est:ba52e01.x1
protein
[H. sapiens] /CLONE=IMAGE:2900184 lUG=Hs.31415
8
ESTs
SEQ ID NO: 18
(DNA)
fibroblast growthgb:NM 022969.1 lDEF=Homo Sapiens203638 s at
factor receptor fibroblast growth factor receptor
2 2 (bacteria-
(bacteria-expressedexpressed kinase, keratinocyte
growth factor
kinase, keratinocytereceptor, craniofacial dysostosis
1, Crouzon~
growth factor syndrome, Pfeiffer syndrome,
Jackson-Weiss
receptor, craniofacialsyndrome) (FGFR2), transcript
variant 2,
dysostosis 1, mRNA. JFEA=mRNA IGEN=FGFR2
Crouzon
syndrome, Pfeiffer/PROD=fibroblast growth factor
receptor 2,
syndxome, Jackson-isoform 2precursor /DB XREF=gi:13186252
Weiss syndrome) /UG=Hs.278581 fibroblast growth
factor
receptor 2 (bacteria-expressed
kinase,
SEQ ID NOS: 19 keratinocyte growth factor receptor,
(DNA) and 139 craniofacial dysostosis 1, Crouzon
syndrome,
(amino acid) Pfeiffer syndrome, Jackson-Weiss
syndrome)
/FL=gb:NM 022969.1 gb:M97193.1
gb:M80634.1
FXYD domain- gb:BC005238.1 /DEF=Homo Sapiens,202489 s_at
FXYD
containing ion domain-containing ion trans ort
regulator 3,
-50-
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transport regulatorclone MGC:12265, mRNA, complete
3 cds.
/FEA=mRNA /PROD=FXYD domain-
SEQ ID NOS: 20 containing ion transport regulator3
(DNA) and 140 /DB XREF=gi:13528881 /UG=Hs.301350
(amino acid) FXYD domain-containing ion transport
regulator 3 /FL=gb:NM 005971.2
b:BC005238.1
G protein-coupledgb:AF062006.1 /DEF=Homo sapiens 210393 at
orphan
receptor 49 G protein-coupled receptor HG38
mRNA,
complete cds. /FEA=mRNA /PROD=orphan
SEQ ID NOS: 21 G protein-coupled receptor HG38
(DNA) and 141 /DB XREF=gi:3366801 /UG=Hs.285529
G
(amino acid) protein-coupled receptor 49
/FL=gb:AF062006.1 gb:AF061444.1
gb:NM 003667.1
hairless (mouse)gb:NM 018411.1 /DEF=Homo Sapiens 220163 s at
homolog hairless protein (putative single
zinc finger
transcription factor protein,
responsible for
SEQ ID NOS: 22 autosomal recessive universal
congenital
(DNA) and 142 alopecia, HR gene) (HSA277165),
mRNA.
(amino acid) /FEA=mRNA /GEN=HSA277165
/PROD=hairless protein
/DB XREF=gi:11036651 /UG=Hs.272367
hairless protein (putative single
zinc finger
transcription factor protein,
responsible for
autosomal recessive universal
congenital
alo ecia, HR gene) /FL= b:NM 018411.1
hemoglobin, alphagb:BC005931.1 /DEF=Homo Sapiens, 211745 x at
1
hemoglobin, alpha 2, clone MGC:14541,
SEQ ID NOS: 23 mRNA, complete cds. /FEA=mRNA
(DNA) and 143 /PROD=hemoglobin, alpha 2
(amino acid) /DB XRFF=gi:13543547
/FL= b:BC005931.1
hemoglobin, alphaConsensus includes gb:T50399 /FEA=EST.214414 x at
2
/DB XREF=gi:652259
SEQ ID NO: 24 /DB XREF=est:yb30b1 l.sl
(DNA) l CLONE=IMAGE:72669 I UG=Hs.251577
hemo lobin, al ha 1
heparanase gb:NM_006665.1 /DEF=Homo Sapiens 219403 s_at
heparanase (HPSE), mRNA. /FEA=mRNA
SEQ ID NOS: 25 /GEN=HPSE /PROD=heparanase
(DNA) and 144 /DB XREF=gi:5729872 /UG=Hs.44227
(amino acid) heparanase /FL=gb:AF165154.1
gb:AF152376.1 gb:NM_OQ6665.1
gb:AF084467.1 gb:AF155510.1
Pudlak Consensus includes gb:AL022313 217354 s at
Hermansky- _
syndrome /DEF=Human DNA sequence from clone
RPS-1119A7 an chromosome 22 12.2-12.3
-51-
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SEQ ID NOS: 26 Contains the TXN2 gene for mitochondria)
(DNA) and 145 thioredoxin, a novel gene, the
EIF3S7 gene
(amino acid) for eukaryotic translation initiation
factor 3
subunit 7 (zeta, 6667kD) (EIF3-P66),
the
gene f... /FEA=CDS_3
/DB XREF=gi:4200326 /UG=Hs.272270
Human DNA sequence from clone
RP5-
1119A7 on chromosome 22q12.2-12.3
Contains the TXN2 gene for mitochondria)
thioredoxin, a novel gene, the
EIF3S7 gene
for eukaryotic translation initiation
factor 3
subunit 7 (zeta, 6667kD) (EIF3-P66),
the
gene for a nov
HERV-H LTR- gb:NM 007072.1 /DEF=Homo Sapiens 220812 s_at
associating 2 HERV-H LTR-associating 2 (HHLA2),
mRNA. /FEA=mRNA /GEN=HHLA2
SEQ ID NOS: 27 /PROD=HERV-H LTR-associating 2
(DNA) and 146 /DB XREF=gi:5901963 /LTG=Hs.252351
(amino acid) HERV-H LTR-associating 2
/FL=gb:AF126162.1 b:NM 007072.1
Homo Sapiens Consensus includes gb:AW593996 213256 at
clone
24707 mRNA /FEA=EST /DB X_RFF=gi:7281254
sequence /DB XREF=est:hg41g06.x1
/CLONE=IMAGE:2948218 /UG=Hs.124969
SEQ ID NO: 28 Homo Sapiens clone 24707 mRNA
sequence
(DNA)
Homo sapiens Consensus includes gb:AL049983.1 217288 at
mRNA; cDNA /DEF=Homo sapiens mRNA; cDNA
DI~FZp564D042 DI~FZp564D042 (from clone
(from clone DI~.FZp564D042). /FEA=mRNA
DI~F'Zp564D042) !DB_~~REF=gi:4884234 /UG=Hs.244136
Homo Sapiens mRNA; cDNA
SEQ ID NO: 29 DKFZp564D042 (from clone
(DNA) DKFZp564D042)
hypothetical gb:NM 017640.1 /DEF=Homo Sapiens 219573 at
protein
FLJ20048 hypothetical protein FLJ20048
(FLJ20048),
mRNA. /FEA=mRNA /GEN=FLJ20048
SEQ ID NOS: 30 /PROD=hypothetical protein FLJ20048
(DNA) and 147 /DB XREF=gi:8923056 /UG=Hs.116470
(amino acid) hypothetical protein FLJ20048
/FL=gb:NM 017640.1
hypothetical gb:NM 017655.1 /DEF=Homo Sapiens 219970 at
protein
FLJ20075 hypothetical protein FLJ20075
(FLJ20075),
mRNA. /FEA=mRNA /GEN=FLJ20075
SEQ ID NOS: 31 /PROD=hypothetical protein FLJ20075
(DNA) and 148 /DB XREF=gi:8923083 lUG=Hs.205058
(amino acid) hypothetical protein FLJ20075
/FL=gb:NM 017655.1
-52-
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interferon consensusConsensus includes gb:AI073984 204057 at
/FEA=EST
sequence bindingIDB_XREF=gi:3400628
protein 1 /DB XREF=est:oy66cO5.x1
/CLONE=IMAGE:1670792 /UG=Hs.14453
SEQ ID NO: 32 interferon consensus.sequence
binding protein
(DNA) 1 /FL=gb:M91196.1 gb:NM 002163.1
KIAA0690 proteinConsensus includes gb:AK000238.1216360 x at
/DEF=Homo Sapiens cDNA FLJ20231
fis,
SEQ ID NO: 33 clone COLF5511, highly similar
to
(DNA) AB014590 Homo sapiens mRNA for
I~IAA0690 protein. /FEA=mRNA
/DB_~REF=gi:7020188 /L1G=Hs.60103
I~IAA0690 protein
matrilin 3 . gb:NM_002381.2 /DEF=Homo Sapiens206091 at
matrilin 3 (MATN3) precursor,
mRNA.
SEQ ID NOS: 34 /FEA~nRNA /GEN=MATN3
(DNA) and 149 /PROD=matrilin 3 precursor
(aanino acid) !DB ~~REF=gi:13518040 !UG=Hs.278461
matrilin 3 /FL=gb:NM 002381.2
metastasis-associatedgb:NM 004739.1 /DEF=Homo Sapiens203444 s at
1-like 1 metastasis-associated 1-like
1 (MTA1L1),
mRNA. /FEA=mRNA /GEN=MTA 1 L
1
SEQ ID NOS: 35 /PROD=metastasis-associated 1-like
1
(DNA) and 150 /DB XREF=gi:4758739 /LTG=Hs.173043
(amino acid) metastasis-associated 1-like
1
/FL=gb:AB016591.1 gb:NM 004739.1
gb:AF295807.1
mucin 2, gb:NM 002457.1 /DEF=Homo Sapiens204673 at
mucin
intestinal/tracheal2, intestinaltracheal (MUC2),
mRNA.
/FEA=mRNA /GEN=MUC2 /PROD=mucin
SEQ ID NOS: 36 2, intestinaltracheal /DB XREF=gi:4505284
(DNA) and 151 /UG=Hs.315 mucin 2, intestinaltracheal
(amino acid) /FL=gb:NM 002457.1 gb:L21998.1
mucin 3B Consensus includes gb:AB038783.1214898 x at
/DEF=Homo sapiens MUC3B mRNA
for
SEQ ID NOS: 37 intestinal mucin, partial cds.
/FEA=mRNA
(DNA) and 152 /GEN=MUC3B /PROD=intestinal mucin
(amino acid) /DB XREF=gi:9929917 /UG=Hs.129782
mucin 3A, intestinal
myosin, heavy gb:NM_003802.1 /DEF=Homo sapiens208208 at
polypeptide 13, myosin, heavy polypeptide 13,
skeletal
skeletal muscle muscle (MYH13), mRNA. /FEA=mRNA
/GEN=MYH13 /PROD=myosin, heavy
SEQ ID NOS: 38 polypeptide 13, skeletal muscle
(DNA) and 153 /DB XREF=gi:11321578 /UG=Hs.278488
(amino acid) myosin, heavy polypeptide 13,
skeletal
muscle /FL=gb:NM 003802.1
b:AF111782.2
- 53 -
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myosin, light gb:NM 002477.1 /DEF=Homo Sapiens 205145 s
at
polypeptide 5, myosin, light polypeptide 5, regulatory
regulatory (MYLS), mRNA. /FEA=mRNA
/GEN=MYLS /PROD=myosin, light
SEQ ID NOS: 39 polypeptide 5, regulatory ,
(DNA) and 154 /DB XREF=gi:4505304 /UG=Hs.170482
(amino acid) myosin, light polypeptide 5, regulatory
lFL=gb:L03785.1 gb:NM 002477.1
nuclear receptorgb:NM_000901.1 /DEF=Homo sapiens 205259 at
subfamily 3, nuclear receptor subfamily 3,
group C, group C,
member 2 member 2 (NR3C2), mRNA. /FEA=mRNA
/GEN NR3C2 /PROD=nuclear receptor
SEQ ID NOS: 40 subfamily 3, group C, member 2
(DNA) and 155 /DB XREF=gi:4505198 lUG=Hs.1790
(amino acid) nuclear receptor subfamily 3,
group C,
member 2 /FL=gb:M16801.1
gb:NM 000901.1
nuclear receptorConsensus includes gb:AF228413.1 210174 at
subfamily 5, /DEF=Homo Sapiens hepatocyte transcription
group A,
member 2 factor mRNA, 3UTR. /FEA=mRNA
lDB_XREF=gi:7677372 /LTG=Hs.183123
SEQ ID NOS: 41 nuclear receptor subfamily 5,
group A,
(DNA) and 156 member 2 /FL=gb:U93553.1 gb:AB019246.1
(amino acid) gb:AF124247.1
pancreas-enrichedgb:NM 016341.1 /DEF=Homo sapiens 205112 at
phospholipase pancreas-enriched phospholipase
C C
(LOC51196), mRNA. IFEA=mRNA
SEQ ID NOS: 42 /GEN=LOC51196 /PROD=pancreas-enriched
(DNA) and 157 phospholipase C /DB XREF=gi:7705940
(amino acid) /UG=Hs.6733 pancreas-enriched
phospholipase C /FL=gb:AF190642.2
gb:AF117948.1 gb:NM 016341.1
peroxisomal trapsgb:NM_018441.1 /DEF=Homo sapiens 221142 s_at
2-
enoyl CoA reductase;peroxisomal traps 2-enoyl CoA
reductase;
putative short putative short chain alcohol dehydrogenase
chain
alcohol (HSA250303), mRNA. /FEA=mRNA
dehydrogenase /GEN=HSA250303 !PROD=peroxisomal
traps 2-enoyl CoA reductase;putative
short
SEQ ID NOS: 43 chain alcohol dehydrogenase
(DNA) and 158 /DB XREF=gi:8923751 !UG=Hs.281680
(amino acid) peroxisomal traps 2-enoyl CoA
reductase;
putative short chain alcohol dehydrogenase
/FL=gb:NM 018441.1
phosducin gb:M33478.1 /DEF=Human 33-kDa 211496 s_at
phototransducing protein mRNA,
complete
SEQ ID NOS: 44 cds. IFEA=mRNA /DB XREF=gi:1771.86
(DNA) and 159 /LTG=Hs.550 phosducin
(amino acid) /FL= b:NM 022577.1 b:M33478.1
-54-
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b:AF076465.1
phosphatase and gb:NM 000314.1 /DEF=Homo sapiens204054 at
tensin homolog phosphatase and tensin homolog
(mutated in
(mutated in multiplemultiple advanced cancers 1)
(PTEN),
advanced cancersmRNA. /FEA=mRNA IGEN=PTEN
1)
/PROD=phosphatase and tensin
homolog
SEQ ID NOS: 45 (mutated inmultiple advanced
cancers 1)
(DNA) and 160 lDB XREF=gi:4506248 lUG=Hs.10712
(amino acid) phosphatase and tensin homolog
(mutated in
multiple advanced cancers 1)
/FL=gb:U92436.1 gb:U93051.1 gb:U96180.1
gb:NM 000314.1
potassium channel,gb:U90065.1 /DEF=Human potassium204678 s at
subfamily K, channel KCNO1 mRNA, complete
member cds.
1 (TWIK-1) /FEA=mRNA /PROD=potassium channel
KCNOl /DB XREF=gi:1916294
SEQ ID NOS: 46 /UG=Hs.79351 potassium channel,
subfamily
(DNA) and 161 K, member 1 (TWIK-1) /FL=gb:U33632.1
amino acid) b:U90065.1 b:U76996.1 b:NM_002245.1
prostaglandin- gb:NM 000963.1 /DEF=Homo sapiens204748 at
endoperoxide prostaglandin-endoperoxide synthase2
synthase 2 (prostaglandin GH synthase and
(prostaglandin cyclooxygenase) (PTGS2), mRNA.
G/H
synthase and /FEA=mRNA IGEN=PTGS2
cyclooxygenase) /PROD=prostaglandin-endoperoxide
synthase
2(prostaglandin GH synthase and
SEQ ID NOS: 47 cyclooxygenase) /DB XREF=gi:4506264
(DNA) and 162 /UG=Hs.196384 prostaglandin-endoperoxide
(amino acid) synthase 2 (prostaglandin GH
synthase and
cyclooxygenase) /FL=gb:M90100.1
gb:L15326.1 gb:NM 000963.1
protease inhibitorgb:NM 002638.1 /DEF=Homo Sapiens203691 at
3,
skin-derived protease inhibitor 3, skin-derived
(SKALP)
(SKALP) (PI3), mRNA. IFEA=mRNA lGEN=PI3
/PROD~rotease inhibitor 3, skin-derived
SEQ ID NOS: 48 (SKALP) /DB XREF=gi:4505786
(DNA} and 163 /UG=Hs.112341 protease inhibitor
3, skin-
(amino acid) derived (SKALP) /FL=gb:NM 002638.1
PTPRF interactingConsensus includes gb:AI692180 212841 s_at
/FEA=EST
protein, binding/DB XREF=gi:4969520
protein 2 (liprin/DB XREF=est:wd37f06.x1
beta
2) /CLONE=IMAGE:2330339 /LTG=Hs.12953
PTPRF interacting protein, binding
protein 2
SEQ ID NO: 49 (liprin beta 2)
(DNA)
retinoic acid Consensus includes gb:AI669229 221872 at
receptor IFEA=EST
responder (tazarotene/DB XREF=gi:4834003
induced) 1 /DB XREF=est:wc13e06.x1
-55-
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/CLONE=IMAGE:2315074 /UG=Hs.82547
SEQ TD NO: 50 retinoic acid receptor responder
(tazarotene
(DNA) induced) 1
Rho GTPase 015366.1 /DEF=Homo sapiens Rho 205980 s
gb:NM at
activating protein_
8 GTPase activating protein 8 (ARHGAPB),
mRNA. IFEA=mRNA /GEN=ARHGAP8
SEQ ID NOS: 51 /PROD=Rho GTPase activating protein
8
(DNA) and 164 /DB XREF=gi:7656903 /UG=Hs.102336
(amino acid) Rho GTPase activating protein
8
/FL= b:NM 015366.1
ribonuclease, gb:NM 002933.1 /DEF=Homo sapiens 201785 at
RNase
A family, 1 ribonuclease, RNase A family, )
1 (pancreatic
(pancreatic) (RNASE 1 ), mRNA. /FEA=mRNA
/GEN=RNASEl /PROD=ribonuclease,
SEQ ID NOS: 52 RNase A family, 1 (pancreatic)
(DNA) and 165 /DB XREF=gi:4506546 /UG=Hs.78224
(amino acid) ribonuclease, RNase A family,
1 (pancreatic)
/FL=gb:BC005324.1 gb:NM 002933.1
gb:D26129.1
serine (or cysteine)gb:NM 002639.1 /DEF=Homo Sapiens 204855 at
serine
proteinase inhibitor,(or cysteine) proteinase inhibitor,B
Glade
Glade B (ovalbumin),(ovalbumin), member 5 (SERPINBS),
member 5 mRNA. /FEA=mRNA /GEN=SERP1NB5
/PROD=serine (or cysteine) proteinase
SEQ ID NOS: 53 inhibitor, cladeB (ovalbuxnin),
member 5
(DNA) and 166 /DB XREF=gi:4505788 /UG=Hs.55279
(amino acid) serine (or cysteine) proteinase
inhibitor, Glade
B (ovalbumin), member 5
/FL=gb:NM 002639.1 gb:U04313.1
spondin 1, (f Consensus includes gb:AI885290 213994 s
spondin) /FEA=EST at
extracellular /DB XREF=gi:5590454
matrix
protein /DB XREF=est:w192a04.x1
/CLONE=IMAGE:2432334 /UG=Hs.5378
SEQ ID NO: 54 spondin l, (f spondin) extracellular
matrix
(DNA) rotein
superoxide dismutasegb:NM 003102.1 /DEF=Homo sapiens 205236 x
at
3, extracellularsuperoxide dismutase 3, extracellular
(SOD3),
mRNA. /FEA=mRNA /GEN=SODS
SEQ ID NOS: 55 /PROD=superoxide dismutase 3,
extracellular
(DNA) and 167 lDB_XREF=gi:4507150 /UG=Hs.2420
(amino acid) superoxide dismutase 3, extracellular
/FL=gb:J02947.1 gb:NM 003102.1
tumor necrosis gb:BC002794.1 /DEF=Homo Sapiens, 209354 at
factor tumor
receptor superfamily,necrosis factor receptor superfamily,
member
member 14 14 (herpesvirus entry mediator),
clone
(herpesvirus MGC:3753, mRNA, complete Gds.
entry
mediator) lFEA=mRNA /PROD=tumor necrosis
factor
rece for su erfamily,member 14
(he esvirus
-56-
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SEQ ID NOS: 56 entry mediator) /DB XREF=gi:12803894
(DNA) and 168 !UG=Hs.279899 tumor necrosis
factor
(amino acid) receptor superfamily, member
14 (herpesvirus
entry mediator) /FL=gb:BC002794.1
gb:U70321.1 gb:U81232.1 gb:NM
003820.1
gb:AF153978.1
tumor necrosis gb:NM 000043.1 /DEF=Homo Sapiens204781 s at
factor tumor
receptor superfamily,necrosis factor receptor superfamily,
member
member 6 6 (TNFRSF6), mRNA. /FEA=mRNA
/GEN=TNFRSF6 /PROD=apoptosis
(APO-1)
SEQ ID NOS: 57 antigen 1 /DB XREF=gi:4507582
(DNA) and 169 /LJG=Hs.82359 tumor necrosis
factor receptor
(amino acid) superfamily, member 6 /FL=gb:M67454.1
b:NM 000043.1
zinc finger proteingb:NM 003438.1 /DEF=Homo sapiens20?394 at
zinc
137 (clone pHZ-30)finger protein 137 (clone pHZ-30)
(ZNF137),
mRNA. /FEA=mRNA /GEN=ZNF 13 7
SEQ ID NOS: 58 /PROD=zinc finger protein 137
(clone pHZ-
(DNA) and 170 30) /DB XREF=gi:4507988 /LTG=Hs.151689
(amino acid) zinc finger protein 137 (clone
pHZ-30)
/FL=gb:NM 003438.1 gb:U09414.1
hypothetical Consensus includes gb:AI339568 222727 s_at
protein /FEA=EST
FLJ22233 /DB XREF=gi:4076495
/DB XREF=est:qk67e10.x1
SEQ ID NO: 59 /CLONE=IMAGE:1874058 /UG=Hs.286194
(DNA) hypothetical protein FLJ22233
/FL= b:NM 024959.1
regenerating gb:AY007243.1 /DEF=Homo Sapiens 223447 at
gene
type IV regenerating gene type IV mRNA,
complete
cds. /FEA=mRNA /PROD=regenerating
gene
SEQ ID NOS: 60 type IV /DB XREF=gi:12621025
(DNA) and 171 /LTG=Hs.105484 Homo Sapiens regenerating
(amino acid) gene type IV mRNA, complete cds
!FL=gb:AY007243.1
Homo sapiens Consensus includes gb:AK025615.1225285 at
cDNA:
FLJ21962 fis, /DEF=Homo Sapiens cDNA: FLJ21962
clone fis,
HEP05564 clone HEP05564. /FEA=mRNA
/DB XREF=gi:10438186 /UG=Hs.7567
SEQ ID NO: 61 Homo sapiens cDNA: FLJ21962 fis,
clone
(DNA) HEP05564
ESTs Consensus includes gb:N37023 225407 at
IFEA=EST
/DB XREF=gi:1158165
SEQ ID NO: 62 1DB XREF=est:yy40d03.s1
(DNA) /CLONE=IMAGE:273701 /UG=Hs.235883
ESTs
phosphoprotein Consensus includes gb:AI~000680.1225626 at
associated with /DEF=Homo sapiens cDNA FLJ20673
fis,
lycos hin oli clone I~AAIA4464. /FEA=mRNA
id-
-57-
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enriched /DB XREF=gi:7020924 /UG=Hs.266175
microdomains phosphoprotein associated with
GEMS
/FL=gb:AF240634.1 gb:NM_018440.1
SEQ ID NOS: 63
(DNA) and 172
(amino acid)
prostate cancer Consensus includes gb:AA633076 226167 at
/FEA=EST
associated proteinlDB_XREF=gi:2556490
7
/DB XREF=est:nq38a06.s1
SEQ ID NO: 64 /CLONE=IMAGE:1146130 /UG=Hs.27495
(DNA) rostate cancer associated rotein
7
Homo Sapiens, Consensus includes gb:AA524690 226168 at
/FEA=EST
Similar to RIKEN/DB XREF=gi:2265618
cDNA 1110060018 /DB XREF=est:ng38e07.s1
gene, clone /CLONE=IMAGE:937092 /UG=Hs.294143
MGC:17236 ESTs, Weakly similar to predicted
using
IMAGE:3864137, Genefinder C.elegans
mRNA, complete
cds
SEQ ID NO: 65
(DNA)
hypothetical Consensus includes gb:BF111925 226171 at
protein /FEA=EST
FLJ20209 /DB XREF=gi:10941704
/DB XREF=est:7138gO5.x1
SEQ ID NO: 66 /CLONE=IMAGE:3523784 /UG=Hs.3685
(DNA) h othetical rotein FLJ20209
Homo sapiens Consensus includes gb:AA532640 226484 at
mRNA /FEA=EST
for KIAA1190 /DB XREF=gi:2276894 .
protein, partial/DB XREF=est:nj 17c04.s1
cds
/CLONE=IMAGE:986598 /UG=Hs.206259
SEQ ID NOS: 67 Homo Sapiens mRNA for KIAA1190
protein,
(DNA) and 173 partial cds
(amino acid)
KIAA1543 proteinConsensus includes gb:AB040976.1226494 at
/DEF=Homo sapiens mRNA for KIAA1543
SEQ ID NOS: 68 protein, partial cds. /FEA=mRNA
(DNA) and 174 /GEN=KIAA1543 /PROD=KIAA1543
(amino acid) protein lDB_XREF=gi:7959352
/UG=Hs.17686 KIAA1543 protein
hypothetical Consensus includes gb:AK002203.1226992_at
protein
MGC20702 /DEF=Homo Sapiens cDNA FLJ11341
fis,
clone PLACE1010786. /FEA=mRNA
SEQ ID NO: 69 /DB XREF=gi:7023932 /UG=Hs.10260
(DNA) Homo sapiens cDNA FLJ11341 fis,
clone
PLACE1010786
Homo Sapiens Consensus includes gb:AA129774 227019 at
cDNA /FEA=EST
FLJ13137 fis, /DB XREF=gi:1690185
clone
NT2RP3003150 /DB XREF=est:z116h09.s1
-58-
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/CLONE=IMAGE:502145 /UG=Hs.288905
SEQ ID NO: 70 Homo sapiens cDNA FLJ13137 fis,
clone
(DNA) NT2RP3003150
hypothetical Consensus includes gb:AW138767 227180 at
protein
FLJ23563 /FEA=EST /DB XREF=gi:6143085
/DB_XREF=est:UI-H-BI1-aep-a-12-0-UI.
s 1
SEQ ID NO: 71 /CLONE=IMAGE:2719799 /UG=Hs.274256
(DNA) h othetical protein FLJ23563
ESTs Consensus includes gb:AW264333 227320 at
/FEA=EST /DB _X_RFF=gi:6641075
SEQ ID NO: 72 /DB XREF=est:xq98e01.x1
(DNA) !CLONE=IMAGE:2758680 !UG=Hs.21835
ESTs
ESTs Consensus includes gb:BF589359 227354 at
/FEA=EST
/DB XREF=gi:11681683
SEQ ID NO: 73 /DB XREF=est:nab25dOl.xl
(DNA) /CLONE=IMAGE:3266737 /UG=Hs.13256
ESTs
Homo sapiens, Consensus includes gb:AW001287 227676 at
Similar to RII~EN/FEA=EST /DB XREF=gi:5848203
cDNA 1810037020 lDB_XREF=est:wu27e06.x1
gene, clone /CLONE=IMAGE:2521282 /UG=Hs.61265
MGC:21481 ESTs, Weakly similar to G786_HUMAN
IMAGE:3852062, PROTEIN GS3786 H.sapiens
mRNA, complete
cds
SEQ ID NO: 74
(DNA)
ESTs, Weakly Consensus includes gb:AA557324 227702 at
similar /FEA=EST
to JX0331 laurate/DB XREF=gi:2327801
omega-hydroxylase/DB XREF=est:n181a02.s1
[H.sapiens] /CLONE=IMAGE:1057034 /UG=Hs.26040
ESTs, Weakly similar to fatty
acid omega-
SEQ ID NO: 75 hydroxylase H.sapiens
(DNA)
Homo Sapiens Consensus includes gb:T86159 227724 at
cDNA: /FEA=EST
FLJ22063 fis, /DB XREF=gi:714511
clone
HEP10326 /DB XREF=est:yd84h07.s1
/CLONE=IMAGE:114973 /UG=Hs.10450
SEQ ID NO: 76 Homo Sapiens cDNA: FLJ22063 fis,
clone
(DNA) HEP 10326
GalNAc alpha-2, Consensus includes gb:Y11339.2 227725 at
6-
sialyltransferase/DEF=Homo Sapiens mRNA for GalNAc
I,
long form alpha-2, 6-sialyltransferase
I, long form.
/FEA=mRNA /PROD=GaINAc alpha-2,6-
SEQ ID NOS: 77 sialyltransferase I /DB XREF=gi:7576275
(DNA) and 175 1UG=Hs.105352 GaINAc alpha-2,
6-
(amino acid) sialyltransferase I, long form
-59-
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ESTs, Weakly Consensus includes gb:AI827789 228241 at
similar /FEA=EST
to JE0350 Anterior!DB XREF=gi:5448449
gradient-2 /DB XREF=est:wf33a07.x1
[H.sapiens] /CLONE=IMAGE:2357364 /LTG=Hs.100686
ESTs, Weakly similar to JE0350
Anterior
SEQ ID NO: 78 gradient-2 H.sapiens
(DNA)
ESTs Consensus includes gb:AI700341 228653 at
/FEA=EST
/DS ~~REF=gi:4988241
SEQ ID NO: 79 /DB XREF=est:wd06e10.x1
(DNA) /CLONE=IMAGE:2327370 /UG=Hs.110406
ESTs
ESTs Consensus includes gb:BG494007 228716 at
/FEA=EST
/DB XREF=gi:13455521
SEQ ID NO: 80 /DB XREF=est:602542289F1
(DNA) , /CLONE=IMAGE:4673182 /LTG=Hs.203213
ESTs
anterior gradientConsensus includes gb:AI922323 228969 at
2 /FEA=EST
(Xenepus laevis)/DB XREF=gi:5658287
homolog /DB XREF=est:wn90h03.x1
/CLONE=IMAGE:2453141 !UG=Hs.293380
SEQ ID NO: 81 ESTs
(DNA)
Homo sapiens Consensus includes gb:AK026984.1229021 at
cDNA:
FLJ23331 fis, /DEF=Homo sapiens cDNA: FLJ23331
clone fis,
HEP 12664 clone HEP 12664. /FEA=mRNA
/DB XREF=gi:10439980 /UG=Hs.50742
SEQ ID N0: 82 Homo Sapiens cDNA: FLJ23331 fis,
clone
(DNA) HEP 12664
ESTs Consensus includes gb:AI559300 229331 at
IFEA=EST
/DB XREF=gi:4509545
SEQ ID N0: 83 /DB XREF=estaq43d03.x1
(DNA) /CLONE=IMAGE:2211557 /UG=Hs.294140
ESTs
hypothetical Consensus includes gb:AI830823 229439 s at
protein /FEA=EST
/DB XREF=gi:5451416
SEQ ID NO: 84 !DB XREF=est:wj52b06.x1
(DNA) /CLONE=IMAGE:2406419 /UG=Hs.95549
by othetical rotein
ESTs Consensus includes gb:BF431989 229657 at
/FEA=EST
/DB XREF=gi:11444103
SEQ ID N0: 85 /DB XREF=est:nab84a05.x1
(DNA) /CLONE=IMAGE:3274280 ILTG=Hs.203213
ESTs
ESTs Consensus includes gb:BF589413 229893 at
/FEA=EST
/DB XREF=gi:11681737
SEQ ID NO: 86 /DB XREF=est:nab26b11.x1
(DNA) /CLONE=IMAGE:3267020 /UG=Hs.55501
-60-
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ESTs
brain-specific Consensus includes gb:BG055052 230104_s_at
protein /FEA=EST
p25 alpha /DB XREF=gi:12512386
/DB XREF=est:nac94g06.x1
SEQ ID NO: 87 /CLONE=IMAGE:3441995 /UG=Hs.29353
(DNA) brain-s ecific rotein 25 al ha
Weakly similar Consensus includes gb:BF110588 230645 at
ESTs /FEA=EST
,
to MMHUE4 /DB XREF=gi:10940278
erythrocyte /DB XREF=est:7n39e12.x1
membrane protein/CLONE=IMAGE:3567071 /UG=Hs.150478
4.1, parent spliceESTs, Weakly similar to KIAA0987
protein
form [H.sapiens]H.sapiens
SEQ ID NO: 88
(DNA)
ESTs Consensus includes gb:BF592062 230760 at
/FEA=EST _
/DB XREF=gi:11684386
SEQ ID NO: 89 /DB XREF=est:7n98h06.x1
(DNA) /CLONE=IMAGE:3572962 /UG=Hs.233890
ESTs
nuclear Consensus includes gb:AI032108 230914 at
hepatocyte /FEA=EST _
factor 4, alpha /DB XREF=gi:3250320
/DB XREF=est:ow92dll.xl
SEQ D~ NO: 90 (CLONE=IMAGE:1654293 lUG=Hs.54424
(DNA) hepatocyte nuclear factor 4, alpha
ESTs Consensus includes gb:AW203959 230944 at
/FEA=EST /DB XREF=gi:6503431
SEQ ID NO: 91 /DB_XREF=est:UI-H-BI1-aeu-b-12-0-ULsl
(DNA) /CLONE=IMAGE:2720590 /UG=Hs.149532
ESTs
ESTs Consensus includes gb:AI139990 231022 at
/FEA=EST _
/DB ~~REF=gi:3647447
SEQ ID NO: 92 /DB XREF=est:qa47d03.x1
(DNA) /CLONE=IMAGE:1689893 /UG=Hs.134586
ESTs
ESTs Consensus includes gb:AI806131 231148 at
/FEA=EST _
/DB XREF=gi:5392697
SEQ ID NO: 93 /DB XREF=est:wf06c06.x1
(DNA) /CLONE=IMAGE:2349802 /UG=Hs.99376
ESTs
hypothetical Consensus includes gb:AB046810.1 232083 at
protein
FLJ23045 /DEF=Homo sapiens mRNA for KIAA1590
protein, partial cds. /FEA=mRNA
SEQ ID NO: 94 /GEN=KIAA1590 /PROD=KIAA1590
(DNA) protein /DB XREF=gi:10047254
/UG=Hs.101774 hypothetical protein
FLJ23045
Homo sa iens Consensus includes gb:AK026404.1 232321 at
cDNA:
-61-
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FLJ22751 fis, /DEF=Homo sapiens cDNA: FLJ22751
clone fis,
I~AIA0483, highlyclone KAIA0483, highly similar
to AF016692
similar to AF016692Homo sapiens small intestinal
mucin (MUC3)
Homo sapiens mRNA. /FEA~nRNA
small
intestinal mucin/DB XREF=gi:10439257 /LJG=Hs.271819
(MLTC3) mRNA Homo sapiens cDNA: FLJ22751 fis,
clone
I~AIA0483, highly similar to
AF016692
SEQ ID NO: 95 Homo sapiens small intestinal
mucin (MUC3)
(DNA) mRNA
Homo Sapiens Consensus includes gb:AC004908 232641 at
PAC
clone RP5-855D21/DEF=Homo Sapiens PAC clone RP5-
855D21 /FEA=CDS_3
SEQ ID NOS: 96 /DB XREF=gi:4156179 /LJG=Hs.249181
(DNA), 176 (aminoHomo Sapiens PAC clone RP5-855D21
acid), 177 (amino
acid), and 178
(amino
acid)
putative microtubule-Consensus includes gb:AJ251708.1234669 x at
binding protein /DEF=Homo Sapiens partial mRNA
for
putative microtubule-binding
protein.
SEQ ID NO: 97 /FEA=mRNA /PROD=putative microtubule-
(DNA) binding protein /DB XREF=gi:6491740
/UG=Hs.326544 putative microtubule-binding
rotein
ESTs Consensus includes gb:AI741469 234970 at
/FEA=EST
/DB XREF=gi:5109757
SEQ ID NO: 98 /DB XREF=est:wgllbOl.x1
(DNA) /CLONE=IMAGE:2364745 /UG=Hs.57787
ESTs
ESTs Consensus includes gb:AI417897 235444 at
IFEA=EST
/DB XREF=gi:4261401
SEQ ID NO: 99 /DB XREF=estag55b06.x1
(DNA) /CLONE=IMAGE:2112659 /UG=Hs.235860
ESTs
ESTs Consensus includes gb:AA827649 235515 at
/FEA=EST
/DB XREF=gi:2900090
SEQ ID NO: 100 !DB_~~REF=est:odOla12.s1
(DNA) /CLONE=IMAGE:1357918 /UG=Hs.105317
ESTs
ESTs Consensus includes gb:AI493909 235562 at
/FEA=EST
/DB _X_RFF=gi:4394912
SEQ ID NO: 101 /DB XREF=est:qz94e02.x1
(DNA) /CLONE=IMAGE:2042234 /UG=Hs.6131
ESTs
ESTs Consensus includes gb:AV741130 235651 at
/FEA=EST
/DB XREF=gi:10858711
SEQ ID NO: 102 /DB XREF=est:AV741130
(DNA) /CLONE=CBCATB06 /UG=Hs.173704
-62-
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ESTs, Moderately similar to ALU8_HUMAN
ALU SUBFAMILY SX SEQUENCE
CONTAMINATION WARNING ENTRY
H.sa iens
ESTs, Weakly Consensus includes gb:AI864053 235678_at
similar /FEA=EST
to I38588 reverselDB_XREF=gi:5528160
transcriptase /DB XREF=est:wj55h10.x1
homolog
[H. sapiens] /CLONE=IMAGE:2406787 IUG=Hs.3
9972
ESTs, Weakly similar to I38588
reverse
SEQ ID NO: 103 transcriptase homolog H.sapiens
(DNA)
ESTs Consensus includes gb:AW339510 235866 at
/FEA=EST /DB XREF=gi:6836136
SEQ ID NO: 104 /DB XREF=est:xz91h08.x1
(DNA) /CLONE=IMAGE:2871615 /UG=Hs.42722
ESTs
ESTs Consensus includes gb:AI076192 236422 at
/FEA=EST
/DB XREF=gi:3405370
SEQ ID NO: 105 /DB XREF=est:oz01g07.x1
(DNA) /CLONE=IMAGE:1674108 /UG=Hs.131933
ESTs
ESTs Consensus includes gb:AL044570 236548 at
/FEA=EST
/DB XREF=gi:5432785
SEQ ID NO: 106 /DB XREF=est:DKFZp434L082_sl
(DNA) /CLONE=DI~FZp434L082 /LJG=Hs.147975
ESTs
ESTs Consensus includes gb:AI968097 237835 at
/FEA=EST
/DB XREF=gi:5764915
SEQ ID NO: 107 /DB XREF=est:wu13a12.x1
(DNA) /CLONE=IMAGE:2516830 /UG=Hs.131360
ESTs
ESTs Consensus includes gb:AI733801 237923 at
/FEA=EST
/DB XREF=gi:5054914
SEQ ID NO: 108 lDB_XREF=est:qk39c04.x5
(DNA) /CLONE=IMAGE:1871334 lUG=Hs.146186
ESTs
ESTs Consensus includes gb:BF594323 238103 at
/FEA=EST .
/DB XREF=gi:11686647
SEQ ID NO: 109 /DB XREF=est:7h79g07.x1
(DNA) /CLONE=IMAGE:3322236 /UG=Hs.158989
ESTs
Homo Sapiens, Consensus includes gb:T69015 /FEA=EST238422 at
clone
MGC:16402 /DB XREF=gi:684163
IMAGE:3940360, /DB XREF=est:yc31~4.s1
mRNA, complete /CLONE=IMAGE:82303 /LJG=Hs.192728
cds
ESTs
SEQ ID NO: 110
(DNA)
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ESTs Consensus includes gb:AA502384 238956 at
/FEA=EST
/DB_XKEF=gi:2237351
SEQ ID NO: 111 /DB XREF=est:ne27f1l.sl
(DNA) /CLONE=IMAGE:898605 /UG=Hs.151529
ESTs
ESTs Consensus includes gb:AI739241 238984 at
/FEA=EST
/DB XREF=gi:5101222
SEQ ID NO: 112 /DB XREF=est:wi14h02.x1
(DNA) /CLONE=IMAGE:2390259 fUG=Hs.171480
ESTs
ESTs Consensus includes gb:AA088446 239065 at
/FEA=EST
/DB XRFF=gi:1633958
SEQ ID NO: 113 /DB_XREF=est:z189f04.s1
(DNA) /CLONE=IMAGE:511807 /UG=Hs.170298
ESTs
ESTs Consensus includes gb:AI493046 239148 at
/FEA=EST
/DB XRFF=gi:4394049
SEQ ID NO: 114 /DB XREF=est:qz49b04.x1
(DNA) /CLONE=IMAGE:2030191 /LTG=Hs.146133
ESTs
ESTs Consensus includes gb:AI243098 239966 at
/FEA=EST
/DB XREF=gi:3838495
SEQ ID NO: 115 /DB XREF=est:qh26e03.x1
(DNA) /CLONE=IMAGE:1845820 lUG=Hs.178398
ESTs
ESTs, Weakly Consensus includes gb:AI633523 240106 at
similar /FEA=EST
to A49175 Motch /DB XREF=gi:4684853
B
protein - mouse /DB XREF=estah68b1 l.xl
[M.musculus] /CLONE=IMAGE:2123805 /LTG=Hs.44705
ESTs
SEQ ID NO: 116
(DNA)
ESTs Consensus includes gb:AI300126 240830 at
/FEA=EST
/DB XREF=gi:3959472
SEQ ID NO: 117 /DB XREF=est:qn54f02.x1
(DNA) /CLONE=IMAGE:1902075 lUG=Hs.257858
ESTs
ESTs Consensus includes gb:AI917390 240964 at
/FEA=EST
/DB~XR.EF=gi: 563 7245
SEQ ID NO: 118 /DB XREF=estas79a05.x1
(DNA) /CLONE=IMAGE:2237456 /UG=Hs.99415
ESTs
betacellulin Consensus includes gb:AI620677 241412iat
/FEA=EST
/DB XREF=gi:4629803
SEQ ID NO: 119 /DB XREF=estau85e09.x1
(DNA) /CLONE=IMAGE:2257864 /UG=Hs.154191
ESTs
ESTs Consensus includes gb:H05025 /FEA=EST241874 at
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/DB _X_RFF=gi:868577
SEQ ID NO: 120 /DB XREF=est:y174g12.s1
(DNA) /CLONE=IMAGE:43864 /UG=Hs.323767
ESTs
ESTs Consensus includes gb:AW024656 242358 at
/FEA=EST /DB XREF=gi:5878186
SEQ ID NO: 121 /DB XREF=est:wu78hO5.xl
(DNA) /CLONE=IMAGE:2526201 /UG=Hs.233382
ESTs, Moderately similar to AF119917
62
PR02822 H.sa iens
ESTs Consensus includes gb:BF696216 242626 at
/FEA=EST
/DB XREF=gi:11981624
SEQ ID NO: 122 /DB XREF=est:602124536F1
(DNA) /CLONE=IMAGE:4281632 /UG=Hs.188724
ESTs
ESTs Consensus includes gb:N57929 242978 x at
/FEA=EST
/DB XRFF=gi:1201819
SEQ ID NO: 123 /DB XREF=est:yv61e06.s1
(DNA) /CLONE=IMAGE:247234 /UG=Hs.48100
ESTs
ESTs, Weakly similarConsensus includes gb:AI457984 243729
/FEA=EST at
to ALU1_HUMAN /DB XREF=gi:4312002 _
ALU SUBFAMILY /DB XREF=estaj66a04.x1
J
SEQUENCE /CLONE=IMAGE:2146446 !UG=Hs.165900
CONTAMINATION ESTs, Weakly similar to ALUC_HLJMAN
WARNING ENTRY ! ! ! ! ALU CLAS S C WARNING
ENTRY ! ! !
[H.sapiens] H.sapiens
SEQ ID NO: 124
(DNA)
ESTs Consensus includes gb:AA581439 244650 at
lFEA=EST
/DB _X_RFF=gi:2359211
SEQ ID NO: 125 /DB XREF=est:nh13c10.s1
(DNA) /CLONE=IMAGE:952242 !UG=Hs.152328
ESTs
Biological Validation of Biomarker Candidates: Modulation of Expression by
Treatment with Ligands for EGFR or by Treatment with Inhibitors for EGFR
To validate the significance of the biomarker candidates to predict the
activity
of the EGFR pathway and thereby the sensitivity of cancer cell to inhibition
of EGFR
by therapy, genes that would be regulated by the EGFR pathway were identified.
Demonstration of that property for the EGFR biomaxker candidates described
above
would add additional credibility as it would link these genes functionally to
the EGFR
pathway. Colon cancer and a lung cancer cell lines were treated with epidermal
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growth factor, in the absence of serum or, in the presence of serum with the
EGFR
modulator BMS-461453 or the EGFR modulator cetuximab (also known as C225, a
chimeric monoclonal EGFR antibody). To identify genes induced by epidermal
growth factor, serum starved cells were treated with 20ng/ml EGF for 0.5, 6,
and 1 ~
hours. Control cells were treated with media alone. The expression profiling
was
performed, and data was analyzed using GeneChip~ Expression Analysis software
MAS 5.0 (Affymetrix, Santa Clara, California).
Genes inhibited by EGFR antagonists were identified by treating cells in the
presence of 10% serum with 0.5uM of BMS-461453 or lug/ml or 5ug/ml of C225 for
6 and 24 hours. Cells exposed to 0.05% DMSO were used as the experimental
control. Expression profiling was performed, and data were analyzed using
GeneChip~ Expression Analysis software MAS 5Ø
The gene expression of the inhibitor or EGFR treated cell lines was compared
pair-wise to the untreated controls. Polynucleotides from the biomarker list,
in which
expression was increased two fold with EGFR exposure or decreased two fold
with
EGFR inhibitor treatment compared to the untreated controls, were considered
to be
modulated by EGFR. These biomarkers are provided in Table 4. Examples of the
biomarkers include EphAl, B-cell translocation gene 2, prostaglandin-
endoperoxide
synthase 2 and serine (or cysteine) proteinase inhibitor (clade B), which are
highly
expressed in sensitive cells and up regulated by treatment with EGFR. On the
other
hand, spondin 1, talin 2 and nuclear receptor subfamily 3 are genes whose
expression
levels correlate with sensitivity or resistance of colon cancer cell lines and
are
consistently down regulated by treatment with EGFR inhibitors BMS-461453 and
C225. It appears that these biomarkers are likely to be directly or indirectly
involved
in the EGFR signaling pathway, based on their expression modulation by EGF or
EGFR inhibitor treatment.
Identification of Top Biomarkers
In an attempt to further prioritize biomarkers for use in predicting response
of
cancer cells to treatment with one or more EGFR modulators, the following
filter
criteria were used on the Table 4 biomarkers to identify a total of fourteen
biomaxkers
(Table 5) as the top biomarkers:
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(1) results from the highly significant correlation of gene expression with
ICSO:
A p-value < 0.01 in the student TTEST or a Pearson value < - 0.6 described
above;
(2) results from the modulation of expression by EGFR ligand and/or EGFR
inhibitor treatment described above; and
(3) biomarkers supported by literature revealing a direct relationship between
the EGFR pathway and the biomarkers.
TABLE 5 - Top Fourteen Biomarkers
Biomarker Name Literature SupportInduced by EGFI
Citation Inhibited by EGFR antagonist
mucin 2, J Biol Chem. 2002 Expression inhibited 2 fold
Aug by EGFR
intestinal/tracheal30;277(35):32258-67antagonist in GEO colon
cancer cell
MLTC2) line
intestinal mucinNo Expression inhibited 2 fold
3 by EGFR
(MLTC3) antagonist in GEO colon
cancer cell
line
Homo Sapiens No Expression stimulated 2
cystic fold by
fibrosis EGFR in H292 lung cancer
cell line
transmembrane
conductance
regulator
ATP-binding
cassette (sub-family
C, member 7)
(CFTR)
f spondin ~ No Expression inhibited 2 fold
by EGFR
(KIAA0762) protein antagonist in LOVO colon
cancer cell
line
3-hydroxy-3- J Invest Dermatol.Expression stimulated 3
2000 fold by
methylglutaryl-Jan;l 14(1):83-7 EGFR in H292 lung cancer
cell line
Coenzyme A
synthase 2
serine (or cysteine)Electrophoresis. Expression stimulated 2
2001 fold by
proteinase inhibitor,Aug;22(14):3001-8.EGFR in H292 lung cancer
cell line
Glade B
(ovalbumin),
member 5
(SERPINBS
BTG family, No Expression stimulated 2
fold by
member 2 (BTG2) EGFR in H292 lung cancer
cell line
talin 2 (TLN2) No Expression inhibited 2 fold
by EGFR
antagonist in GEO colon
cancer cell
line
arachidonic J Biol Chem. 1994 no
acid Aug
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a oxygenase 26;269(34):21786-92.
prostaglandin 3 Biol Chem. 1994Expression stimulated 6
G/H Aug fold by
synthase and 26;269(34):21786-92.EGFR in H292 lung cancer
cell line
cyclooxy enase
EphAl (EPHA1) No Expression stimulated 2
fold by
EGFR in CAC02 colon cancer
cell
line
hemoglobin, alphaNo Expression inhibited 2 fold
1 by EGFR
(HBA1) antagonist in GEO colon
cancer cell
line
bone morphogeneticDevelopment 2000 no
rotein 2 Nov;127(22):4993-5005
betacellulin Biochem Biophys no
(BTC)* Res
Commun. 2002 Jun
28;294(5):1040-6
*The gene betacellulin showed counter regulation with EGFR expression as
defined
for the EGFR-A list but had just a p value of 0.04 in the Student's TTest for
correlation with ICSO. It was still selected as a top biomarker for the strong
literature
support, as betacellulin is one of the published ligands of EGFR.
Utility of Biomarkers
Polynucleotides that correlate to a specific property of a biological system
can
be used to make predictions about that biological system and other biological
systems.
To show the predictive utility of biomarkers that correlate to EGFR modulator
sensitivity and resistance, these polynucleotides were tested for their
ability to predict
the response of twenty two colon cancer cell lines to a small molecule EGFR
modulator.
The invention includes single biomarkers including, for example, the fourteen
top biomarkers which were tested in a voting scheme. For that purpose, the
mean
expression value was calculated for all fourteen biomarkers. Colon cancer cell
lines
which showed an expression level above the mean were then voted to be
sensitive,
and colon cancer cell lines with expression levels below the mean were voted
to be
resistant. After this procedure, the voting was compared to the actual
sensitivity/resistance status according to the definition based on ICSQ (see
above) and
an error rate was calculated. The error rates of the fourteen top biomarkers
are shown
in Table 6.
TABLE 6 - Error Rates of Fourteen Top Biomarkers
~ Biomarker Name ~ Pearsons value ~ TTEST P value ~ Prediction error rate
mucin 2, -0.531 0.0083 20%
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intestinal/tracheal
(MUC2)
intestinal mucin-0.639 0.0004 11.72%
3
(MUC3)
Homo sapiens -0.646 9E-OS 5.9%
cystic
fibrosis
transmembrane
conductance
regulator
ATP-binding
cassette (sub-family
C, member 7)
(CFTR)
f spondin -0.622 0.0004 12.8%
.
(KIAA0762) protein
3-hydroxy-3- -0.575 0.0029 21.75%
methylglutaryl-
Coenzyme A
synthase 2
serine (or cysteine)-0.62 0.0028 21.75%
proteinase inhibitor,
Glade B
(ovalbumin),
member 5
(SERPINBS
BTG family, -0.544 0.0042 20.5%
member 2 (BTG2)
talin 2 (TLN2) -0.874 3E-OS 8.8%
E hAl (EPHAl) -0.647 0.0021 22%
hemoglobin, -0.744 8E-OS 20%
alpha 1
(HBAl)
bone morphogenetic-0.555 0.0091 31.8%
protein 2
betacellulin -0.536 0.047 43.5%
(BTC)
The biomarkers talin, the Cystic fibrosis conductance regulator (CFTR), and
mucin 3
were the best single biomarkers with error rates below 12%.
EXAMPLES
EXAMPLE 1 - METHODS
IC50 determination--in vitro cytotoxicity assay
A small molecule EGFR inhibitor, erlotinib HCl (BMS-461453), was tested
for cytoxicity in vitro against a panel of twenty-two human colon cancer cell
lines
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available from the American Type Culture Collection. Cytotoxicity was assessed
in
cells by MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carbaxymethoxyphenyl)-2-(4-
sulphenyl)-2H-tetrazolium, inner salt) assay (T.L. Riss et al., 1992, Mol.
Biol. Cell, 3
(Suppl.):184a).
To carry out the assays, the colon cells were plated at 4,000 cell/well in 96
well microtiter plates and 24 hours later serial diluted drugs were added. The
concentration range for the EGFR inhibitor was from 5 ~,g/ml to 0.0016 ~,g/ml
(roughly 10 ~,M to 0.0032 qM). The cells were incubated at 37 °C for 72
hours at
which time the tetrazolium dye MTS (333 ~.g/ml final concentration) in
combination
with the electron coupling agent phenazine methosulfate (25 ~M final
concentration)
was added. A dehydrogenase enzyme in live cells reduces the MTS to a form that
absorbs light at 492 nm that can be quantified spectrophotometrically. The
greater the
absorbency, the greater the number of live cells. The results were expressed
as an
ICSQ, which is the drug concentration required to inlubit cell proliferation
(i.e.,
absorbance at 450 nm) to 50% of that of untreated control cells. The mean ICSQ
and
standard deviation (SD) from multiple tests for each cell line were
calculated.
Resistant/sensitive classification
The cell lines with ICSO below 6 ~M were defined as sensitive to the EGFR
inhibitor, whereas those with ICSO above 6 ~,M were considered to be
resistant. The
resistant/sensitive classification are shown above in Table 1, with five cell
lines
classified as sensitive and seventeen cell lines classified as resistant.
Gene expression profiling
The colon cells were grown using standard cell culture conditions: RPMI
1640 supplemented to contain 10% fetal bovine serum, 100 IU/ml penicillin, 100
mg/ml streptomycin, 2 mM L-glutamine and 10 mM Hepes (all from GibcoBRL,
Rockville, Maryland). RNA was isolated from 50-70% confluent cells or drug-
treated
cells using the RNeasyT"" kits commercially available from Qiagen (Valencia,
California). Quality of the RNA was checked by measuring the 28s:18s ribosomal
RNA ratio using Agilent 2100 bioanalyzer (Agilent, Technologies, Rockville,
Maryland). Concentration of total RNA was determined spectrophotometrically.
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~,g of total RNA from each cell line was used to prepare biotinylated probe
according
to the Af~'ymetrix Genechip~ Expression Analysis Technical Manual, 2001.
Targets
were hybridized to AfFymetrix high density oligonucleotide array human HG-U133
set chips (Affymetrix, Santa Clara, California). Arrays were then washed, and
stained
using the GeneChip Fluidics station according to the manufacture's
instructions. The
HG-U133 set consisting of two GeneChip~ arrays contains nearly 45,000 probe
sets
representing more than 39,000 transcripts derived from approximately 33,000
well-
substantiated human genes.
Preprocessing of microarray data for selecting biomarkers
Scanned image files were visually inspected for artifacts and analyzed with
GeneGhip~ Expression Analysis software MAS 5.0 (Affymetrix, Santa Clara,
California). The "Detection Call" (see Affymetrix manual) was used to
determine
whether a transcript was detected within one sample, as well as the "Signal"
(see
Affymetrix Genechip° Expression Analysis Technical Manual, 2001)
which
measured the relative abundance of a transcript. The trimmed mean intensity
for each
chip was scaled to 1,500 (see Affymetrix manual) in order to account for any
minor
difFerences in global chip intensity, so that the overall expression level for
each cell
line is comparable. Affymetrix control sequences were removed prior to
analysis.
Induction Studies of colon and breast cell lines with EGFR inhibitors or EGFR
ligand
and selection of genes modulated by the inductions
The five colon cell lines and one lung cell line indicated with asterisks in
Table 1 were used in the drug induction study. Three of the colon cell lines
express
EGFR and are sensitive to the EGFR inhibitor BMS-461453. The SW480 cell line,
while expressing EGFR, is insensitive to the EGFR inhibitor, and the COL0320
DM
does not express EGFR and is EGFR inhibitor resistant. The lung cancer cell
line
H292 expresses EGFR, but its sensitivity status is unknown. Cells were seeded
in a
10 cm2 culture plate with the medium described above and cultured for 24
hours.
For the EGF induction studies, the colon cell line CAC02 and the lung cancer
H292 cell line were washed 2X PBS, and the media was changed to RPMI without
serum. The next day the cells were treated with 20 ng/ml EGF, and eventually
lysed
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i
for RNA isolation 0.5, 6 and 18 hours post treatment. Gene expression was
profiled
as described below.
EGFR inhibition studies were conducted on the colon cell lines GEO, CCD33-
CO, SW480 and COL0320DM. The expression profiling was performed as
described above and data was analyzed using GeneChip~ Expression Analysis
software MAS 5Ø The expression data of EGFR inhibitor treated cell lines
were
compared pair-wise to that of untreated same cell line. A change was
considered
significant if a two fold difference in expression was demonstrated between
the
treated and the untreated control. Analysis was done for all four cell lines
to compare
the gene expression with or without EGFR inhibitor treatment.
EXAMPLE 2 - RT-PCR EXPRESSION PROFILING
RNA quantification was performed using the SYBR Green real-time PCR.
The SYBR Green real-time PCR assay is one of the most precise methods for
assaying the concentration of nucleic acid templates.
RNA can be prepared using standard methods, preferably, employing the
RNeasy Kit commercially available from Qiagen (Valencia, California). cDNA
template for real-time PCR can be generated using the SuperscriptTM Fixst
Strand
Synthesis system for RT-PCR. SYBR Green real-time PCR reactions are prepared
as
follows: the reaction mix contains 20 ng first strand cDNA; 50 nM Forward
Primer;
50 nM Reverse Primer; 0.75X SYBR Green I (Sigma); 1X SYBR Green PCR Buffer
(SOmMTris-HCl pH 8.3, 75 mM KCl); 10% DMSO; 3 mM MgCl2; 300 ~M each
dATP, dGTP, dTTP, dCTP; 1 U Platinum~ Taq DNA Polymerase High Fidelity
(Cat# 11304-029; Life Technologies; Rockville, Maryland). Real-time PCR is
performed using an Applied Biosystems 5700 Sequence Detection System.
Conditions are 95 °C for 10 minutes (denaturation and activation of
Platinum~ Taq
DNA Polymerase), 40 cycles of PCR (95 °C for 15 seconds, 60 °C
for 1 minute).
PCR products are analyzed for uniform melting using an analysis algorithm
built into
the 5700 Sequence Detection System.
cDNA quantification used in the normalization of template quantity is
performed using SYBR Green real-time PCR. Expression of EGFR is normalized to
GAPDH expression as described below.
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The sequences for the GAPDH oligonucleotides used in the SYBR Green real-
time PCR reactions are:
GAPDH-F: 5'-AGCCGAGCCACATCGCT-3' (SEQ ID NO: 191)
GAPDH-R: 5'-GTGACCAGGCGCCCAATAC-3' (SEQ ID NO: 192)
The sequences for the EGFR oligonucleotides used in the SYBR Green real-
time PCR reactions axe:
EGFR-F: 5'- GCGTCTCTTGCCGGAATGT-3' (SEQ ID NO: 193)
EGFR-R: 5'- AGCCGAGGCAGGGAATGCGTG-3' (SEQ ID NO: 194)
The Sequence Detection System generates a Ct (threshold cycle) value that is
used to calculate a concentration for each input cDNA template. cDNA levels
for
each gene of interest are normalized to GAPDH cDNA levels to compensate for
variations in total cDNA quantity in the input sample. This is done by
generating
GAPDH Ct values for each cell line. Ct values for the gene of interest and
GAPDH
are inserted into a modified version of the ~BCt equation (Applied Biosystems
Prism~ 5700 Sequence Detection System User Manual) which is used to calculate
a
GAPDH normalized relative cDNA level for each specific cDNA. The ~BCt equation
is: relative quantity of nucleic acid template =2ssct = 2~scta-sctb~~ where
BCta = Ct
target - Ct GAPDH, and BCtb = Ct reference - Ct GAPDH.
EXAMPLE 3 - PRODUCTION OF ANTIBODIES AGAINST THE BIOMARI~ERS
Antibodies against the biomarkers can be prepared by a variety of methods.
For example, cells expressing an biomarker polypeptide can be administered to
an
animal to induce the production of sera containing polyclonal antibodies
directed to
the expressed polypeptides. In one aspect, the biomarker protein is prepared
and
isolated or otherwise purified to render it substantially free of natural
contaminants,
using teclniiques commonly practiced in the art. Such a preparation is then
introduced
into an animal in order to produce polyclonal antisera of greater specific
activity for
the expressed and isolated polypeptide.
In one aspect, the antibodies of the invention are monoclonal antibodies (or
protein binding fragments thereof). Cells expressing the biomarker polypeptide
can
be cultured in any suitable tissue culture medium, however, it is preferable
to culture
cells in Earle's modified Eagle's medium supplemented to contain 10% fetal
bovine
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serum (inactivated at about 56 °C), and supplemented to contain about
10 g/1
nonessential amino acids, about 1,00 U/ml penicillin, and about 100 p,g/ml
streptomycin.
The splenocytes of immunized (and boosted) mice can be extracted and fused
with a suitable myeloma cell line. Any suitable myeloma cell line can be
employed in
accordance with the invention, however, it is preferable to employ the parent
myeloma cell line (SP2/0), available from the ATCC. After fusion, the
resulting
hybridoma cells are selectively maintained in HAT medium, and then cloned by
limiting dilution as described by Wands et al. (1981, Gastr-oenterology,
80:225-232).
The hybridoma cells obtained through such a selection are then assayed to
identify
those cell clones that secrete antibodies capable of binding to the
polypeptide
immunogen, or a portion thereof.
Alternatively, additional antibodies capable of binding to the biomarker
polypeptide can be produced in a two-step procedure using anti-idiotypic
antibodies.
Such a method makes use of the fact that antibodies are themselves antigens
and,
therefore, it is possible to obtain an antibody that binds to a second
antibody. In
accordance with this method, protein specific antibodies can' be used to
immunize an
animal, preferably a mouse. The splenocytes of such an immunized animal are
then
used to produce hybridoma cells, and the hybridoma cells are screened to
identify
clones that produce an antibody whose ability to bind to the protein-specific
antibody
can be blocked by the polypeptide. Such antibodies comprise anti-idiotypic
antibodies to the protein-specific antibody and can be used to immunize an
animal to
induce the formation of further protein-specific antibodies.
EXAMPLE 4 - IMMUNOFLUORESCENCE ASSAYS
The following immunofluorescence protocol may be used, for example, to
verify EGFR biomarker protein expression on cells or, for example, to check
for the
presence of one or more antibodies that bind EGFR biomarkers expressed on the
surface of cells. Briefly, Lab-Tek II chamber slides are coated overnight at 4
°C with
10 micrograms/milliliter (p.g/ml) of bovine collagen Type II in DPBS
containing
calcium and magnesium (DPBS++). The slides are then washed twice with cold
DPBS++ and seeded with 8000 CHO-CCRS or CHO pC4 transfected cells in a total
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volume of 125 p,l and incubated at 37 °C in the presence of 95% oxygen
/ 5% carbon
dioxide.
The culture medium is gently removed by aspiration and the adherent cells are
washed twice with DPBS++ at ambient temperature. The slides are blocked with
DPBS++ containing 0.2% BSA (blocker) at 0-4 °C for one hour. The
blocking
solution is gently removed by aspiration, and 125 p,l of antibody containing
solution
(an antibody containing solution may be, for example, a hybridoma culture
supernatant which is usually used undiluted, or serum/plasma which is usually
diluted, e.g., a dilution of about 1/100 dilution). The slides are incubated
for 1 hour at
0-4 °C. Antibody solutions are then gently removed by aspiration and
the cells are
washed five times with 400 ~l of ice cold blocking solution. Next, 125 ~1 of 1
~g/ml
rhodamine labeled secondary antibody (e.g., anti-human IgG) in blocker
solution is
added to the cells. Again, cells are incubated for 1 hour at 0-4 °C.
The secondary antibody solution is then gently removed by aspiration and the
cells are washed three times with 400 p,l of ice cold blocking solution, and
five times
with cold DPBS++, The cells are then fixed with 125 p,l of 3.7% formaldehyde
in
DPBS++ for 15 minutes at ambient temperature. Thereafter, the cells are washed
five
times with 400 pl of DPBS++ at ambient temperature. Finally, the cells are
mounted
in 50% aqueous glycerol and viewed in a fluorescence microscope using
rhodamine
filters.
-75-
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
SEQUENCE LISTING
<l10> Amler, Lukas C.
Januario, Thomas
<120> BIOMARKERS AND METHODS FOR DETERMINING SENSITIVITY TO EPIDERMAL
GROWTH FACTOR RECEPTOR MODULATORS
<130> D0304 PCT
<150> US 60/438,735
<151> 2003-01-08
<160> 194
<170> PatentIn version 3.2
<210> 1
<211> 2058
<2l2> DNA
<213> Human '
<400> 1
cggtttctgc tgggtttctg aactgctggg tttctgcttg ctcctctgga gatgcagcgt 60
ctgttgactc cagtgaagcg cattctgcaa ctgacaagag cggtgcagga aacctccctc 120
acacctgctc gcctgctccc agtagcccac caaaggtttt ctacagcctc tgctgtcccc 180
ctggccaaaa cagatacttg gccaaaggac gtgggcatcc tggccctgga ggtctacttc 240
ccagcccaatatgtggaccaaactgacctggagaagtataacaatgtggaagcaggaaag300
tatacagtgggcttgggccagacccgtatgggcttctgctcagtccaagaggacatcaac360
tccctgtgcctgacggtggtgcaacggctgatggagcgcatacagctcccatgggactct420
gtgggcaggctggaagtaggcactgagaccatcattgacaagtccaaagctgtcaaaaca480
gtgctcatggaactcttccaggattcaggcaatactgatattgagggcatagataccacc540
aatgcctgctacggtggtactgcctccctcttcaatgctgccaactggatggagtccagt600
tcctgggatggtcgttatgccatggtggtctgtggagacattgccgtctatcccagtggt660
aatgctcgtcccacaggtggggccggagctgtggctatgctgattggcccaaaggcccct720
ctggccctggagcgagggctgaggggaacccatatggagaatgtgtatgacttctacaaa780
ccaaatttggcctcggagtacccaatagtggatgggaagctttccatccagtgctacttg840
cgggccttggatcgatgttacacatcataccgtaaaaaaatccagaatcagtggaagcaa900
gctggcagcgatcgacccttcacccttgacgatttacagtatatgatctttcatacaccc960
ttttgcaagatggtccagaagtctctggctcgcctgatgttcaatgacttcctgtcagcc1020
agcagtgaca cacaaaccag cttatataag gggctggagg ctttcggggg gctaaagctg 1080
1/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
gaagacacct acaccaacaa ggacctggat aaagcacttc taaaggcctc tcaggacatg 1140
ttcgacaaga aaaccaaggc ttccctttac ctctccactc acaatgggaa catgtacacc 1200
tcatccctgtacgggtgcctggcctcgcttctgtcccaccactctgcccaagaactggct1260
ggctccaggattggtgccttctcttatggctctggtttagcagcaagtttcttttcattt1320
cgagtatcccaggatgctgctccaggctctcccctggacaagttggtgtccagcacatca1380
gacctgccaaaacgcctagcctcccgaaagtgtgtgtctcctgaggagttcacagaaata1440
atgaaccaaagagagcaattctaccataaggtgaatttctccccacctggtgacacaaac1500
agccttttcccaggtacttggtacctggagcgagtggacgagcagcatcgccgaaagtat1560
gcccggcgtcccgtctaaaggtgttctgcagatccatggaaagcttcctgggaaacgtat1620
gctagcagagcttctccccgtgaatcatatttttaagatcccactcttagctggtaaatg1680
aatttgaatcgacatagtagccccataagcatcagccctgtagagtgaggagccatctct1740
agcgggcccttcattcctctccatgctgcaatcactgtcctgggcttatggtgcctatgg1800
actaggggtcctttgtgaaagagcaagatggagcaatggagagaagacctcttcctgaat1860
cactggactccagaaatgtgcatgcagatcagctgttgccttcaagatccagataaactt1920
tcctgtcatgtgttagaactttattattattaatattgttaaacttctgtgctgttcctg1980
tgaatctccaaattttgtaccttgttctaagctaatatatagcaattaaaaagagagaaa2040
gagaaaaaaa aaaaaaaa 2058
<210> 2
<211> 532
<212> DMA
<213> Human
<220>
<221> misc_feature
<222> (519)..(519)
<223> n is a, c, g, or t
<400> 2
taactatggaaaaccatgtttatttttaataaaggatgacatttccaatcagtaaaatat60
cataaaagtataaaaatgtactaagtacaatcattagcattatgttataggggaatagtg120
gttataacttttccctgtaagatggcacattggatggtcacagttggcttgatttacaga180
ggggcaagagtaggtgaccagttgtaccagttgctccagtttcctaggatttgggactct240
tgtaaaatgagaaagtcccaggcaaactgggacggttggtcctacaagaaaaagagcagc300
atcagagtgttggctatagtttggaacttaggaacaggatcagacattattttttaactt360
2/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
ctccacctat tttcccttta gctgtgaaat aaaaatccct tttgttatta ctgagggtgt 420
tacagctttc agaggctttt ttaccactgg gtttcatgta attttgactt aatacctatg 480
tcaagcctgg gaagaaaggc agttctaatc aacttgcang tgtggcattc tg 532
<210>
3
<211>
1547
<212>
DNA
<213> n
Huma
<400>
3
ggggacttcttgaacttgcagggagaataacttgcgcaccccactttgcgccggtgcctt 60
tgccccagcggagcctgcttcgccatctccgagccccaccgcccctccactcctcggcct 120
tgcccgacactgagacgctgttcccagcgtgaaaagagagactgcgcggccggcacccgg 180
gagaaggaggaggcaaagaaaaggaacggacattcggtccttgcgccaggtcctttgacc 240
agagtttttccatgtggacgctctttcaatggacgtgtccccgcgtgcttcttagacgga 300
ctgcggtctcctaaaggtcgaccatggtggccgggacccgctgtcttctagcgttgctgc 360
ttccccaggtcctcctgggcggcgcggctggcctcgttccggagctgggccgcaggaagt 420
tcgcggcggcgtcgtcgggccgcccctcatcccagccctctgacgaggtcctgagcgagt 480
tcgagttgcggctgctcagcatgttcggcctgaaacagagacccacccccagcagggacg 540
ccgtggtgcccccctacatgctagacctgtatcgcaggcactcaggtcagccgggctcac 600
ccgccccagaccaccggttggagagggcagccagccgagccaacactgtgcgcagcttcc 660
accatgaagaatctttggaagaactaccagaaacgagtgggaaaacaacccggagattct 720
tctttaatttaagttctatccccacggaggagtttatcacctcagcagagcttcaggttt 780
tccgagaacagatgcaagatgctttaggaaacaatagcagtttccatcaccgaattaata 840
tttatgaaatcataaaacctgcaacagccaactcgaaattccccgtgaccagacttttgg 900
acaccaggttggtgaatcagaatgcaagcaggtgggaaagttttgatgtcacccccgctg 960
tgatgcggtggactgcacagggacacgccaaccatggattcgtggtggaagtggcccact 1020
tggaggagaaacaaggtgtctccaagagacatgttaggataagcaggtctttgcaccaag 1080
atgaacacagctggtcacagataaggccattgctagtaacttttggccatgatggaaaag 1140
ggcatcctctccacaaaagagaaaaacgtcaagccaaacacaaacagcggaaacgcctta 1200
agtccagctgtaagagacaccctttgtacgtggacttcagtgacgtggggtggaatgact 1260
ggattgtggctcccccggggtatcacgccttttactgccacggagaatgcccttttcctc 1320
tggctgatcatctgaactccactaatcatgccattgttcagacgttggtcaactctgtta 1380
3/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
actctaagat tcctaaggca tgctgtgtcc cgacagaact cagtgctatc tcgatgctgt 1440
accttgacga gaatgaaaag gttgtattaa agaactatca ggacatggtt gtggagggtt 1500
gtgggtgtcg ctagtacagc aaaattaaat acataaatat atatata 1547
<210> 4
<211> 5019
<212> DNA
<213> Human
<400> 4
gcctccgctg cagtcgctgc gtctccaagc aacatggctg acaaggccaa gcctgccaaa 60
gctgccaaca ggacgccccc caagtccccg ggggacccct cgaaggaccg ggcagccaag 120
aggctgtcgc tggaatcgga gggtgctggt gagggggcag ccgcatcccc tgagctcagt 180
gccctggaggaggccttccggcgctttgccgtgcacggggacgccagggccaccgggagg240
gagatgcacggcaagaactggtcgaagctgtgcaaggactgccaggtgatcgacggcagg300
aacgtgaccgtcactgacgtggacatcgtcttcagcaagatcaaagggaagtcttgccgg360
accatcacctttgagcagttccaggaggcgctggaggagctcgccaagaagcgattcaaa420
gacaagagcagcgaggaggccgttcgcgaggtgcacaggctcatcgagggcaaggcgccc480
atcatctcaggggtgacgaaagccatctcgtcgcccacagtgtcgaggctcacggacacc540
accaagttcacgggctcccacaaggagcgcttcgacccctctggcaagggcaagggcaag600
gctggccgcgtggatctggtggacgagtcaggctatgtgtccggctacaagcacgcaggc660
acctacgaccagaaggtgcaagggggcaagtagcccccgctccatgcctcgcggcactgc720
cggtgtccccagagcagggactctgtcacctcgcacttcattacattcctgtactaactg780
gggcagaactcagacgggtgccccagagggggctggggggcggccaggcccaggcctccc840
tcctgcccctcctcctaccggatgcccccagcactcccctctcaaaccaggtttgggccc900
cagttcgctgaccctcctaatacacctgcctcgtcctcagccatttccaaagtgtctcgc960
ggatcacaccacactgggcacgtggtttgcaggtcaaaggggcgttttaaagcagctggc1020
tgtcatggcaacaggaggctgtgctgacctcctgagcggcagacaccttccaggagccct1080
gagggtggcaggagctaaccccaaccagcaggcaactaacacggaattggccccacaccg1140
gacgtgggaggtgtctgtggggcccgaggcctgtcctgtgtgcagcggacaccacggggc1200
cttcctgctttcctgggcagagggcagagtgaggccacctggcgggggtgctgggcgcct1260
ggcacatgtgtggggaagccggtcacatggacacacctgtgcacacatgcctacaggcca1320
gctctgtgccaagggcaacctaggtaaaacgaaagccgtcaggggcagtgggcggcttcc1380
4/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
cggctgaccacagtggcttggactgtgagggtagagtaggctcgctttgctttcctgaga1440
agatgcggtggctgcctatgttctcagagcgggtctgggaagattcagaatgtccggtcc1500
ctgtggtgttgccaggcaagagacacgaagtgccgagacactcctcgcctcaccgcgtga1560
cagagcctctgcccggccctcccgttcgcccgtcctcactagctgcaccctgtttgctcg1620
cagacctcccattgccacagcccaagcaccttcttcaactctcccaaaatggctcagcct1680
aacctctcctggccaatcccccccgccggagagcaggacactagggaggacccccagtcc1740
tgcagtgtctgtgggggtttctctgccagcagggggctgagcagagcccatccaggacac1800
tccacactgccaggacacacccaggcggcccgcccttgcctgtctgcacctggggagaag1860
ccggcgctcctgctccctcctggggaggctgacgggtgtggccacccgctgtcacaatgg1920
cacactgccactgtcccttggcacgcacacagccacagccacacgtgtgacctgctgggc1980
cgtggttctggagtctacctgcggatgagcctgcggcagtcctggggaaacttttccaga2040
gcctgttagc'ccgtggctacggtcaggctctggccagggcagagggctgcccagggccag2100
gctcacagtacaggagggtggcgaggcccctccctcactggcacgcatgagcaccacccg2160
cctccccgactcccaagagtgcacctgctgcggccacagctccgtggaaggactccccct2220
acctgagcagagcagaagccccagggcggagctcccagccagcatggtccgctgagggct2280
ggggggcggtctccgaggcccctcaacagagaagcctccacctgaggatggggaggacct2340
ggcaggcagcttccacggcagggctgggaagttcagtgcctggaaataaagagcaaggaa2400
aaatggacctcaggcttcgtggctcctttaggatgtcacctcaccggcctggggaaggcg2460
gggggtgcccaagcccagccctgtgcccccgctgaacctggctggaccgcgtgtgaaagg2520
cagaactaacgtgcggaaacatttgaaaacaactctgaatgtgcggttcggaatcacccg2580
atcacagacgagcggtcaccggaatcgcccggtcacagacgagcagtcatcggactcacc2640
cgatcacagacgagcggtcaccggaatcgcccgatcacagacgagcggccaccggaatcg2700
cccaatcacagacaagcagtcatcggaatcacccgatcacagacgagcagtcatcggact2760
cacccgatcacagacgagcggtcaccagactcgcccgatcacagacgagcagtcatcgga2820
atcacccgatcacagacgagcagtcatcggactcacccgatcacagacgagcggtcacca2880
gaatcgcccgatcacagacgagcagtcatcggaatcacccgatcacagacgagtggccac2940
cggaatcacccgataacagcccatcacaactccaaagcccttgtgttgaaaaggccgagg3000
acgagtggtcaccaaacagggtggctccccaggtcccgaagcctgagacccggaaggccc3060
tggcacccttacaccctcggactcctgccctcctcggcctccctggccccagcgcggctc3120
caccctgggctgcgtctcctggtcacaggctgcgtttctcctttctgtccgtgggcagcc3180
5/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
cagtccccac agtcacggcc aagccacgca gaacgaacat gactccagag gacctcgccc 3240
tggagctgag cctggcgccg ggtcaggacg gagggaaggg cgggttgggg tccgcgggtc 3300
ctcacaccgc acggcaggca cagaggctcg ccaggccctg atccggtctg tggggacgag 3360
ggacactgag gagaggtgct gggcaccagg acgctgcctc ctggtccctg gttggcctca 3420
gacaagcacg gcctcgagaa aagagccaag cgcatcggga gcacaccaga aaccggccct 3480
gagcacgaga agagcctccg cccggcccgg gcaccacccg acctcgcagg gagcaggccc 3540
tgtcaccgac gggtcacctc gcccacacgg ccagcaccga ctcaccacag cccttcccag 3600
acctggctgg agtggccgga gcggcggggc tcatggctcc catcttggcc cctggaggtg 3660
agctcattca cagaagtggt cccttcactc tgagagagaa aatcgtggcg tgcatcccaa 3720
accctaggcc acgcctgtgg gtttcgtgaa tgagatcgag gctgctgtgg caccctgccc 3780
gtcctggcct ggagcaccct gggatcctgg agggagaggc cccacgcccc cactctccct 3840
ccacacttcc agggttggtg cccacgagtt agaggcacgg cctcccccag cggccctcag 3900
gcttttctca gacatgcggg agccaggaga gcacccttct ccactcagct ccaaagcgaa 3960
tctttgaaaa cacccactcg gctcccatct ctgtcaccta gccaggaggg gtagcaaaaa 4020
taaagtcacg aggacatagt ggtcaccact gtcagttaca acttgtctgt ggaatccgta 4080
attgcatctg tgtgccgcct ccgaacacag aacattgttt ggacggcagc cccactgcac 4140
ataacagacc cgtgcatctt cctcagtcag tttctgaata ttgtgaattc aggcaggtgt 4200
gtgttctctt ctgcatgttt ttatgcactg ccaattagct tctactaacc acggttcaac 4260
agaaaataaa tgtgtatttg tgaataacaa actgcacaac ctgcaaacca ggagagaggg 4320
acaggttctg tcaggggtga caccaggaca cagggacagg ttctgtcggg ggtgacacca 4380
ggacacaggg acaggttctg tcatgggtga cacgaggaca cagggacagg ttctatcatg 4440
ggtgacacca ggagagaggg acaggttctg ttgggggtga caagaggaga cagggacagg 4500
ttctgtcggg ggtgacacca ggagagaggg acaggttctg tcaggggtga caccaggaga 4560
gagggacagg ttctgttggg ggtgacacca ggacacagga ataggttctg tcgggaggac 4620
agtgctgatc gtgtctcagc atcaggaaag gagaaaggca gagggagagc gctgagaaga 4680
ctgttcacgc cagagtgctt atttattttt aatttactgc tataggataa gcaaccaggt 4740
agtgttccta acaattagcg ttaccaaaat taaagttcaa attatatgtt taaaatattg 4800
tagaagatat atatttatac tggactactt ttacaccttc taatatcctg tccaagtttg 4860
ggcgcagatg gtggagttgg gctggcatca tgtcctgtgg ccgccccact tgcctgttgg 4920
6/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
tgccactcca tcccgggccc cagggatgcc agctcagggc tgaccacagc agccctgcgt 4980
gggcatcacc tcctacccca gcccccatcc tgggctgct 5019
<210> 5
<211> 1155
<212> DNA
<213> Human
<400>
atggattgcagtaacggatcggcagagtgtaccggagaaggaggatcaaaagaggtggtg60
gggacttttaaggctaaagacctaatagtcacaccagctaccattttaaaggaaaaacca120
gaccccaataatctggtttttggaactgtgttcacggatcatatgctgacggtggagtgg180
tcctcagagtttggatgggagaaacctcatatcaagcctcttcagaacctgtcattgcac240
cctggctcatcagctttgcactatgcagtggaattatttgaaggattgaaggcatttcga300
ggagtagataataaaattcgactgtttcagccaaacctcaacatggatagaatgtatcgc360
tctgctgtgagggcaactctgccggtatttgacaaagaagagctcttagagtgtattcaa420
cagcttgtgaaattggatcaagaatgggtcccatattcaacatctgctagtctgtatatt480
cgtcctgcattcattggaactgagccttctcttggagtcaagaagcctaccaaagccctg540
ctctttgtactcttgagcccagtgggaccttatttttcaagtggaacctttaatccagtg600
tccctgtgggccaatcccaagtatgtaagagcctggaaaggtggaactggggactgcaag660
atgggagggaattacggctcatctctttttgcccaatgtgaagacgtagataatgggtgt720
cagcaggtcctgtggctctatggcagagaccatcagatcactgaagtgggaactatgaat780
ctttttctttactggataaatgaagatggagaagaagaactggcaactcctccactagat840
ggcatcattcttccaggagtgacaaggcggtgcattctggacctggcacatcagtggggt900
gaatttaaggtgtcagagagatacctcaccatggatgacttgacaacagccctggagggg960
aacagagtgagagagatgtttagctctggtacagcctgtgttgtttgcccagtttctgat1020
atactgtacaaaggcgagacaatacacattccaactatggagaatggtcctaagctggca1080
agccgcatct tgagcaaatt aactgatatc cagtatggaa gagaagagag cgactggaca 1140
attgtgctat cctga 1155
<210> 6
<211> 2717
<212> DNA
<213> Human
<400> 6
cagggtaacg ctgtcttgtg gacccgcact tcccacccga gacctctcac tgagcccgag .60
7/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
ccgcgcgcgacatgagccacgggaagggaaccgacatgctcccggagatcgccgccgccg120
tgggcttcctctccagcctcctgaggacccggggctgcgtgagcgagcagaggcttaagg180
tcttcagcggggcgctccaggaggcactcacagagcactacaaacaccactggtttcccg240
aaaagccgtccaagggctccggctaccgctgcattcgcatcaaccacaagatggacccca300
tcatcagcagggtggccagccagatcggactcagccagccccagctgcaccagctgctgc360
ccagcgagctgaccctgtgggtggacccctatgaggtgtcctaccgcattggggaggacg420
gctccatctgcgtcttgtacgaggaggccccactggccgcctcctgtgggctcctcacct480
gcaagaaccaagtgctgctgggccggagcagcccctccaagaactacgtgatggcagtct540
ccagctaggcccttccgcccccgccctgggcgccgccgtgctcatgctgccgtgacaaca600
ggccaccacatacctcaacctggggaactgtatttttaaatgaagagctatttatatata660
ttatttttttttaagaaaggaggaaaagaaaccaaaagttttttttaagaaaaaaaatcc720
ttcaagggagctgcttggaagtggcctccccaggtgcctttggagagaactgttgcgtgc780
ttgagtctgtgagccagtgtctgcctataggagggggagctgttagggggtagacctagc840
caaggagaagtgggagacgtttggctagcaccccaggaagatgtgagagggagcaagcaa900
ggttagcaactgtgaacagagaggtcgggatttgccctgggggaggaagagaggccaagt960
tcagagctctctgtctcccccagccagacacctgcatccctggctcctctattactcagg1020
ggcattcatgcctggacttaaacaatactatgttatcttttcttttatttttctaatgag1080
gtcctgggcagagagtgaaaaggcctctcctgattcctactgtcctaagctgcttttctt1140
gaaatcatgacttgtttctaattctaccctcaggggcctgtagatgttgctttccagcca1200
ggaatctaaagctttgggttttctgagggggggaggagggaactggaggttattggggtt1260
aggatggaagggaactctgcacaaaacctttgctttgctagtgctgctttgtgtgtatgt1320
gtggcaaataatttgggggtgatttgcaatgaaattttgggacccaaagagtatccactg1380
gggatgttttttggccaaaactcttccttttggaaccacatgaaagtcttgatgctgctg1440
ccatgatccctttgagaggtggctcaaaagctacagggaactccaggtcctttattactg1500
ccttcttttcaaaagcacaactctcctctaaccctcccctcccccttcccttctggtcgg1560
gtcatagagctaccgtattttctaggacaagagttctcagtcactgtgcaatatgccccc1620
tgggtcccaggagggtctggaggaaaactggctatcagaacctcctgatgccctggtggg1680
cttagggaaccatctctcctgctctccttgggatgatggctggctagtcagccttgcatg1740
tattccttggctgaatgggagagtgccccatgttctgcaagactacttggtattcttgta1800
8/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
gggccgacac taaataaaag ccaaaccttg ggcactgttt tttctccctg gtgctcagag 1860
cacctgtggg aaaggttgct gtctgtctca gtacaatcca aatttgtcgt agacttgtgc 1920
aatatatact gttgtgggtt ggagaaaagt ggaaagctac actgggaaga aactcccttc 1980
cttcaatttc tcagtgacat tgatgagggg tcctcaaaag acctcgagtt tcccaaaccg 2040
aatcaccttaagaaggacagggctagggcatttggccaggatggccaccctcctgctgtt2100
gccccttagtgaggaatcttcaccccacttcctctacccccaggttctcctccccacagc2160
cagtcccctttcctggatttctaaactgctcaattttgactcaaaggtgctatttaccaa2220
acactctccctacccattcctgccagctctgcctccttttcaactctccacattttgtat2280
tgccttcccagacctgcttccagtctttattgctttaaagttcactttgggcccacagac2340
ccaagagctaattttctggtttgtgggttgaaacaaagctgtgaatcactgcaggctgtg2400
ttcttgcatcttgtctgcaaacaggtccctgcctttttagaagcagcctcatggtctcat2460
gcttaatcttgtctctcttctcttctttatgatgttcactttaaaaacaacaaaacccct2520
gagctggactgttgagcaggcctgtctctcctattaagtaaaaataaatagtagtagtat2580
gtttgtaagctattctgacagaaaagacaaaggttactaattgtatgatagtgtttttat2640
atggaagaatgtacagcttatggacaaatgtacacctttttgttactttaataaaaatgt2700
agtaggataaaaaaaaa 2717
<210> 7
<211> 2249
<212> DNA
<2l3> Human
<400>
7
ctcctctacaaagaggtggacagagaagacagcagagaccatgggacccccctcagcccc 60
tccctgcagattgcatgtcccctggaaggaggtcctgctcacagcctcacttctaacctt 120
ctggaacccacccaccactgccaagctcactattgaatccacgccattcaatgtcgcaga 180
ggggaaggaggttcttctactcgcccacaacctgccccagaatcgtattggttacagctg 240
gtacaaaggcgaaagagtggatggcaacagtctaattgtaggatatgtaataggaactca 300
acaagctaccccagggcccgcatacagtggtcgagagacaatataccccaatgcatccct 360
gctgatccagaacgtcacccagaatgacacaggattctataccctacaagtcataaagtc 420
agatcttgtgaatgaagaagcaaccggacagttccatgtatacccggagctgcccaagcc 480
ctccatctccagcaacaactccaaccccgtggaggacaaggatgctgtggccttcacctg 540
tgaacctgaggttcagaacacaacctacctgtggtgggtaaatggtcagagcctcccggt 600
9/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
cagtcccaggctgcagctgtccaatggcaacatgaccctcactctactcagcgtcaaaag660
gaacgatgcaggat'cctatgaatgtgaaatacagaacccagcgagtgccaaccgcagtga720
cccagtcaccctgaatgtcctctatggcccagatgtccccaccatttccccctcaaaggc780
caattaccgtccaggggaaaatctgaacctctcctgccacgcagcctctaacccacctgc840
acagtactcttggtttatcaatgggacgttccagcaatccacacaagagctctttatccc900
caacatcactgtgaataatagcggatcctatatgtgccaagcccataactcagccactgg960
cctcaataggaccacagtcacgatgatcacagtctctggaagtgctcctgtcctctcagc1020
tgtggccaccgtcggcatcacgattggagtgctggccagggtggctctgatatagcagcc1080
ctggtgtattttcgatatttcaggaagactggcagattggaccagaccctgaattcttct1140
agctcctccaatcccattttatcccatggaaccactaaaaacaaggtctgctctgctcct1200
gaagccctatatgctggagatggacaactcaatgaaaatttaaagggaaaaccctcaggc1260
ctgaggtgtgtgccactcag,agacttcacctaactagagacagtcaaactgcaaaccatg1320
gtgagaaattgacgacttcacactatggacagcttttcccaagatgtcaaaacaagactc1380
ctcatcatgataaggctcttacccccttttaatttgtccttgcttatgcctgcctctttc1440
gcttggcaggatgatgctgtcattagtatttcacaagaagtagcttcagagggtaactta1500
acagagtgtcagatctatcttgtcaatcccaacgttttacataaaataagagatccttta1560
gtgcacccagtgactgacattagcagcatctttaacacagccgtgtgttcaaatgtacag1620
tggtccttttcagagttggacttctagactcacctgttctcactccctgttttaattcaa1680
cccagccatgcaatgccaaataatagaattgctccctaccagctgaacagggaggagtct1740
gtgcagtttctgacacttgttgttgaacatggctaaatacaatgggtatcgctgagacta1800
agttgtagaaattaacaaatgtgctgcttggttaaaatggctacactcatctgactcatt1860
ctttattctattttagttggtttgtatcttgcctaaggtgcgtagtccaactcttggtat1920
taccctcctaatagtcatactagtagtcatactccctggtgtagtgtattctctaaaagc1980
tttaaatgtctgcatgcagccagccatcaaatagtgaatggtctctctttggctggaatt2040
acaaaactcagagaaatgtgtcatcaggagaacatcataacccatgaaggataaaagccc2100
caaatggtggtaactgataatagcactaatgctttaagatttggtcacactctcacctag2160
gtgagcgcattgagccagtggtgctaaatgctacatactccaactgaaatgttaaggaag2220
aagatagatccaaaaaaaaaaaaaaaaaa 2249
<210> 8
<211> 3583
10/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
<212> DNA
<213> Human
<400>
8
gcttctaaagtgaagattcagttttcacttaaacaaccagcaagtcttgaagtctcttcc60
caagcaaatgggagcttctttggaccttggagcacacagaggattctactttctttaaaa120
ctttgttttcaggcaatttccctgagaaccgtttacttccagaagattggtggagcttga180
tctgaaggctggccatgaaatctcaaggtcaacattggtattccagttcagataaaaact240
gtaaagtgagctttcgtgagaagcttctgattattgattcaaacctgggggtccaagatg300
tggagaacctcaagtttctctgcataggattggtccccaacaagaagctggagaagtcca360
gctcagcctcagatgtttttgaacatctcttggcagaggatctgctgagtgaggaagacc420
ctttcttcctggcagaactcctctatatcatacggcagaagaagctgctgcagcacctca480
actgtaccaaagaggaagtggagcgactgctgcccacccgacaaagggtttctctgttta540
gaaacctgctctacgaactgtcagaaggcattgactcagagaacttaaaggacatgatct600
tccttctgaaagactcgcttcccaaaactgaaatgacctccctaagtttcctggcatttc660
tagagaaacaaggtaaaatagatgaagataatctgacatgcctggaggacctctgcaaaa720
cagttgtacctaaacttttgagaaacatagagaaatacaaaagagagaaagctatccaga780
tagtgacacctcctgtagacaag(~aagccgagtcgtatcaaggagaggaagaactagttt840
cccaaacagatgttaagacattcttggaagccttaccgagggcagctgtgtacaggatga900
atcggaaccacagaggcctctgtgtcattgtcaacaaccacagctttacctccctgaagg960
acagacaaggaacccataaagatgctgagatcctgagtcatgtgttccagtggcttgggt1020
tcacagtgcatatacacaataatgtgacgaaagtggaaatggagatggtcctgcagaagc1080
agaagtgcaatccagcccatgccgacggggactgcttcgtgttctgtattctgacccatg1140
ggagatttggagctgtctactcttcggatgaggccctcattcccattcgggagatcatgt1200
ctcacttcacagccctgcagtgccctagactggctgaaaaacctaaactctttttcatcc1260
aggcctgccaaggtgaagagatacagccttccgtatccatcgaagcagatgctctgaacc1320
ctgagcaggcacccacttccctgcaggacagtattcctgccgaggctgacttcctacttg1380
gtctggccactgtcccaggctatgtatcctttcggcatgtggaggaaggcagctggtata1440
ttcagtctctgtgtaatcatctgaagaaattggtcccaagacatgaagacatcttatcca1500
tcctcactgctgtcaacgatgatgtgagtcgaagagtggacaaacagggaacaaagaaac1560
agatgccccagcctgctttcacactaaggaaaaaactagtattccctgtgcccctggatg1620
cactttcaatatagcagagagtttttgttggttcttagacctcaaacgaatcattgggta1680
11/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
taacctccagcctcctgcccagcacaggaatcggtggtctccacctgtcattctagaaac1740
aggaaacaccgtgttttctgacacagtcaattctgattttctttttcttttgcaagtcta1800
aatgttagaaaactttctttttttggagatagtctcattctgtcacccagactggagtgc1860
aggggggcaatcacggctcactgtagtctcgacctcccaggctcaagctgtcctcccacc1920
tcagcctcccaagtagctgagactacaggtgtgtgtccatgcacagctaactttttattt1980
tttttgtggagatggggtttcactatgttgcctaagctggtctcaaactcctgggctcaa2040
gcgatcctcccacctcagcttctcaaagttctgggactacaggcatgaaatactgtgcct2100
ggcctggggaccaggtgcattttaaggttccttggtgttcaaaaaccacgttcttagcct2160
agattgagcttagattgcctctctagacaactaccccttagttataattctgtgtcccct2220
ctgcatgcccttaaacattggacagtgaggtcacagtccacccaccctctctctgatctc2280
ccccttcctaagacttctcttttgcacatctagtgaggtgaaaatttggtctatgccagg2340
cccatttcctgcttttgtgtaaggaaggtgctcacataggaagtttttatttggttagag2400
acaggtttccctgtaggaagatgatggctcatttacactcagctgctctgcaagcagaaa2460
ctttacaacctgatgtcatattccattttggactgggtgcggtgactcatgcctgtaatc2520
ccagtactctgggaagccaaggcaggcagatcacttgaggtcaggagttcgagaccagcc2580
tggccaatacggcaaaacctcatcattactaaaaacacaaaaattagccaggtgtggcgg2640
cgagcacctgtaatcccagctactcgggaggctgagacaggagaatctcttgaatccagg2700
aggcagaggctgtggtgagccaagatgacacaactgcactccagcttgggcaacagggcg2760
agaccttgtttaaaaaaaaaattcaatattggggttggaacatttcagttgccattgaca2820
gaacacccaattcaaattgactgaagcaaagaagggaatttattgcctctttcacattga2880
aacccaggagtggataacactggcttcaggcaaagcttgaatcaggactcaatctacagg2940
ccagcacctttctcttggccggatgtcctcagggctggcagatgcagtagactgcagtgg3000
acagtccccaccttgttactgctactacactttgctcctctggcccaaggcatgaggaga3060
gaggctgtgtcagaaactgaagctgttctcaggatcactgggctcttcttggcagagggg3120
atgtctggcttgcctgaagggagtggctctgtaaggacgccttgatgctttcttcattaa3180
gattttgagcatttttacgtacttgagcttttttttttttttttttcaatttctagagga3240
actttttctctgttaattcctggaactgtattttgaatccttaaaggtgagccctcatag3300
ggagatccaaagtcctgtggttaacgccttcatttatagatgaggcagctgaggcctggg3360
gatgtgaacaacctgctcacagtcctcatttactggatttgacttcagccaggtgaactg3420
12/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
gaatgccttg gggcgtggaa gggcattagg agtgtttcat ttgatatgtg aatgctcata 3480
aaaaaatgtc aaggaatgaa gaacaacaac tctcagtggt gcctgcattt ataattattt 3540
atgtgaaagt caaattcatg tacagtaaat ttgttataag aat 3583
<210> 9
<21l> 5516
<2l2> DNA
<213> Human
<400>
9
ccggccggaattccggctggatttcctcccggacatgacggtcgagggccgcctgctcgt60
tcctgacagaattaacggcacagccaacaagatgaacggagctttggatcactcagacca120
accagacccagatgccattaagatgtttgtcggacagatcccccggtcatggtcggaaaa180
ggagctgaaagaactttttgagccttacggagccgtctaccagatcaacgtcctccggga240
ccggagtcagaaccctccgcagagtaaaggttgttgtttcgtaacattttatacaagaaa300
agctgcacttgaggcccagaatgcactgcacaatattaaaactttacctgggatgcatca360
tcccattcagatgaaacctgcagatagtgaaaagtccaacgctgtggaagacagaaaatt420
gttcataggaatggtttcgaagaaatgtaatgagaacgacatcagggtgatgttctctcc480
atttggccagatagaagaatgccggatcctccggggacctgatgggctgagtcgaggctg540
tgcgtttgtcacattttctacaagggcaatggcacagaatgcaatcaaagccatgcatca600
gtctcagaccatggagggctgctcttcacctatcgtggtgaagtttgctgacactcagaa660
ggacaaagagcaaaggcgcctccagcagcagctcgctcagcagatgcagcagctcaacac720
tgccacctgggggaacctgacagggctgggcggactgaccccacagtatctggcgctcct780
gcagcaggccacctcctccagcaacctgggtgcgttcagcggcattcaacaaatggcagg840
catgaatgctttacagttgcagaacctggcgacgctggctgctgctgcagctgcggccca900
gacctcagccaccagcaccaatgcaaaccctctctctaccacgagcagcgccctgggagc960
cctcacgagtcccgtggctgcttcaacccccaactccactgctggtgcagccatgaactc1020
cttgacctctctcgggactctgcaaggactggctggagccactgttggactgaataatat1080
taatgcactagcagttgctcaaatgctctcaggtatggcggctctgaatggaggacttgg1140
cgccacaggcttgacgaatggcacggctggcaccatggacgccctcacccaggcctactc1200
aggaattcaacagtacgcagccgccgcgctgcccactctgtacagccagagcctgctgca1260
gcagcagagcgctgcaggcagccagaaggaaggtccagagggggcaaacctctttattta1320
ccaccttccacaggaatttggagaccagcacattctgcagatgttcatgccttttggaaa1380
13/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
tgttatctct gctaaagtct tcattgacaa acagaccaat ctgagcaagt gctttggttt 1440
tgttagctac gacaatccag tctctgcaca agctgctatc caagctatga atggctttca 1500
gatcggcatgaaacgcttgaaggtgcagctgaagcgttccaaaaacgacagcaaacctta1560
ctgatcctaaccccagaggctccctgctctcattttagctttcttaggacatcttcatgc1620
ccgttagttcatcgtttgcctagcatgtccctgtggcgtctcaaaaaaaagtttcatcgt1680
cccgtcattgtttctgatgtctttctgacctcacatcatatttggttctcctactgacct1740
ttgatctagtttgacctttgaaatttgcatgtgacctcatctagctatgaattctgggaa1800
gtcaatgtgaaaaacattgctgcattcatgcaagactgaaatttattattagacaaattc1860
attatagaaaaaacctgtggcaaaaacgtttctttcttattttttttcttttcctaaaac1920
agacttgaaagtattatacagggattggcattcttcccggtcactggtaacaatagcaat1980
atgtgtccagggacacagaatgttggtttctaacagactacttccaaaaacagtttgaga2040
aaaaaactgtctgattttaagtctctagaggtctgtaatagtttttacatttttcaggca2100
gtgtaaagttttttgataaggccattttaggtggctcactttctcattaagatatatata2160
tagaaccactttttgtagattagtataagaaaaatatttaccctgttttggggcaaatgc2220
tacctatttgtgtcaccttttgctgaactcacagttagacaatccatggtttaatgcaca2280
tgaaattacctatattttatactgtttcaatgtacaggagaaaggttactgtaaactgtg2340
ttatgttggtgcttctgtgaattaagttgtggtttcatcatgagtcttaatgttctttgt2400
tgataagacaagtttagaattggtttacttaatacaaaaaaaaaaaaaagaatttcaaaa2460
aaaaaagttgtttgcttaaaaaaaatttcatgtgagggaaaaaaaaaaaaacctattcca2520
gaataagttttgtgttggcttgtgaagcattgatgtcattttttttaattgtggactatt2580
tagatgtgtttgtgttcagcaaaatgtgatctgtttttttcttttaaagaaaaaaagtga2640
aaatatatagtgccaaattccaaaggtacttccttcctagagcttcagtgtgtttcttgt2700
gagaagtaatttgataacatgggtattttattatgtgttttgtataaatccctaatattt2760
aaaaaaaaaaacaaaacaaaaaaaggttacaaagtttgttaacttgctatcctgtggtct2820
tgttgcctgaaattgttattgtttgttatttctctctgatgttttttgtaagacattgta2880
taagtgcccatgtcccacttttttaaccactccgcacatcagtgctgtgaaggcaacctc2940
accatgtattttcttcataatctatggaaacctctaaggtgagaaagttttgaactttta3000
accctttctacccagagctatctggaatgttgatgactttttatactgtcatgatttgag3060
tttgttttggggtgtttccaatttggatttttttccctgcatctatcctctaagttgttt3120
cggtttgactactttgttctttggttaagatccaaaagaaaacagaaaacaattccacga3180
14/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
ggccaatcta aagggaaaaa atcctacact acttttacta cttttgatta tttctcattt 3240
ttgggaaaag aattcctaat gtgctactag aattccttct tcagttttaa cgagtaattg 3300
gataaaccct gagggaaaac ggaggtagat tcagcaccta acaatcctgt atgcttttga 3360
gatcacgttt agtgctatgt cctagtctag aatattttca tataccttgc agtaaaacca 3420
ctttgtggca ggacagtctc ttgaggggtt ttgtttctgt ttcctaaata ctcctaaata 3480
atatttctaa tcagccatta tgctggggca tctctgatcc cagtaggtac ctctgaatat 3540
accaggtgtc tggagttaga agcccatagc cctttcccag cctttttggt ttttttaatt 3600
gaacacattt catctaagta aagctcagtt ctttatcaca atttactgac caaataccta 3660
gcaccagttc ctgctgccac tttttaaagt gccatatgac tttctacgaa caggtacctt 3720
gctgtcttga caaatcctaa tgtcacgcct acagccccaa cacaagctcc agtcttcctc 3780
ttcggcatgc cctggaagct tcttggcctc agctcccctt ccccgctcag caccctgtta 3840
ggatcagtgt gtgtggatgg gatagccctg ggatggaaag gactagcctc tactgatgca 3900
aaaaaacaaa aagcaacaca aacgtttcct tcttatagca catgcacttc cttacaatga 3960
catgatttgt attatcctca catgtgttta ctactgctgg ggccttcctt catcctctga 4020
gggctatttt gtactttctg cagcaatcag cttaataaca acacttattg cacctgtctc' 4080
tctctgagaa cacggtgtgt ctcgacacgt accacgtaac gtggaaacac aagagcccac 4140
cacttgaatt tctaagacca tttcattctg aaacttctta tcaattacct aaatctcaac 4200
gaaaaacaat ttactgaagc cgactcccct ccccatctcc ctctcaacct caacccacct 4260
gcatgcatctcccccagaggaaaacactgagggtaggggacagggaggctcaggacgcgc4320
cctctgaatcggagtgtttcttcttcacaagtcaccaagagaggacatgagggggaaagt4380
ccttttttgcccttctccaaaaaataaccttccacagagacaaactgtccttctatccac4440
ttttatcttttaataaatatcaaaaggaaaaagctgcaagggtgcaaagggcctgtgcca4500
gaagaaaacacacacagggaaaccgctttttttaatcaattgtagagaatagtcattttt4560
aatctaaattagagaattgtgatacaatggcagtcctcaaaggcgtaacgagttcatctt4620
tctttcaccataggggttatagttggcttgtgctactctggaatcattttactgtttgtt4680
tttattatcttaagtgctaattaaaaaaaaaataaaattttaaaaaaacctgtagtttca4740
ttacctttttgaataatgtcatacaaaaaatgtatttgtttttttgtgctgtgagaattg4800
atgtttgtagattaataatcattttgtttagaattacaaaatagtttttaaatattgtct4860
gagaaaagccaaagttaatgcaacctagtggaaactgtaagaccatttgagtattgtttg4920
15/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
ttttattgat gcatttggat tttgttgttt gatggaattt gagccaaaaa aaaaaatacg 4980
caggctttcc tatttctaca actgattgta cttatgcatt ttgtaccagt ggaacttttt 5040
atactggagattaaaaaaaaaatggaaatttttgtggcttgctctggtgggcccctgaca5100
atgactgatttcaagtttgatttcgggttgattgattgattgattgatagaaagaaagtt5160
gcttttcttttgagaattaaaaactttggcttgatttcttttttccctttgcttatatct5220
agcattagaattttgtcttaaaataacagcggtaagtttcactttttattctgtattgtg5280
cagttacacaataaggtaattagatttagaagtactcagtcactttaagtggataaatgt5340
attagttaaaactttagggtttgcttttttgctgtttagatcaaagttttttctgattct5400
tctgtcctcattgtgaacataaccgtgtagttgaaacagtcaaacttatttttgtaatgt5460
atgttattgtgtgatgcagtttttttgcttctgtctccaatattaaaccattttcc 5516
<210> 10
<211> 736
<212> DNA
<213> Human
<400>
ggctctcaccctcctctcctgcagctccagctttgtgctctgcctctgaggagaccatgg 60
cccggcctctgtgtaccctgctactcctgatggctaccctggctggggctctggcctcga 120
gctccaaggaggagaataggataatcccaggtggcatctatgatgcagacctcaatgatg 180
agtgggtacagcgtgcccttcacttcgccatcagcgagtacaacaaggccaccgaagatg 240
agtactacagacgcccgctgcaggtgctgcgagccagggagcagacctttgggggggtga 300
attacttcttcgacgtagaggtgggccgcaccatatgtaccaagtcccagcccaacttgg 360
acacctgtgccttccatgaacagccagaactgcagaagaaacagttgtgctctttcgaga 420
r
tctacgaagttccctgggaggacagaatgtccctggtgaattccaggtgtcaagaagcct 480
aggggtctgtgccaggccagtcacaccgaccaccacccactcccacccactgtagtgctc 540
ccacccctggactggtggcccccaccctgcgggaggcctccccatgtgcctgtgccaaga 600
gacagacagagaaggctgcaggagtcctttgttgctcagcagggcgctctgccctccctc 660
cttccttcttgcttctaatagacctggtacatggtacacacacccccacctcctgcaatt 720
aaacagtagc atcgcc 736
<210> 11
<211> 6129
<212> DNA
<213> Human
16/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
<400>
11
aattggaagcaaatgacatcacagcaggtcagagaaaaagggttgagcggcaggcaccca 60
gagtagtaggtctttggcattaggagcttgagcccagacggccctagcagggaccccagc 120
gcccgagaga~ccatgcagaggtcgcctctggaaaaggccagcgttgtctccaaacttttt 180
ttcagctggaccagaccaattttgaggaaaggatacagacagcgcctggaattgtcagac 240
atataccaaatcccttctgttgattctgctgacaatctatctgaaaaattggaaagagaa 300
tgggatagagagctggcttcaaagaaaaatcctaaactcattaatgcccttcggcgatgt 360
tttttctggagatttatgttctatggaatctttttatatttaggggaagtcaccaaagca 420
gtacagcctctcttactgggaagaatcatagcttcctatgacccggataacaaggaggaa 480
cgctctatcgcgatttatctaggcataggcttatgccttctctttattgtgaggacactg 540
ctcctacacccagccatttttggccttcatcacattggaatgcagatgagaatagctatg 600
tttagtttgatttataagaagactttaaagctgtcaagccgtgttctagataaaataagt 660
attggacaacttgttagtctcctttccaacaacctgaacaaatttgatgaaggacttgca 720
ttggcacatttcgtgtggatcgctcctttgcaagtggcactcctcatggggctaatctgg 780
gagttgttacaggcgtctgccttctgtggacttggtttcctgatagtccttgcccttttt 840
caggctgggctagggagaatgatgatgaagtacagagatcagagagctgggaagatcagt 900
gaaagacttgtgattacctcagaaatgattgaaaatatccaatctgttaaggcatactgc 960
tgggaagaagcaatggaaaaaatgattgaaaacttaagacaaacagaactgaaactgact 1020
cggaaggcagcctatgtgagatacttcaatagctcagccttcttcttctcagggttcttt 1080
gtggtgtttttatctgtgcttccctatgcactaatcaaaggaatcatcctccggaaaata 1140
ttcaccaccatctcattctgcattgttctgcgcatggcggtcactcggcaatttccctgg 1200
gctgtacaaacatggtatgactctcttggagcaataaacaaaatacaggatttcttacaa 1260
aagcaagaatataagacattggaatataacttaacgactacagaagtagtgatggagaat 1320
gtaacagccttctgggaggagggatttggggaattatttgagaaagcaaaacaaaacaat 1380
aacaatagaaaaacttctaatggtgatgacagcctcttcttcagtaatttctcacttctt 1440
ggtactcctgtcctgaaagatattaatttcaagatagaaagaggacagttgttggcggtt 1500
gctggatccactggagcaggcaagacttcacttctaatgatgattatgggagaactggag 1560
ccttcagagggtaaaattaagcacagtggaagaatttcattctgttctcagttttcctgg 1620
attatgcctggcaccattaaagaaaatatcatctttggtgtttcctatgatgaatataga 1680
tacagaagcgtcatcaaagcatgccaactagaagaggacatctccaagtttgcagagaaa 1740
17/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
gacaatatagttcttggagaaggtggaatcacactgagtggaggtcaacgagcaagaatt1800
tctttagcaagagcagtatacaaagatgctgatttgtatttattagactctccttttgga1860
tacctagatgttttaacagaaaaagaaatatttgaaagctgtgtctgtaaactgatggct1920
aacaaaactaggattttggtcacttctaaaatggaacatttaaagaaagctgacaaaata1980
ttaattttgaatgaaggtagcagctatttttatgggacattttcagaactccaaaatcta2040
cagccagactttagctcaaaactcatgggatgtgattctttcgaccaatttagtgcagaa2100
agaagaaattcaatcctaactgagaccttacaccgtttctcattagaaggagatgctcct2160
gtctcctggacagaaacaaaaaaacaatcttttaaacagactggagagtttggggaaaaa2220
aggaagaattctattctcaatccaatcaactctatacgaaaattttccattgtgcaaaag2280
actcccttacaaatgaatggcatcgaagaggattctgatgagcctttagagagaaggctg2340
tccttagtaccagattctgagcagggagaggcgatactgcctcgcatcagcgtgatcagc2400
actggcccca cgcttcaggc acgaaggagg cagtctgtcc tgaacctgat gacacactca 2460
gttaaccaag gtcagaacat tcaccgaaag acaacagcat ccacacgaaa agtgtcactg 2520
gcccctcagg caaacttgac tgaactggat atatattcaa gaaggttatc tcaagaaact 2580
ggcttggaaataagtgaagaaattaacgaagaagacttaaaggagtgcctttttgatgat2640
atggagagcataccagcagtgactacatggaacacataccttcgatatattactgtccac2700
aagagcttaatttttgtgctaatttggtgcttagtaatttttctggcagaggtggctgct2760
tctttggttgtgctgtggctccttggaaacactcctcttcaagacaaagggaatagtact2820
catagtagaaataacagctatgcagtgattatcaccagcaccagttcgtattatgtgttt2880
tacatttacgtgggagtagccgacactttgcttgctatgggattcttcagaggtctacca2940
ctggtgcatactctaatcacagtgtcgaaaattttacaccacaaaatgttacattctgtt3000
cttcaagcacctatgtcaaccctcaacacgttgaaagcaggtgggattcttaatagattc3060
tccaaagatatagcaattttggatgaccttctgcctcttaccatatttgacttcatccag3120
ttgttattaattgtgattggagctatagcagttgtcgcagttttacaaccctacatcttt3180
gttgcaacagtgccagtgatagtggcttttattatgttgagagcatatttcctccaaacc3240
tcacagcaactcaaacaactggaatctgaaggcaggagtccaattttcactcatcttgtt3300
acaagcttaaaaggactatggacacttcgtgccttcggacggcagccttactttgaaact3360
ctgttccacaaagctctgaatttacatactgccaactggttcttgtacctgtcaacactg3420
cgctggttccaaatgagaatagaaatgatttttgtcatcttcttcattgctgttaccttc3480
atttccattttaacaacaggagaaggagaaggaagagttggtattatcctgactttagcc3540
18/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
atgaatatca tgagtacatt gcagtgggct gtaaactcca gcatagatgt ggatagcttg 3600
atgcgatctg tgagccgagt ctttaagttc attgacatgc caacagaagg taaacctacc 3660
aagtcaaccaaaccatacaagaatggccaactctcgaaagttatgattattgagaattca3720
cacgtgaagaaagatgacatctggccctcagggggccaaatgactgtcaaagatctcaca3780
gcaaaatacacagaaggtggaaatgccatattagagaacatttccttctcaataagtcct3840
ggccagagggtgggcctcttgggaagaactggatcagggaagagtactttgttatcagct3900
tttttgagactactgaacactgaaggagaaatccagatcgatggtgtgtcttgggattca3960
ataactttgcaacagtggaggaaagcctttggagtgataccacagaaagtatttattttt4020
tctggaacatttagaaaaaacttggatccctatgaacagtggagtgatcaagaaatatgg4080
aaagttgcagatgaggttgggctcagatctgtgatagaacagtttcctgggaagcttgac4140
tttgtccttgtggatgggggctgtgtcctaagccatggccacaagcagttgatgtgcttg4200
gctagatctgttctcagtaaggcgaagatcttgctgcttgatgaacccagtgctcatttg4260
gatccagtaacataccaaataattagaagaactctaaaacaagcatttgctgattgcaca4320
gtaattctctgtgaacacaggatagaagcaatgctggaatgccaacaatttttggtcata4380
gaagagaacaaagtgcggcagtacgattccatccagaaactgctgaacgagaggagcctc4440
ttccggcaagccatcagcccctccgacagggtgaagctctttccccaccggaactcaagc4500
aagtgcaagtctaagccccagattgctgctctgaaagaggagacagaagaagaggtgcaa4560
gatacaaggctttagagagcagcataaatgttgacatgggacatttgctcatggaattgg4620
agctcgtgggacagtcacctcatggaattggagctcgtggaacagttacctctgcctcag4680
aaaacaaggatgaattaagtttttttttaaaaaagaaacatttggtaaggggaattgagg4740
acactgatatgggtcttgataaatggcttcctggcaatagtcaaattgtgtgaaaggtac4800
ttcaaatccttgaagatttaccacttgtgttttgcaagccagattttcctgaaaaccctt4860
gccatgtgctagtaattggaaaggcagctctaaatgtcaatcagcctagttgatcagctt4920
attgtctagtgaaactcgttaatttgtagtgttggagaagaactgaaatcatacttctta4980
gggttatgattaagtaatgataactggaaacttcagcggtttatataagcttgtattcct5040
ttttctctcctctccccatgatgtttagaaacacaactatattgtttgctaagcattcca5100
actatctcat ttccaagcaa gtattagaat accacaggaa ccacaagact gcacatcaaa 5160
atatgcccca ttcaacatct agtgagcagt caggaaagag aacttccaga tcctggaaat 5220
cagggttagt attgtccagg tctaccaaaa atctcaatat ttcagataat cacaatacat 5280
19/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
cccttacctg ggaaagggct gttataatct ttcacagggg acaggatggt tcccttgatg 5340
aagaagttga tatgcctttt cccaactcca gaaagtgaca agctcacaga cctttgaact 5400
agagtttagc tggaaaagta tgttagtgca aattgtcaca ggacagccct tctttccaca 5460
gaagctccag gtagagggtg tgtaagtaga taggccatgg gcactgtggg tagacacaca 5520
tgaagtccaa gcatttagat gtataggttg atggtggtat gttttcaggc tagatgtatg 5580
tacttcatgc tgtctacact aagagagaat gagagacaca ctgaagaagc accaatcatg 5640
aattagtttt atatgcttct gttttataat tttgtgaagc aaaatttttt ctctaggaaa 5700
tatttattttaataatgtttcaaacatatattacaatgctgtattttaaaagaatgatta 5760
tgaattacatttgtataaaataatttttatatttgaaatattgactttttatggcactag 5820
tatttttatgaaatattatgttaaaactgggacaggggagaacctagggtgatattaacc 5880
aggggccatgaatcaccttttggtctggagggaagccttggggctgatcgagttgttgcc 5940
cacagctgtatgattcccagccagacacagcctcttagatgcagttctgaagaagatggt 6000
accaccagtctgactgtttccatcaagggtacactgccttctcaactccaaactgactct 6060
taagaagactgcattatatttattactgtaagaaaatatcacttgtcaataaaatccata 6120
catttgtgt 6129
<210> 12
<211> 1876
<212> DNA
<213> Human
<400>
12
gagccatgctcgcggcgatgggctctctggcggctgccctctgggcagtggtccatcctc 60
ggactctcctactgggcactgtcgcctttctgctcgctgctgactttctcaaaagacggc 120
gcccaaagaactacccgccggggccctggcgcctgcccttccttggcaacttcttccttg 180
tggacttcgagcagtcgcacctggaggttcagctgtttgtgaagaaatatgggaaccttt 240
ttagcttggagcttggtgacatatctgcagttcttattactggcttgcccttaatcaaag 300
aagcccttatccacatggaccaaaactttgggaaccgccccgtgacccctatgcgagaac 360
atatctttaagaaaaatggattgattatgtcaagtggccaggcatggaaggagcaaagaa 420
ggttcactctgacagcactaaggaactttggtttaggaaagaagagcttagaggaacgca 480
ttcaggaggaggcccaacacctcactgaagcaataaaagaggagaacggacagccttttg 540
accctcatttcaagatcaacaatgcagtttccaatatcatttgctccatcaccttcggag 600
aacgctttgagtaccaggatagttggtttcagcagctgctgaagttactagatgaagtca 660
20/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
catacttggaggcttcaaagacatgccagctctacaatgtctttccatggataatgaaat720
tcctgcctggaccccaccaaactctcttcagcaactggaaaaaactgaaattgtttgttt780
ctcatatgattgacaaacacagaaaggattggaatcctgcagaaacaagagactttattg840
atgcttaccttaaagaaatgtcaaagcacacaggcaatcctacttcaagtttccatgaag900
aaaacctcatctgcagcaccctggacctcttctttgccggaaccgagacaacttccacaa960
ctctgcgatgggctctgctttatatggccctctacccagaaatccaagaaaaagtacaag1020
ctgagattgacagagtgattggccaggggcagcagccgagcacagccgcccgggagtcca1080
tgccctacaccaatgctgtcatccatgaggtgcagagaatgggcaacatcatccccctga1140
acgttcccagggaagtgacagttgataccactttggctgggtaccacctgcccaagggta1200
ccatgatcctgaccaatttgacggcgctgcacagggaccccacagagtgggccacccctg1260
acacattcaatccggaccattttctggagaatggacagtttaagaaaagggaagccttta1320
tgcctttctcaataggaaagcgggcatgcctcggagaacagttggccaggactgagctgt1380
ttattttcttcacttcccttatgcaaaaatttaccttcaggcccccaaacaatgagaagc1440
tgagcctgaagtttagaatgggtatcaccatttccccagtcagtcaccgcctctgcgctg1500
ttcctcaggtgtaatattgttaagaaagaaaggggcaaggaaagtaagaagacatggcac1560
gtgttctgaaaccactggtgtctgctcagatgtgttgggacaaaatgaaagtgactttca1620
agaaagatcagaggaatttgactcagagaaaactagatccaaatcccagctctactgtct1680
cgtccgaattagccttgggaaaatcatttatatgctaaataatttacctttttatctagg1740
agatgaaaagaggataatgtttccttccataaagaaagttcttgtaagaatcaaaagaaa1800
tggtgagctttaagtggtttgtaaaccataaaacacatcataaaagttctatctataaaa1860
aaaaaaaaaaaaaaaa 1876
<210> 13
<211> 2375
<212> DNA
<2l3> Human
<400>
13
atgaagacaccgtggagggttctcctgggactgctgggtgctgctgcgcttgtcaccatc60
atcaccgtgcccgtggttctgctgaacaaaggcacagatgatgctacagctgacagtcgc120
aaaacttacactctaactgattacttaaaaaatacttatagactgaagttatactcctta180
agatggatttcagatcatgaatatctctacaaacaagaaaataatatcttggtattcaat240
gctgaatatggaaacagctcagttttcttggagaacagtacatttgatgagtttggacat300
21/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
tctatcaatgattattcaatatctcctgatgggcagtttattctcttagaatacaactac 360
gtgaagcaatggaggcattcctacacagcttcatatgacatttatgatttaaataaaagg 420
cagctgattacagaagagaggattccaaacaacacacagtgggtcacatggtcaccagtg 480
ggtcataaattggcatatgtttggaacaatgacatttatgttaaaattgaaccaaattta 540
ccaagttacagaatcacatggacggggaaagaagatataatatataatggaataactgac 600
tgggtttatgaagaggaagtcttcagtgcctactctgctctgtggtggtctccaaacggc 660
acttttttagcatatgcccaatttaacgacacagaagtcccacttattgaatactccttc 720
tactctgatgagtcactgcagtacccaaagactgtacgggttccatatccaaaggcagga780
gctgtgaatccaactgtaaagttctttgttgtaaatacagactctctcagctcagtcacc840
aatgcaacttccatacaaatcactgctcctgcttctatgttgataggggatcactacttg900
tgtgatgtgacatgggcaacacaagaaagaatttctttgcagtggctcaggaggattcag960
aactattcggtcatggatatttgtgactatgatgaatccagtggaagatggaactgctta1020
gtggcacggcaacacattgaaatgagtactactggctgggttggaagatttaggccttca1080
gaacctcattttacccttgatggtaatagcttctacaagatcatcagcaatgaagaaggt1140
tacagacacatttgctatttccaaatagataaaaaagactgcacatttattacaaaaggc1200
acctgggaagtcatcgggatagaagctctaaccagtgattatctatactacattagtaat1260
gaatataaaggaatgccaggaggaaggaatctttataaaatccaacttagtgactataca1320
aaagtgacatgcctcagttgtgagctgaatccggaaaggtgtcagtactattctgtgtca1380
ttcagtaaagaggcgaagtattatcagctgagatgttccggtcctggtctgcccctctat1440
actctacacagcagcgtgaatgataaagggctgagagtcctggaagacaattcagctttg1500
gataaaatgctgcagaatgtccagatgccctccaaaaaattggacttcattattttgaat1560
gaaacaaaattttggtatcagatgatcttgcctcctcattttgataaatccaagaaatat1620
cctctactattagatgtgtatgcaggcccatgtagtcaaaaagcagacattgtcttcaga1680
ctgaactgggccacttaccttgcaagcacagaaaacattatagtagctagctttgatggc1740
agaggaagtggttaccaaggagataagatcatgcatgcaatcaacagaagactgggaaca1800
tttgaagttgaagatcaaattgaagcagccagacaattttcaaaaatgggatttgtggac1860
aacaaacgaattgcaatttggggctggtcatatggagggtacgtaacctcaatggtcctg1920
ggatcgggaagtggcgtgttcaagtgtggaatagccgtggcgcctgtatcccggtgggag1980
tactatgagtcagtgtacacagaacgttacatgggtctcccaactccagaagacaacctt2040
gaccattacagaaattcaacagtcatgagcagagctgaaaattttaaacaagttgagtac2100
22/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
ctccttattc atggaacagc agatgataac gttcactttc agcagtcagc tcagatctcc 2160
aaagccctgg tcgatgttgg agtggatttc caggcaatgt ggtatactga tgaagaccat 2220
ggaatagcta gcagcacagc acaccaacat atatataccc acatgagcca cttcataaaa 2280
caatgtttct ctttacctta gcacctcaaa atactatgcc atttaaagct tattaaaact 2340
catttttgtt ttcattatct caaaaaaaaa aaaaa 2375
<210>
14
<211>
2248
<212>
DNA
<213> n
Huma
<400>
14
cccagcgccccggaagtgatctgtggcggctgctgcagagccgccaggaggagggtggat60
CtCCCCagagcaaagcgtcggagtcctcctCCtCCttCtCCtCCt tCCt CCtCCt120
CCtCC
ccagccgcccaggctcccccgccacccgtcagactcctccttcgaccgctcccggcgcgg180
ggccttccaggcgacaaggaccgagtaccctccggccggagccacgcagccgcggcttcc240
ggagccctcggggcggcggactggctcgcggtgcaggtaaagctccagatggctctggaa300
cttatgaggaaagagttggaggacgccttgactcaggaggccaacgtggggaaaaagact360
gtcatttggaaggagaaagtggaaatgcagaggcagcgcttcagattggagtttgagaag420
catcgtggctttctggcccaggaggagcaacggcagctgaggcggctggaggcggaggag480
cgagcgacgctgcagagactgcgggagagcaagagccggctggtccagcagagcaaggcc540
ctgaaggagctggcggatgagctgcaggagaggtgccagcgcccagccctgggtctgctg600
gagggtgtgagaggagtcctgagcagaagtaaggctgtcacaaggctggaagcagagaac660
atccccatggaactgaagacagcatgctgcatccctgggaggagggagctcttaaggaag720
ttccaagtggatgtaaagctggatcccgccacggcgcacccgagtctgctcttgaccgcc780
gacctgcgcagtgtgcaggatggagaaccatggagggatgtccccaacaaccctgagcga840
tttgacacatggccctgcatcctgggtttgcagagcttctcatcagggaggcattactgg900
gaggttctggtgggagaaggagcagagtggggtttaggggtctgtcaagacacactgcca960
agaaagggggaaaccatgccatctcctgagaatggggtctgggccctgtggctgctgaaa1020
gggaatgagtacatggtccttgcctccccatcagtgcctcttctccaactggaaagtcct1080
cgctgcattgggattttcttggactatgaagccggtgaaatttcattctacaatgtcaca1140
gatggatcttatatctacacattcaaccaactcttctctggtcttcttcggccttacttt1200
ttcatctgtgatgcaactcctcttatcttgccacccacgacaatagcagggtcaggaaat1260
23/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
tgggcatccagggatcatttagatcctgcttctgatgtaagagatgatcatctctaaaat1320
tctgttcccaagatgcagtcctagcgtagcgaacgttcctggagtggggtgaaggatatc1380
aatatactaagttttaacagataccccatttaggtcagcacttgattcgttgttgctgtg1440
aaatatgtccatgggacaaaagagggaatatgaaatatttgcatatgggaagattataga1500
gcataataattttgtaaatggagcaatctcaacctctatttctagatcacattttcttga1560
tgtcttccttcaaattaatgaccttggattacataaggatttctatgcattcattataat1620
ttgttattcctttcaatatccttgtatttcaaatcttccatataagaattagacatggca1680
attcttaaattgattcagaatggtctgatactattccagtatcacctccttaattctgtt1740
tCtCCt ttCCtgattttCCttCtCattCt CtCCttCCCCgCtCtgtCtCtCtCtCC1800
Cgtt
ctgtcactctctctctctcgttccttattttttgtttcttacctcttactgtttaacctg1860
ttgcttccttctggattaatacatttagagccattcctttatatggtcacatttcctatg1920
actttactcaattacttttaaaatcctttctattctgagactaatttttaagaattacaa1980
agctcattcttctgaatctaatatcactaactcctagactttttccgttttctttggata2040
cactttaagtaggaatttatcagaattttcattcaactcgttctttaatgcagatattta2100
ctggttataagaccttaaggctgggtgcagtggctcacgcctgtggtcccagcgctttgg2160
ggggctgaggcgggtggatcacaggctcgggagttcggggccagcctggccagcatggtg2220
aaaccctgtctctactagaaaaaaaaaa 2248
<210> 15
<211> 330
<212> DNA
<213> Human
<400>
15
gcggccgcaggtacccgggctccacgtcagggtagacctggcgtccctcaatgccttcca60
tgtagttggccacgtaatccaccatctccttccctctccttcggaattcacttgcgttca120
tggtgtctgggctctgtcagaggtgaaaaatgctggaaattcgaattccttacagggcta180
ctctccttgatgggattctccaactttggggactgaagagcatgtggagaagctgctgag240
gcactcggcactgagacagtcactcttcttgaaactccaagccacacgtttccctcttct300
tgcatttccagccacatgtgcccctcgtgc 330
<210> 16
<211> 3370
<212> DNA
<213> Human
24/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
<400> 16
gcccccgccc ggcccgcccc gctctcctag tcccttgcaa cctggcgctg catccgggcc 60
actgtcccaggtcccaggtcccggcccggagctatggagcggcgctggcccctggggcta120
gggctggtgctgctgctctgcgccccgctgcccccgggggcgcgcgccaaggaagttact180
ctgatggacacaagcaaggcacagggagagctgggctggctgctggatcccccaaaagat240
gggtggagtgaacagcaacagatactgaatgggacacccctctacatgtaccaggactgc300
ccaatgcaaggacgcagagacactgaccactggcttcgctccaattggatctaccgcggg360
gaggaggcttcccgcgtccacgtggagctgcagttcaccgtgcgggactgcaagagtttc420
cctgggggagccgggcctctgggctgcaaggagaccttcaaccttctgtacatggagagt480
gaccaggatgtgggcattcagctccgacggcccttgttccagaaggtaaccacggtggct540
gcagaccagagcttcaccattcgagaccttgcgtctggctccgtgaagctgaatgtggag600
cgctgctctctgggccgcctgacccgccgtggcctctacctcgctttccacaacccgggt660
gcctgtgtggccctggtgtctgtccgggtcttctaccagcgctgtcctgagaccctgaat720
ggcttggcccaattcccagacactctgcctggccccgctgggttggtggaagtggcgggc780
acctgcttgccccacgcgcgggccagccccaggccctcaggtgcaccccgcatgcactgc840
agccctgatggcgagtggctggtgcctgtaggacggtgccactgtgagcctggctatgag900
gaaggtggcagtggcgaagcatgtgttgcctgccctagcggctcctaccggatggacatg960
gacacaccccattgtctcacgtgcccccagcagagcactgctgagtctgagggggccacc1020
atctgtacctgtgagagcggccattacagagctcccggggagggcccccaggtggcatgc1080
acaggtcccccctcggccccccgaaacctgagcttctctgcctcagggactcagctctcc1140
ctgcgttgggaacccccagcagatacggggggacgccaggatgtcagatacagtgtgagg1200
tgttcccagtgtcagggcacagcacaggacggggggccctgccagccctgtggggtgggc1260
gtgcacttctcgccgggggcccgggcgctcaccacacctgcagtgcatgtcaatggcctt1320
gaaccttatgccaactacacctttaatgtggaagcccaaaatggagtgtcagggctgggc1380
agctctggccatgccagcacctcagtcagcatcagcatggggcatgcagagtcactgtca1440
ggcctgtctctgagactggtgaagaaagaaccgaggcaactagagctgacctgggcgggg1500
tcccggccccgaagccctggggcgaacctgacctatgagctgcacgtgctgaaccaggat1560
gaagaacggtaccagatggttctagaacccagggtcttgctgacagagctgcagcctgac1620
accacataca tcgtcagagt ccgaatgctg accccactgg gtcctggccc tttctcccct 1680
gatcatgagt ttcggaccag cccaccagtg tccaggggcc tgactggagg agagattgta 1740
25/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
gccgtcatctttgggctgctgcttggtgcagccttgctgcttgggattctcgttttccgg1800
tccaggagagcccagcggcagaggcagcagaggcacgtgaccgcgccaccgatgtggatc1860
gagaggacaagctgtgctgaagccttatgtggtacctccaggcatacgaggaccctgcac1920
agggagccttggactttacccggaggctggtctaattttccttcccgggagcttgatcca1980
gcgtggctgatggtggacactgtcataggagaaggagagtttggggaagtgtatcgaggg2040
accctcaggctccccagccaggactgcaagactgtggccattaagaccttaaaagacaca2100
tccccaggtggccagtggtggaacttccttcgagaggcaactatcatgggccagtttagc2160
cacccgcatattctgcatctggaaggcgtcgtcacaaagcgaaagccgatcatgatcatc2220
acagaatttatggagaatgcagccctggatgccttcctgagggagcgggaggaccagctg2280
gtccctgggcagctagtggccatgctgcagggcatagcatctggcatgaactacctcagt2340
aatcacaattatgtccaccgggacctggctgccagaaacatcttggtgaatcaaaacctg2400
tgctgcaaggtgtctgactttggcctgactcgcctcctggatgactttgatggcacatac2460
gaaacccagggaggaaagatccctatccgttggacagcccctgaagccattgcccatcgg2520
atcttcaccacagccagcgatgtgtggagctttgggattgtgatgtgggaggtgctgagc2580
tttggggacaagccttatggggagatgagcaatcaggaggttatgaagagcattgaggat2640
gggtaccggttgccccctcctgtggactgccctgcccctctgtatgagctcatgaagaac2700
tgctgggcatatgaccgtgcccgccggccacacttccagaagcttcaggcacatctggag2760
caactgcttgccaacccccactccctgcggaccattgccaactttgaccccagggtgact2820
cttcgcctgcccagcctgagtggctcagatgggatcccgtatcgaaccgtctctgagtgg2880
ctcgagtccatacgcatgaaacgctacatcctgcacttccactcggctgggctggacacc2940
,
atggagtgtgtgctggagctgaccgctgaggacctgacgcagatgggaatcacactgccc3000
gggcaccagaagcgcattctttgcagtattcagggattcaaggactgatccctcctctca3060
ccccatgcccaatcagggtgcaaggagcaaggacggggccaaggtcgctcatggtcactc3120
cctgcgccccttcccacaacctgccagactaggctatcggtgctgcttctgcccgcttta3180
aggagaaccctgctctgcaccccagaaaacctctttgttttaaaagggaggtgggggtag3240
aagtaaaaggatgatcatgggagggagctcaggggttaatatatatacatacatacacat3300
atatatattgttgtaaataaacaggaaatgattttctgcctccatcccacccatcagggc3360
tgcaggcact 3370
<210> 17
26/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
<211> 386
<212> DNA
<213> Human
<220>
<221> misc_feature
<222> (155)..(155)
<223> n is a, c, g, or t
<220>
<221> misc_feature
<222> (266)..(266)
<223> n is a, c, g, or t
<220>
<221> misc_feature
<222> (280)..(280)
<223> n is a, c, g, or t
<220>
<221> misc_feature
<222> (295)..(295)
<223> n is a, c, g, or t
<220>
<221> misc_feature
<222> (304)..(304)
<223> n is a, c, g, or t
<220>
<221> misc_feature
<222> (330)..(330)
<223> n is a, c, g, or t
<220>
<221> misc_feature
<222> (354)..(354)
<223> n is a, c, g, or t
<220>
<221> misc_feature
<222> (375)..(375)
<223> n is a, c, g, or t
<400> 17
gggaataagc ttgcgaccgc ttaattaaag atcttttttt tttttttttt ttttttttaa 60
gattcaagtc aaaattgttt tattgtcact cacatattta acataaaaag aaatgcagca 120
aatggctcag tatcgtattg aaaaaaaatc caggntgtgc agcttgttct attaacatct 180
gggagaagag ctgttcccac atcaggtcac agcagctgca gttctccaac gtccctttgc 240
agtacacagc cgtgggcaca cttggncaca gcccacgggn cagacaggta gcagncagct 300
cttnctttgc agggagggtg catttgcctn ctttgcactt gcagggagcc ggtncaggtt 360
ttagggagac acccnttggg tccagg 386
27/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
<210> 18
<211> 448
<212> DNA
<213> Human
<400>
18
tttgaattggatattttttaatgcaaattgttgtttttcttcatttgtctactttattaa60
gctgtcctcaggccccaagaaacatactgtcccctcatttagaaacagactaactccgtt120
ttcctccactatcccctcccctgtccttgatctgtagatcctgttaagacaggaaaaaca180
gtgttggtcaaagggtacacgctttcagttacaagatgaacaagttctgaatacgtaaga240
tagaacatgggaggtgatgtggccgggtgcagtgactcacgcctgtaatcccagcacttt300
gggaggccgaggtgggcggatcatgaggtcaagggatcgagatcatcctggccaacatgg360
tgaaaccccgtctctactaaaaatacaaaaattagctgggcatggtggcacacgcctata420
gtcccagctacttaggaggctgaggcaa 448
<210> 19
<211> 4574
<212> DNA
<213> Human
<400> 19
gagcgggcga gggagcgcgc gcggccgcca caaagctcgg gcgccgcggg gctgcatgcg 60
gcgtacctggcccggcgcggcgactgctctccgggctggcgggggccggccgcgagcccc120
gggggccccgaggccgcagcttgcctgcgcgctctgagccttcgcaactcgcgagcaaag180
tttggtggaggcaacgccaagcctgagtcctttcttcctctcgttccccaaatccgaggc240
agcccgcgggcgtcatgcccgcgctcctccgcagcctggggtacgcgctgaagcccggga300
ggcttggcgccggcgaagacccaaggaccactcttctgcgtttggagttgctccccacaa360
ccccgggctcgtcgctttctccatcccgacccagccggggcgcggggacaacacaggtcg420
cggaggagcgttgccattcaagtgactgcagcagcagcggcagcgcctcggttcctgagc480
ccaccgcaggctgaaggcattgcgcgtagtccatgcccgtagaggaagtgtgcagatggg540
attaacgtccacatggagatatggaagaggaccggggattggtaccgtaaccatggtcag600
ctggggtcgtttcatctgcctggtcgtggtcaccatggcaaccttgtccctggcccggcc660
ctccttcagtttagttgaggataccacattagagccagaagagccaccaaccaaatacca720
aatctctcaaccagaagtgtacgtggctgcgccaggggagtcgctagaggtgcgctgcct780
gttgaaagatgccgccgtgatcagttggactaaggatggggtgcacttggggcccaacaa840
28/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
taggacagtg cttattgggg agtacttgca gataaagggc gccacgccta gagactccgg 900
cctctatgct tgtactgcca gtaggactgt agacagtgaa acttggtact tcatggtgaa 960
tgtcacagat gccatctcat ccggagatga tgaggatgac accgatggtg cggaagattt 1020
tgtcagtgag aacagtaaca acaagagagc accatactgg accaacacag aaaagatgga 1080
aaagcggctccatgctgtgcctgcggccaacactgtcaagtttcgctgcccagccggggg1140
gaacccaatgccaaccatgcggtggctgaaaaacgggaaggagtttaagcaggagcatcg1200
cattggaggctacaaggtacgaaaccagcactggagcctcattatggaaagtgtggtccc1260
atctgacaagggaaattatacctgtgtggtggagaatgaatacgggtccatcaatcacac1320
gtaccacctggatgttgtggagcgatcgcctcaccggcccatcctccaagccggactgcc1380
ggcaaatgcctccacagtggtcggaggagacgtagagtttgtctgcaaggtttacagtga1440
tgcccagccccacatccagtggatcaagcacgtggaaaagaacggcagtaaatacgggcc1500
cgacgggctgccctacctcaaggttctcaagcactcggggataaatagttccaatgcaga1560
agtgctggctctgttcaatgtgaccgaggcggatgctggggaatatatatgtaaggtctc1620
caattatatagggcaggccaaccagtctgcctggctcactgtcctgccaaaacagcaagc1680
gcctggaagagaaaaggagattacagcttccccagactacctggagatagccatttactg1740
cataggggtcttcttaatcgcctgtatggtggtaacagtcatcctgtgccgaatgaagaa1800
cacgaccaagaagccagacttcagcagccagccggctgtgcacaagctgaccaaacgtat1860
ccccctgcggagacaggtaacagtttcggctgagtccagctcctccatgaactccaacac1920
cccgctggtgaggataacaacacgcctctcttcaacggcagacacccccatgctggcagg1980
ggtctccgagtatgaacttccagaggacccaaaatgggagtttccaagagataagctgac2040
actgggcaagcccctgggagaaggttgctttgggcaagtggtcatggcggaagcagtggg2100
aattgacaaagacaagcccaaggaggcggtcaccgtggccgtgaagatgttgaaagatga2160
tgccacagagaaagacctttctgatctggtgtcagagatggagatgatgaagatgattgg2220
gaaacacaagaatatcataaatcttcttggagcctgcacacaggatgggcctctctatgt2280
catagttgagtatgcctctaaaggcaacctccgagaatacctccgagcccggaggccacc2340
cgggatggagtactcctatgacattaaccgtgttcctgaggagcagatgaccttcaagga2400
cttggtgtcatgcacctaccagctggccagaggcatggagtacttggcttcccaaaaatg2460
tattcatcgagatttagcagccagaaatgttttggtaacagaaaacaatgtgatgaaaat2520
agcagactttggactcgccagagatatcaacaatatagactattacaaaaagaccaccaa2580
tgggcggctt ccagtcaagt ggatggctcc agaagccctg tttgatagag tatacactca 2640
29/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
tcagagtgat gtctggtcct tcggggtgtt aatgtgggag atcttcactt tagggggctc 2700
gccctaccca gggattcccg tggaggaact ttttaagctg ctgaaggaag gacacagaat 2760
ggataagcca gccaactgca ccaacgaact gtacatgatg atgagggact gttggcatgc 2820
agtgccctcc cagagaccaa cgttcaagca gttggtagaa gacttggatc gaattctcac 2880
tctcacaaccaatgaggaatacttggacctcagccaacctctcgaacagtattcacctag2940
ttaccctgacacaagaagttcttgttcttcaggagatgattctgttttttctccagaccc3000
catgccttacgaaccatgccttcctcagtatccacacataaacggcagtgttaaaacatg3060
aatgactgtgtctgcctgtccccaaacaggacagcactgggaacctagctacactgagca3120
gggagaccatgcctcccagagcttgttgtctccacttgtatatatggatcagaggagtaa3180
ataattggaaaagtaatcagcatatgtgtaaagatttatacagttgaaaacttgtaatct3240
tccccaggaggagaagaaggtttctggagcagtggactgccacaagccaccatgtaaccc3300
ctctcacctgccgtgcgtactggctgtggaccagtaggactcaaggtggacgtgcgttct3360
gccttccttgttaattttgtaataattggagaagatttatgtcagcacacacttacagag3420
cacaaatgcagtatataggtgctggatgtatgtaaatatattcaaattatgtataaatat3480
atattatatatttacaaggagttattttttgtattgattttaaatggatgtcccaatgca3540
cctagaaaattggtctctctttttttaatagctatttgctaaatgctgttcttacacata3600
atttcttaattttcaccgagcagaggtggaaaaatacttttgctttcagggaaaatggta3660
taacgttaatttattaataaattggtaatatacaaaacaattaatcatttatagtttttt3720
ttgtaatttaagtggcatttctatgcaggcagcacagcagactagttaatctattgcttg3780
gacttaactagttatcagatcctttgaaaagagaatatttacaatatatgactaatttgg3840
ggaaaatgaagttttgatttatttgtgtttaaatgctgctgtcagacgattgttcttaga3900
cctcctaaatgccccatattaaaagaactcattcataggaaggtgtttcattttggtgtg3960
caaccctgtcattacgtcaacgcaacgtctaactggacttcccaagataaatggtaccag4020
cgtcctcttaaaagatgccttaatccattccttgaggacagaccttagttgaaatgatag4080
cagaatgtgcttctctctggcagctggccttctgcttctgagttgcacattaatcagatt4140
agcctgattctcttcagtgaattttgataatggcttccagactctttgcgttggagacgc4200
ctgttaggatcttcaagtcccatcatagaaaattgaaacacagagttgttctgctgatag4260
ttttggggatacgtccatctttttaagggattgctttcatctaattctggcaggacctca4320
ccaaaagatccagcctcatacctacatcagacaaaatatcgccgttgttccttctgtact4380
30/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
aaagtattgt gttttgcttt ggaaacaccc actcactttg caatagccgt gcaagatgaa 4440
tgcagattac actgatctta tgtgttacaa:aattggagaa agtatttaat aaaacctgtt 4500
aatttttata ctgacaataa aaatgtttct acagatatta atgttaacaa gacaaaataa 4560
atgtcacgca actt 4574
<210>
20
<211>
546
<212>
DNA
<213>
Human
<400>
20
gatttctcccggaacctctgctcagcctggtgaaccacacaggccagcgctctgacatgc 60
agaaggtgaccctgggcctgcttgtgttcctggcaggctttcctgtcctggacgccaatg 120
acctagaagataaaaacagtcctttctactatgactggcacagcctccaggttggcgggc 180
tcatctgcgctggggttctgtgcgccatgggcatcatcatcgtcatgagtgcaaaatgca 240
aatgcaagtttggccagaagtccggtcaccatccaggggagactccacctctcatcaccc 300
caggctcagcccaaagctgatgaggacagaccagctgaaattgggtggaggaccgttctc 360
tgtccccaggtcctgtctctgcacagaaacttgaactccaggatggaattcttcctcctc 420
tgctgggactcctttgcatggcagggcctcatctcacctctcgcaagagggtctctttgt 480
tcaattttttttaatctaaaatgattgtgcctctccaaaaaaaaaaaaaaaaaaaaaaaa 540
aaaaaa 546
<210> 21
<211> 2880
<212> DNA
<213> Human
<400>
21
tgctgctctccgcccgcgtccggctcgtggccccctacttcgggcaccatggacacctcc 60
cggctcggtgtgctcctgtccttgcctgtgctgctgcagctggcgaccgggggcagctct 120
cccaggtctggtgtgttgctgaggggctgccccacacactgtcattgcgagcccgacggc 180
aggatgttgctcagggtggactgctccgacctggggctctcggagctgccttccaacctc 240
agcgtcttcacctcctacctagacctcagtatgaacaacatcagtcagctgctcccgaat 300
cccctgcccagtctccgcttcctggaggagttacgtcttgcgggaaacgctctgacatac 360
attcccaagggagcattcactggcctttacagtcttaaagttcttatgctgcagaataat 420
cagctaagac acgtacccac agaagctctg cagaatttgc gaagccttca atccctgcgt 480
ctggatgcta accacatcag ctatgtgccc ccaagctgtt tcagtggcct gcattccctg 540
31/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
aggcacctgtggctggatgacaatgcgttaacagaaatccccgtccaggcttttagaagt600
ttatcggcattgcaagccatgaccttggccctgaacaaaatacaccacataccagactat660
gcctttggaaacctctccagcttggtagttctacatctccataacaatagaatccactcc720
ctgggaaagaaatgctttgatgggctccacagcctagagactttagatttaaattacaat780
aaccttgatgaattccccactgcaattaggacactctccaaccttaaagaactaggattt840
catagcaacaatatcaggtcgatacctgagaaagcatttgtaggcaacccttctcttatt900
acaatacatttctatgacaatcccatccaatttgttgggagatctgcttttcaacattta960
cctgaactaagaacactgactctgaatggtgcctcacaaataactgaatttcctgattta1020
actggaactgcaaacctggagagtctgactttaactggagcacagatctcatctcttcct1080
caaaccgtctgcaatcagttacctaatctccaagtgctagatctgtcttacaacctatta1140
gaagatttacccagtttttcagtctgccaaaagcttcagaaaattgacctaagacataat1200
gaaatctacgaaattaaagttgacactttccagcagttgcttagcctccgatcgctgaat1260
ttggcttggaacaaaattgctattattcaccccaatgcattttccactttgccatcccta1320
ataaagctggacctatcgtccaacctcctgtcgtcttttcctataactgggttacatggt1380
ttaactcacttaaaattaacaggaaatcatgccttacagagcttgatatcatctgaaaac1440
tttccagaactcaaggttatagaaatgccttatgcttaccagtgctgtgcatttggagtg1500
tgtgagaatgcctataagatttctaatcaatggaataaaggtgacaacagcagtatggac1560
gaccttcataagaaagatgctggaatgtttcaggctcaagatgaacgtgaccttgaagat1620
ttcctgcttgactttgaggaagacctgaaagcccttcattcagtgcagtgttcaccttcc1680
ccaggccccttcaaaccctgtgaacacctgcttgatggctggctgatcagaattggagtg1740
tggaccatagcagttctggcacttacttgtaatgctttggtgacttcaacagttttcaga1800
tcccctctgtacatttcccccattaaactgttaattggggtcatcgcagcagtgaacatg1860
ctcacgggagtctccagtgccgtgctggctggtgtggatgcgttcacttttggcagcttt1920
gcacgacatggtgcctggtgggagaatggggttggttgccatgtcattggttttttgtcc1980
atttttgcttcagaatcatctgttttcctgcttactctggcagccctggagcgtgggttc2040
tctgtgaaatattctgcaaaatttgaaacgaaagctccattttctagcctgaaagtaatc2100
attttgctctgtgccctgctggccttgaccatggccgcagttcccctgctgggtggcagc2160
aagtatggcgcctcccctctctgcctgcctttgccttttggggagcccagcaccatgggc2220
tacatggtcgctctcatcttgctcaattccctttgcttcctcatgatgaccattgcctac2280
32/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
accaagctctactgcaatttggacaagggagacctggagaatatttgggactgctctatg2340
gtaaaacacattgccctgttgctcttcaccaactgcatcctaaactgccctgtggctttc2400
ttgtccttctcctctttaataaaccttacatttatcagtcctgaagtaattaagtttatc2460
cttctggtggtagtcccacttcctgcatgtctcaatccccttctctacatcttgttcaat2520
cctcactttaaggaggatctggtgagcctgagaaagcaaacctacgtctggacaagatca2580
aaacacccaagcttgatgtcaattaactctgatgatgtcgaaaaacagtcctgtgactca2640
actcaagccttggtaacctttaccagctccagcatcacttatgacctgcctcccagttcc2700
gtgccatcaccagcttatccagtgactgagagctgccatctttcctctgtggcatttgtc2760
ccatgtctctaattaatatgtgaaggaaaatgttttcaaaggttgagaacctgaaaatgt2820
gagattgagtatatcagagcagtaattaataagaagagctgaggtgaaactcggtttaaa2880
<210> 22
<211> 5534
<212> DNA
<213> Human
<400>
22
tctcccgggagccactcccatgggcgcctctccagcccctggcctggaagcaccaggaac60
cctggggatggggcagaccctcacagcccggggtctggagccggtgtcggagctcatctg120
ggcccatgacctctccagacatttggcaaaatcaaggcccttagaccagggacagaccca180
agcccaggccctcccagaggtcctaggacgcaaccctttgtgcccttgggctctggaaga240
ggtttgggaagggtttggggtggaagatggcaaagagcagcttggccaggtgaggatgag300
gcagggcagacacaggccagtggggcgtgccatgtgccacagatggagaggaccaggagc360
cagtggcccggcaggcacagcccggttggcgtgggccagagcgcccatcactgacccgtg420
agaactcgactgcccctgccagctctggcactgccccctcccagccgccccgccctagca480
ccctggggggcaccccgcccaaccgtggcctggtccggcccctcccgccctttgctccag540
ttcccgggcttggcacctatagtgggggtgccgcccgcctgccaggctccggggccgggc600
ccacgggagggtggggcggctgggaagctggcacgctgccccgggggagcctctctcggc660
aggcgcccgggtgccgcgggggggagggggaacaaagggctcattctccccgtgcgcagc720
cggtggcatcgccggggcgttggcggaagcccccggggcccgggagggggcaggcccagg780
cgcggccgccgaatcacgggctcctgtttcccgcagggtgctggaggaggaaaccggcgg840
agcagcttccccactctcagttgcgcttctggcgatggcgatcagaggtcctgctgcgct900
ctccgccgcgctctacctccattagccgcgctgcgcggtgctgcgccctcgccggtgcct960
33/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
ctctcctggg tcccaggatc ggcccccacc atccaggcac gacccccttc cccggcccct 1020
cggcctttcc cccaactcgg ccatctccga cccggggcgc gtgttccccc cggcccggcg 1080
ccttctctcc ctccgggggc acccgctccc tagccccggc ccggccctcc ccgcggcgca 1140
gcacggagtc tcggcgtccc atggcgcaac ctacggcctc ggcccagaag ctggtgcggc 1200
cgatccgcgc cgtgtgccgc atcctgcaga tcccggagtc cgacccctcc aacctgcggc 1260
cctagagcgc ccccgccgcc ccgggggaag gagagcgcga gcgcgctgag cagacagagc 1320
gggagaacgc gtcctcgccc gccggccggg aggccccgga gctggcccat ggggagcagg 1380
cgcccggtgc cggccacgac gaccgccacc gcccgcgccg cgaccggccg gtgaagccca 1440
gggacccccc tctgggagag ccccatgagg gcaggagagt gatggagagt acgcccagct 1500
tcctgaaggg caccccaacc tgggagaaga cggccccaga gaacggcatc gtgagacagg 1560
agcccggcag cccgcctcga gatggactgc accatgggcc gctgtgcctg ggagagcctg 1620
ctcccttttg gaggggcgtc ctgagcaccc cagactcctg gcttccccct ggcttccccc 1680
agggccccaa ggacatgctc ccacttgtgg agggcgaggg cccccagaat ggggagagga 1740
aggtcaactg gctgggcagc aaagagggac tgcgctggaa ggaggccatg cttacccatc 1800
cgctggcatt ctgcgggcca gcgtgcccac ctcgctgtgg ccccctgatg cctgagcata 1860
gtggtggcca tctcaagagt gaccctgtgg ccttccggcc ctggcactgc cctttccttc 1920
tggagaccaa gatcctggag cgagctccct tctgggtgcc cacctgcttg ccaccctacc 1980
tagtgtctgg cctgccccca gagcatccat gtgactggcc cctgaccccg cacccctggg 2040
tatactccgg gggccagccc aaagtgccct ctgccttcag cttaggcagc aagggctttt 2100
actacaagga tccgagcatt cccaggttgg caaaggagcc cttggcagct gcggaacctg 2160
ggttgtttgg cttaaactct ggtgggcacc tgcagagagc cggggaggcc gaacgccctt 2220
cactgcacca gagggatgga gagatgggag ctggccggca gcagaatcct tgcccgctct 2280
tcctggggca gccagacact gtgccctgga cctcctggcc cgcttgtccc ccaggccttg 2340
ttcatactct tggcaacgtc tgggctgggc caggcgatgg gaaccttggg taccagctgg 2400
ggccaccagc aacaccaagg tgcccctctc ctgagccgcc tgtcacccag cggggctgct 2460
gttcatccta cccacccact aaaggtgggg gtcttggccc ttgtgggaag tgccaggagg 2520
gcctggaggg gggtgccagt ggagccagcg aacccagcga ggaagtgaac aaggcctctg 2580
gccccagggc ctgtcccccc agccaccaca ccaagctgaa gaagacatgg ctcacacggc 2640
actcggagca gtttgaatgt ccacgcggct gccctgaggt cgaggagagg ccggttgctc 2700
ggctccgggc cctcaaaagg gcaggcagcc ccgaggtcca gggagcaatg ggcagtccag 2760
34/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
cccccaagcg gccaccggac ccttttccag gcactgcaga acagggggct gggggttggc 2820
aggaggtgcgggacacatcgatagggaacaaggatgtggactcgggacagcatgatgagc2880
agaaaggaccccaagatggccaggccagtctccaggacccgggacttcaggacataccat2940
gcctggctctccctgcaaaactggctcaatgccaaagttgtgcccaggcagctggagagg3000
gaggagggcacgcctgccactctcagcaagtgcggagatcgcctctgggaggggagctgc3060
agcaggaggaagacacagccaccaactccagctctgaggaaggcccagggtccggccctg3120
acagccggctcagcacaggcctcgccaagcacctgctcagtggtttgggggaccgactgt3180
gccgcctgctgcggagggagcgggaggccctggcttgggcccagcgggaaggccaagggc3240
cagccgtgacagaggacagcccaggcattccacgctgctgcagccgttgccaccatggac3300
tcttcaacacccactggcgatgtccccgctgcagccaccggctgtgtgtggcctgtggtc3360
gtgtggcaggcactgggcgggccagggagaaagcaggctttcaggagcagtccgcggagg3420
agtgcacgcaggaggccgggcacgctgcctgttccctgatgctgacccagtttgtctcca3480
gccaggctttggcagagctgagcactgcaatgcaccaggtctgggtcaagtttgatatcc3540
gggggcactgcccctgccaagctgatgcccgggtatgggcccccggggatgcaggccagc3600
agaaggaatcaacacagaaaacgcccccaactccacaaccttcctgcaatggcgacaccc3660
acaggaccaa gagcatcaaa gaggagaccc ccgattccgc tgagacccca gcagaggacc 3720
gtgctggccg agggcccctg ccttgtcctt ctctctgcga actgctggct tctaccgcgg 3780
tcaaactctg cttgggccat gagcgaatac acatggcctt cgcccccgtc actccggccc 3840
tgcccagtgatgaccgcatcaccaacatcctggacagcattatcgcacaggtggtggaac3900
ggaagatccaggagaaagccctggggccggggcttcgagctggcccgggtctgcgcaagg3960
gcctgggcctgcccctctctccagtgcggccccggctgcctcccccaggggctttgctgt4020
ggctgcaggagccccagccttgccctcggcgtggcttccacctcttccaggagcactgga4080
ggcagggccagcctgtgttggtgtcagggatccaaaggacattgcagggcaacctgtggg4140
ggacagaagctcttggggcacttggaggccaggtgcaggcgctgagccccctcggacctc4200
cccagcccagcagcctgggcagcacaacattctgggagggcttctcctggcctgagcttc4260
gcccaaagtcagacgagggctctgtcctcctgctgcaccgagctttgggggatgaggaca4320
ccagcagggtggagaacctagctgccagtctgccacttccggagtactgcgccctccatg4380
gaaaactcaacctggcttcctacctcccaccgggccttgccctgcgtccactggagcccc4440
agctctgggcagcctatggtgtgagcccgcaccggggacacctggggaccaagaacctct4500
35/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
gtgtggaggtggccgacctggtcagcatcctggtgcatgccgacacaccactgcctgcct4560
ggcaccgggcacagaaagacttcctttcaggcctggacggggaggggctctggtctccgg4620
gcagccaggtcagcactgtgtggcacgtgttccgggcacaggacgcccagcgcatccgcc4680
gctttctccagatggtgcagggcctggtgagcacagtcagcgtcactcagcacttcctct4740
cccctgagacctctgccctctctgctcagctctgccaccagggacccagccttccccctg4800
actgccacctgctttatgcccagatggactgggctgtgttccaagcagtgaaggtggccg4860
tggggacattacaggaggccaaatagagggatgctaggtgtctgggatcggggtggggac4920
aggtagaccaggtgctcagcccaggcacaacttcagcaggggatggcgctaggggacttg4980
gggatttctggtcaaccccacaagcaccactctgggcacaagcagggcactctgttcccc5040
tcccccttaagccaacaaccacagtgccaccaagctcacacctgtccttctcaggctggc5100
atctcccccaccctgtgccccttttcatggtaccaggcccgcactgggggcaattgactt5160
cctccaatccccactcctccgagacccaggagacaaacagcccttccttggggaaacttg5220
ggaatcattctggcttaaacaacacctcctcctgctgctcactcccgctgagcccactct5280
actgccccagctccgtttctaccaccgcatcctcactgggctcactgcaggcatgctgaa5340
caaggggcctccaaccttctgccctcctgccaaaagatctggggagtgtgaggagagggt5400
ggcatcaggagctgctcaggcttggcggagggagcggcatgggcgatgtcactcagccce5460
ttcccggtccgcccgcttccctccttcatgatttccattaaagtctgttgttttgtgaaa5520
aaaaaaaaaa aaaa 5534
<210> 23
<211> 633
<212> DNA
<213> Human
<400> 23
actcttctgg tccccacaga ctcagagaga acccaccatg gtgctgtctc ctgccgacaa 60
gaccaacgtc aaggccgcct ggggtaaggt cggcgcgcac gctggcgagt atggtgcgga 120
ggccctggag aggatgttcc tgtccttccc caccaccaag acctacttcc cgcacttcga 180
cctgagccac ggctctgccc aggttaaggg ccacggcaag aaggtggccg acgcgctgac 240
caacgccgtg gcgcacgtgg acgacatgcc caacgcgctg tccgccctga gcgacctgca 300
cgcgcacaag cttcgggtgg acccggtcaa cttcaagctc ctaagccact gcctgctggt 360
gaccctggcc gcccacctcc ccgccgagtt cacccctgcg gtgcacgcct ccctggacaa 420
gttcctggct tctgtgagca ccgtgctgac ctccaaatac cgttaagctg gagcctcggt 480
36/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
ggccatgcttcttgccccttgggcctccccccagcccctc ctccccttcc tgcacccgta540
cccccgtggtctttgaataaagtctgagtgggcggcaaaa aaaaaaaaaa aaaaaaaaaa600
aacaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa 633
<210> 24
<211> 393
<212> DNA
<213> Human
<220>
<22l>feature
misc
<222>_
(75) .(75)
<223>n is a, c, or
g, t
<220>
<221>feature
misc
<222>_
(81)..(81)
<223>n is a, c, or
g, t
<220>
<221>feature
misc
<222>_
(89) .(90)
<223>n is a, c, or
g, t
<220>
<221>feature
misc
<222>_
(95) . (95)
<223>n is a, c, or
g, t
<220>
<221>misc_feature
<222>(167)..(167)
<223>n is a, c, or
g, t
<220>
<221>misc_feature
<222>(179)..(179)
<223>n is a, c, or
g, t
<220>
<221>misc_feature
<222>(194)..(194)
<223>n is a, c, or
g, t
<220>
<221>feature
misc
<222>_
(237)..(237)
<223>n is a, c, or
g, t
<220>
<221>misc_feature
<222>(249)..(249)
<223>n is a, c, or
g, t
<220>
37/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
<221> misc_feature
<222> (276)..(276)
<223> n is a,
c, g, or t
<220>
<221> misc_feature
<222> (285)..(285)
<223> n is a,
c, g, or t
<220>
<221> misc_feature
<222> (295)..(295)
<223> n is a,
c, g, or t
<220>
<22l> misc_feature
<222> (312)..(312)
<223> n is a,
c, g, or t
<220>
<221> misc_feature
<222> (358)..(358)
<223> n is a,
c, g, or t
<220>
<221> misc_feature
<222> (370)..(370)
<223> n is a, or t
c, g,
<220>
<221> misc_feature
<222> (377)..(377)
<223> n is a, or t
c, g,
<400> 24
tttttttttt tgccgcccactcagactttattcaaagacc aggaagggcc ggtgcaagga60
ggggaggagg gcccnttgganggccagcnnggaanggaac ggctaccgag gctccagctt120
aacggtattt ggaggtcagcacggtgctcacagaagccag gaacttntcc agggaggcnt180
gcaccgcagg ggtngaactcggcggggaggtgggcggcca gggtcaccag caggcantgg240
cttaggagnt tgaagttgaccgggtccacccgaagntttt gcgcntgcag gtcgntcagg300
gcggacagcg cntttgggcatttcgtccacgttgcgccac ggcttttggg tcagcgcntc360
ggccaccttn tttgccntggccctttaacctgg 393
<210> 25
<211> 3726
<212> DNA
<213> Human
<400> 25
cagcgctgct ccccgggcgc tcctccccgg gcgctcctcc ccaggcctcc cgggcgcttg 60
gatcccggcc atctccgcac ccttcaagtg ggtgtgggtg atttcctggc ggggggagca 120
38/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
gccaggtgagcccaagatgctgctgcgctcgaagcctgcgctgccgccgccgctgatgct180
gctgctcctggggccgctgggtcccctctcccctggcgccctgccccgacctgcgcaagc240
acaggacgtcgtggacctggacttcttcacccaggagccgctgcacctggtgagcccctc300
gttcctgtccgtcaccattgacgccaacctggccacggacccgcggttcctcatcctcct360
gggttctccaaagcttcgtaccttggccagaggcttgtctcctgcgtacctgaggtttgg420
tggcaccaagacagacttcctaattttcgatcccaagaaggaatcaacctttgaagagag480
aagttactggcaatctcaagtcaaccaggatatttgcaaatatggatccatccctcctga540
tgtggaggagaagttacggttggaatggccctaccaggagcaattgctactccgagaaca600
ctaccagaaaaagttcaagaacagcacctactcaagaagctctgtagatgtgctatacac660
ttttgcaaactgctcaggactggacttgatctttggcctaaatgcgttattaagaacagc720
agatttgcagtggaacagttctaatgctcagttgctcctggactactgctcttccaaggg780
gtataacatttcttgggaactaggcaatgaacctaacagtttccttaagaaggctgatat840
tttcatcaatgggtcgcagttaggagaagattttattcaattgcataaacttctaagaaa900
gtccaccttcaaaaatgcaaaactctatggtcctgatgttggtcagcctcgaagaaagac960
ggctaagatgctgaagagcttcctgaaggctggtggagaagtgattgattcagttacatg1020
gcatcactactatttgaatggacggactgctaccagggaagattttctaaaccctgatgt1080
attggacatttttatttcatctgtgcaaaaagttttccaggtggttgagagcaccaggcc1140
tggcaagaaggtctggttaggagaaacaagctctgcatatggaggcggagcgcccttgct1200
atccgacacctttgcagctggctttatgtggctggataaattgggcctgtcagcccgaat1260
gggaatagaagtggtgatgaggcaagtattctttggagcaggaaactaccatttagtgga1320
tgaaaacttcgatcctttacctgattattggctatctcttctgttcaagaaattggtggg1380
caccaaggtgttaatggcaagcgtgcaaggttcaaagagaaggaagcttcgagtatacct1440
tcattgcacaaacactgacaatccaaggtataaagaaggagatttaactctgtatgccat1500
aaacctccataatgtcaccaagtacttgcggttaccctatcctttttctaacaagcaagt1560
ggataaataccttctaagacctttgggacctcatggattactttccaaatctgtccaact1620
caatggtcta actctaaaga tggtggatga tcaaaccttg ccacctttaa tggaaaaacc 1680
tctccggcca ggaagttcac tgggcttgcc agctttctca tatagttttt ttgtgataag 1740
aaatgccaaa gttgctgctt gcatctgaaa ataaaatata ctagtcctga cactgaattt 1800
ttcaagtata ctaagagtaa agcaactcaa gttataggaa aggaagcaga taccttgcaa 1860
39/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
agcaactagt gggtgcttga gagacactgg gacactgtca gtgctagatt tagcacagta 1920
ttttgatctc gctaggtaga acactgctaa taataatagc taataatacc ttgttccaaa 1980
tactgcttagcattttgcatgttttacttttatctaaagttttgttttgttttattattt2040
atttatttatttattttgtgacggagagagattccatctcaaaaaaacaagttattaaaa2100
atgtatatgaatgctcctaatatggtcaggaagcaaggaagcgaaggatatattatgagt2160
tttaagaaggtgcttagctgtatatttatctttcaaaatgtattagaagattttagaatt2220
ctttccttcatgtgccatctctacaggcacccatcagaaaaagcatactgccgttaccgt2280
gaaactggttgtaaaagagaaactatctatttgcaccttaaaagacagctagattttgct2340
gattttcttctttcggttttctttgtcagcaataatatgtgagaggacagattgttagat2400
atgatagtataaaaaatggttaatgacaattcagaggcgaggagattctgtaaacttaaa2460
attactataaatgaaattgatttgtcaagaggataaattttagaaaacacccaatacctt2520
ataactgtctgttaatgcttgctttttctctacctttcttccttgtttcagttgggaagc2580
ttttggctgc aagtaacaga aactcctaat tcaaatggct taagcaataa ggaaatgtat 2640
attcccacat aactagacgt tcaaacaggc caggctccag cacttcagta cgtcaccagg 2700
ggatctgggttcttcccagctctctgctctgccatctttagcgctggcttcattctcaga2760
ctctggtagcatgatggctgtagctgtttcatgggccccttcaaacctcatagcaaccag2820
aggaagaaaatgagccattttttgagtctccttcatagacttgaataactctttttcaga2880
gcttctcacagcaaacctctcctcatgtctcctcatgtcttattgttcagaaatgggtaa2940
tgtggccatttcaccagtcactgccaacaacaacgaggttcctataattgtctctgagta3000
accctttggaatggagagggtgttggtcagtctacaaactgaacactgcagttctgcgct3060
ttttaccagtgaaaaaatgtaattattttcccctcttaaggattaatattcttcaaatgt3120
atgcctgttatggatatagtatctttaaaattttttattttaatagctttaggggtacac3180
actttttgcttacaggggtgaattgtgtagtggtgaagactcggcttttaatgtacttgt3240
cacctgagtgatgtacattgtacccaataggtaatttttcatccattaccctccttccgc3300
cctcttcccttctgagtctccaacatcccttataccactgtgtatgttcttgtgtaccta3360
cagctaagcttccacttataagtgagaacatgcagtatttggttttccattcctgagtta3420
cttcccttaggataacagcccccagttccgtccaagttgctgcaaaatacattattcttc3480
tttatggctgagtaatagtccatggtacatatataccacattttctttatccacttatca3540
gttgatggacacttaggttaattccattcaatttcattcaatttaagtatatttgtaagg3600
agctaaagctgaaaattaaattttagatctttcaatactcttaaattttatatgtaagtg3660
40/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
gtttttatat tttcacattt gaaataaagt aatttttata accttgaaaa aaaaaaaaaa 3720
aaaaaa 3726
<210> 26
<211> 127145
<212> DNA
<213> Human
<400>
26
gatcacaggtgtgagacaccacacccagccagaaattgaaccttggtgagagacactgag60
tggggaagggcagagactgggagttaggagttacagcatctgaaggccacatcctggaga120
gatggccacagactcagccagtgaagaggaagtgctggggctggggccagaaccctgtct180
gtgtgacccctgagactgagctcagacacccctaaccctgaaggcacctctctttcagga240
ccaacagccaaaggcacagaagccactggcctgggagggactgtccctgggaatgaccct300
gctctctgagggctgggcatctggactccctctgctccagctcctctgtggttgtattcc360
tccatttctattctaattagtcagtttccatggctggataccataaaatctcagtagaag420
gaagaacaggccaaccatcagagctgttcaatttcagaaaatctctttttgttgctgggg480
acagagtctcactatgtcacccaggctggagtgcagtggcgcgatctcagctcactgaaa540
cctctgcctcccgggttcaagcgattctcctgcctcagcctcctgagtagctgggattgc600
aggtgcatgccaccttgcctggctaatttttgtatttttagtagagatggggtttcacca660
tgttggccaggctggtctcaaactcctaacctcaggtgatccacccacctcagtctccca720
aagtgtttggattacaggcgtcggccaccgcgcctggcccagaaaatctctttagtcggg780
acttgagaaagggactgggttccatctggtgggaatgggagggaggttcagtgtctgctg840
ccagtgagacctgggtttgttccctcccccctggctgtgtgatggaggcaagacccttca900
ttctttgagcctcagtgtcctgtctgtgaaacaggcaatgagcacatttatctcacaggg960
tcccggtgaggcacattgggataacataggtgaagcccttaacacagttctgggcaaagc1020
aatgtgacttctctcctccccagcggcacttgcaccacgtggggagaaactaggttaata1080
catccctgccacacataactaccaagtgcctgctgtgtgctggccacaacactaagagcc1140
ttacatgtggtccttcatttaattttcaaagtgatgacgatgattctcagtgcacagatg1200
gagactctga gcccagagag gctaaataaa ctgctctcaa ggacaccagc actttctgca 1260
aagagcccca gatcctaact aggacttacg ttgcctgcgc tgggaagaga cccaaatgcc 1320
tcccggctgt aggagtccct gattgcagac gtagggtctc agtccccgcc ccaagaagct 1380
gtaggtccag ttgaagaaga gacacacaca aggaaaagga aattgaactg agaaggcaaa 1440
41/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
gcgtgactgt ggggcctctg ctatatccag ggtctccaga gaaaggacta gaagccacta 1500
ttccaattct gaggcctcag ggaagcagca agttcctgtg aggaaacagg atcccacagg 1560
tttcatcctc ctcctgtcac tcttctaggt ggggagggag ggctccccca cgtcccacat 1620
aagcacacagaaaggagaggccagggcagcacaggctcagaacctgaaggacttggggac1680
atcgccagccccatatccttgttttatacaccaggtagggcaggaactatggcaggtcca1740
cagaaaggggccggcagaagcacagccacgacgcaggccccctgggctgtccagtttctc1800
ccggacagaacatttcccttccctagcagcccccaacgtggagcactggatttggagtca1860
ggagacctgtgtcttctgcaatcactctgagaccaactcctgtgtaatcgtgagtgagcg1920
ccttcccatctctgggcctcagcttccacctctctaaaatgagggggttggattccatcc1980
aatgttataagagccaaaggttatgagttggtagcgcccccaccattccgggtttctcca2040
atctctccaggggcctcagagaccccagacagaagaggaacttggacagaggcttgggtg2100
ggggtggaggtggggattctgagccgtggatccaccctctgctgagtgccaggcctacag2160
gcaggcaggcagagcaggcaagagccgtcccctacacaaagggaattggcccctcatggt2220
gggacagaggccagaacccagctgggccctcaaccacccttctttcctccacaaccccct2280
cccagggatggtggcatccgaagccagcctggcaagggaactggttgccacgtggggact2340
tcccggagctgggggtgatgggaaacagggtgacgggaaacgtcctgaggttgcttcctc2400
cccttttgtttggatctcagactgacctgggaaccaactgggcagccatggggtattctg2460
atggtggggagttggagggggagaagggacctgccccatcccctcaggctgctttgcaag2520
ttaaaatagctgtgaagatctatctcccagaattctaaaagctaaaataccttttgaacc2580
accaccagaccattatgcctggagtggaaggatgcttagaggaatcccttcttttttttg2640
agatgaagtctcgctccatcacccaggctggagtgcagtggcgctatctcggctcactgc2700
aacctccacttcccagggttcaagcaattctcctgctttagcctctcgattagctgggat2760
tacaggcgtgcaccaccacgcccggctaatttttctattttttagaagagacgagggttc2820
accatgttggccaggctggtctcgaactcatgaactcaaatgatccacccgcctcggcct2880
cccaacacgctgggattacaggcgtgagccactgtgcccatctcgaatccctttttaaaa2940
cttcaggtatggctgggtgcggcggctcatgtctgtaatcccagcactatgggaggctga3000
gtcgtgaagatcatttgagcccaggagttcaagaccagcctgggcaacataggagaactc3060
gtctctattcaaaaaaataccaaaaaccaaaaaccaaaaaattgtaagtcatgacccact3120
ggtggatcttgaaattaattaagtcggtactctgagtaaatcagaatttttttttgagat3180
42/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
ggagtctcac tctgtcaccc aggctggagt gcagtggtgt gatcttggct cactgcaacc 3240
tccacctcct gggatcaagc aattctcctg cctcagcctc ccaagtaact gtgactacag 3300
gtgtactccg ccatgcctgg ctaatatttt gtattttagt acagacgggg tttcaccatg 3360
ttgcccaggc tggtcttgaa ctcctgagct ctggcaatct gcccacttcg gcctcccaaa 3420
ctgctgggat tataggcgtg agccaccgtg cctggccgca aataaggatt taataatgac 3480
gatgataaaa tagaagggaa aatctcagag cacatcctgg gtagtaatag caaactgtct 3540
tggctgtgtg gtggctcatg cctctaatcc cagcatttta ggaggccaag gcaggaggac 3600
tgcttgaggc taggagttaa aatcagccta ggcaacacag tgaggcccca ttcctacaaa 3660
aaaaaaaaaa aaaagaaaga aagaaaaaat tagccgggta tggtggtgtg tgcctatagt 3720
cctagctact ccagaggctg aggcgggagg attgcttgcg cccaggagtt caaggctgca 3780
gtgagccatg atcgtgccat ggtacggcag cctgggtgac agagcaaggc cccaactctg 3840
aaaaacaaaa taaatacaat aaaataaaat ggtcaaaatg gcctggtgca gtggctggtg 3900
cctgcaacca gagctacttg agaggctgag gcaggagaat cactggagcc caggaggttg 3960
aggcaccact gaactccagc ctgggtgaga gtgagatcct gtctctttaa aaaagaaaaa 4020
acaaaaaaag caaactgtct catgaaactc ttgtttccat gttgcacgct ctgccaggtt 4080
gtgatgtaat gtatttctta ctctgggtca cagtcacaaa accttgaaat gtcactcact 4140
gtcttggctc atgcgtcgta agcctttgtt ccccaacagg gggaagtgaa ccagcacaca 4200
aggcccttcc gtcctgcgga gctcactgcc ttcctcagct cctggcccgc acttccgacc 4260
acacactggg gacacaccct cgggggggcc ccaccccagc agctgcccat gttcacacct 4320
cttcagttat ttcaaactcc gcctctctcg gcctgatgcc caacacttcc ttcacccaag 4380
gaggtcctgt tcaaatatca cttctggcca ggcgcggtgg ctcaggtcta taatcccagc 4440
acttcgggag gccccgaggc aggcagatca cctgaggtca ggagtttgag accagcctgg 4500
ccaacaggtg aaaccccgtc tctactaaaa atacaaaaat tagccaggtg tggtggcacg 4560
tgcctgtagt cccagctact caggaggctg aagcaggaga attgcttgaa cctgggaagc 4620
ggaggttgca gtgagccaag attgagccat tgcactgcgg cgtgggaggc agaggtagac 4680
tctgtctcaa aaaaaaaaaa agtcactttc tctgccagtc atatcttctg caaccctgag 4740
gagccaggca ggacgacccc tttaccctct gaatcaattg gtctgtatca gggtctggca 4800
gagggagggg aagttggccc ctctgattta atggatgaat caagaaaatg tgtgactgag 4860
ccatggattc atggggatgg ggtcctggag cagaggcttg ctgtgcacct actaggtgct 4920
gtgtacctca caagccactg gggacatcag accaccagaa taagtccact ttccccaagg 4980
43/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
aaagtggtcaaatgtgggagccaggtgtgcaaatccccaccccagggtgataacagcccc5040
aataaaggcacatgcaagggggaccttcggagctgatgacactgtacaggcatctaagag5100
gctggtgacagggtcaccaagcagaggtctagagcagggctgagtggggtagggggggtt5160
cttccaggcaaaaggcaaaaactctgttggtaccgtgtaggtcttccacagcacatgcca5220
catgagaagaaacattcgcctggcgagtggctgaagtctataatcccagcactttgggag5280
gctgaggcaggtggatcgcttgagccaaagagtttgagatcagcctgggcaacatggcaa5340
aaccccgtctctacaaaaaatacaaaaattagccaggtgtggtaacccatgcctgtggtc5400
ccagctactcgggaggctgaggtgggaggattgcttaagcctaggaggtcaaggctgcag5460
tgagccatgattgtgccaccacactccagcctcagtgacagagtgagaccctgtctcgaa5520
aaaaaaaaaaaaaaaagagagggaaaggaaaaattttattttacatttatgtattgaggg5580
cagggaccatgcctgctgggctgctcaccactgctgagcaggattcctggtgtggcatcc5640
taacacaataaatatttactgaatgtgtactcaggaaactgcaaagggttcaggctggcc5700
tgagagtaaagtgaaagaaggaagtggtagaagagcccagaggtctgtgaccccagaacc5760
tggagggcacctgtggcctgggtctttctcctgcaggcactggggaaaagtcggagggtt5820
tattttatttaattaacttatttattaatcaattaattttttgagatggagtctcactct5880
gtcacccaagctggagtgcagtggtgcgatctcagctcactgcaacctctgcccaccggg5940
ttcaagcgattttcctgcctcccgagtagctgggattacaggcattcgccaccatgcccg6000
gctaatttttgtatttttagtagagatggggtttcaccaggctggccaagctggtctcga6060
actcctgacctcaagtgatcctcctgcctcggcctcccaaagtcctgggattacaggtgt6120
gagccaccgcgccaggccggtaggagggtttaaacaggaaagagataagcagtcagattc6180
atagtttagaaaatcctcaggttctggtgttcgggtggatgcctggagtggggatctgga6240
aatcaggggcaggggttagtaataacccaggtgaggagacttgagtctagaggcagccaa6300
gtggggacctatggaggagttcacgtgctgcaggtgtgcgccgccgaggcggagccaggc6360
tctggagctgccaggggctcagaagcctccctctcagatctctccccttttggccacaga6420
tgggaaggagagaggcactcacccgacccagcgtggcagtacagtagtgtccaacctgtc6480
actgttgggcgtggtggcgtgtacctgtagtcccagctactgaggaggctgagatggcag6540
cagcacttgagcccaggagttggaggctgcagtgagccgacagcgccactgaactctagc6600
ctgggtgacagagcgagaccctgtctctaaaaaacagaaaagaaaaattacaggtcgggc6660
gcagtggctcacgcctgtaatcccagcactttgggaggccgaggagggtggatcacgagg6720
44/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
tcaggagttc aagaccagcc tggccaatat ggcgaaaccc cgtctctact aaaaatacaa 6780
aaattagcca ggcgtggtgg tgtgcgcctg tagtttcagc tacttgggag gctgaggcag 6840
gagaatagct tgaacccggg aggcggaggt tgcagtgagc cgagatcacg ccactgcact 6900
ccagcctggc aacagagcga gactctgtct caaaaaaaaa aaaaaaaaaa aaaaaaaaag 6960
aaaaagaagaaaaagaaaaaagagaaagaaggaaagaattacataacagtaagcaaccta7020
gctagatttgaaccaggccctgcagttctaaagcactggcttttgcggagcggcactcac7080
tccgcatcgtggcataggtagatttcttttctaaaggtgaggtcagtgctgggcacttag7140
caggcgcccggtgggctgcgccgtcctggaggaaggctgattcctcccaccccgactcct7200
ggctcgtgggtgggtaatccagcacattctccccaccccggcaaccaactttgtggccga7260
acaagccctccccggcttgttccgctggtcccaggcgcctgcgcatccggacacgatgag7320
gagcaggtgcgcggggccggggtgtgttcgagggggtcgtgcgcgcctgggctgcctccc7380
cgcggacggcggactgggccggggcggcgcttcctggcagagaggcgcggaggggcgtgg7440
ctttggagaggtgcccccggcgggctggcggcctggctgcggtgaaaggcgggcggacgc7500
aggtgacgacaaccgctccataaagggcgccgcggcgcgacgctcgccttatatgggcag7560
gctcggcgcgggaggggcggggcgttccacccagctggctccgcaccgaggcccggccga7620
acccccgaggggggaaacttctctgcgagggtggagcctcctcagcggcgtccccaggtc7680
ccgagaggggtccctacccaggctaagactcacgacgggctccaccctgcaggggctcaa7740
cttgcagaaaccctggggcctgccttccccaggggtctgccctcctcaggccctgctagg7800
gcactgactcggtttgtgctgtgtggcgttttttccttcaccccacctgggccgcaggtc7860
ctcgctagatagccgagggagggtcctttaagtgagctcacctcggagcccccagataac7920
caagcctgagcctcccggctacatggcgaggcttccccaatccggtcagccccaagcagg7980
tgcctttctctaactggcacaaaggaagtctcctagccaggctgagcccaagcctcggta8040
aacatgagccttggatccactggaagtgtttggctaactgggcccttcttggccagacaa8100
gactttaaccctaagaggaagctgccagcatgacgcagcccaccatattctccctccaag8160
ctctcttcatagcccgggtccttaaaaacccaaatctgtccaattgctacttgccgtcca8220
ctcgttgacagttactccgcttcacagcctcccgatcacctgagtgtcctccctcggctc8280
agtgcacagg gctctgtgag cttacagttc cctggttgcc gttccgtgcc tcccagccct 8340
gcacctgctg ctcctttctg gaaagccctt tccttgcaca ctcccagaca cgtgctcacc 8400
cttcagagag atacttctta gcgtcttctt cctgacattt gtagtgatta cttaaccttt 8460
ctgagcatca atttcttcat ctgcaagatg ggggtaaaat aatccccacc tcactgtgtt 8520
45/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
attgtgagga tcgaatgagt taatgtttgt aaaatgcctg gcatatagta gctgctcatg 8580
aaaaactcgt tgaccaaatt cctcttcctg tgctctaatt gctcatgtat gtgttgtgag 8640
tgccatgaag gctggcctct tccttttcca gctatgcata cctagttcct ggcacatata 8700
tagatcttga accagtgttt gttggcgaat gaatgaattt caggcagtag gggtcgggga 8760
gagaagagac ccctaactgt gatggtcatc aaccctcaca tctgccggga tgtagggcat 8820
tctaatgctt cccccctcag ttgcccagag cttcatggca accaggaggg acacagcatg 8880
gatatggacc ccgttttcca gataaaccta tgagtgatta gaggtgaagt aacttcccca 8940
cggttacaca atgagtggaa gagtcggcat cagggtgacc aacgtgtact tttttttttt 9000
ttttttgaga cggagatttg ctcttgtcgc ccaggctgga gtgcaatggc gcgatctcgg 9060
ctcactgcga cctctacctc ccaggttcaa gcaattctcc tgcctcagcc tcccaagtag 9120
ttgggattac agttgcccac acgcccagct aattttgtat ttttagtaga gatggggttt 9180
cttcatgttg gtcaggctgg actcaaactc ccaacctcgg gtgatctgcc cgcctcagcc 9240
tcccaaagtg ctgggattac aggcgtgagc cactgtgccc ggcccaatgt gtattattat 9300
tattattatt attttagcac tgagagttcc acgtcccagg aatctcttta gtctcaggca 9360
gccaggatgg ttggtcaccc aagatcaact tctaaacgtt agtctctgag gaccgccacc 9420
ttccaacctc ccctgcaccc gtcccattat tcccaagtat tttactgcgt tcctgaaggg 9480
gacacaggct ctccagccca gaaggtccaa cagattttaa aaagtcacac tctgattccc 9540
caaaaaagtt agactcacag cacagtaggg atgggggaca aggacattgg aagggcattg 9600
aggccaggtg tggtggctca cgcctgtaat cccagcactt tgggaggctg aggcgggtgg 9660
atcacttgag gtcaggagtt cgagaccagc ctggccaaca tggtgaaacc ccgtctctac 9720
taaaagtaca aaaacaagcc aggtgtggtg gtgcgcacct gtagtcccag ctactcggga 9780
ggctgaggca ggagaatcgc ttgaacccgg gaggcaaatg ttgcagtgag ctgagatcgt 9840
gccactgcac tccagcctgg gcgacagagt gagactctgt ctcaaaaaag aaaaaaaaga 9900
aggcccaggt aggagtttgc ttcactttga cagggactca tgggccactc ctgcaccagg 9960
ccctgggcct gggaccagga actgagagaa ggctggcccc cacctgtggg actctagcca 10020
ggtgggggag acagatgtat agacacaatg ccaacagttt ggttcctcga cggctggaga 10080
agggagtgat cgaccagggt ttctgaagaa ccccctcctg acgtggccac tcaccagctg 10140
acctcaggcc tgtcccttcc tttggctggc cctggacctt ctctgtcaac tcaggcagtt 10200
ggagctggtc cctgagggcc ttcctgccct gaagtcatga cttgtgggga gctgagttct 10260
46/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
gggaaatgca tcctctggag aggcaccaga ggccgcgcat gcctgagtga gtgtgggggt 10320
gcgccctggc ctcactagcc aaacaccaac ttcatcttcc caggctaccc tggcccgagc 10380
agctccggct ccttccctgc ctgcctcatc ctcccaggcc actgtccagg aagctggcct 10440
ctctgcctgt tccccacagc ccctgggggt ggggccagag tagggcaaaa agggcctggg 10500
cctggcccag cagagcctct gcccctcctt cgggggctcc tgttcttgtg ggctgagagc 10560
tgcagccctg cagccggcct ggctgtggct cagtggtcag ggccaagtgc agagcaaaca 10620
ccctgcccac tgggcagcca tttcacggtc attcccaggc tgcatggggt ccccagtcgg 10680
gcaactaagt gcagatgtga aacaacgagc tttccaagat ccagggattt gacccttggg 10740
aaagagactc cctaagggaa ctgcttcctg tcactcccca accaccactt tgagaaataa 10800
ttttctctcc ctcaacctca ctgccagcct cagtcaagag caaaccgagg actggtagtg 10860
ggagctcagg gccaccttgg gattctctgc tctcgctgct ggctgagccc aggcaaggcc 10920
cctgccctct ctgggcttcc atttccctct cctgctccaa acttgctagc ttccttccct 10980
atctcaacat catagggacc cttcgagatg ggaactacta ataggggaaa tcatatggga 11040
aaccaggctg ggcgcagtgg ctcacaccta taatcccagt actttgggag gccgaggtgg 11100
gaggatcacc tgaggtcagg agttccagac cagcctgacc aacatggtga aaccctgtgt 11160
ctactaaaaa tacaaaaatt agccgggcgt ggtggcaggt gcctgtaatc ccagctactc 11220
aggaggctga gaggtagggg aatcacatga acctgggagg tggaggttgc agtgagctga 11280
gatcctgcca ctgcactcca gcctgggtaa cagagtgaga ctccatctca aaaataaaat 11340
aaaaaatgac catatcctta taggaaccat tattttgaac tcagaatctc agaaaaacca 11400
ggatttgggg cctggaactt tctttgtctt attttgtttt gttttggatt ttttggggag 11460
acagagtctt gctctgtcac ccaggctgga gtacagtggc gcgatctagg cttactgcaa 11520
gctccgcctc ccgggttcac gccattctcc tgcctcagcc tcccgccacc acgcctggct 11580
aattttttgt atttttagta gagatggggt ttcaccgtgt tagccaggat ggtctccatc 11640
tcctgacctc gtgatctgct cacctcggcc tcccaaagtg ctgggattac aggcgtgagc 11700
caccgtgcct ggctggggcc cggaactttc taaggcagag gcggcagaga caaagaggtg 11760
gctggaggtg gggcagtgcc gagccaagtc tcaggacatc cctactgccg agcctcccct 11820
cccacaaagt aaaccggcag gtgggcagtg caggcggggc ccagctcggg tttcactcct 11880
tCCCCgCt Ct cggggacaat aaaatgctcc ctttgccctg gaaatcccac ttgtataaaa 11940
tccaaaagaa gaaataagct cttatgttca aacaggtttg ttccaacctc atttataatg 12000
gaaaaatatt aactgaaaaa ttccttagta tccgacaatg ggggagaagt taacagtttg 12060
47/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
accggagctg agtgaeatgc aaaagggtgt ttgtggagtg cagggagctc ctgctgtgtg 12120
tgtgggaggg tggagagggc atggggagag gagcagggac cccagagtca gactgtctag 12180
gtttaaatcc tgtctgctcc ttcctagctg tgtgaccttg agtcataacc caaagccctc 12240
tgtacctcca tgtccccctc cataaactgg cactgggctg ggcatggtgg cttatgcctg 12300
taatcccagc attttgggag accaaggcag gtggatcacc tgaggtcagg agttagagac 12360
cagcctggcc aacatggtga aaccccgtct ctactaaaaa tacaaaaatt agccaggtgt 12420
agtggcaggt gcctgtagtc ccagctactc aggaggctga ggcaggagaa tcgcttgaac 12480
ccaggaggca gaggttgcag tgggccgaga ttgtgccact gtgctccagc ctgggtaata 12540
ggtgacagag cgagactccg tctcaaaaca aaacaaaaca aaaaaaagga gagagagact 12600
tgggggatgt gtgtgcccag aggaaaatcc atgtgaggac ccagcaagaa ggtggccacc 12660
cgcaagccaa gcagagaggc ttcaggagaa accaaccctg ccagcacctt gattttggac 12720
ttccagcccc agaactgtga aaaaataaac atctgttgtt taaaccaccc agtctgtgat, 12780
attttgtgat ggctggccta gcaaactaat acacattact aacacacaat aagagaagcg 12840
tttaataggg cgcttaccac gtaattgcat tgtgttctga cattacattt acgatctcat 12900
aaccatgagg agggtcctgt cctcccattt cagagatgaa ggaaactgag gcttggctag 12960
tgacggagag ggctgtgact ggagccagga ctgtgtgact ccaaggcccc accaaagcct 13020
cctcctggga tggaccatgg actttcctgc ctctgtgctg tgcatacgct ctcccttctg 13080
cctggaatac ccttcccacc acttgcctct caggacgagt cccagtcgat tcttcaaaac 13140
tcttcttggc ccggcaaggt ggctcacacc tgtaatccca gcactttgga aggccaaagt 13200
gggtggatca cttgaggtta ggagtttgag accggcctgg ccaacatggt gaaaccctgt 13260
ctctactaaa aatacaaaaa ttagctgggc cttgtggcag gtgcctgcaa tcccagctat 13320
tcaggaggct gaggcaggag aattgcttga acctgggagg tggaggttgc agtgagccaa 13380
gatcacacca ctgcactcca gcctgtgcaa cagagttaga ctgtctcaaa acaaaaacaa 13440
aaaacaactt ttctcaagca tcacctcctt cccatgcttt acccgacaat ctccttttgc 13500
agatgtgctg cttttcaggg cttgcggcca gtctgtactc tgtcaccatg gtggtaaatg 13560
tcatctctcc tgtagcattt agactttaga tgtgtccatg tgtttgctgt gaactcctgg 13620
aaggcagggg ctgtgtcttg ctctagttcc tatcacccag caggcccaga ggggctccgc 13680
acagacgctt gctggctgag gtagccagtt tggcctggag agagtattcc cgcctcagga 13740
gtggatcatg aggaaatgga atctcctgcc tccttgtggg gtgggggttg ggggaggtgg 13800
48/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
ataaaagaga ggctccacct ggcacggtgg ctcgtgccca taatcccagc actttgggag 13860
gccgaggtgg gtagatcacc tgaggtcagg attttgagac cagcctggcc aacatggtga 13920
aaccccatct ctactaaaaa tacaaaaatt agctgggcac ctgtaatccc agctactcgg 13980
gaggctgagg ctggacaatc gcttgaatcc aggaggtgga gcttgcagtg agccaagatt 14040
gtgccactgc actccagcct gggggaaaag agcaaaattc catctaaaaa aaaaaaaaag 14100
cggatcaagg tccctactct gggcatgaga ggagggatcc tttgacactc ctgggagcag 14160
cagtgtggca gaggaggagg agcagggcat ggggtcagcc accctcagtc catttcccag 14220
ggtgtggcct taggcacggt cactacctct ctgggcttct gtctccacat gtatgaaatg 14280
gaatcagtcc ctccttccac aggtgttagg tcgaagaagg cacctctggt ggtatcggca 14340
cagaggctgg acactggatg acttctttgc tgggacactg aggtaggggg cagaccagag 14400
acagacagct acttgcctaa gctcacccag caagctggct gaaggtggag aactggcttg 14460
tcctccagtt ggtagttaac agctgtctag caggagtgtt cttgctccca ggagacgctc 14520
cgttggctgc cacagaggta agcgtgagag tgcgctcaga agtggctggg aggcatggag 14580
aacagaggag caggttcagg gtgaattcca gtgggcattc tccaagggtg aggtcactgc 14640
ctccaactcc ctagggctgc ctgagacaca ggcaccacca agccagctcc agagcaggag 14700
gaggtggtgg cagggaccag ggccaggtca cagggctgaa tgtaaggccc tcagcctggt 14760
acagcgacgg gcccctccca tggtgctggg gtccttacct tgggaagccc ggtgtttcct 14820
gtttaagatg tggctggggg taggggaaag gagaaagcca cacagataac acttctggaa 14880
cttccaatcg gtgccagcgt gcttccacct gctgagccgt gacctcattt gcagggactg 14940
tcatgagccc caacttggag atggtgcaac tggggctcaa aatggtgaaa accttgtccc 15000
aaaaggaaag cagtatagct aatgagcaag aacaaagaga atttgaaatt aaagacattg 15060
gggttcattc ttttcccctt ttttaaaatt tatttttggg ccgggcacgg tggctcacgc 15120
ctgtaatccc agcactttgg gacgctgagg tgggcggatc atttgaggtc aggagtttga 15180
gaccagcctg gccaacatgg tgaaaccctg tttctactaa aaatacaaaa attaaccagg 15240
catggtggca aatgcctgta atcccagcta ctcgggaggc tgaggcagga gagctgcttg 15300
aactcaggag gcgaaggagg ttgcagtggg cagagatcat gccattctac tccagcctgg 15360
gcaacagagc aagattccat ctcaaaaaca ataaaataaa taaataaaat ttatttttta 15420
tatttttatt ttttagaaca agatctcact ctgtcaccca ggctggagtg cagtggtgag 15480
atcacagctc actatagcct caaactcctg ggctcaagtg atcctcccac ctcaccctcc 15540
caagtagctg ggactacagg cgcacaccgc catgccaggc taattttttt ttaaattttg 15600
49/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
tgtaaagaca gggtcttgct atgttgccca ggttggtccc gaactcctag gctcaaacga 15660
tcctcttgcc ttggcctccc aaagtgctgg gattacaggc gtgagccatc gtgtccggcc 15720
acatcggagt tcaaatctga gctctgaact ccattcatgc caagttactt aagccctcca 15780
agcctcagtt tccttgtctg taaaatggcg gtaacaatgg tccctgctgt tggggttgcg 15840
gtggagactc agtgagagga ttcatgtagc acacactcag taagtgccag ctgtcactgc 15900
cagcctattt caccaccgtg aacacagagc ctcagaatgg aaaagcagcc tgcccaaggt 15960
cgcacaactt gcaggtggca caggcaggat ctgaatccag atcagattct tcccgcccta 16020
cttctatcac cgtggaaggg cctggggggg cctgcagcca ggaggtggct ggaaagggag 16080
gttccttgga acaaccagtg gcccaggctt cctgcagagc cggggacccc agccctggcc 16140
agggtaaggg tcacgcctgc agctggtgtt ccaggcatcg gagaggaact gcggctgcag 16200
gcctggcagc cttaccgtcg ccagcatcct gccctccatg gacacggccc caacattgtt 16260
ttctgggccg ttccctgccc agagcccaca cattcgggat ttccgcagct tggccagcac 16320
taccttcgct tcctggagca gctttcccca ggcggccggg gtgggggttg agctggccct 16380
ggcccctggt aggggcaggc actgctcgga aggcagtggc agcagcgccg tcaacatcct 16440
cttgacctga caggtcctta cccgagttct acctcctcag aaacacagcg gccctcctca 16500
ctcccctctc ctgaggccag cgtagaaaag gccctacctc atttccactt tagggtaggc 16560
tggagtgaga gcccgggtta aaatcctagc cctactacaa aggtgctgtg acctgggcaa 16620
gcctcccctt ccctctgcct cacaagggat gctgggtagc ctgaggtgcc ttaggctgcc 16680
ctgacatcag ctcagggatg accggcgccc cgtgctctga ggtctctggg cataataagc 16740
tccttgatga cagggtcagt ttctctcccg tgttctgcaa gtttattttt attattatta 16800
ttatttttga gatggagtct tgctctgttg cccagactag agtgcaatgg tgtgttctca 16860
tctcaccgca acctctgcct cccaggttca agcgattctc ctgcctcagc ctcccaagta 16920
gctgcgatta caggcgtgca ctgccacgcc cggcaaattt ttgtattttt agtagaaaag 16980
gggtttcgcc atgttggcca ggctggtctc gaactcctga cctcaggtga tccacccgcc 17040
tcggcttccc aaagtcctgg gattacaggc gtgagccacc gcgcccggct ccatgttctg 17100
tatatttaga aggaacctgt gtgagtggcc accaaacgtt cactctgaac catgctggcg 17160
ctgcctgcag gtgagcgtgc ctgcccagag tggtgtctca gttgtctcac tgcccaccct 17220
ggcgctccgt ctcctctgtg ggctggcacc tgctccctgg tagggcggag ctgaggggca 17280
caagggagcg tggaagtcaa gcagccagcc cagcaaactc gagcttccac ccctgccgcc 17340
50/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
tctctgcagg caaccacgtg cactgggtgt caagaaaaaa tatacagggg ccatatcccg 17400
ggttgtcttc aggctcggga agcctgcgac tttgtcccct ttccccggct tcccaacctg 17460
gtggctaaag gcttccagca ggtgtctgcc aaccccatcc acagtcatgg ggcccaatgt 17520
ggcacccaga gaatgaccgt gggctgacag cccagagcca gcggcatccc cggtgaggtc 17580
agtgtcctgg aattggtcaa acaggatcac caggaggatt ccgtgagcac agccagcatg 17640
actcacggcc atgatcagcc tcacgggcag aggctgccaa cctgggatgg ccacagccac 17700
cggctcacct tgcagggcaa cgcacctttt aaggagggag ctggagcagc gcccgggtcc 17760
tgcctctggc caaggcctct gccacacttc tccacgccca cccgggcaga gaggccagac 17820
ccccactggg ttcaaatttg gcaccacttt tcagacatga ccttgggcaa gtcgatttct 17880
ctgaactgtt tttttcactt atgatatgga aataatactt gcctcacaag agtggaattc 17940
gatgaggtaa tgtgtttaga aagtgcgtgg caaacggtgc cttttaagga gcggcagtgg 18000
ggtccggtgg aaagggccag ggctcgggag tcgaggcgcc ccagcattgt gctctggccc 18060
caccctgggc tcactgggtg tctttgaaag agttactcaa cctccgatct gctctgctcc 18120
cactgtgtca aatgagctga caccacttgc cttgttgcct gttgtgagat gaagatcaca 18180
cacacgccac cttctatcag atgacaggag gcagcgaggg tggttcctgg gggtgggtgt 18240
ggaaggctgc ctggccttga atcccagctc agccactcag gggctttgtg acctggggaa 18300
ggctcctcaa cctctcgggg caggtctcag gtggaatctg aagggcaacg ccttcccgcg 18360
gggctgtgct gagctgagac cctcaaaaca gtgccaggta cctgggaggt gcctcctgag 18420
tctgggcagg tcctgctcat cttaaccagg gcttttggcc tttgcaggat gttcactcca 18480
ccagcttccg tctccactga cgccagttgc tggttttgtc ccctccatgt gcttgtgaca 18540
gaccccaggg tctggggtcc ttcagaggcc acgggcccct ctcctccctc ggtctcggca 18600
gccttcccaa ggcagtcctt gggtgggccc ctggagaatg cagacagttc taatagaaca 18660
gggtgagcct ctgagaacag agcaatacca gccccatggc atccctgggg ccacggagta 18720
gggtgtcagg atccccctgc cgccaagcac ctgattcaca ggaagctggg gcctcatcca 18780
ggcaaccgag ccctaatgac agcttggccc taggagcaag gcagacggaa ggaaggcttt 18840
cttgactggc aagcctggct cccttggcac actcctctat ggccaagggg agctgggggc 18900
caagaggggt tgtctggtcc caaggcccag aagttcctgc aggcacccat gggaaggata 18960
gcctgatccc cacagggcca ggcacctgct ggggcagcca ggagccctgt cagttgggga 19020
ggcctcagaa gggtcaaggg gatcagctgt gggagcccag gtttcagagg caaccacgtc 19080
tggatagaaa ccccagctct gcatcccatg agccacagtg tctacatcgg ggtaatgggg 19140
51/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
acaacagcct cttgccttag gagggcacga ggactggcac atggcatcct tagaatagca 19200
gccactgctg acaagcatgt tagtgaacag gaagggctgg ttggagagag tgttgtggag 19260
ttaggggagg atgtggggac agtggacaag ccccctggga aagggtgaca agtgctctga 19320
gcccacacag atgtgacatt gcagatggtg cagacccttg ctttatttgt ctgacttgtt 19380
cacagttcag ccccctgctc agaaaaccaa cgggccagct aaggagagga ggaggcacct 19440
tgagacttcc ggagtcgagg ctctccaggg ttccccagcc catcaatcat tttctgcacc 19500
ccctgcctgg gaggcagctc cctggggggt gggaatgggt gactagaggg gatttcagtg 19560
tgggacccag ggtctgttct tcacagtagg aggtggaagg gatgactaag ttctttatca 19620
cagacctaca aaaaatgaga taattagata ttactctcac tagtttgggc ttcttttttc 19680
tttttctttt tacaaaacag cagctggaaa gagaaatgta ggtggcagac gagccaggca 19740
cgaggtttca gattggaagg gaccaagatg aggaccaagg tgtggctgcc tgactaggaa 19800
cgctgtgggc tggcccaggc tctcgccaca catcctggga gaactgccat aggccctaga 19860
aggagggatg aaaggcgtat gggagggaag acagcggtcc ccggatcagc agcagcacca 19920
ccatcctctg atggcccctg ggcagtccgc cagctcggaa gcactcaggg ctggagcctg 19980
ggctctaagc atgggcccca ggagccagac aggagggagg cagcaggaag ggctggcatg 20040
gaagggctga gttctattgg ggtcccacgc gggcaaggga accaggactc atccctgctt 20100
gtcagccaat cagcttcttc aggaaggcct ccaactgatc ctcatccttg atgcccacaa 20160
acttgtccac cacgtcccca ttcttcatgg ccagcacagt gggcaccgct gacacctggg 20220
tggagaggac aagggggtcc aagtgaattg ggagtgaata cttctcaact gccactcctg 20280
agcctttgtg gggaaggctg gtggcttatc cagggcactg acttcccaaa gccatgggca 20340
ggcctagagg aacatggctc ttctctcggt gcaggggtac tgcagggccc gggggccacc 20400
cgctgaagaa acgtcttcca ttgcgggctc ccaacagtac ccttcctccc ttaaccacaa 20460
gactgactca ctggcccagt ggttttgctg gaatgacagg agagatgaaa ataacccttg 20520
cagctgcagg ccagggctgg gggcagggag gagctcaggg gaagcctggc ccaggaggag 20580
acagaagctg ggggacagtt cgagtcctgg ctttgcactc actagcaagg gggccttggc 20640
cgggtcacag cacctttctg agcctcagtg tccttttcca taaaatgggg gtaatgtcta 20700
cctttagggt ttgggatgaa cattaaagat tcaagtatag gctgggcaca gtggcttata 20760
tctataatcc cagccttctg ggagactgag gctggaggat tgcttgagtt caagagttcc 20820
agaccagctt gggcaatata gtgagaccct ttgtttacta aaccccccca aaatattagc 20880
52/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
caggcatggt ggtacatgcc tgtactccca tactcgggag gctgaggcag gaggatcgct 20940
tgagcctggg agactgaggc ttcagtgagc tgtgattgtg ccactgcact ccagcctggg 21000
tgacagagac cctgcctcaa aaaaaaagag aaagatttga gtataaagca gagctcaggc 21060
tgggcgcggt ggctcacacc tgtaatccca gcattttggg aggctgaggt gggcagatca 21120
tttgaggtca ggagttcgag accagcctgg ccaacatggt gaaaccctgt ctctactgaa 21180
aatacaaaaa ttagtcgggc atggtggcag gcacctgtaa tcccacctac ttgggaggct 21240
gaggtgagag aattgcttga acctgggagg tggaggctgg agtcagtgga gattgcacca 21300
ctgcactcca gcctgggtga cagagtgaga ctccatctca taaataaata aataaataaa 21360
taaataaata cataaataaa gcagagctca ggttctggcg gacgcaatcc ggctcctacc 21420
agccaggtga gctggggcac gcccctcagt cactaagcct cagtgttctc agatgcagga 21480
tggagatact aagggcactg ccattagagg gcatgaaagc tgaatgaaat aacgcaagta 21540
aaggctcagc acagcgcccg gcaaataagc ttaggaacct ggcattgtgc ctggcatact 21600
gtgggcattc aaaaaacagt ggctacagag ggcacaagga aaagtccaac acaggcccca 21660
cgagagcaca ttagcttgct gctgtgatga gtgacagggt ccagaaactc agggacttct 21720
actggacagc atgagaggag aggcttggcc atacacaacc tgacgcttat tagcaggttg 21780
caggcagatg gcaaggacaa cattcttggt ctgtgaagca tttactcagt tccctcaggg 21840
acctgcatag gttatgtgga acgtggatga ggctgtggcc caccagactg gcattgtgag 21900
gtctctgctg cctgggatcc ctgcctggca ttcgtgggca tttgagaaaa ccatttaaac 21960
agaacaagat aggccggtcg ctgtggctca cgcctgtaat cctagcattt tgggaagcca 22020
aagcgggcag atcacttgag gtcaggagtt cgagaccagc ctgaccaaca tggtgaaacc 22080
ccgtctctac taaaaataca aaaattagcc gggcgtggtg gggcatgcct atagtcccag 22140
ctactcggga ggctgaggca ggagaatcgc ttgaacccgg gaggcagagg ttgcactgag 22200
ctgagattgt gccattgcat tccagcctgg gcgacagagc aagactctgt tccccccctc 22260
aaaataaata aataaaaata aacagaacaa gataaacaca gacttttctt acatacaaat 22320
taaactacaa agtaagagca gagattcaca caaacatacc aggtcttcac atatcccagt 22380
gctgccctgc cacggcccat cttggaagcc agtaagattc agaatgttca aaaaccatgc 22440
acatggtagt taggaaaggc acgcaggcca gaccatcccg ccctcaccca ctaactttac 22500
gtggcaggcc ctgcacccca ctcctcacgg acactttggg gacaaacaca gcaggtcaca 22560
ggacacagtc cttgtccttg ttagtgcctc aggccccttc aaaggctgtc cctgggctga 22620
tgtgggtggc aaaccctgtc tccaggcaga gcagggcccg aaagagtttg ctccaggaag 22680
53/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
cgcctgaagc caccagggcc ttcccaggca ttctttggtg ccctctagtg gtctgcaaag 22740
gcagctggag tgcctcaaag ccggagcctc ttggcagaag cagagagctc agccaccggc 22800
tcccacctgc acactgtcct attcctttaa ttaaaatata tgctttatgc cactgtataa 22860
gaagtggcct aacttttttc acggcaagac tctaagttca ctgaagaggc tcagagagtg 22920
gacttagcgt tccttaagaa ctccagatag gcacaagcac agtggctcac acctgtaatc 22980
ccaagtactt tgggaggcca aggcaggagg actgcttgag gtcaggaatt catgaccagc 23040
ctgggcaaca tagcaagacg tcgtctccat aaaaatatta aaaaaaaaaa aaaagaactc 23100
cagatgaagg ccataatgat ctcactcatg taaacctcca cacatgcttg aacacgcaca 23160
gaccctgctg gtgtcaggta gacagcagat gtgctgtcaa tggaggtctg gtcactactg 23220
atcaagggga tattttgaag ttgagcttaa acacacacac gcatacacac atatatacac 23280
acacacacat acacactacc cgcactaggg gctcacagga aacctgagct ggaatgggac 23340
ttccctcgac cctgaggagg cggctgaagc tctgctgctc ctgtgtctgg ctcacacatc 23400
aggaggtgcc ggtgcctgta aacactgcct tacatggaag tgcacagggc cttggcacat 23460
tcttctggaa tgttttgagt gtgaaagagg cagtgactga gccaactgag gggctgagga 23520
aaagatacgc tacgacgtgt tgcctgtcct gttccgtgaa gccacttgga acctcctatc 23580
cttggataaa gaccctctga actcggcagg agtgggggag tgtgtacgtg tgcgcagtct 23640
ctttctgcta acccgtagct cgcctgcacc gccactgagc tccgtgtcct ggtatgtctt 23700
ctcctgtccc accccgatgg catccatctg ttaactcagc taagggccta ccaagggaaa 23760
ggcacagtgc tgggtgctgc gggatgttgc aacctcctcc tcggctcatt gcagagttaa 23820
aaggaaaaga tcgctgtcac atgctgggtg ctttttcgtg tcaggaatga tataaacacc 23880
tctatacact atctcacact ctcctggctg tgggcaggat cattttaacg atgagaatac 23940
tgaggctcaa agggtgagca actgttccaa aatgatgtgg tgtaggacag gcgcggcagc 24000
tcctgcctgt aatcccagca ctttgggagg ctgaggaagg tgaatcatct gaggtcagga 24060
attcgagaca aggccggcca atgtggtgaa accttgtctc taccaaaaat acaaaaatta 24120
ggccgggcgt ggtggctcac gcctgtaatt ccagcacttt gggaggctga ggcaggagaa 24180
gtgcttgaat gcgggagatg gaggtcgcag tgagccgaga ttgcgccact tcactccacc 24240
tgggtgaaaa gagtgagacc ccctctaaaa aaaaaaaaaa aaaaaagctg ggatctgaaa 24300
caagatctgt ttgactttgc agtccagggg atcaaactct gttgtgcttc tgcccagcag 24360
caaagagaga gagacatcta ctgagtccca gcagggggaa gaacgtgggg acgcattaaa 24420
54/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
ggatttcatg cttcaaatgc aaaatgccaa gtgctttgta aaagctttta gatatgagag 24480
ggttcttgga aaaacgatta ttgaaaaaat gaactacata acattctggc agaattaggt 24540
agacagtgaa aagatcaaga gtcgccaggc ctggagggag gaggaaggag agatgaacag 24600
gcagaggaga gaggacatgg aggcagtgaa atgactctgg atgatgctag aatgtggaca 24660
ccggctatga cacatttgtc caaacccaca gcaggcacaa caccaagagt gatcccctat 24720
gtaaactttt ggctttgggg gataatgatg tccgtgtagg ttcataagtt gtgacaaatg 24780
gaccaccctg gtatgggctg ttgatagtgt gggaggctgg gcatgcggga ggacagggga 24840
cttatgggaa gtctctgtac cttccccttc ctctcaattt tgccacgaac ctaaaactgc 24900
cctaaaaaca taaaatcctc aaaaagaaca acaacaaaaa atgagatcag tgactgctgg 24960
ggggttaagg gggtgagggg caggaaggag aggtgaactg ctggaaaaca ggggaaccga 25020
gggcggtgga acggttctgt atggcgctgg aatggtggac acatgccatt atacatttgt 25080
ccatgaactt tctcactggc aagcagtctg tgctgagagc ggcagctgag acacggcctt 25140
ccaaagagca gttcctcccc acagaaagtc agtccggggc cttcagaacc agaaagtcaa 25200
tctggggcct tcagaatgaa aaagtcagta tggggccttc agaacattgg,cttctctcca 25260
tgtcggctca ggacacccag ccctggcatt acctgggagc ttgttagaaa tgcagtcttg 25320
gtggccgggc gcggtggctc atgcctgtaa tgccagcact ctgggaggcc gaggtgggcg 25380
aatcacttga ggtgaggagt ttgagaccaa tctggtcaac atggtgaaac cccatctcta 25440
ctaaaaatac aaaaattagg ccaggtgtag tggctcacgc ccgcaatcct agcactttgg 25500
gaggccgagg cgggctgatc acctgatgtc aggagtttga gaccagcctg gcaaacatgg 25560
taaaaccttg tctctattaa aactacaaaa attagctggg cgtggtcgtg ggcacctgta 25620
atcccagcta ctcgggaggc tgaggcagga gaatcgcttg aacctgagaa gcggaggttg 25680
cagtgaaccg agatcgtgcc attgcactcc agcctgggcg acagagcgag actccatctc 25740
aaaaaagaaa aaggatttta ggccttaaag aaagccatca tggggggcac tgtagttctc 25800
tcagaggaaa cttcttcctc aggctctctt cagaaagaaa agaggaagga aggaaagaag 25860
gaagggaggg agagagggag ggggtcagga agaaccctgg ctggagcttc ctaaaccctg 25920
caatgatgtc agaccagggt ttggctaaac aacacggctg agaccaagtg atgtgggcct 25980
agcagccttg aggcctttct gtgtgacagc acagtcccca ggcagtggac agggcgggag 26040
cggtgggtgt ggggggagat tgagaggatt ccacaggagg catctccttc tcacttccca 26100
ggcttcaccg caggccttca gtgcccactc ccacaacagc ctcccgggga cggtcctcgg 26160
cattcccgcc accccacgag acactggagc agggcctgtg ggcttctttg catctgcagt 26220
55/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
agttaccata gtccctgcac atggctggcc ctcagggggt gtctgctgaa gagttatgaa 26280
tacattggct gaagctgaag ctgtagtgtc tggcagagcc aggaggcctg agacatctga 26340
agcccacgcg tgacctgtgg gaggccctag gagccccagc ccgggetctc acccgaggca 26400
tagccaggca ggggaaagcc aggggcatcc aaatgggcag atagatgcct ccctcactga 26460
gcaatcagtg gccaaacttt ttgaaaaagt gactcacccc tcccccagcc cctgtaaaca 26520
gccctcagtt cctaactccc aaagcaggcc tgctccagtg gtcacctgta gtggccaccg 26580
tgtttgtctg cctggtctcc atctcccctg cttctggtca ttgcagactg atgttccttt 26640
gggtaatcac tccccactcc ctgcgtagct caaggggcgg ccagcctgtt ctcaccccgc 26700
tcccaaccac ccatttcttg ctgcaggaga ctggttcagg gatgggtgcc tctatttgag 26760
ctggtctagt aagagtgaaa cctggacttg tatactctga ggaataaagc ggcctctttc 26820
attcacttgt tacctggagg aggaaggagg gaggggtgaa ggctcactcc ggccaggtta 26880
agatatttca agaaaatcag atatcgagat tttcacatga aatctgagtt tcaaatatca 26940
gcatctgctt cctattactt taaaatactt cgagtgccag actaaaagtg tctgtgagcc 27000
aggttgggcc cagaggctgc caggagcgcc ctcggctctg taacagcgct accttcagca 27060
tggctattca gagaccctcc caatccggct gcattatgct ttccccagct ccgtactcgg 27120
cccttcactc tggccaccca gacaaagtgg gcctctcccc tttctccagg tagtggtctc 27180
caaggcccag aggaagcccc caacccagac acctceaggc acctggcccc tgctggtctg 27240
taagcaaccc aggctcatca gacctcaggg cttttgcttt gcctgaattg ttcttccaaa 27300
gacccacatg cttcagtcac tcccttcctg tttttgccca aaggtcagct tatcagggag 27360
atctacccta tcccaccctt taaaaaagaa acccgctggg cgcggtggct tacgcctgta 27420
atcccagcac tttgggaggc caaggcaggt gggtcacccg aggtcaggag atcaagacca 27480
gcctggctaa catggtgaaa cctcatttct actaaaaata caaaaaatta gccggcgtgg 27540
tggcgcgtgc ctgtaatctc agctactccg gaggctggga caggagaact gcttgaaccc 27600
gggaggcaga ggttgcagtg agccgagatt gtgccactgc actccagctt gggcaacaag 27660
agcaaaactc tgtctcgaaa aaacaaaaac cctgcctcat acgcagtact cccatcctct 27720
cttcctgatg tatttttctc cattgaactt attatctaaa acaggggtca gcaaactata 27780
gttcacaggc ccaatacagc ctactgcttg tttttgtaaa taaagtttta ttgtaacaca 27840
gccatgccca tttgtttgta tagtgtctat ggctgctttc ggctacgagc ccagctgaat 27900
ggttgtagca gcgaccactg ccctgcaatg cttccaatac caaccagtcc tttagagaaa 27960
56/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
aagtttgctg acccttgatt taaaatacta gaatgtagac tccacggagg cagagatttt 28020
gtcagttttg ttcactgcct tatcctcaac accaagtaac actacctggc acttgaggga 28080
ctctcaaata tctgctgaat aaacagacaa accaaccaac caagtgagac gactccatgt 28140
ctttgtgcac gctgtttcct cagcccttcc tcctcctctg cgcatccctc atggctcagc 28200
tcagaggttc tctctaacgt gaagcattcc ctgtcccctc cagctccccc acaagcaaac 28260
agtcccttct tcctttatgc gcctcttctt ttagcacttc tatattgaga tgatctttct 28320
acctgctgtt ctctcctgct agactaggag agatcttgct tggaaacaag atctcatctt 28380
gtgtcagaat cacaaatgct tggcacatcg agctcccaaa tgactgctca ctgaacatgt 28440
gggtagatgg ataaaggaat gtaccaatgt ctgagactaa gtgaatgacc tggtgttttt 28500
gggtcatacg atctacttcc taaaggtggt gaagagagac.aggtggctca gaggatcaag 28560
agccacctct gcaaagtgct ctgagctctt aaaagctctc gaaaaaccgg ctgggcgcag 28620
tggctcatgc ctgtaatccc agcactttgg gaggccaagg tgggtggatc ataaggtcag 28680
gagttccaga ccagtctggc caacatggtg ataccctgtc tctactaaaa atacaaaaaa 28740
ttagctgggc gtggtggtgt gcgcctgtag tcccagctac ttgggaggct gaggcaggag 28800
aatcgcgtga acccgggagg cagaggttgc aatgagccga gatcatgcca ttgcactcta 28860
gcccaggtga cagtgagaga ttccgtctca aaaaaaaaaa gctctggaaa aaccaagaca 28920
ccttgcttac tggctacctg tgctccccaa gatacctcct acaccagcta tccctgggcc 28980
tgacacctcc tatactggct tccctgtggc aactccctgt caatccatac ctcatactca 29040
atggcgaggt ctgtgtggtc atcaatatcc accttggcca tcaccacctt cccgtgctgc 29100
ttggccacca tcttctctaa cctcggcccc aggatcttgc agggtccaca ccacctcaaa 29160
aggcgagaaa ggaagcatcc agtcagtcaa aagagcgctc agcatcccct actggcttcc 29220
cagacctgca tctttccaag gaatcttttg cccttattat ctctgtttac catgtttaaa 29280
aattaacaca ccaaatggta atgccaggag attctgcaca tgggaaatct tcacagatcc 29340
cagactttta aaacacaggc ctcatcagaa gactcataat aaaagtgact catttcagta 29400
tatctcagat aaatatactg tcatataaaa ggatatggga ttggaagtta aaaggttcaa 29460
acagaggctt ctcaccaacc agctgattat tctggggccc tagtttcctt tttttctttt 29520
tttgagacgg agtctcgctc tatcccccag gctggagtgc agtggcgcga tctcggctca 29580
ctgcaagctc cgcctccctg gtttacgcca ttctcctgcc tcagcttcct cagtagctgg 29640
gactacaggt gcctgccaac acgcccagct aattttttgt attttttagt agagacgggg 29700
tttcaccgtg ttagccagga tggtctcgat ctcctgacct cgtgatccgc ctgtctcggc 29760
57/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
ctcccaaagt gctgggatta caggcatgag ccaccgcgcc cggcctgggc cctagtttct 29820
tcatctgaaa aagagagatt atggctctca aagctattag gagagatcaa ctaaggcaat 29880
gtgggtaaac atgcattgga agctgtgggg atatttcaaa caccatgtgg actcagaact 29940
aaaaggaggg gaaccaatgg cctggagcgt ctacaacgca ccagtccctg gctcactttc 30000
tctgctttta ccaaacacac ccctcaactc tgcaaagaga acacaccttc caaagaaact 30060
gaagcccata cgagttaaga aacctgtgca agattagaga agcacagctg ggatcgatca 30120
caacccaaag ctgtgttgaa agtgttttct ttggccgggt gcggtgaccc acgcctataa 30180
ttccagcact ttgggaggcc gaggcaggcg gatcacctga ggtcaggagt tcaagatcag 30240
cctggccaac atggtaaaac ctcgtctcta ctaaaaatac aaagattagc caggagtggt 30300
ggtgtgcgcc tgtaatccca gcttctagga aggctgaggc aggagaatca ctttaacctg 30360
ggaggcagag gttgaagtga gctgagattg tgccactgca ctccagcctg ggcgacagag 30420
actctgtctc aaaaaaaaaa aaaaaaaaaa aagagaaagt gttttatttc acccacaggc 30480
tactctgatc ccacagcccc tgagttgacc attatcactg ccctgatcat aggtattccc 30540
ctctcgctgg ggaagctcat ccaggacagg cctggtgctg tcatctctat gtatgtggca 30600
ccaaggaaag tgcctggcac tgaatgaaca actcacacca ccccacttcc ttactgaaca 30660
aaatgaggca ttatcccatt tattgttcat ttcggaaggc ctctctggaa tgctcactac 30720
accaggaggc caagacagtt ccacctttca caaacccctg gctgacaact cctattttat 30780
tctcagcact tacttattta tttttgagat ggagtctcac tctgttgccc aggctggagt 30840
gcaatggcgc gatctcggct cactgcaact tccgcctccc gggttcaagc aattctcctg 30900
cctcagcctc ctgagtagca ggtgtggtgg tgcacaccgc acccagccag gcctgacggt 30960
tttaaatgct gaaaaatagg ccgggcataa tggctcacac ctgtaatcct agcactctgg 31020
gaggccaagg cgggagagaa tcacctgtgg tcaggagttt gagagactag cctggccaat 31080
atggtgaaac cccgtctcta ctaaaaatac aaaaaaatta tctgggtggt agtcccaact 31140
acttgggagg ctgaggcagg aaaattgttt taactcggga ggtggaggtt gcagtgagct 31200
gactgaacca ctgcagtcca gcctgggtga cagaatgaga ctctgtctca aaaacaaaaa 31260
aggaaaaaaa accctcaggc ctggcgcagt ggttcatgcc tgtaatccta gcactttggg 31320
aggccaaggt gggaggattg cttgagatca ggaggtagag actgcagtga gccgtgatcg 31380
caccactgca ctctacattc tagcctgggt gacagagtga gaccttgtct ctaaaagaag 31440
aaaaacaaaa acaactcata acactgaaaa acccagtgtg caagacctta tctcctatta 31500
58/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
caagtgaaga aagggagcac aaagatatca agtggcctgc ccaaggccac agggtgagtc 31560
agagaaacaa ctggaaagcc agcgaaacaa tctgtcagag acctgaccag aaggcccttc 31620
aatttctttt tctttttttt tttttttgag atggagtttc cctctgtcac ccaggctgga 31680
gtgcaatggc gcgatctcag ctcactgcaa cctccacctc ccaggttcaa gcgattctcc 31740
tgcctcagcc tcttgggtag ctgggattac aggtgcccgc caccacgccc gattaatttt 31800
tgtatttttg gtagagatgg ggtttcacta tgttggctgg gcaggtctca aactcctgac 31860
ctcaggtaat ccacctgcct cggcctctga aagtgctggg attacaggtg tgagccactg 31920
cgtccgacct gaaggcccct gaatttttaa cttatgctac actggtttct cccaggatgc 31980
ctcattcaga gggctttgtc cagcttttgt gtagttgggt gtctagccag gccccaaaga 32040
tctagaaatg aaaaagccca ggctaaaatt cagaaggcca gagggactta aatatctcta 32100
aagcaaactc agatagcact gaaaggaaac tccttcctat gccctgtatg cttgggcacc 32160
acggtagtga caccgataac tttttttttt tttttttgag atggaatttc actctttttg 32220
cccaggctgg agtgtaatgg cgcgatcttc agctcactac aaacactacc tcttaggttc 32280
aagtgattct cctgcctcag cctcccgagt agctgggatt acaggcacac accaccacgc 32340
ctagctaatt ttgtattttt aatagagaca gggtatcacc atgttggcca ggctggtctt 32400
gaactcctga cctcaggtga tctgcccgcc ttggcctccc aaagtgctgg gattacaggc 32460
atgagccacc gcacccggcc gacactgata actttttgcc agcccttctt gcggttttca 32520
tggcaggatg ttaacatcag cttatctgca gggccaggaa ctggtataca ccaaaagcaa 32580
ggtgacagtc atatttttcc aactctggtc catgctaaag atgacgctga gctttctggg 32640
gattgagaaa cagaacatgt gtttcccagc actaacagtc agctttgcag actgttcact 32700
tgtctgtctt ccaccagact gcattcccct tgagggcagg gactgggcct gaccagtctg 32760
tatattgagt ctacatatga gcagcataga acatggccgt gggacacagc aggcattcaa 32820
taaatacttg aacaagtagg accctagtct tctgtggacc cccaatactc actgtgcgtg 32880
gaaatccaca accactggtg tctcactgtt gaccactcgg tcttgaaagt caggtccatc 32940
ctggatatta aaggttgtca aggagatcct cgtggtgtat attgtccggg ctgggttggg 33000
tgttacagtc aggccaccag gactgcattg tggggtctgc agggctctgg aagtgagggg 33060
tggccactga ccctgagagg gcttcctgga gatgacagag gccaggaacc tcctcagaag 33120
aagtcgctga gccatctgtg agggaaagag gcagaagaac tggggcacac aaaaggaagt 33180
cgacacacta gaaaaagatt tggggagtac tcagggctca ggaagaggca gagttggaag 33240
caaaatgcaa ggaaatcata tgtaagattt gtagcgtgga agtgaggaag caatgagaat 33300
59/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
caaagggaag gaacagctag gcaaaccaga aggacaggaa aactggcttc acaaccaaaa 33360
agaaatcggg atttagatta taacggaaga atgggaggaa gaaaccaaca gatttaataa 33420
tgtatgtaag gaccaagtac cttacacaca ttattggtct tcctacagca acttccagga 33480
agttgctatt gtactgccca cactgcgagt aagggaagga atacgaggct caagtaagtt 33540
aagtgacatg cccaaagtaa ccccgctatt aaatgacagc caacactgga acccagggtc 33600
gtctgaaaag atgaaacgca acaattcaag gaggaactaa gagtgtgaga ggaaccaaaa 33660
acgaagagac atgtactgga gggaaccaat aaagaaggga catgtgtgga gggaactggg 33720
aaaaatcgga catcaccagg gaccctggct ctccggcgag ctagatcccc ccgcccgccc 33780
ggccgccagc ctgcgcagga acgcgctcgc ggcatgcctc agccgcgaca ccacctcgag 33840
ccacccccac agggctccta cctccctgca atgcgagcgg agggatgcac agcctagccc 33900
tccctgcctg tcaagggcac gcctgtcgtc acttcctcgg ggggggacgt acataacgtc 33960
acttccgggt acaggcaggc ggaagagcgt ccctctccaa tttttttttt tttttttttt 34020
ttttttgagc cagagtctcg ctctgttgcc aggctggggt gcagtggcgc gatctcggct 34080
cactgcaacc tccgccttcc gggttcaagc gattctcctg cctcagcctc ccgactagag 34140
gcgcgcgcca ccacgcccag ctaatttttt tatttttagt agagacgggg tttcaccacg 34200
ttggccagga cggtctcgat cttttgacct cgtgatccgc ccgcctcggc ttctcagagg .34260
gttgtgatta cgggcgtgag ccacagcgcc catctgtccc tctccaattt gaggggcgtc 34320
tgggattttc cgccaatggg aatggcgggc tgaggcacag ttgaaggggc ggggcctcag 34380
ctacggaccg gaagcaatgg gcaggccgtc ggggaacgga ttggaagagg cgggcgggcc 34440
ctggtctggg cgaaggcggg ggcggggcgg ggcggaaacg gaaggggtgg gcgggcccta 34500
gaggagggac cggaagagga ggtgatggag caggggtagc aatggagggt acttaaggga 34560
gaaaaggcag ttgagaagtc cccgtggttt tggattttgc aaactcttgt tgctttattt 34620
tatttacata tatttattta ttaatgacag agtctcgctc tgtctcccag gctacagtgc 34680
agtggcgtga tctccgctca ctgcaacatc caaatcccgg gttcaagtga ttttcctgcc 34740
tcagcctccc aggtagctgg gattacaggc gcgcgccacc acgccgggct gatttttgta 34800
tttttagtag agacggagtt tcgccatgtt ggccaggctg gtctggaact cctgagctca 34860
agtgatccgc ccgcttcagc ctcccaaagt gctgggatta caggcgtgag ccaccttgcc 34920
tggcctcctg tttataactg gcgctgtcca cttcctacag atgttgacag gttctgtttc 34980
tccatttaat atgtaaagct aagctcctca aaggcatgat gccctttata tgtaaaagaa 35040
60/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
ctcaaccggg agtttagggg ccatccttta agtggccctc gtctgtgtcc gcctaaagga 35100
aaacaaatga aaactgaggc gagcctaatt taagcaggga gtttttttgg gtcaagttcg 35160
aagactgcaa ctcggagcag agattcaagt tgtcctgaat atacactcgg attagcagca 35220
gctgaaagag cgtttttaaa agaacaggca gtttccaaat tgttgatcaa agtttttttt 35280
tttttttttt ttttttttga gacagagtct cgctcttgtt gcccaggctg gagtgcagtg 35340
gcgcgatctc ggctcactgc aacctctgcc tcctgggttc aagggattct tctccctctg 35400
cctccccagt agctgggact acaggcgtgc ctcaccacgc ctagctaatt tttatatttt 35460
tagtagagac ggagtttcac catgttggct aggatggtct cgatctattg acctcatgat 35520
ctgcccacct gggcctccca aagtgctgga attacaggcg tgagccactg cacccagcct 35580
tttttttttt ttttttgaga cggagtcttg ctctgtagct aggctggagt gcagtggcat 35640
gatcttggct caccgcaacc tccacctcca gggttcaagg gattctcctg cctcagcccc 35700
ccaagtactt gggattacag gcgagcacca ccacacctgg ctaatttttt atatttttgg 35760
tacagaaatt ttatatttca ccatgttggc caggctggtc tcgaactcct gaccttaagt 35820
tatcgctcgc ctcggcttcc caaagtgctg ggataacagg cgtgagccac cgcgcctggc 35880
cgccctgccc atttttgtat cggttttctg tgtctctagc actttctttt ccacagccac 35940
ctatcaatcc tattcagcac ttccacagta ttttctagag agccaatttt cctgcctaat 36000
tcacattctg aatttcacag gcggaccagt cctgtttgtc cttatgccat agtcacttca 36060
ccctgatcgg cctcaggctt ctcatctgag caatgggaag aatgcctttc tcatagctgg 36120
gctgagggtt gcagtagaga cagaatccac atcattgctg cctgatgact cctgcaggga 36180
aagcctgaga gacacagaga aggctgagct ctcggcgcgc tacaaaaggg ctctcagcta 36240
catggtggct cctctgtcca gctagagctg agctggcctg ggtctggctt agtcacaagc 36300
aggctcaggg cacagctgag aggcaaaggg aaggaagcca ggactggcag cctgggctaa 36360
gggtaaaact tctacctcct accaatattt attgcagtgt ttttcaaact gcaggatatg 36420
gacgtcagtg ggtttgcaaa attaatttag tgggtggtga tctgcttttt aaaaaaacaa 36480
acatggtgcc aggcgtggtg gctcacacct gtaatcccag cactttggga ggccaaggcg 36540
ggcagttcac ttgaggtcag gagttcgaga ccagcctggc caacatggtg aaaccccatc 36600
tctactaaaa atacaaaaat tagccaagcg tggtggtaca cgcctgtagc cccagctact 36660
cgggaggctg ggcaggagaa tggcgtgaac ccgggaggcg gagcttgcag tgagccgaga 36720
tagtgccact gcactctggc ctgggcgaaa gagcaagact ctgtctcaaa aaaaaaaaaa 36780
aaaaaaatag ctctaaggtc ttgcactaac cggtatgacc tgtctggcgt ctttacaggc 36840
61/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
agtattggaa tgttataggg agacatacag ggtttaagaa atccatcacg gagaagacct 36900
tcaattatca attataggtt ttaaatttac ctcggctttg aaaggaatag gatacattgc 36960
tttctcttta ctacttcccc aggggtttgt aatttaacat gaaactgagt aatctgtaac 37020
tttcctcgat tctcgtcttt tgaccatacc ttgggatgaa tgagttcttt gtctgtggtg 37080
gggagcaagt ttagggaggg gaggaatctt ccctgattaa tatagaggcc taagccaaat 37140
tttagcatta aatctctcta ataggtttgt tcctgcctct ggaataaaca gaaatttaat 37200
attagctgat ttgcttttat atatgacttt tgttcttttt cccatttggg acattttctt 37260
ttgaagtgac ctatttttaa tctgaaacat ttattttgtc ctctttctct ccctttgcct 37320
ctccctctct gcctcttttt ctctctcact ctttctcttt gcctctctct ctgcctctct 37380
cttcctcttt gactctctcc ctttgccttt ctctctgcct ctctctttcc ctttttgcct 37440
gtctctctct ctttgactct gtctgttctg tcagtctttc tctctcctct aagttttttt 37500
tttctttact tttgagtctc ctggctttac tctttcatac tctatatatt gcctggagag 37560
tgggggtcta ggttcttttt tttttttttt tttttttttt gagacggagt ctcgctctgt 37620
cgcccaggct ggagtgtagt ggcgcgatct tggctcactg caacctccgc ctcctgggtt 37680
cacgccattc tcctgcctca gcctcccgag tagctgggac tacaggcgcc caccaccatg 37740
cccggctgct tttttttagt agagacgggg tttcaccgtg ttagccagga tggtcttggt 37800
ctcctgacct cgtgatccgc tcgccttggc ctcccaaagt gctgggatta caggcgtgag 37860
ccgccgcgcc cagccctcag tctaggttct ttataggttc tggccccctg ggtactttgt 37920
tgtatggtag acagcagaat ttttgccttc tgcttttgtt tttcatcatc ttttcttata 37980
tatacctttt gggcttctct tagaagctct tctataggtt tatctttcca gttctctatc 38040
ttttgtaatt tcttgttaat atctggccaa ctgttagtga caaaatgaag ttttaacatt 38100
ccctgcccaa gaggatcctt gagacctaga ccagtgtatt ttctcatttg ttcctttaat 38160
ctatctaaaa attctatagg cccttcatct ttcccttgct gtatatcaaa tattcgggta 38220
agatactgag ttcggggtac caattttttt tttttttttg agatggagcc ttgctctgtt 38280
gctcaggcta gagtgctgga gtgcagtggc gtgatctcgg ctcactgcaa gctccgcctt 38340
ctgggttcac gccattctcc tgcctcagcc tcctgagtag ctgggactaa aggcgcctgc 38400
cactatgccc agctaatttt tttgtatttt ttagtagaga cggggtttca ctgtgttggc 38460
caggatggtc tcgatctcct gaccttgtga tctgcctgcc tcggcctccc aaagtgctgg 38520
gattacaggc gtgagccact gcgcccagcc tcggggtact gatgctttaa tcccctttat 38580
62/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
tatcaattcc ttaaggtcct gcatattttc tcggtgggct gcgttgttat tgtcccactg 38640
ggggtcttgg gtgggagttt tttgatctgc tgtaggaacg ttttggccag gagggtgttc 38700
gtgttcctag gctcccatag cagctctatg gatcatgtct ctttcttccc ccgagaagag 38760
gggaaaggga aattctgaat atctttttta cattgctcta tctcacgttg aagtccttta 38820
agggaaaggt acttaggtcg gtagtgagtg ggctcttggg acgattctca agaggcaggg 38880
ttgtaagaaa ggggacatca gagataggag aagggtctgg gacagcagct gcttttgttt 38940
ttggtccttt cattatcctt ctaacatttt aacattaggc ctgggggaat attactgttg 39000
ctagctttct cctttttatc tcttacctta cttggggcat ttcccatctt gggtcctggt 39060
taagctcaat ctcccctgtt ggagatgtct cgcctatcct ttagccccac ctgctggagg 39120
ctccttgcat tcatgcacac tttcaacccc cagaatatcc tgaccaccaa ggaaatactt 39180
tgtcacccct gcgatgtttc ttagcttggt ctctgcacac ttacttggtc gctgtggtac 39240
atgaggatcc tttcccccag gtcgccagcc cgtttctttc tgccttgctg agagtatagg 39300
tttattcgtc acactggttg gtctcgattc cttacccctg tggccaccgc aacaaggcag 39360
tgggacgtgc ctcctcatgg gagaggtcta gaccctcctc agaggaggat gggaatccca 39420
aatgagaccc caaatttgtt agaaataaat tttcagtgcc acaaaagaaa tagcactcaa 39480
acatacattt tctcagcaag gcaattttac ttctatacaa gagtgcgtct catggatggt 39540
gcaatggcga gagcacaccg gaacaaggga ggggaatggg ttcttatccc tgatgcaggt 39600
accccctact gctgtgttgt tcccctatgg gctagggttg gaccgcacaa tctaagctaa 39660
ttctgactgg ctattttaaa gagagcaggg gtataagcca gagtggtggg gtgagaagtt 39720
tagacaggaa agatggttac ggaccaggtg actaaaggtg actcaggtca gagcaggtga 39780
cagaggctag gaggggattg tttactgaaa ctaggggcaa ggagacataa agaatgagga 39840
aattaaaagt taaaatgaag aacaaagaac aggtgagctg aacatactga tacattggtt 39900
ctttggagag gatctcagaa ctcaatgtac ttaacaaatt acaggctaaa acctttgaag 39960
aagaatttat gatatcctac attatcatgg ggtaaacaat tcgtccctga cagaataagg 40020
ctactggagt tctcttcttg taactctggg aaggactaga gggaactgtg tctgcagtgg 40080
ggccaggtag ttaaaaagtc tggactgggc cgagcgtggt ggctcatgcc tgtaatccca 40140
acactttagg aggccaagac aggtggatca cctgaggtca ggagttcgag accagcctgg 40200
ccaatgtggt gaaaccctgt ctctactaaa aatacaaaaa ttagctgggc gtggtggcag 40260
gcgcttgtaa tcccagctac ttgggaggtt gagggaagag aattgtttag acccgggagg 40320
cagaagttgc agtgagccga catcgtgcca ttgcactcca gcctgggtga caagagcgaa 40380
63/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
atccattgca aaaaaaaaaa aaaagaaaaa gaaaaagtct ggaccaagcc aagaggggaa 40440
gaggacgtcc ccatgaaaga gctttggatc cagaaagccc gggttcttgg aattcttttt 40500
ctcttttcac ttttgttgta gcatactttg ttctttttta ttttttattt ttttgagatg 40560
gggtgtgggg gctttactgt gggtcttgct ttgtcaccta ggctggagta cagtggctcg 40620
gtctctgctc actgcaacct ccacctccca ggttcaagca attctcctgc ctcagcttcc 40680
caagtagctg ggatgacagg catgctccac catgcccagc taattttttt taccgttagt 40740
agagacaagg ttttgctatg ttggccaggc tggtctcgaa ttcctgagct caggtgatcg 40800
gcccactttg gcctcccaaa gtgctgggat tacaggtgta agcaactgta cccagcgcat 40860
gttttatttt aatttaattt aattaactta ttttttgaga tggagtttcc ctcttgttac 40920
ctaggctgga gtgcaatggc gcaatctcgg ctcactgcaa cctctgcctc ccgggtttaa 40980
gtgattctcc tgcctcagcc tctccagtag ctgggattat agacatgtgc taccacgcct 41040
ggctagtttt gtatttttag tagagatagg gtttctccat gttggtcagg ctggtctcaa 41100
actcctgacc tcaggtgatc cacctgcctg ggcctcccag agtgctggga ttgtccttgg 41160
aattctgagt ggatacatga agagttagta agaaccagtg aaaaagcaat cacttatgat 41220
cctgggcttt gaaaaatcac tgtgattatc ttatgcactt acaaatgaga ctaagacgcc 41280
tgatgggaaa gtgcagattg ctggtgagga agggcaatga agaagagact aggaaccaaa 41340
ttcatcatca ttatcacaca aaggcatttg gaaatgtcac cttacacatg gtgagcacat 41400
atgggtgcca gcccgagaca gcaggataag tttcacaaaa cttgaccagg caggttagaa 41460
gcaaggcatg gttcaggatg gcagagggca gggagacaga agggagtagg atgggagaga 41520
agagccagct ggaagatgag tcagggggtg caactgggga gagcagctct gaatcctgct 41580
tctcagtgag aaagttgcta agatggcttt gcagggagct gtcctatcgc tgctcgagat 41640
cagcctgctg ggcctatgat gataagcagg gctgaccctc ttgggctctg tagctaagcc 41700
caaaccctgc tgaaaatggg gcggggaggt tgaggcagtg tgtggcaagt gacacagacg 41760
gggactccca gctgggggtc cctggaatta cttgacatcc cacagctggt gtcttcagca 41820
gtcatctggg gcaacaatcc cacctgccca ttgtggttgt tgaggatatc agagcttttg 41880
ttttaaagcg cttgccacaa actcttaaga tgcggatggg tttcccctgt gaagcactcc 41940
acaggcggga tgcaggccca tctgaggagg ggcttggaag gaagaggagc acttgagacg 42000
gggcagaact gggctggcct ggggctcagc gacagctcca ttgcagacaa actgggctgg 42060
ggaaggcagc tcccacctgg cagaggatgc ccttctgccc cctgacagga gggaggagac 42120
64/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
caccgcatcc ccgactttca gccctcacgt gccatctggt ggctttgctg cagacactgc 42180
catgatctga gtggtctttg gcaatcacgc attggcggga gtgtgaggtt gcggggaaag 42240
agggactgac catgggccta ggtggggagg cctggccact gtgcccacag cttaggaagg 42300
gacagtcaga gctcctcttt gttgctatcg acggactgag ccagaggccc tggagccagg 42360
ggggaaccta gtggctcttg gtcgccaagc tgctggctgc tgtcctccag gcgcctgcct 42420
gtgggggcat agtcccgcag gagcctgctc tccactctgt gctgccaaag gctctcggta 42480
ctcacgagtc cctgcatcct caggtacccc tgctggcaaa agggtggcaa cttctggcgc 42540
gtgagggcga acaggaagca ggactctaca caaaagcaaa atgaggagaa tgagccaggc 42600
tgggacatgt ggggaggggt gcagaaaggg gagctgccaa tgccaggtgt gggggcttca 42660
ctgcaggcct tgcctggtat cttccatccc ttgaaactgg gagctgacct ttctgggcat 42720
ctcacgtcca acctgagtag gtcatgaatc atgaccctcc acgaggctcc agggcagggg 42780
gctgccttga cactctggaa gaacaaggct ccaaaataaa agcaaaccac agcaatgcct 42840
cagctcccag acatcagggc tgagcaccgg gctctgcagg caaccacact gggggcgggg 42900
ctccgacctt catgagcaga ccctcggcct ggtgcggctg ggaactcagt ggtcagttcc 42960
actgtgagct cagatctgcc tgcaaagacg cagtccctca acaacatttg agttgcaaat 43020
accatgtgca aagttctgat ctaaacagtg tgggggataa agaaaaacgg gtatatcctc 43080
atctgtccca caacagaaag ctggtgcatg aatcaaattt ggtcaatcat aagatagctg 43140
tggatactta tcatgtagaa atatgaagaa acggccgggc gtggtggctc acgccttaat 43200
ccgacaactc tgggaggccg aggccggtgg atcgcctgag gttaggactt cgagaccagc 43260
ctggccaaca taatgagaaa gaaaccccgt ctctagtaaa aatacaaaaa ttagccaggc 43320
gtagtgacaa acacctgtaa tcccagctac tcgggaggct gaggcaggag aatcactcga 43380
atccaggagg cggacgttgc agtgagccaa gatcgtgcca ctgcactcca gcctgggtga 43440
cagagactct gtctcgaaaa aaaaaagaaa gaaaaagaaa tatgaagaaa caaccaaaag 43500
aagccatgca aagagagaag ctactgaaag gaacaaccgc taggtctggg agttcctcgt 43560
gggaatgaga atgaaggtag ggaaagcggg tgacatagtt tgggtctgtg tccccgccca 43620
aatctcatgt tgaaatgcaa tctctaatgc tggaggtggg gctgctggga ggtgactgca 43680
tcacaggagt ggtttctttt tctttttttt tcttgaggca gagtctccct ctgttgccca 43740
ggcaggctgg agtacagtgg cacgatccca gctcactaca acctctgcct tctgggttca 43800
agtgattctc ctgcctcagc ctccccagta gctgagacta caggtgcccg ccaccacgct 43860
cagctaattt ttgtgttttt taagtaggga gagggtttca ccatgttggc ctggcttgtc 43920
65/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
ttgaactcct gacctcaagc tatctgcctt tctcggcctc ccaaagtgct gggattacag 43980
gcgtgatcca gcatccagaa atagatgctg ccatgcgtcc atacagcctg cagaactgtg 44040
agccaattaa acctgtttct ttataaatta cagtctcagg tatttcttta tagcaatgtg 44100
agaacagact aatacagtga gaaaaagtca tttagccaag tacttataag actttaaaca 44160
aacagaagag ctgacacaga tatgggctca gccttctgag ggagttagag acaagggcag 44220
acagagtgtc aggaatgggc tggagtcctt ctgtaactct gagcgagcct tcttgcctcc 44280
ctgagcccct ctatctcaag tgaaaaatgg gcacagcaca aaggatgtcg tgaggcttcc 44340
atgggtgacc aggctgaaag gtgctccaga aatatgactt cctgtttatt tctgactctt 44400
agcatggagg cccctgggag gccaggccat ggcaagcctc tccaagcggg taagagagca 44460
gatgaggaag aggacagcgg gaagactggg agggcagcaa ggtggctgtt tggcaggcac 44520
caccttctga caacatcatc ccttctgcag ggggctcaga tgctcagcag aatctggggc 44580
cagcactaac agctgcacat cagctacagt aacagaggga cggctgccac tatgccagct 44640
ggccgcctgc tgggcggatt ctctccagtc caaggcagca gcacacagtg gcctgtacag 44700
tcaaacagtg tctagaaagt gggagacagg aggctaaagg gcctgggaca atgcattggt 44760
gggacccaca actcagggtg ggaattcact ccctcacaca ccctggcatt tttgttgttg 44820
ttggttttga gatggagtct cgctctgttg cccaggctgg agtgcagtgg catgatctcg 44880
ggtcactgca acatccgcct tccgggttca agcgattctc ctgcctcagc ctcccgagta 44940
ggtagctggg attacaggca cccaccactg cccccagcta atttttctac ttttagtaga 45000
aatggggttt caccatgttg gccagggctg gtctcgaact cctgacctca ggtgatccac 45060
ccacctcggc ctcccaaagt gttgagatta caggcgtgag ccactgcacc tggcctaaaa 45120
gtgtatttct tgagaaggtg tgcatttgct tctgtgattt ctatagctca atgatctcat 45180
gaagtttggc cccaaattta cataagcagg gcctactggt tgaatatttt cagagatttt 45240
tctctcccac tctatctagg gccaaaacca tgcatgtcat ctatctcctc ctttggaggg 45300
ttttggctcc cagcttccct actgagatcc aagctttatt ggagtgtctc taaacaggcc 45360
tcccatcctg ctccagctct gtcttcccac ccatacctgg ccctggcgcc ttcccatggc 45420
gcctggccct gctaatcctt ttgaaaagac atattatcag ctgggtgcgg tggctcacac 45480
ttgtaatccc aacacttcag caggctgagg caggcggatc acgaggtcag ttcgagacca 45540
gcctggccaa tatggtgaaa ccccatctct actaaaaaat aaaaaaatta gttgggcatg 45600
gtggcatgtg cctgtagtcc cagcttcttg ggaggctgag gcaggagaat cgcttgaacc 45660
66/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
cgggaggcgg aggttgtagt gagctgagat tgcgccacta cactccagcc tgggcaacag 45720
agcgagactc catctcaaaa aaaaaaaaaa gaagacatat tatccattat ttttaggtga 45780
gttgtaattt aacccacggc attgtcggga acagtagtct ggggtttgga tttccagata 45840
tgggtcctga aactccacgg gtcttgggtc tctgtgacct ttcttcaacc tggagctcag 45900
accctttgtc tttctgggag cttaagttac ctgcatagaa gcttcgcaaa tcggtgtcca 45960
aacagttctc caggaagcgc ctcagaggta ggatgtgccc gatcggggca gtccagtctg 46020
ttaagaagtc ttccacgatg tgatggatgg ccgtgggccg aggcaggggc cagtgtgcag 46080
ggcggaacct cacctcctgt tctgtgggga ggagagaggg ggccatgtca gagctgtgag 46140
gctgggcttc ccctcctcgg gccgacacag cacggatccc acacagccca aacacttccc 46200
tcgttcactc gtgctcggct ttcccgacag cctcctatgc tgggctgtgg tcagactgtt 46260
caagagccac ctgcagatat ttgaaaggct gccatgagga agaggaacta ggcttttccc 46320
ttgtggtttc ggaaggcagt gctgaagcta acaacgtgag gctggcgttt ccctaagact 46380
cacatggact gagatctact gtggctgctt tttattttgt attattattt gttggagaca 46440
gtctcgctct attgcccagg ctgtcatgca gtggcacaat ttaggctcac cgcaacctct 46500
acctcctggg ttcaagcgat tcttgtgcct ctgcctccag agtagctggg attacaggtg 46560
cccgccacca caccgagctc atattttaca tttttcgtag agatggggtt tctagtctct 46620
accatgttgg ccaggctggt ctcaaactcc tgacctcagg tgacccaccc gcctcagcct 46680
cccaaagtgc tgggattaca ggcatgagcc actgcgcctg gctgtggctg ctttcaaact 46740
ggcctttctc tgagaagact cagatagagg cgaggggtct cagcactcat ctagttcagc 46800
ttctccctgg tgtgggctcc cttctgtggt gttccagtca gatggccatc gagtcaagac 46860
ttggccgtcg ctattctggg aaacctgaat ttggaggtga ccaattcccc cactgaacag 46920
ctttaactct tagtgcctcc tttttctttt tttttgagac agagtctcgc tctgtctccc 46980
aggctagagt gcagtggcac aatcttggct cactgcagcc tctgcctcct gggttcaagc 47040
gattctcctg cctcagcctc cctagtagct gggactacag gcgcacgcca ccacgctggc 47100
taatttttgt atttttatta gagacggggt ttcactatgt cggccaggat ggtctcgacc 47160
tcctgacctc gtgatccgcc cgcctcggcc tcccaaaatg ctgggattac aggcgtgagc 47220
gaccgcgccc ggcctttttg tttgtttgtt tgtttttttt gagacagagt cttgctctgt 47280
agcccaggct ggagtgcagt ggtacaatct cggctcactg caacctctgc ctcccggatc 47340
ccggttcaag caattctcct gcctcagcct cctgaatagc tgggattaca ggcatgtgcc 47400
accatgccca gctaattttt gcattttttt catgtttttt tagagatggg gtttcaccat 47460
67/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
tttggccagg ctggtcttga actcctgacc ttataatccg cttgccttgg tctctcaaag 47520
tgctgggatt acagtcatga gccaccatgc ccagcctctt agtgcctcct tatactgacc 47580
acagacctgc acccgtcact gctacctgct gacacgactt ctgcctttgg gaacaacccc 47640
tgtttaaacc accctcttct acctgactgc ccttcaagct ctgaagcagg gggtgcgttc 47700
ccgaggttgt tcacttattg gtagctactc tgtgcctgca gtgggctggc attctgtgta 47760
cactgtcagg tttaacctca tggaacccta caagaaaggt actgttgtaa tccccatttt 47820
acagagggga ggttgaggct cagagaggtt aagtaatggt ccaaggtcac acagtgacaa 47880
aatgacaggc ctagggattt tgcccagttt ctctgtactg tgttaaccag ctccagttcc 47940
ctctactctt cagacccctc ccgccccacc acagtcagcc gcctctggag acctgcagca 48000
gggccgtgtc cctcttacta cacagtgcct ggcggagagc acgacacccc ccgcatggcc 48060
tgtgccagtc acggtatgtg tcagaatctg gaagcatcgt tcatcattct cggaccttct 48120
gcccaagtgg tctctaggca gagtcccgca gccatcccac ctgtcagctg agcatgtgtg 48180
tgaaggtttc agggtgggtg acaaccttgc agacggtgag gtctgaggag cccacaggtt 48240
ggggaagggc agagacctgc tcaccggtgg ggaggtatct atagtagtag atgacaggat 48300
gaagaaagtt agactgccag gcatcttctg tgtgccccac agaccggtca tcaaagaaga 48360
cgtccttgtc ggggccagag aaatttctgc catattccat gttgatgacg aagagcccgt 48420
gctttgcctt cctccctgtg agtgtctcca gctgggccag catctgtatg gggaactcct 48480
ccaggtactc aaaggccgtg gaattcctgg gagaacagca acgcggggga ggccctcagt 48540
gctgtggcag aggtgagggg tgcagcccgg gggtgagcat gtgtgtgtgc gtgtgtatct 48600
ccccctctaa ggagcgtcaa tcaagcagca cacccctcac ttaacattac tttttcagct 48660
cagctctcac gcacatgtgg ggtagagacc agaaaattcc atgtaacctg aatgggatat 48720
ctggggaaag agtgtcccag gcagagagaa cagtcaggaa aaagccctga ggagtatgtg 48780
agcactttgt gttcaaggaa cagaagaggc cgacgtggct gaggggagtg aacagcaggc 48840
agagggcagg agagggggcc ggaggccttg agaggtcaag gagggctgcg cctcccatga 48900
cgagacgtga ggagtcgtct ggcccgagag gtgacactgc tggttgcttg ggaggactga 48960
gcagagctgg gatcagcatg cctcaggttt ctaaggacca ctctggttac tgtgctgaga 49020
acagacgcca ggccaagtgg ggcggctgtt gtatgggtgc aggtgataca gcctggtgat 49080
cgggaccgag gtggtggtgg tagagcaggt gagagctggt tgggctccag acatcatctg 49140
aaggcagagg tgacaagact tgcccatggt ttgcatgtgg ggtgttgaga caggggtgcc 49200
68/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
aggcgtgctg actcacgcct gtaatctcag cactttggga gaccaaggcg ggtggatcac 49260
ctgaggtcag gagtttgaga ccagcctagc caacatggtg aaacctagtc tctactaaaa 49320
atacaaaatt agccaggtgt ggtggcatgg gcctgtaatc ccagctactc gggaggctga 49380
gacacgagaa tcgcttgaac ctgggaggtg ggctgcagtg agccaagatc gcaccactgc 49440
actccagcct gggcaagaca tagtgagact ctgagtcaaa aaaaaaaatt agccaggcat 49500
ggtggtgggt gcctgtaatc ccagctactt aggaggctga ggcaggagaa gtgcttgaac 49560
ccaggaggca gatgttgcag cgagcagaga tcgcaccact gcactccagc ctggatgaca 49620
gagcgagact gtctcaagaa aaaaaaaaga ggggcagggg catggagggt gatgcgaggg 49680
ttttgtgcag aaagcggctg cactacctgc atgtccctga acttggtgtg ctatagcacg 49740
ccctgccttt ggatcgggct gttccctctg actgaaggtt gctcccttgc ttctccctgc 49800
cacctgtctc cccccgcccc tcacccctct gtgctctgca ccgtttcctt ctcaggaact 49860
gtccatcctc tgggatctgc tgcttatcac taaattgact ctgacgatgg tggccggcaa 49920
ggccctggcc tgagggagct ctgagatcca cgtggctgcc tctgactact gctcatccac 49980
gtgatgccaa acactttcca caagtgacct ttactccttc ctttactgct gcaaggtagg 50040
cacaattatc cccattttgc agatgaggaa gaagggctca gagaggctca ctaatgtgcc 50100
cgtggccact cacaggactg tctgtagagt taatgtcatt gtttttcccc agaacaggca 50160
tgttccccac agcagccttc atcttaggaa agaactgggc acctcacacc tggaatagga 50220
agagaagcgc tatgcagcac gtcgggaaag ctgggccgag gggagtaggg tggggacggg 50280
ctactcactc cttcaacagg atgacatcgg ccagcacacc gaacatctgg tagagcccag 50340
aagcctcatt cacgcgccgc acgatggagc tggtcagctg tgtgatgggg agctcagtgg 50400
cgggccaggt gacgctgtgg tggcggtgct ccaggagccg gtgaacagca cgcactggaa 50460
cagccagagg gaggaacggc acgctgcact taccatttta tctctggtca ctgggaggga 50520
tgcccaggcc tcattgaccc ctgagaacgc catacacact ggtctccatg gcccagcgca 50580
aacgcctagg tggtgaacac atgaggggag gagatggcag ctgcctttag agcagggcca 50640
gcaggtattt tctggaaagg gccagacaat ccatattctc tgctttgtgg gtcatacacg 50700
actcagtgat gctgctcaat tctgccccta gtgtaaaagc ggccaagaca acaggcaaag 50760
gagtgagcac agctggagtt ggtctccagg ccagagtcca tctgcccctg cttcaggcca 50820
tctgcacgtg ggagtcccac cggccccacc tcacacaagg aacgtcaagt ccaacacgga 50880
gccttcccca gaaacctccc ccccttcaca gctctgtttc catcagagac gcgcctacag 50940
aaatctttga tttcgccctc tctttcacag cctaaatcca tctgtctcta agttcttttt 51000
69/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
ttaaatattt tttattttat ttttttgaga cagggtctcg ctctgttgcc caggctggag 51060
tgcagtggtg cgatctcggc tcaccgcgac ctccgcctcc tgggttccag gaggaaccga 51120
ctcccagaat tgagtccaat cctttgcccg tactgtaaga cccctctgca gtggtcccta 51180
cacttattat tgtagtcctc taacctggaa taaagtccac cttaccgtct tcatttgtat 51240
tatgattttt gagacagagt ctcactctga tgcccaggct ggagcgcagt ggcacgatct 51300
tggctcactg caacctctgc ttcctggatt gaagtgattc tcctgcctca gcctcccaag 51360
tagtagggat tacaagcctg gctaattttt gtatttttag tagagatggg gtttcaccat 51420
gttggtcagg ctggtctcga acttctgacc taagctgatc tgccagcctc agcctcccaa 51480
aatgctggga ttataggcat gagccactac gcccagcctg ccttactgtc tttaaaaaga 51540
aaaaagaaat ataaatattg aatgtctttg agtggcagaa tataaagatt actccccgta 51600
attccctaca ttttcacatt tttgatgctc aggctaggca tggtggctca tgcctgtaat 51660
cccaacactt tgggaggctg aggtgggtgg atcgcttgag cttgggagtt tgagaccagc 51720
ctgggcaaca tggcgaaaac ttgtctctac cacacaaaaa taaaaacaac aaaattagct 51780
gggtgtggtg gtgcacgcct gaagtcccag ccactcagaa ggctgaggtg ggaggatggc 51840
ttgagtctgg gaagtcgagg ctgcagtgag ccgagatggc gccattgtac tccagcatgg 51900
gaaacaggaa gagacgctgt ctcaaaaaaa ataataatac taatttttta aagctcagct 51960
gtaagattat gactccattc tttcaaatag actcacctaa ccacctaact gaatactgta 52020
tgcctcactg agtgaatttc aaccaacaec ctgtccttct cagaaggtta accacaggag 52080
caggaacatc taatttttat ttatttattt atttttgaga cagagtttca ctctttttgc 52140
ccaggctgga gtgcaatggt gtgggcttgg ctcactgcaa cctccacctc caaggttcaa 52200
gtgattctct tgcctcagca tcccgagtag ttgggattac aggcgcccgc caccatgccc 52260
ggctaatttt gtattttaag tagaggtggg atttcaccat actggccagg ctggtctcga 52320
actcctgccc tcaggtgatc cacccacctc agtctaccaa agtgctggga tgacaggtgt 52380
gacccaccgt gcctggccac atctaacatt ttagactcct ctccacagaa agggcaccag 52440
tttgctttct atgaaagaag agaagacctt tgtagaaagt gtctttcagg aaagctcctg 52500
ggccttggag tttaattccc ataatggtga gaaaatcacc aaaactctga gcctcagagt 52560
tttacactct tgaggaaaat ggagatttca cacccacctt tcggggtgct ggcggccctg 52620
ccagggtcgt gtgttcagtg ctcagcccac tgaagtcacc caacatgcgt gaattcatct 52680
ctctcacttc ctttttattt cccatttact cctaaaatca caagtatcaa tttttggttg 52740
70/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
gggattattt tagtgcaata aatagaatta tgtttttaaa agatatttta gtattttctt 52800
tgtaaacatt ctcaagttgg cagaaaattt atacccttgg tactgagagt tttgaaaaag 52860
aactgatata atccaattac attttttttt ttttttttga gatggagttt tgctcttgtt 52920
gcccaggctg gagtgcaatg gtgcgatctc agctcaccgc aacctccacc tcctgggttc 52980
aagtgattct cctgcctcag cctcccgagt agctgggact gcaggcgcac gccaccacac 53040
ctggctaatt tttgtatttt tagtagagac agggtttcgc cgtgttgccc aggctggtct 53100
tgaactcctg gcctgaagca atccacctgc cttggcctcc caaagtgcta ggattacagg 53160
cgtgagccat tgcacctggc ctacacttaa ttttatttta tttttgagac caagtctcgc 53220
tctgtcaccc aggctggagt gcagtggtat catcatggct cactgcaacc ttgacttcct 53280
ggactcaagg gatcctcctg cctcagcctc ccaagtagct aggactacag gcgtggactt 53340
ttacacttta tctgatactt tcctaaacat gtcgtcagac cacaaaaacc tgttgtcact 53400
tccccaagac aatttatgac aatgagctac tgacaagcaa tcccctaatg cttctggaca 53460
taggagtaga tttataaacc ctgggatgct gagagtggtt ccgtctgggg acagttctgc 53520
cttctcagct gggctcacct gtgtatcgga atccgtggat gaagccccca gcagatttcc 53580
ggtagtccac cgagtggctg gcagtaccca ggataaacag accccggctt cctttggatt 53640
cgtagctagc tcgaatcagc gggtacttct tgccgaatgc atttcccgag ttaagtctga 53700
gggacctgtc agtggaaagg gctgttcatg aaaatagctg ctatgtaaga ggcacttatt 53760
tatttagtta gttttgagat ggagtttcgc tcttgtcgcc caggttagag tacaatggcg 53820
tgatctcggc tcactgcaac ctctgcctcc tgggttcaaa ctattatcct gcctgagcct 53880
cccgagtagc tgggattata ggctcctgcc accatgccca gctaattttt gtatttttag 53940
tagagaccag gtttcaccac gttagccagc ctggtctcga tgtcctgacc ttaggtgatc 54000
tgtctgcctt ggcctcccaa agtgctggga ttacaagcgc gagccactgc acccagccag 54060
gaggcactta ttacagtggc acttattact ggcactgagt gccttagatt tctcgtctca 54120
tttaaacctc accatgaccc caggaggtgg gtattatcat ctccatttaa gagatgaagt 54180
cggccaggcg aggtggctca cgcctgtaat cccagcactt tggtaggccg aggcgggcga 54240
gtcacaaggt caggagttcg agaccagcct ggccaacaca gtgaaaccct gtcgctatga 54300
aaaaatacaa aaagagttag ctgggggtgg tggtgcaatg gctgtaatct cagctactca 54360
ggagactgag gcaggagaat cgcttgaacc taggaggcag aggttgcagt gagccgagat 54420
tatgccattg cactccagcc tgggcaacag agtaagactc tgtctcaaac aaacaaacaa 54480
acaaacaaac aatgaagtca ggccaggcac agtggctcac gcctgtaatc ctagcacttt 54540
71/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
gggaggccga tggaaaggag ggtctggaca ggcacaccag cttctccttt gtctttctgc 54600
accctggtca gaagacaagt gaaagactgg atgctgcttt gataccaaac ctcccgaggt 54660
agtcggcagc aatgtttaaa atctaggctt cataaaatag cccttcaaaa tacaatgata 54720
aataacttaa gcaactaaca ttttattgag cacataatac atgccaagta ctttctttat 54780
tttaagagat agggtctcat tatgttgccc aggttggagt gcagcagcta ttcacaggca 54840
tgatcatagc acactgtagc cttgacctcc tgggctccag tgatcctcct gcctcagcct 54900
cctgagtagc taggtactca tcactgcacc tagctcccag cactttcttt cctttctttc 54960
tcccctctct ctccttcctt ctctcctctc tctttttttg tttttgagat ggagatcttg 55020
cactgtcgcc tgggctggag tccacaatgg cgcgatctcg gctcactgca acctccacct 55080
cccaggttca ggcgattctc ttgcctcagc ctcccgagta gctgggatta ccggcacgtg 55140
ccaccatgcc tggctaattt tttgtatttt tggtagagac ggggtttcgc tacattggtc 55200
aggctggtct tgaactccta accttgtgat ccgcccacct cagcctccca aagtgctggg 55260
attacagcat gagctactgt gaccagccat ctcttttttt ttttgagaca gggtctcact 55320
ctgttgccca ggctggaatg cagaggcatg atcttagttc accacagcct cgacctcctg 55380
ggctcaagta gtcctcccac cttggcctcc tgagtagctg ggaccacagg catgtgccaa 55440
cacacctggc taatttttgt attttttgta gaggtggggt ttcaccatgt tgtccaggct 55500
agtcttgaac tcctgagctg aagtagtatg cctgccttgg cctcccaaag tgctgggatt 55560
ataggtgtga gaccatgagc cactgcacct ggcctctgca cacattcttc tttctttttt 55620
tttttttttg agataagagt ctcgtcaccc aggctggagt gcagtggtgt gatctcggct 55680
cactgcaact tctgcttccc aggttccagc aattctccca cctcagcctc ctgagtagct 55740
gggattacag gcacccacca ccacgcttgg ttaaattttt gtatttttag tagagatggg 55800
gtttcaccat gttggccagg ctggtctcga actcctaacc tcaagtgatc cacctgtctc 55860
ggcctcccta agtgctggga ttacaggtgt gagccaccgc acccagcctc caagcatatt 55920
cttatgttaa tcctcgcaat aaccatatga gaaacaaact ttgaatccca ttttagacat 55980
gagaatactg ggccacagcg tggttaaata acttccgccg aggtcacaga tttggcaagc 56040
agagaatctc aggacaattc cggcacctgt gctctcagcc actacgctat attgccttcg 56100
agcaaattcc cctctgtatt ctctctgagc cggcctttcc aactcacagg tggaggctcc 56160
caatgctgat gaagatctgc tggtgttgct ccaggaccaa gggcctcagg gccacctggg 56220
accctcaatg gtcagagctc atgtcctgga gggaaatcag gcagcactca catccattct 56280
72/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
ttgggtgctg tcctgagagc tctgtcgcca gcctactgaa cagccaccct gttcccctag 56340
ggaggggtca ggagggtttg ctaggagagc ccacctcctt ccgcatggaa ctcacttatt 56400
gaaaatggag aagtcaaagt tccagcccag gcagcggatt acccggtcat agggcacgcg 56460
catggcaaag ttgtcattgt cgtcctgggg gagggtgatg gagtcggcac tctggttggt 56520
gttggcttct tccaggaaga atttcggggt gacatggaac ttgcctttgc tgtccttcag 56580
gatggccaga tccgtcaggt cagactcgag cagcccgtcc agggacttga gctggtaggt 56640
atccagcagg ccattgttga tggctctgag cccacagaga atgcagggga gagagactca 56700
gaggaaagct gggcagtgca gctggggtca ggaagggcag gggagggttg gggaggctct 56760
ttccacactc tgggctccca gcacagaaca cacatgcggg gatgtggcct acctgaggtc 56820
tccaacgtag tgggtggccc aggacagacg gacccgggag cggctgagca tatggataaa 56880
gtttgtgaca cccaagatgt tctctgctgt ctcaaaggcc gagttcccac gacccaggat 56940
cagcacattc tggcctacaa agtcctcagg gtccacggac acggactcgt aaccctctgc 57000
atattcggag ccagggaagt caacctggtt ggggactgat aaaccagtgg ctacaaagag 57060
gacgctgcag gcggggacag aggaaagatg gcttagtctc ttagctataa gaccactaag 57120
tgaaaaccac tccctggacc cacccaccca cctgcctggc tccaaccgcc ggcccctaaa 57180
agaaaatagg acattcattc attcattttt cattcattca tctgtttacg ccctcatccc 57240
agtgcacttg agaggctctg cccttgcctc tccctgagct cacagtattt tccctagcac 57300
tgtactgggg gttaaatttg ccctgtgaga gaggagaaga tgacagtatg agaaatggag 57360
aattcaccta actttgcaca tagcagtcag accaggtatg actgctggtg atgaaatgaa 57420
acctgacatt ctactttccc ctttctgagt cctctgacag atacatctat ccactgagca 57480
gtaattctgt accaggccct gtactaagtg tatctgtgca ccatctttct gactcctcca 57540
agcaacctgg aggtggtatg tggcctgctt tacaggtgag gaggcacagg ccctgcaggc 57600
ccatggcttg agagctccta aaagcagcag agccagagtc taaacacaga taggcttgat 57660
tccaaagtcc tgctccttcc attggtgagg atcgccatcc aggggagggc agctggggac 57720
ttggatcctg ccggcttgca gaagaatgct ttgatcacag agtggtttca aaaatagaat 57780
tgaaggccgg gtgcggtggc tcatacctgt aatcccagca tttggggagg ctgaggtggg 57840
tggatctcct gaggtcagga gttcgagacc agcctggcca acgtcgtgaa atctcatctc 57900
caccaaaaat ataaaaaaat tagccgggtg tggtggtgct tgcctgtaat cccagctact 57960
ggggaggctg aggcaggaga atcgcttgaa ctagagaggc ggaggttgca gtgagctgac 58020
ctcgtgccat tgcactccag cctgggcgac agagtgagac tccgtcttaa aaaaaaaaaa 58080
73/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
aagcgaaata ccctttttcg tccattcctc ccatacctac tggccaatca aggtgtgtgg 58140
ttcgtgtggg gaaggtccca gcttccgcag gtgagctctg gcaccggcct tacctgcact 58200
gatgcacctg gcccttctgg tcagttagga tgaagtagtg gccattccag gcctgtcggt 58260
ccttgtccag agtgacgtgg gcgatggtgg tgttgtactg gacacggagc cccagcgtgt 58320
ccgcgaagtc acccaggtag cgcaccatgt cgcgggcgtc ggggaagtag gcacgcgagt 58380
agtgtctgaa gagcagccgg gggtcgtggc tgagcagaga gttccagtcg tggcggaggt 58440
tgaactcggc gttagccttg cccgtgtacc gcttgttgat gctgatgagc ttgcggtgcc 58500
gcgggtagcg tgtgaagaag ctgccgggcc gcggggcccg ctcgaacact gcgtagtcgc 58560
gtccagcgcg ctgcaggaag taggccatct gcaggcccgc gggcccagcg cccagcacgc 58620
agtagtcccg gcgcgggggc accgacagcg ctgggtgcag ggcgatggcc aggagcagcc 58680
ccgggggacc ccacaacggg gccgcagcgg agaggcccat cctgcagcag atcagagggg 58740
taaggcctcg cacccggccc ggcggctggg agacacgagg cccagaaaga ggcggggcct 58800
gcgggaactc tcactgcaat ctgggtcacg gccaggccca gaagccgtcc tcagagctca 58860
tttgcccgga ctccaccgtt tcaagctggg acttggggct ccccggaatc ccgagcccct 58920
ccatcttatc tccctcaggg tctccttcct caggggcacc ggctccccgc ttatgattgt 58980
agtaacctcc accctgggga aggagagcgt actccccaat tttcccctaa tttgagggtg 59040
cccaacaccc ctttgaacca ccctccaggt tggaccttcc agaggccttg gcccctctcc 59100
agcgaccggg tgggagcctg aagtgggtgt ggcctgcgtg cgccccgccc cctgccaggg 59160
tccgcgcgcc ccaggctctt cggccacgtg acagggatgc cgcgcacacc tgccgcccgc 59220
ccgcgtgcgc ttcaggagcc gccaggtccc tacgcccgca gctccggcct ccccgcctcc 59280
gaccgaaccc tgagaaacgc gcgaacctcc cagccgctcc ggctgcaacc cgtggtctaa 59340
tgaggccgcg cttggctcgc ttgctccgcg gcggctccgc ccctcgcgcc cggaccaatg 59400
gcagggggcg gggtcacgtg cgcggcgcgc ggcacgccgg gaccagctgg caggctgcct 59460
gctccggccc agcgcgggag aggcgcgcgc gtgctgcgtt cgctgctccg ggggctggta 59520
gaggggcctg gggctagcgc gcacccgcga gggtggaagg tctggagatc cgggatgggg 59580
aactgggtcc ttcgttttaa aaggtgcctc tctacacgga gggaggggag cacgtgattt 59640
ttggagctaa tcctagctct catattccat gaatgtagcc aaacgctaaa actagttggc 59700
ctacccagtt ttgtgggact ggaaaccagc gtggtggagc caggaccgat aagccaatta 59760
acaagcgttt gctacagtga ctcagtgtac tgcttaccaa gtaacataca cgactgtcct 59820
74/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
aatcttccac caaataggag aggtgggcaa ggcattgttt ccgacatttg gtagctgact 59880
ggtcaaatgg agacataggg atgaagggat atgtttacaa tcacaggaag tggagcctgg 59940
aattaaaact cagtggaggc aagataaatg gcaggaggaa gataacgtga actggatgat 60000
gaaggttggc ttcccagggg tggcaagtgg cccctgcatg agatttacat ggggagaaat 60060
acgaagtcag tgtaggaacc ttcaaagtcc agtgaaatgg ggctgagtgt tcttggggga 60120
agggcaggtg gaaagaactg cgagcctgca gatttgcatg gctggagatt ctttgaatta 60180
aaaatcgtag ctggggactc cttagaaaaa ttttcctgac ctctcaggcc tacaagtacc 60240
taccaaagaa tgtcatttac tttttctttt tttttttttt ttgagatgga gtctcactct 60300
gtcgcccagg ctggagtgca gtggcgtgat ctcggctcac tgcaagctcc acctcccagg 60360
ttcacgccat ttttctgccc cagcctccct agtagctggg actacaggtg cccgccacca 60420
cacccggcta attttttgta tttttagtag agacagggtt tcactgtgtt agccaggatg 60480
gtctcgatct cctgacctcg tgatccgccc gcctcggcct cccaaagtgc tgggattaca 60540
ggcgtgagcc accgcgcctg gccgaatgtc atttactttc ttcagtctgt gtcaacatca 60600
gagaaaagct ccctcagagc agaaattgtc cagtatctga catacggaag tttaagcatt 60660
tgttgaataa gcattgcaac cagagaggtc aggcagaata ctttgccaaa aataaagtag 60720
ggatgtctta tttcttcttt ttgagacaga gtctcactgt cacccaggct ggagtgcagt 60780
gacacaatca tggctcactg cagccctgac cttccaggct caagcgatcc tgcttcagcc 60840
tcccaaagtg ctagggatta caagtgtgtg ccatggcccc tggccaattt ttcaaaaaaa 60900
tttttggggg catatgtgta tatatttatg gggcatatga gatgttttga tagtcatgca 60960
atttggggat gtctgtttct tagtggttgt gaagattatg agaatgggtg ctggcaaaca 61020
agttcctaaa ataattgctg gtcttatgtg gtgaatacag tagtgggaaa ttaaacagaa 61080
ttcgtcaagt atggtagggc cctacgagta ggctgaacct agattgtaag caacaggatg 61140
ctactgggag tttctgaatg taggattact gcagcagtca acttggtagc cccatgcagg 61200
acagataaaa gcagtggaca gctactcggg aggctgaggc aggagaatgg cgtgaaccca 61260
ggaggcggag cttacagtgc ctgagattgc gccactgcac tccagcctgg gcaacagagc 61320
aagactccgt ctcaaaaaaa aaaaaaaaaa aaaaaaaggc agtggaaact gatgcaaagt 61380
attttcaggg aatgagcttg agtcacttcc acttgcttct gttaatcctg ttggacaggg 61440
ccatggtttg caagaggcaa tttggtgaat actggtccaa cctggaaacc cccggcacta 61500
gtcacaccac tttaatctgt tttttaacac tctgtattca cattgaaaac tccccaagta 61560
cactttttct ctccactgct tctaacacag ttcaagaaac cttttgcttg ctgaggttcg 61620
75/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
attcattaaa attaattttg tgttttttca agctacttta aaaaaaaaac ctgtaacttt 61680
agaaatgctg agcttttttt gagagtctct gtaatccaaa ttggagtgca gtggtgtgat 61740
CtCagttC3C tgCaaCCtCC gCCtCCtggg ttCgagtgaa tCtCCagCCt CagCCt .CCCa 6180
agtagctgga attacaggcg tgtgccacca tgcctggctg ttttgtattt ttagtagaga 61860
cggggttttg ctatgttgct caggctggtt ttgaactcct gacctcaagt gatccaccca 61920
cctcggcctc ccaaagtgct gggattacag gcatgagcca ctgcacctgg cctttttttt 61980
tttgataaag ggtctccttc tgtcacttag gctggagtgc agtggtgtga tcatagctca 62040
ctgcagcctt gaactcctgg gctcaagcaa tcctcccacc tcagcctcct gagtagctgg 62100
gaccacaggt ggaagcatca tgactggcta ataatttatt tttttgcaga gacaggccct 62160
ggtctccctg tgttgcccag gctggtctca aacttctagg ctaaagtgat ccttctgcct 62220
cagcctctca aagtgttggg attagaggtt tgagccacca tgcctgtttc ctcacctcta 62280
caatggtact actcctgcca gcatcacagt tctgtatgag gcttagatac tacagaaagc 62340
tcagcattaa tacctggcag ggtaattact ccatcaagtg tccagaacag aacagtgtcc 62400
acttacatag tttacatagc ctcggctggg tgcggtggct cacgcctgta atctcagcac 62460
tttgggaggc caaggcgggt agatcacctg aggtcaggag ttcgagacca tcctgaccca 62520
tatggcgaaa ccccgtctct actaaaaata caaaaattag ccaggcatgg tggtgcatgc 62580
ctgtaatccc agctactggg gggctgaggc aggaggatcg cttgaacctg ggaggtggag 62640
gttgcagtga gccgagatca tgctactgca ctccagcctg ggcaacaaag tgagattccg 62700
tctcaaaaaa aaaaaaaaaa aaaaaaaaag tttacatatc ctcaacatgc agagctctta 62760
tgacacaatg ctttgtaggg acaggcctga gtgtcaccag cccaagccaa gcttaaaaac 62820
aattcataaa ccattacaca atcacccagt gggacatcca tcaagctctc tgtggcagcc 62880
tccctcaggc gcagcagccc cacctcaccc acaccctgct tcacgctgta ctagtgctct 62940
gcactccagc tcctcacagt gaactctcca aaagcaacag gtggcccttc acacagccag 63000
caggcactca tgcttgtgga aatggacttc ttataacaaa tgaggacacc cagattctga 63060
attccacata gaaattgctg aatetcatcc ccactctgtc aggaatcttt gaagaaacga 63120
ctgtaaatcg ttaatgcagg cagacgatga gggaaagact aaacagatat atattttatt 63180
tcatctgcta aatgtcagag agcaagttag acacacattc cactaagcat caaaggccct 63240
cgtagtctcg gtggaaggac aaactccagc tccacatcac tggtttaagt ttcttcctct 63300
gaaagacaca aaaaatgtaa gagaaatgag ccaggttgtg tgatatgatg ttcactttcc 63360
76/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
tttctgaacc tctgctggac tgtgcgtgag ttttcaacac ttccattccg aagttaagcc 63420
tttcagatgc tcacagggct gggcaggtat ttccttcagt caccagctgg tggagcagga 63480
gagacaactt tcaggctatt taacccggag cggagctttt ccctctagac caccggcttc 63540
aatctgggac ttccctcatc ttcctctacc tctgccacag tccagccgct tctctaaaac 63600
accgctatcc tccccaacca cttgatgtga tctaaaggct ctagaagaag ctcttggagc 63660
caaagtgaat gcttcttcat acttaagtct cagggaattc tcgaagtttt atcaaggtta 63720
aagatcacaa tggctacaga gcttgctccc gtgctagccc acagatcact ctagacctca 63780
gaaagtgggc tgctacacac cttcttcttc ctcttcttcc tcctcctctt cctcctcatc 63840
ttcatcagag ctgaaggtgc catcagggag gctgtagaca cggatgacct gcttgttggg 63900
gtccttgagg atgaggtatt tgccctcctc cagcttcatg cagatgtcaa tgacgcagcg 63960
taaaatgccc caggcattct ccacgctcag gttgatctgg ctggcaaact cattaggctt 64020
gaactgctgg gtgcctagga tgacgtggcg tgaggagtct ttcacgtggt accgagacac 64080
ataactaaca ggggaaggga tatcagtggt cagagcaggg cagcacagag acagcaacac 64140
ttgggatcaa atgtcaatta aatggtgata cctggtccac tgctattttt tctttttttt 64200
ttttttgaga cggagtctgg ctctgttgcc caggctggag tgcagtggcg ccatcttggc 64260
tcactgcaag ctccgcctcc cgggttcaca ccattctcct gcctcagccc cctgagtagc 64320
tggggctaca ggcgcccgcc actacgcccg gctaattttt tgtattttta gttgagacag 64380
ggtttcatcg tgttagccag gatggtcttg atctcctgac ctcgtgatct gccagcctgg 64440
gcctcccaaa gtgctaggat tacaggcatg agccaccgcg cccggcagtc cactgctatt 64500
ttcaagggaa agggaaaaca tcgtcttctg agttctcagt tctggatttc attgacacca 64560
ttgccctagt tcaggactcc attcagcatg cctgctgttt ggcatttgtc tcctaactga 64620
cccctccatc tctaccccac ccctggattt atctctgcca gtcaattgtc cagtacacgg 64680
ggaggggagg gtcaacctcc ctacccagac ccttcctttc acaagatcag ctgccagctc 64740
ctgcacagga atctcaccca agcttgaggt actcagatcc agccagcaaa gcacagcagg 64800
tccaccgggc caacttgtag ctgttgttct tcagctccgt ggcaatgaca gcccctcgct 64860
gagagtccag cttctgacgc cagtcaacgc cattacagtg ctgcaggaga gccccgttag 64920
agaaacagaa gcaagctcca aatgcccaag gtgctgggac ctcctctggc agagaaggaa 64980
ctccctagtc tgcttgctta gaaagtgggt aggtacgcac taaatcttac catttaagag 65040
acaaagacat agtcccttcc cttgcacagc ctgccgcaca gcagtcactc aacgacttac 65100
aattcctctc ttctaaaagc tcgcctagac agggaatgat ggatggacac acacggacac 65160
77/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
acacacacac acacacactt tagaagtgtc atataaacag cagagccaag tgtttactat 65220
gtgttgcgtg gtaaggaagg gcttcacaga ggacgtgtaa cagtgagcca agtggagaat 65280
attggctcaa gtgcaggtgt agccaggagg tcttgatctg agaggcatgg tgggatagga 65340
aagacaggca gagttggcct tagatggggg tggaagcctg cagtgggtgc aaagctgagt 65400
ctgacatttt acataaatgc acacacagta gaaaaggacc ccagagagat cctcttttct 65460
acccatatca tttgtagacg tgggaagttg gacccagagt gaaatgactg gtcaaaggtc 65520
acatgacaga ggttcccaaa ctttcttggt tcatggcaaa cacagggcaa aagaaatact 65580
caagaatttc ttttaaattt tttttctttt tttttttgag acggagtttt gctcttgttg 65640
cccagggtgg agtgcagtgg cacgatcttg gctcactgca acctccgcct cccgggttca 65700
agtgattctc ctacctcagc ctccctagta gttgggatta caggtgcccg ccaccatgtc 65760
cagccaattt ttgtattttt ggtagatacg gggtttcatc atgttggcca ggctggtctc 65820
gaactcctga cctcaggtga tccactcgcc ccggcctccc aaagtgctgg gattacaggc 65880
gtgagccacc gtgcccggcc aagaattcct tttatttagt tagggtcaaa ccatgtatta 65940
gtattctgac aagatgtctc tgtgtttccc taaaaaattt aaaatatcct gcagcactcc 66000
tgtgagtttg ctgtggcaca ttttttggag atggggtctc actatgttgc ccaagctggt 66060
gagttcagga tttgaactca tgaacccaag cgattctccc acctcaggct cctgagtagc 66120
taggactata ggtgcatact actgcataca gcttgctggg gcatgttaga attcttctcc 66180
caatctgcac tgctgatgaa gcgtgtattg gacaattgac tggcggagat aaatcaaata 66240
tagaagttgg gtggaggtag agaaatcagt taggagacaa atgtcaaaca ggcatgatga 66300
aatggggccc tgaactaggg caattatcag tgaaatccag gacagattca gaagacagca 66360
aagccttcta ttttgctaac agcaaaacag aataatgtaa aaaagaagtt ggagatgttg 66420
gaggctcaga gcttaggtgg aagaaagaca atgctgatgg acagctggcc cagaggcaat 66480
gacgggactg gggacacatg gaaggggaag gtgttttagc agaaaaacaa tgggaagtat 66540
aataaatcag agtagatttg agaaatcatt ttcaaagagt tcatggttga ggcctgggat 66600
gggcagaatt ctaagatgac ccccagtgac ccttgccctt gcagagtctc ctccccttga 66660
ctacgggcag aacctatggc taggatcaag tatcaccccc atgatcatcc taccttgtat 66720
gtcaaaaggg attttgcaga tgtaaggccg caaatcagtt taccttaata tacactacct 66780
ggctgggctc acccaaccgt atgagtctct taaatctagg tgtagaggtc ggagacggag 66840
gaagtcagag atctgaagca caagaaggat ctgatgtgct gttgctatct tggagatgga 66900
78/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
gggggccatg tgacaaggaa tgcaggtggc ctctaggagc caagagaggc tcccagctga 66960
caactggcag ggggatgggg gcctcagtca tctaactgca gggaaatgaa ctttacccac 67020
aataagaatg ggcttggaag tggcttttct ttcagaacct ccagatgaga actcagttct 67080
atttctattg acaccatgat ttctgccttg tttggatttg tggccccacc caaactgcat 67140
gtcaaattgt aaactccaat gttggaggag gagcatggtg ggaggtgact ggatcatggg 67200
ggcagacttc cccctttggc actattcttg tggtaagagt attcaagaga tctggttgtt 67260
taaaagtgta taccaacctc ccccctctct ttctcctgct ctggccatga tgtgcctgct 67320
tctcctttgc tttctgccac cattgcaagt ttcctgaggt ctcctcagcc acgcttcctc 67380
tagagcctgc agaactgtga gccaattaaa cctcttttct ttataaatca cccactctca 67440
ggcatttctt tacagcagtg tgacaatgga ctaatacaag gaccaagcac acagcactgg 67500
acttctaacc tacaaaaccg tgagctaata aattggtatt gttaggccgg gtgctgtggc 67560
tcacgcctgt aatcccagca ctttgggagg ccgaggcagg cagatcacct gaggccggga 67620
cttcaagacc agtctgacca acatggagaa accccatctc tactaaaaat acaaaattag 67680
ctgggtgtgg tggtgcatgc ctataatcct agctactcgg gaggctgagg caggagaatc 67740
gcttgagccc gggaggtaga ggttgcagtg agccgagatc gcaccgttgc actccagcct 67800
gggcaacaag agcgaaactc cgtttcagaa aaataaaata aaaaataaaa gtaaaataca 67860
taaatcggta ttaagtcatt aagtttctgt taatttgtta tggtgcgaaa gaaaactaat 67920
acaaagttat ataatacaga agtatgtatg gcgaagagag ctgtccaggt gactccactg 67980
ggatcaaaaa ggaggggagc cagcaaagac gacatgcaaa cggaacaggg aaacgggtga 68040
gaccagagta acgcggtaac acagacggca aaacgacaca ggcacgacgg ccctgaatgc 68100
tttggggagc tcaccaggaa aaatccaaga aaaggccgct ggccccagag cggcaaacct 68160
tccagtgtgc tctttcaaca ggtgatgtgg gcgggggggc ggattgggag gggtggggtg 68220
gaaatagagg aggaaaagtg aaggaagcat gtttctttca aggtgcctct gaagagtcaa 68280
ttctgagcca gatcttagaa tccatgagtt aaagaaatga ggaattgcaa aaaatgtgtg 68340
aaaagattga aggcagtggc tcagtcaatg aaagaagagg tcaaaaagaa gagcggccag 68400
acttacagga aaactgccaa cccagataat aaggagagga aaaaatcaga tgctcaggga 68460
gcagaagtca acaggaggcc acaatggaac agagatgaag aaagtactgg aagaagggag 68520
ttaactggtt cctgcgtaaa aaataagcag aaaagttctt aacacttaac atagttctac 68580
acacacagtc atgctctttc tcagcaagga actaagcaga ggaaaaaact cacaagacaa 68640
aaaaaaacat ccaggtagct ctataagtaa cgaaagggga taagaaacag tttatacaac 68700
79/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
ctagcctgcg taaacaggca ctgtagggaa tagagacatg gtgtcaccag gagggtgatg 68760
gagatggcgg ctcaccctgg aatcccactc attgagtgtc ttgatgttga tgaaggacac 68820
ttccccgttg gctccagtca tgacgccatc gtgctcacaa cggacaataa ggtcaatatc 68880
atctccaagc ttccacctgc ggtaactgca gcaaaaaaga aactcatgtg gtcactgggg 68940
attctataga gtggggcccg tgctccagtc tggccacaat acccaccaga gaggtgacct 69000
accggtacgc aacagaggcg atttcattct tatccatgtc gtcctccaca aacgggtttg 69060
ggttggggaa gttgtatctt tccttcccct gcaaaaacaa aggtgtcaca agacagagct 69120
aactttgttg acaaggccaa ggccaatcag tcagacccag cacctctgct tagttgcagc 69180
cctggccagg ttcctggggc ccttgatggg gctctgagct cgctgcctgt tttgtgccta 69240
cttgacccct cccaactgtt agcacctgat gaattagaac aatgacttag taaccatgct 69300
catctctact tcattttttt gccatggcat atattcacca tttgatgtaa atcaatttat 69360
tatttattgt tcactgtgtt tcctcctcca ctatcattaa attctgtaag ggcaggaact 69420
ttgttcaaag tcagagagcc taacatccaa gcccaggcat gtaactcccc tgctaaaggt 69480
ggggactgcg tctgacctgc tcagtcccac aaccaagagc ctagcacaaa gcagatgctc 69540
cacaaacagc agctgattaa ataagaatga atcaatgccc agagactcgt ttcctcacca 69600
ttctcaagca ctgctgggag aaattgtggt tgatgtaggt tgcctccatg gccaggttgc 69660
ggggtgaatt gaaggaatta ccttcatctt gagggggctc attggcagtc tcactcactg 69720
tcaggaggtc tgcaaaagcg tggcatggtc actcaccatg caacaaagag tcactgacaa 69780
tgtgcgcagc gctgtgggga gatgtggaga ggcaaacaac acaagtcctt ccttcaaaga 69840
actgccctct cctaaagtgg gtctccctgg tgtggaacac ataagcgggg gagtggggca 69900
gctgctccag gataactcaa gatactgtcc aacattcaat tcaatcacac agtaacgaag 69960
ctgtcccttt tcagtcgttt tggattcctc aagagaatga ttttgcaagc tttttaataa 70020
agacctcagg cttcaggctc agaatataaa cacttttttt tttgagatgg agtcttgctc 70080
tgtcacccag gttggagtgc agtggtgtgt ccacggctca ctgcaacctc tgcctcctgg 70140
gttcaagcga ttctcctgcc tcagcctcct aagtagctgg gattacatgt gtccaccacc 70200
acacctggct aatttttgta tttttagtag agactgggtt tcaccatgtt ggccaggctt 70260
ggtctcgatc tcctgatgtc aagtgattct ccgcctcggc ctcccaaagt ggcaggatta 70320
caggttgtga gccaccgtgt ccagcctgtt ttgttaattt ttgagtgaca tggttttcct 70380
ttatggtgta taaatacata tatgtatggt ataaaaaata tatatgtata tacagtaagc 70440
80/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
aaacactgaa caaggtatgc aagatggcaa aagtcgaaaa aggggtattt aaatgaataa 70500
catttgggcc aggtgtgttg gctcacacct ctaatcgcag cactttggga ggccaaggct 70560
gatggatcac ttgaggccag gagttcgaga ccagcctcgc caacatggtg aaaccgtctc 70620
tactaaaaat atagaaagta gccaggcgta atggcacatg cctgtaatcc cagctattcg 70680
ggaggctgag gcagaagaat cacttgaatg tgggaggcag acgctgcagt gagccaagac 70740
tgcgccactg cactccagcc tgggtgacag agtgagactc tctgtctcaa ttaaaaaaaa 70800
aaaaaaacaa caaaaaagca acatttggaa gcttgctatt agggtgctgt gaggactcca 70860
aaagctgagg cctcaagcag gtactgcagt gacagtctct tctcctaacc tctaaagagt 70920
gtgggagatt cagacactgc tgctgtcaat tcccttggga agacagacca ctttctatcc 70980
attctctagt accagagact tgttctgtac caacaaaaat actcaatgcc tttgagttgc 71040
tccccaggca cgcttcttac caaagtcaga gttgtctctc ttgtcaaaga agagtttgga 71100
cccaactctc tggacgacaa tatcccagga atacactgag cgggtacagc tcatcagcgt 71160
ggccaggatg gcatcagtgg caaacacatt cccctgagtt tttgccagct gcaaagagga 71220
tcaaagagag aagatggaaa gacactccca ggtctcactg cccactcaca tggatgggaa 71280
agaactcctt tgctgaccac ataaatcctt aataaggagg ccccacctca ttgaccaaaa 71340
acactgcagc cagtgagcca gcaagtttcg ggtggcagtg gcactgcagc accctaagca 71400
cctgctagat tccagccaag tgcttcagat gctttcacct ttgccccagt ggtagtgcta 71460
tgtacatcta ccccttgttg cagatgagag aactaaggct ccagagacta agccaggaag 71520
cgcggcagaa ctgggcttca agtccagctg tgcttaacat ccacatttcc ggtctacctg 71580
gcaaagtgct tttacctata atacatacgt tattcccatlg tcttctgttc tttctgcagc 71640
ttcagctgta gaagccgaca gcattcctaa caagggggag aggggcagaa ggaggcgcac 71700
accttgcgga tgacagggtc gtctgtggtg gtgacagtgt ggaagatgcg cttgatgctc 71760
cgcagtggct tctcactcct cgtggtgatg cggtcaaagg ctttgtcgta gtattctagg 71820
gccccacaac actcactgtg ggaagagcag gcaaagacat gcaaagtaag agagataacc 71880
cccagttttt tcttttaagc catacatcca gaagtcttat ccaaaagtct aaaagaggtg 71940
gaaagcaatc tctggccaga gcaggagaga cgaatcctca gtgcttgctc agttcctgtc 72000
cacttaacac ctggcataga acacagcaag cacaactcat ctagcccaac gcccccattt 72060
taaaggtagg gtgaccgagg ctaagacagg agatgactag ttatagaagc acctgggtag 72120
gctgacttct cgtctggtgc tctggtttcc cactacctaa attccaccta cttgtccttt 72180
gaggtaagaa gctatttgaa atgtcaggag aagcaaagat tcctcctgaa gaattgctgt 72240
81/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
gtttcttttc ctgacaagag ttttataact taatcttatt gctcttttgc tcaggatgcc 72300
aggaaacaga aatatacagt ttaataatca gcaaattcca ttctgctttc tctttctgcc 72360
aaaagagttg tataactcat ttcttctttc ctcaggatac caggaagtta aaaagaagtt 72420
tgcagtcagt gaacttctgc ttttcccctt ggtcttgatt tttttttttt tgagatggag 72480
tttcgctctt gttgcccagg ctggagtgca atggcaagat ctcagctcac tgcaacctcc 72540
acctccaggg tttaagtgat tctcgtgcct cagcctcctg agtagctggg attacaggtg 72600
tgtgccacca cacccggcta agtttttgta tttttagtag agactgggtt tcaccatgtt 72660
ggccaggctg gtcttgaact cctgacctca ggtgacccac tgcacctggc cggtcttgat 72720
ttttttcaaa tacctctgtt aaccttatga aatgtgtttt gagtaagtgg cttcaaagcc 72780
tttttggaaa tactagggct taagaaaata cccatcacca gctggtccac acacataaga 72840
gcagtgtaga aagtagtaaa agatgctgct tacatgtcct gtggctctga tacttccaag 72900
tagcgcatct tcatcaactg aggaaaatcc atttcctctt tcacttccca atcactacga 72960
acttcaactg aagagtctcg gggtttctgc agttgaaaac cattagagga aaaaaaagtt 73020
atagtccata caaaacataa ataaaagaca ggctaaaaat atgaagagct ggcctggtgc 73080
agtggctcat gcctgtagtc ccagcacttt gggaagctgg ggcaggatga ttgcttgagc 73140
ccaggagttt gaggctgcag tgagctatga ttgcactact gcactccagc ctgagtgaca 73200
cgagatcctg tctcaaacaa caaccacata aaacggaggg gctcagtggc cctttgggag 73260
gccaaggcgg gcagatcacc tgaggtcagg agttcgagac cagcctgtcc aacatggtga 73320
aaccccatct ctactaaaaa tacaaaaatt agccaggcat ggtgatgcat gcctgtaatc 73380
ccagctactc gggaggctga ggcaggagaa cagcttgaat ctgggaggcg gaggttgcag 73440
tgagctgaga tagcaccact gcactccagc ctgggtgaca gagcaagact gcgtctcaat 73500
aaaagagaga aaagaaaaag agcttttatt caataaatgg agtgctgact gttttataag 73560
acagaatccc tgactcccag gaatttatgg tgtggaagag gaccaaaggg atcaaaagtt 73620
caaaagcaaa tggggttcca ctcccaggta atgatgtcac ctgatgaaca tgtagaaggt 73680
cctttatatt tctctcgggt tattaactat tcttgataca gcatcatatc caacaaaatg 73740
tagcttcact tttgcttaca tgtgttctgt tctcagaatg cccacacaag cacacgcagg 73800
tgaacgttca cagcagcatc aataatagtc aaaaagtgaa aaacaactca aatgttcatc 73860
agcatgtgaa tggctcaaaa caacatgatg tataattcaa aggactctta tttggcaata 73920
aacaagaaaa gaagctcatc tgggctgggt gtggtgcctc acgcctgtaa tcccagcact 73980
82/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
ttgggaggct gaggtgggtg gatcatctga ggtcaggagt ttgaaaccag ccgggccaac 74040
atggtaaaac cctgtctcta caaaacatat gaaaaaaaaa aaaaaaaagc cagacatgtt 74100
ggcacgtgcc tgtaatccta gctacctggg aggctgaggt gtgagaatca ctttaacccg 74160
ggaggcggag gttgcagtga gccaagatcg cgccactggc actgcagctt gggtgacaga 74220
gtgagattcc atcttaaaaa aacaaaaaac aaaaaccaaa aaaaccaaca acagatgaag 74280
cacagctgaa cttgaacaac atgggtttga agtacatggg tctacttaat atgcagattt 74340
tcttcaaaca aacatggatt gaaaatacaa gccaggcgca gtggctcatg gctgtaaccc 74400
cagcactttg ggaggctgag gtgggtggac tgcttgagct caggagtttg agaccagcct 74460
ggggaacatg gcagaacccc ctatctacag aaaatacaaa aattagccag gcgtggtggt 74520
gcatgcctat agtctcagct actcagaagg ctgaggtagg aggatcactt gaacccagca 74580
ggcagaggtt gcagttggct aagattcatg ccactgcact ccagcctggg tgacagagca 74640
agactctgtc tcaaaaaaga aaagaaaaag aaaacagtat tcttgggatg caaaccccga 74700
gtatatggag ggccgacttt tcatatatgt ggctaccaca ggccgaatgt gggacttgag 74760
aatgtgtaga ctttcatata ctgaaggaaa actgtaccga cacatgctac cacatggatg 74820
actcttgaaa acacgctaaa taaaagctgc cagttactaa agaccacata ttgtatgatt 74880
ccatttatgt aaaatgtcta gaacaaaaaa tcccgagaca gaaaacagat tcatagctgc 74940
ctactgctgg gctactgggg gtgctggtgt ttgggtgtgc ctcctggaat tcatttggca 75000
atctggttgc tactgcggca gtgtcgggag gtagggcctt taagagatta ggtcgttaaa 75060
aggaataaat gcctcatgcc cttctctcag gaatgggcta actacccaaa gtttagccct 75120
tttctctgtt gcaccctgct cccgcttctg ctttttctgc catgctatca agcagcatga 75180
ggccctcacc agatgtggct cctgatctgg gacttcccag tccccagaac catgagctaa 75240
agaaaccgct ttataactta cccactctca ggtattctgt tctagcaacg gaaaacagat 75300
caagacaggg tgactgctaa agggtaaggg attcttttga gggtgatgaa aatggtctga 75360
aattgaccag ttacagaact cttcaaatat attaaaaacc actaaattgt acggtatgtg 75420
aagtatatct catctaagct attaataaag acaaccaaat aaacagaacc aaattccaag 75480
gcagaattct ggtataaata cattacctgt gatttctgat cccatttctg cctaacccca 75540
aattgtttct ggaacttttt ctgcagtcga atgcgttctc tggaaagaca gacatatgat 75600
ctcagtgcag acctttaaac cagtggcttc ttcaaaaggc acacgctgcc attctcttca 75660
gctaaacctt accatcacca ctaactcctt taaactacga aaaatgggct tagagaaagg 75720
aagagaccca gacggtgcat actggaggtg ttagaaaagg tacactgcct ccaaatactg 75780
83/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
accagatgat tttacttcat ctatagtgac tgttcactga tagttccaat ctggggtgta 75840
gtggccgctg gaccacacaa caccaggagg ctcaaaggac cagcatacag ggggcttcct 75900
agagttgacc cacagcagaa ctgagcccag gtaagctcca gagcctcttc ttgcctgcct 75960
gtgtttccct ttagtgcgca tgaccagcac aaggagttag tttcctgccc atgctatctg 76020
ccatgaacca gcctgagaac gacaagctaa aagggggctt aactggttgt agaaagtatt 76080
ttcctttttt gcagtggtgg ggaatacaac catcctcctg ctttggtcct gtggtttcca 76140
aatacggcca gtctgggaag ggtgtcttgt tccagcagga tgaaaatctc acctctcttt 76200
ctgtttggca ctcttaggca ggatctgcag gttgaactgc aacatgttcc gacgatcttt 76260
gtctctgcgg aggttcctct gggcatcagc aagaaacatc catgttaaaa tcttggagat 76320
ttggctcaca ataggcagaa caagtgggag gtctttggag taaatttagg atgccaaatc 76380
ccaagtttca catcttactc tgtgctttca ctctacggca tcaacagctt gggggtgtt,a 76440
gggggtaagt g~cttggactt tgcttagacc tatactccca tgatatattt ttcattgaag 76500
tatgtttact gggtctcatt agattttctg agtttgcctc tttaaataat aataggcaat 76560
ctgactggac catctactta ataaagtctg cacacagcaa ttaagtgtgg taacaggcac 76620
aggtgcacct tcttatccag cacaaatgtt tttagcatac aagtctgatg tcctagctac 76680
tggcaaacag aaatataaac tatttaaatg catccctgat cctagtgcaa gttcaccttg 76740
gtaccacttg ttatggaacg gtgacccgag attcacgaaa agacctataa tatgcttccc 76800
tctctcatta ggagtcacaa ggtagcattt tttagcaggt gatggceaac agtaacagcc 76860
ccaagatggt gtggttgctg gctcttggcc tacctgggca aatctcattc gattccgctg 76920
gtaggccgtc ttctgtgtgc gcgctgtatc caccagctgg aagctacttt catcctcctc 76980
atggaaataa gcatattgac ttccaccacc aaactgagag gagtacttat ctggaggcaa 77040
aggtgatggc atgtagtaac tgcacccaca gactttacca gatatgcacc agtctaaagc 77100
cttgctattt caagtgtggt cttgagacct gtagcattgg ctgaaagctt gttagacaca 77160
cagactcaca gtcccacccc atacccactg aatcagaacc agcattttaa caagatcccc 77220
ggatgattca tatgcacatt caattttgaa caactctggc ctaaagaact ttctaagcca 77280
agaatctgaa ggactcaaac taacccattt cactctctgc gttattgtgt gagaatctga' 77340
ggtatttatt gctaaccacc atctccatta tcaggggccc atggcaggta tgtctaatag 77400
atcacgatat actttcttgc caatctcagc ctcagctatc ctaacttagt tctccaggca 77460
gccacctcca actatctgaa gtggcagaga gaaaaagcct ttttatggta ccaggatctt 77520
84/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
aaaaccaggg gttttacttt tttttttttt tttttttttg gagacaggat ctggctctgt 77580
caccaggctg gagtacaata gcatgatctc tgctcactgc aacctctaac ttctgggttc 77640
aagtgattgt cctgcctcag ccacccgagt agctgggatt acaggtgcac gccaccacgc 77700
ccagctaatg ttttcaacag gtttttaaaa gggcccaaaa ccccatttta ataggctaga 77760
cctctttaat gaatggtcta agttttgagg gctatttcca aaaatgtggt tattgttaaa 77820
gcccagaata catccctaaa agttatgaat tattgttggc agtttcttcc cattctaaaa 77880
agctttcaga agaaggtcat tagaataaag aacaactttc ccaaggccct gattggggca 77940
ttcagttgca gaaacactta cttgtgtacc tcttatcttg gtatgtggct cctgtccagt 78000
ctgcaaccta cgaagaacaa gaaaagacag agaatgcaca ggtcaaccag gcaagtttct 78060
gcagaaccag aaatccctga gcgcgagagg acagcgtgga agagtctcag aatttgttca 78120
caacacctct gtaagtgccc agctcttcta tgactacacc cagagataac ctttctcagc 78180
tggcatccct ataagaaatt caggagttaa gattttgaga caataaaatc taaacaggga 78240
ctcgagagta gcagccacag ctgcaaagat tcagactcct gctgacaggc atgtaccttt 78300
cctagccgat ctcctttgct gaacggctgg tagggcatat cccgaaactg ctcgggaacc 78360
gcacagggac cccagcctga ggggttgtcc tggatcacgg gtgtcatgaa ctttgccatc 78420
ttccaaaatc tgaaaaatat aaatcatgtg agtagcggca tgaacgaagg cctcagagta 78480
caaaacaccc tccatatgaa gtaagcaaag acataaatga tagaactcaa aaagcaacac 78540
gcaaaatgga accctcaact gttgagcgac tactactgtt tttgttaatt atactgtgaa 78600
tatgtactta aaactgagaa gaatgcaaac aaaactgatt tttcatattt cattaattcc 78660
acgacactct ctttttactg taacatcttt aaaatgaggc tgcaccttgt gtttgacagg 78720
gtgttgtatt gattggtagt ttttcttttt ctgtgttaca taagtgttta aaaaaattta 78780
atggtgtcag atttgataaa atgtcctaat gttttttcaa atatagtaac cttgttttgg 78840
ttctgagata taccttcacc aattcataca aactcaactt ccctaagact tagtagtctt 78900
ttctttcttt cttttttttt tttgagacag agtctcactt tgtcacccat gctggggtgc 78960
agtggcgtgc aacttccgcc ttccgagttc aagcgattct cctgcctcag cctcctgagt 79020
agctgggatt acaggcaagc gccgcctggc tattttctgt gtttttagtg gagacagggt 79080
ttcaccatgt tgtccaggct agtcttgaac tcctgacctc aaatgatcct cccgcctcga 79140
cctcccaaag tgctgggatt acaggcgtga gccaccacgt ccagccacct tagtcttttc 79200
catctgcaaa ataaacaaga tccttgttct aagcactttg tataatgcca cacaagtatt 79260
cagacttgca aaagtgcatt tatgtatata gagtgctgag aaaaaaagat ctttaagtat 79320
85/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
atcctgaaat tcaattttcc tttctcattg tttcaatttt ctgccatcaa cgcaaatcct 79380
gtgtgcagtg caagcggaca taaagccagg cagaagaact gccagagggc caaggaggtc 79440
cccacagacc tcaggcccaa agttgccatg ttaaatgttc atgaatactg ccaggcactg 79500
ttcttactgt ttaccactca ttcattcata cagtcctgcc aacaatcctg tgaggtagga 79560
gccaatgtta tccgcactct ccagataaga aaaccaaagc acagagaaat gaagaaattg 79620
cccaaagttg aaatgctagt ggatgaaaaa cgtgaaccaa agcagtctga ccccagagtc 79680
tgcactctgc ataatgctat agccctcttg ggaattaaaa aaccggcgct gtatagcaga 79740
tggctgcccg acacttctat aaaaaaacct atgcatttat cttccgttgt aaccttctga 79800
aaatgcttag aaggcgagtt cctagaggaa aattcactac acaagtattt cttggaggcc 79860
gggcgcggtg gctcacgcct gtaatcccag cactttgaga ggccgaggtg ggcggatcac 79920
gaggtcagca gttcgagacc agcctggtca acatggtgaa acccagtctc tactaaaaat 79980
acaaaaatta gctgggcgtg gtggcgggca cctgtaatac cagctactca ggaggcggag 80040
gttgcagtga gccaagatcc tgccattaca ctccagcctg ggcaacagag caagactccg 80100
tctcaaaaaa acaaaaatca aatgtttctt ggaggctgga gagcaatcaa aagaacaggt 80160
atgctgaact tagtaaactc tcctcaaagc cccatgctgg ggagattgag gcttccttca 80220
gagatgacat ttgggtgaca gcaacacagg atgaacctag aagtttcatc tttctaatag 80280
aaactatagg aagaggacag aagaaaaagg gtggtggtct cagaacaatt tgtattaaat 80340
aaatattgct gagctcctac gtgttaggcc ctataccaga taatttaaca ccattgacca 80400
cccccccacc cctactttag aggcaaaaat ttgaagctca gcctactcaa gcagctgacc 80460
tcatcatttc aaaacagatt tgatttccag ggttgcctgc tgtcagtcca gccttctttc 80520
cattatatta cagctgggca gcagcccgca aagatcaggg gtttgagacc gtacatcata 80580
ataccaagac aacgagtctc aaaacacact ttaaaaaatc gggttctgtc agaagctcaa 80640
gaagggaaga ggcccgaggc tcgacctgca tcacctccct ggaaagccag ggatgagata 80700
ccctggcttt aataaatgtt ttttttttta agagcagagc ggaaccagga ggagaaactg 80760
agccgctcag caaaaacgaa gtaacagctg tactagtcac aggggcagga tagggaggtt 80820
ccaagagggc actcagaagg ggctctgtgg ttggcaggcc actacagatc ataagccgtc 80880
catcgctgaa cagggggtgg ggtagattta agatcagaga tcaaatctac ttctctatcc 80940
tagcctccag tttcacaaaa aaggaaagat aacctatgca ctgtgaattc ctaagaacag 81000
gggccaaaca ccgctcagcc tggtacccct aagacctcac tcaaaaagtc agggagtttt 81060
86/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
cggccacttc agaaagactt tgttgttacc cctccgtctt aacccaggtg agttaagtga 81120
caatcaaatt cacccagctc atgggcactg agcagggccg agggccaagg acctcaccca 81180
caaggtcgtg tcccgcgttc agtagcgtgc gggacgcggg gcccccgaaa gtggattcct 81240
gccccgccca gcggagggac ggcaacagca ggaagggact aagagaggtc tcttccggga 81300
ggccccccga aggctggacc tagtccgaac cggctccgga gggccgcagg aacctatgaa 81360
acacgccgct cacctgcaat ggcctcggcc ggccgggatg gcaacagatg gtgcgtgccg 81420
gggaccgcgt tagcagcagc actcttgaga aaccaggaaa agaggaaaca tgcgcgcgca 81480
gcgggcgccg ccgtaaacac gaccggcgct gtcgtaaact gctctcccgc ttcctctggg 81540
ttgggcggaa gaactcacga gccgtaaagc gaaggtccac ccggaaatcc gttactgcgt 81600
ttcgccaggc gtcctcatta gcctccgagg cgccgagacg cgagaggtgt gattggcact 81660
acgtcaggcg gtatccgggg acgcccaaag agggcgttca tcactgaaac ttggcggccg 81720
cgcaatcgaa gctcgaggcg gggagcgact ggcgcccttc tgtgtcccac aatgcttcgc 81780
ggcgcgcctc agcccccatg tatcccaccg tcacccgcga ctccccgcct gttctacctg 81840
cctgcttaat gtgaaactca gcgcagggga ggtccgtcgg tgtcttaggc ggtccttatt 81900
gttactcctc cgcctttata gttgtggaaa ctgaggctca gaagtgccaa gtgacctgcc 81960
tagatcagac tgttagttta gggttctaac cgccagagtt caaaccatac ttccgcagtt 82020
ctcaaactta attgtaggac agggatttct ggaacagtgt ttttatttat ttttatttat 82080
tttttgagac agggtttcgc tctgtcgccc aggctgaaat gtagtggcag gatcacggct 82140
tattgcaccc tcgacttctc aggtacaagc gatcctccca gttcagcctc ccgagtcgtt 82200
ggtgtacaca ggcacgcaca accacgcctg cctaattttt gtatttttgg tagagatggg 82260
gttttgctat gttgctcagg ctggtctcaa actcctgagc tcaacagtcc acccactggg 82320
gctagggtta caggcatgag tcaccgtacc cggccagcta atgattttta aaaattttgt 82380
agagacagcg tctcactatg ttgcccgggc tggtctttaa ctcctggtct aaagtggtcc 82440
tctcgcctca gcgtgcggag cagctgaggc tacaggtgca tgccaccatg cctggctaat 82500
tttttttttt agacggagtc ttgctctgtc ttccaggctg gagtggagtg cagtggcgct 82560
atctcagttc actgcaacct ccgcatccca ggttcaggtg attctcctgc ttcagtctcc 82620
cgagtagctg ggattgcagg cgtgtaccaa catgcccggc taattttcct tttagtagag 82680
acggggtttc accttgctga ccaggctggt ctcgaactcc tgacctcagg tgatctaccc 82740
acctcggcct cccaaagtgc taggattaca ggcgtgagcc actgcgtccg gctgcctggc 82800
taattaaaaa aaaaaaaaaa aacttctgtg gagacgaagt ctcatcatgt tgccaaggct 82860
87/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
agtctcaaac tcctgggctc aagcagtcct cctgtctcgg tctcccaaag tgctgggatt 82920
acgggcgtga gccaccacac ctgaccagga tagtattttt aaaaattcag attctgggtc 82980
tcattttgat agattatacg gatatgttta tgctggagcc caagagctcc gcattagctg 83040
tgattctgaa gtgacgactc aggaactgct ttactacagt agataacagt gctgtcctct 83100
cagcaactcc caggctatgg agttcctcct ggtgtctttc tttcggaatt ttaaaacaat 83160
gaaagataat ctgagggcat gactttattc aaacctcaga tcctttctac ctgacatagg 83220
tttccttagc cgcctagtat gtctccttta ttagaaaata tacctgaagt ctaggctctg 83280
ccacattctt ttttttttct tttcttttct tttttttttt ttgagacgga gtgtcgctct 83340
gttgccaggc gggagtgcag tggcgcgatc tcagctcact gcaacgtcca cctcctgggt 83400
tcaagtgatt ctcctgtctc agcctcctga gtagctggga atacaggcat gcgccaccat 83460
gcccagctaa tttttatatt tttagtagag acagggtttc accatgttgg ctgggatggt 83520
ctcaatccct tgaccttgtg atccccccgc ctcggcctcc caaagtgttg ggattacagg 83580
cataagccac tgtgcccagc cagctctgcc acttgatagc tatgtgtggc cttcacattc 83640
cttgccttgt ttccttattt gtaaattgaa gatgataatt agagggcgct gtgggggtga 83700
aaataaatgt gtgtgaaagg acttagtaat tccacttatc atttgggtga acttggacag 83760
gttattcaac ctcttttttt tttttttttt ttttttgaga cagagtctcg ctctgttgcc 83820
caggctggag tgcagtggcg agatctcggc tcgctgcaac ctctgcctcc caggttcaag 83880
caattatctg ccccagcctc ccgagtagct gggattacag gtgcccacca ccatatcegg 83940
ctaatttttt gtactgttag tagagacggg gtttcaccat gttggtcagg ctggtctcga 84000
actcctgacc ttgtgatcca cccgcctcag cctctcaaag tgctgggatt acaggcgtga 84060
gccaccgcac ctggcctatt caacctctct aaacctgctt attcatctga aaaatgagaa 84120
tgctaatagc agcacctatt tccataagct ctctcccaac tgctcatttt ttttttttcc 84180
taatttttgt taatggtgtc tggtgaattg tgcccagtgg aaagccttgt agtcatcact 84240
ggtagttcgt ttttccttcc ctcccacatt tagttcttca ctatgttctc tttattctac 84300
ttgcacaatg catcttgaat gctatcactt tttttttttt tttttttttg agacagagtc 84360
ttgccctgtc acccaggctg gtgtgcagtg gcgcaatctc agctcactgc aacctccgcc 84420
tcccgggttc aagcaattct cctgcctcag cctcccaagt agctgggatt acaggcgtgt 84480
gccaccacgc ctgcctaatt ttttgtatct ttagtagaga tggggtttct ccatgttggt 84540
caggctggtc tcgaactctt gaccttgtga tccacccgcc tcggcctctc aaagtgctgg 84600
88/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
gattacaggc gtgagccact gtgcccagcc gaatgctatc actttttatc cccatttcac 84660
atcacgcttg gatacactct tgctgctcta gggtttcttc tctatatggt ggtcaaagga 84720
atctgtccac aaccttctac tagcttccca ttatatgctt agagggaaat atgaatatct 84780
ttttgtggcc tgtgtggtca ctgtctacct ttgttatttt taaaatattt acttctttga 84840
gacagggtct tgctctgttg tccaggctgg agtgcagtgg tgtgatcatg gctcactgca 84900
gtcttgacct tttgggctca agcaatcctc ccacctcagc ctccgagtag gtgggactag 84960
aggctcatgc tgccactcct ggctaatttt taattttttg tagaaatggg gtctcactat 85020
gttgccccgg ctggtctgga actcctgggc ttaagccatc ctccagcctt ggcctcccaa 85080
tatgctggga ttacaggtgt aagccacctc acctggccac tggtctacct ctagccacca 85140
tattcttctt gtgccttaaa tacactgaac ttctttcttt ctttttcttt tttttttttt 85200
tgaaacggag tctagctctg ttgtccagcc tggagtgcag tggtgtgatc ttggctcact 85260
gcaacctctg cctctggggt tcaagtgatt ctcctgcctc agcctcccaa gtagctggaa 85320
ctacaggtgt gtgcctccac accaggctag tttttgtatt tttagtagag acggggattc 85380
atcatgttgg ccaggctggt ctcaaactcc tgacctccag tgatccatcc accttggcct 85440
cccaaagtgc tgggattaca ggcgtgagcc actgtgccca gcccaccagc cttctttcca 85500
tctcagcagg gcctctggac ttgacgttct ttctgcatgg cacactcttc ccccaggttt 85560
cctggtagtt gaattggtct catcatctat gcctctgctc gagagttaac tccttatgca 85620
ggtcttttct gaccatcatt tctaaaacag gtgattgtat tagtccattt tcatgctgct 85680
gataaagaca tactggagac tgggaaattt acagaagaaa gaggtttaat ggacttacag 85740
ttccacatgg ctggggaggc ctcacaatca tggcagaagg caaggaggag caagtcacat 85800
tttacatgga tggtagcagg caaagagaga gcgcttgtgt aggggaactc ccccttttaa 85860
aatcgtcaga tcttgtgaga cttattcact atcatgagaa cagcatggaa aagacctgcc 85920
cccatgattc gattacctcc ccctgggtcc ctctcacagc acatgggaat tcaagatgag 85980
attttggtga ggacacagcc aaagcgtatc actggcatag agtaggtgct taagtaggta 86040
ctcattgact gagttaatga aaaaaagaat ctggccagtg gtggtgtctc atgcctgtaa 86100
tcccagcact ttgagaggcc aaggcgggca gatcacctga ggtcaggagt ttgagaccag 86160
cctggccaaa atggtgaaat cctctactaa aaaaacaaaa attagccagg tgtggtggaa 86220
ggcaccctgt gatcccagct acctgggagg cggaggttgc agtgagctga gatagcacca 86280
ctggactcca gcctgggctg caagagcgaa actccatctc aaaaaaaaaa aaaaaaaaga 86340
aagaatcaaa attggaggac caggtgtggt gtctcatgcc tgtagtccca gcactttggg 86400
89/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
aggccgaggc aggtggatca cctgaggtcg ggagtttgag atcagcctgg ccaacatggt 86460
ggaacctcat ctctactaaa aatacagaaa ttagccaggc gtggtggtgg gtgcctgtaa 86520
tcccagctac tggggaggct gaggcaggag aattgcttga atctcgtaag tggaggttgc 86580
agtgagccaa gatcacacca ctgcactcca gcctgggtga cagagtgaga gtctgtctaa 86640
aaaaaaaaaa aaaaaaattg gtatgagatt aactggcatt aatgaggacc actcctcggc 86700
agcagacctg ttgtatttat gatcaataat gtgagattct tgctttcaaa gggcttccat 86760
tccaaccaaa ggaatgatga cagaaatgtt tttttttctt ttttaaaatt ttttaatttt 86820
aattatatat ttcattttac tcaatatatc caaaatatta tcaccatacg atataaaagc 86880
cttattaatg ggaatgtttt acattctttt ttgtgctaag ttaccaaaat ctggtatata 86940
tttcacatgc atggcataac tcaatttgca ctagctatat ttcaaatgtt caaaagccac 87000
atgtagctaa tgactattat attggacaga tctaaatata gagttttcct gaaacttaaa 87060
gacgtttcat gagactagca cttagtaagt gtggacaaga gaggaatgag atgaagctgg 87120
agtgggacag gcagtgatag atcacacagg gcctggtagg cttgggaagg agtttggatt 87180
ttatactaat ggcattaggt cacctcctac aagaagtctt tcctaatgtc ccaaaaagag 87240
ttaaccactc catctcttgt gccaccatgg cttttgatga aaaacccaat atggcacccc 87300
ggattcttta ttatatcttt tagtatatac atggctgatt tctcctcaag ggcagtgaat 87360
gtgtctttat tcatctcttt attcccaagg cctggcacac ctcttagcat ataataggta 87420
ctatatattt attggaagag tgaatgagtg ggggtgcgag aatggattcc ttcagatcta 87480
ttttccagct cattaattct ccctctagct atgtctcatc tgctatttaa cacatccctt 87540
gagttttcat tttaacaact atgttttcat ttctaaaata tctgtatggg ttctttttca 87600
aattagcctg gtcaatttag agtttcttct acttatctcg ttttgtgatt ctacatttca 87660
tatctttaaa tatttcatag ttattttata ttccataccg aatagttcca atgtatcaag 87720
tgccttggga tctaaatctg ctggtgattg attttcctga ctctcactca tggtggctta 87780
ttttcttctg tatctgattt tcttcagttg tgagttcaca tttgttcgat cttaacctgt 87840
cctgctttag cagtggtttt caaagtgtgg ttcctggacg agcacaataa acagcacctg 87900
ggaatttttt agaaatgcaa gttctagggc tgggcacggt ggcacatgcc tgtaatccca 87960
gcactttggg aggctgaggt gggtggatca tgaggtcagg agttcgagac cagccggacc 88020
aacatagtga aaccccatct ctactaaaaa cacaaaaatt agccaggcgt agtggcatgt 88080
gcctgtaatc ccagctactc gagaggctga ggcaggagaa tcacttgaac ccggaaggtc 88140
90/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
gcggtgagca gagatcgctc tactgcactc cagcctgggc gacacagcga gactccgtct 88200
caaaaaaaaa aaaaaaaaaa tgcaagttct agagccccca tcccagactt gctaaatgag 88260
aaatgctgaa agtgaggccc agtaacctgt atttgacaag ccctatagaa ggttctgaca 88320
cacactggcg tatgaaaacc actgcttgca agataatttg gtttacctct ttaggaagcc 88380
aaggagtgct accgaccagc agccacttta gtttttattt ttaatttttt agttttttat 88440
tgactatgcc ttataaaagg accagcagcc actttaactt tttggggctg ggcttaaact 88500
agagttgcag gctcagcttt actatgctgc tgctggccta aggctgttta ctgcctgtag 88560
tgctggtatc atttgcagtc agggcaatct tacctttagc gctgtgttct tctccactgc 88620
tttcccctcc tgttccacct caatataatt ttgtgggagg aggaggggag ggttgaagga 88680
actgtcttca aagatttctg taatttacag tgaacccaaa aattacatta aaagtctgta 88740
ttatccagga tcgagctgtt ttaccatggg aaagcccatc agagtaccca accctccata 88800
tggccagaaa gaacaactct gtctgaatac acgagtttca ggggctgctt gtgccttcac 88860
tcattagggt taaaacatgg tcttaaagct gaaggccgcc tctgacctga cagctccaag 88920
tcctgcggac tcctgcgccc agtaatcacc tccatggcga agcactgttc ctgctcccgc 88980
aggcggctat aggtccacag caggctctga aagtgctccc acagctggac acgctgcccc 89040
aggtctgggg gccgcagcct gagggcagag ccagagaggg cgggagagac cacgagaaag 89100
ctggtctctc ccacacccaa caaaaggacc agagtcccag ctcagtgtta gagccaggtg 89160
agcccatgtg acctgcccac acagctggga aagcgggtcg ggtttctggc ccagctctag 89220
ctgtggagtg gggtgggata ggcacggagc cagaaggcag gcagctgagc aaatcacctc 89280
actcttcaat ctctgtcaca caaacacatg tcatataaac ccagctagag agagccaggg 89340
tggtgcttaa gcttctcaca cagaggccac tgaacacaga aaggtctggt ctatcatcag 89400
ggccctacac agggttgcag ccatctcgga tgctggcaag gtctgcactg gccaatgtgg 89460
ttcatgtaac aggcatctac cacctgcagc atttgccact gaaaccatga cctatctggg 89520
ctaaaatggc tcatgaaaca atgtttgtgc atttga.gaaa tgcctcgagc atgtacagct 89580
tccgctgcag gtccccctcg ctcttggtgt ggtcgccatt gatggcaatg aacaggcatt 89640
ctccaaacag gtgaaggaca tacagggagt tgctgttttc catggagaag caggtgtagg 89700
tgtccgagag cttctccagc atcgtcatgg aggagatgat gaccggggct aggagggggc 89760
tgagctggtc ctgtagggca gggagctctt cttcctcatt ctctgactgc ccgaacttca 89820
gctggagact ctcttcaaac tcctcatccg tccagtagaa gagggcctct gtgccctcaa 89880
tggccaccaa gatgcacttc atcttggtaa ggagcacagt ggagcgtcca gacagccaga 89940
91/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
ggttcagaaa gggctgcagc agacagactc tgtgactgcc tcatcggaga gcagcacaac 90000
atccctggtc ctgcaaatgc ggatcgcggc gtgcacagca ccccgcctgc gggacagaaa 90060
tgttttctga actgaaaaag ggggactaca ggtgcctgcc aggccctcca tatacataca 90120
tccccctatg tctgtgtcta gaagtgagat acaccgttat ttctgttttc tgattggcct 90180
ttttagtttt ttgagacaga gtctccctct cttacccagg ctggagtgca gtggctcgat 90240
cttggctcac tgcaacctct gcctccgggg ttcaggcaat tctcctgcct caggctccgg 90300
agtagctgga attacaggcc tgcaccacca cgcctggcta atttttgtat ttttggtaga 90360
gacggggttt ggccatgttg gctaggctgt tctcgaactc ctaaactcat gttatccacc 90420
ccccctcggc ctcccaaagt gctgggatta caggtgtgag ccaccgcaac tggcccattg 90480
gcctttcttg ttgtactgtt ctgtcccttc caggtaagac aggtacattt tctagtagta 90540
agctcctgtg tcttaaaaaa gaaaataaca ttcattgagt gcttacttta tgccaggcac 90600
tgtgctatgg gctttatata aataatttcc tctctgaaaa aaacaaagac aacaaaaaaa 90660
attacttctt tgattctttt ctaaaagttc cttgaaattg ccatggaccc tcccattcgt 90720
gcaggtgggg agaaagaagc tcagagtcgt tgagtacttg gcccagtgag taaatggtgg 90780
agccaggatt tgtgaacagt tttgtggact cagaagcttc catcccttac aggggtggtg 90840
aagaaggcct ttccgagagg cccgagaggc cccaaggcag aaccatccag ccaagcccac 90900
cccaaattcc tgtcccacag aaaccaagag agataataaa aagacggttg cagggttgtc 90960
tcgcccctcc tctgtctctt gcctgctctc tctaaggaat tcagagcctt cccatcttga 91020
ataccagcgg cagctccaga atttccccgt gggacaggct tactgagagc cgtcttgtga 91080
agggggtagc cctggacttg cctgggagct gtgtctgtgt agcaggtact ctgctttcag 91140
gaggatgcag gttttgttgg gggagagtgt tccagggact gtgaggggac tgagcctgct 91200
cctgaagcca tctccttttt atttaatttt atttttttga gacagagtct cgctgtgttg 91260
cctaggctgg agtgcagtgg caagatcttg gctcactgca acctccatct cccggttcaa 91320
atgattctcc tgcctcagcc tcccgagtag ctgggattac aggtgcccgc caccatgcct 91380
ggcaaattgt tgtattttta gtagagatga ggtttcacca tgttggtcag gctggtcttg 91440
aactcctgac ctcaggtgat ccacctgact tggccttcga aagtgctggg attacaggca 91500
tgagccactg cgcccgaagc catctcttgg taaaatactg ctgagcattc agacagaaca 91560
gaattaggag aaagagaagg aaccagcatt gatttcttca acacactgtg ctaggtacct 91620
caggcatttc gattattcta ggctgtgagt gaagagttgt tgccagaatc taaagtgtgt 91680
92/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
tctgagaact tggccaaatg tagggtgacc atatgactta ccattcaaat ttgggacact 91740
ttgggggtga cgaagggatt actatcaata attatgccct gggattgtct cacttaaact 91800
gggaggtatg gtcaccctag gcagaaggga agtaaaatgg tcctctgtta ctgattatct 91860
gttgctgtgt aaccaatcac accaaaattt agtggtttaa aacaacaaca gtctttttat 91920
tatatctctt agtttctgtg ggtcaggaat tgggagaggg cttggctggg tggttctgac 91980
ctggggtctc tcatgcatta tagtttggtg tgggtggagc ttctgttttt ctctctctcc 92040
atttagcctc agggtcattc tgtagtgagt ccatgtgggg agttcagagc aagtattctg 92100
gcgaacaagc tggaagccat gctgccttct gtgatctagc ctccgaagtt atacagcatc 92160
tctcccatcc ccgtaacttg ttggttccaa gtgagtcaca agcctgccta gagtcaaggg 92220
cgagggagga cagagactga atttcttgct gggtaaggca caaagttatg gaacaagtat 92280
gtggagtggg aggtattgtc gtggccatct taggggtatg aactctgcca tggatgcaga 92340
ctggcctttt ctaagagtca tcagtttggt tatctgcaaa catgactgaa gagtgtgggg 92400
tacatcaatg ccaggcaaag tttctgaagg agtctggctc agagggggag gcctggaata 92460
cgatcctagt ttaccaaggg gaacctggtc agttaccttg caactttgga gaaagagtga 92520
atggaagtgt ccctcagtag gggacattta ggaaggggat ggtcacagag ccagggctgg 92580
cattgtccag ggcacaggtt cttggttgcg ctggctcaag catcatcccc attccccggg 92640
taagactgtc ctcccaaaac agaggtggct tcaagctgct ctgtgataaa cacttttttt 92700
tttttttttt tttgagatgg agtctggctg tgtcacccag gctggagtgc agtggtgcaa 92760
tcttggctca ctgcaacctc tgcctcccag gttcaagtga ttcttatgcc tcagcctccc 92820
tagtagctgg gattacaggt gcctgccacc atgcctggct aatttttgta tttttagtag 92880
agatggggtt tcaccacgtt ggtcaggctg gtctcgaatt cctgacctca tgatccgccc 92940
gcctcggcct cccaaagtgc tgggattaca ggcgtgagcc accgtgcctg gccgataaat 93000
gcttcttaat gctgttgttt attctgactc cctgccacca agcagtgctg tgacaccgtg 93060
gatcctcatg gaacttgtgc tgtagggaag cacgtgctgg ttaggctgat ggaagtgctc 93120
cattctgctg gtggggtatt tactgtgctc tccaataata aatggatctt ctgctatgcg 93180
tcagccttgt aagtttggtc aaagggagtc tgccaccgcc ttgtgtgcag aaagatcccg 93240
gatatcctgt ggtggattca cctcattggg accggtcagt gtggccaacc tctcttccag 93300
agtggcaact tgcgtttcct tgcttatctt ttaagaagca ccataggaat catcacccca 93360
ttttatagac gagaacactg aggctcagag aggaggaatg tcttgcccca ggtgagccag 93420
ctggtcaggg tgcatttgga atggaaaccc aggtgtggct gaaaccaaag ctggcactct 93480
93/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
ccatgcacaa ttccaaaacc cacaaagctc tgaaaatcta aagctttttc atgagattgg 93540
ggcaagcatt tgatggcaaa cctgatatga attggatgtg aggttattta tagtctttat 93600
tttgtcccac ttagcgtgaa tatttataca ttttgctgca gaaaaattaa agggtttatg 93660
gaatattgct ccagagctca ctggcatgtc acctgatatg cggtagatcc actcgaaaac 93720
ctttcaggaa tccaaagaat tccaagttat aaagcacatt gaggccggat gtggtggctt 93780
cagacctgta atcccagcac tttgggagcc caaggcgggc agctcaccag aagtcagtag 93840
tttgagacca gcctgggtga aacctcatct ctactaaaat acaaaaatta gccaggcgtg 93900
gtggtgggtc cctgtaatcc cagctactgg gggaggctga ggcatgagaa tcgcttgaac 93960
ccaggaggtg gaggttacag tgagccaaaa tcgggccact gcactccagc ctggccgaca 94020
gagtgaaact gtgtctcaaa ataaataaaa tataaaataa aatacataaa ttgataaagc 94080
acattgagcc gcgaggattt cagataagaa attgtggagc tgtgctacct gtaccaaact 94140
tttctgtctc ggttaggcag agatcactac ccccattctg cagatgagga agactgaggg 94200
caaggaacat ggtgtcccag gtaggacggc agccatttta tcatcctgtt ggaggctgtg 94260
ccagcaggaa aggaagcttt ggagccacca gcccacccca gcctcccaag aaccttgttg 94320
tctcagcaaa atttcagaac tagaaaacct ggaaagatta aagccccaaa gaatgccaca 94380
agtcccccag gaagaaaggg aggctttgct gtgcgttcca gtggtcgaca ttctaaatca 94440
ttttttattt cagctgcatg tacactcacc catcacagga ccagttctca gaatagagag 94500
gtacctgttg aatcatccac cctacttcct gcctcgtgtg ggcatgtctc caagtgctga 94560
gccatccgct tcgctgccgt ggcctgagat atatcaggat ttgcaggcct ggcgacagga 94620
gacaaaatag attcccattt ccttcagaac catttagcta gtttagagag tgtttgactg 94680
tttcaatggg atgagcaata accaggcctc tccttggctc cttctctctg ccccatatgt 94740
tttcttctgt tggaagctgg gatttggggt cttagggcca aagataaata ctgattttgg 94800
ctcgatctgg ccgcacagct gtgggctagt aggtgcccct ctctgaacct caggccccca 94860
ctttctgcag cacagtgttg ttctcatctc tgtttttttt tttttttttt ttttttgaga 94920
tggagtctct ctctgttgcc taggctggag tgcagtggtg cgatttcagc tcaccgcaac 94980
ctccatctcc tgggttcaag caattctccc cacctcagcc tcccgagtag ctgggattgc 95040
aggtgcctgc caccaggccc agcggatttt tgtgtttttt agtagagaca gagtttcacc 95100
atgttggcca ggctggtctc gaactcctga cctcaggtga tccgccctcc tcagcctccc 95160
aaaatgctga gatgacaggc atgagccacc gcatccggtc tctcatctct tcataccaca 95220
94/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
tgccttggtt cccactgccc cggcgggtgc ctggagagcc ttgtggctgg ggctgagtga 95280
ccgcaaggtg atatttaagg tggtctcatg gagcagtctg acatcactgt aatgcaagca 95340
gacatctggg gagtcagact gactgaattt gaattccagc gatttaaatt tttaccactg 95400
ttgtgtgacc ttgggcaagt tgtgtgacca tttgagccat agcttcttca tctgtaaaat 95460
agatggaatc atagcatgta ccacttcggg agggagggag aatagaatta ggtcagattt 95520
tatatgtgac atgcttaagg cagtgcctgg catgcaaata agcccttgat acatgccagt 95580
ggggttactc tggttaccag aaacttggaa gtaggggctt tggctggggc aagatctcgc 95640
aacatttaaa~aagcaatcac tgaccgggca ccgtggctca tgtctgtaat cccagcactt 95700
tgggaggccg aggcaggtgg atcacgaggt cagaagatcg agaccatcct ggctaacacg 95760
gtgaaacctc gtctctacta aaaatacaaa aaattagccg ggtgtggtgg tgggcgcctg 95820
tagtcccagc tactcgggag gctgaggcag gagaatggca tgaacccggg aggcgaagct 95880
tgcaatgagc caagatcatg ccactgcact ccagcctggg tgacagagag agactccgtc 95940
tcaaaaaaaa aaaaaataaa taaataaaaa gcaatcactg gtcactcgtg aggaaccagg 96000
ccccgagttg gtcactcagc gttcaggtgg agaccttgcc atgctatcaa gtaacctaga 96060
gtctattttt ttttttaaga tggagtttca ctctgtcgcc caggctggag tgcaatggca 96120
cgatcttggc tcactgcaac ctctgcctcc catgttcaaa cgattctcct gcctcagcct 96180
cccgaatagc tgggattaca ggcacccgcc accacacccg ggtaatttct gagtagagac 96240
tgggtttcac catgttggcc aggctggtct'tgaactcctg agctcaagtg atccacccgc 96300
cttggcctcc caaagtgctg ggattacagg tgtgagccac tgtgcccagt caagtaactc 96360
agagtctaat ggggaaagta gatgtggcta atccaggggc tgcaatacct ataaagtcct 96420
taatcaaata tattttgcgt ctatgtttaa aaagcagatt tcacctaaaa atctagtttt 96480
ttggcttctc ttaagatctg gcaacaccgg gctggccttc ctgcgatacg agaagaagct 96540
ggagctgaat aggagttgcc cccttggcca ggggctctct actttgcctc agtccccact 96600
actccctatt gcaccagatt caaacttctt catagtcatg catgtttgcc gctggggcct 96660
gtgggagttt gctgataagt tgcagtgcaa tgctgtgggt gctgtgagag cacgatgagc 96720
aataataact cagccttggg cagtcaggaa aagcttccca agggaggcga agtcacagct 96780
gcttctctat aaaacctgca gatgctgctg aacaccctca tctttatggc tcaaggacat 96840
gaataaagga cgcaaagtca gagctcacga ggaatctctg gcataaagcg actgaggccc 96900
agtgacttat ctcgggtcac acagcctgct gatggcagaa gtggggctag aactaggatt 96960
accaaccaga aacctttttg gactactttc cctagaacca gagctgtcaa ccagaaacag 97020
95/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
ttctgggcca ctctacctcc cctgtctctg gattcctcgg gagttaggag gatttgtact 97080
ctggaatctt agacttgagt cctgtctctg ccatttactt gcagtatgac ctcagatgag 97140
tcacttcctt tccttgaacc tcagtttcct catctgtaag gtagagctaa ggattctgac 97200
ctcaaaggag tgttctgagg gccaaacgtt gggaaagtgg acaggaggca atctcagaca 97260
tctcattagc tcaagaggac tctagatacc tgagggtcat tatgactgtt gacaagtagc 97320
caccttctcc caagagattt tgttaccatc tgtttaacag tgaccttgaa ggggatccat 97380
cccccacttt gcccttgcca gtcccttaaa ggagcacgca tggcctttgg tcaggcttgg 97440
accctggaag ggaatgcttt gggattctct gactttgggt gtgaactggg ccctggatgc 97500
agagcccaag ggttcccctc tcctgggagg ctccaaggtc acagcgagta ctagggtaga 97560
gttgggaagg aagcagaatt tcctgggcaa aagaaatgtc aataattctt ttgttttctt 97620
caaggcatct acctgcctat ctggggctcc ccttaaatcc catgtctgtg gctggaacta 97680
ttgagactct cctactttga ggaggtccca ctgtcctgag ttcaaatcct gacttttctc 97740
cttattagtt gagtgtgact ttggttggac aagatttcaa attcctctaa actccaatgt 97800
cctcatctac aaaatgggcc tcttaagagt acacatttgg taaggtttag tgggaattaa 97860
gtgagattat gtgtgaaagg gtttagcaca gtgtagagct cagtcaatgc ccgttattac 97920
tgtgattgga aattagaatg attgccaccc atcgtgtttg tataacactt gaccatttct 97980
gaacttatgc ttctcttacg ccatttgatc ttcgcaatga ctctttgagg tggccggtgc 98040
agggatcatg acctcattgc acagatgaga caactggagc tcagagaagg caaccgtcta 98100
ctcaaggtca cacagcttga gtatggcaga gtggcagagc caagttcact tcttgttctt 98160
tttttttaag atggagtccg gctctgttgc ccaggctaga gtgtagtggc atggtcttgg 98220
ctcactgcaa cctccgcctc ccgggttcaa gcgatttcct gctaattttt gtatttttag 98280
tagagaaggg gtttcaccat gttggctagg ctggtcttga acccctcacc tcaagtgatc 98340
cacccgcctc ggcctctcaa agtgctagga ttacaggcgt gagccaccac acctgatctc 98400
aagtcttctg agatgaagat taaacagcac cttccacagg gtcagaccgg acgagacaag 98460
accaggcttt gaccacgtgg ttgggttgtt ccctgggtgc ttcatatctc ccaaaaactc 98520
cttgatagaa ataatccaca atgctgtttc aaaccctttt tgcctctgtt tatgctctga 98580
gcctgtacca cctctagggg cgaagaaact tctcctttct ccgtggcgtc aaacggactt 98640
ttccttgtat ttgtcctaaa gggacctcag cagcccctcc ccgttgggtc cgtcaaagca 98700
ctctgccaga aggtctgtgt gttcttcagt gtgggcacat gatggcgctg ctccacaacg 98760
96/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
catgaaaaat caggcccaac ccacccctca ccccccgccc cccggactgc atttcaacgc 98820
atcaaagatc aattaaacac ctactatgtg caagtgactg tgattgctcc ggggagggct 98880
tcagttattc aatactgtta tgtttagcta tattaataat agccgtaata acatcggtac 98940
agggcttcat agtttatcga gcaatttacg tggattatct ggttctatct gccaagcagt 99000
cctgatgcgt tagatcgggt gggtctttct gtcccacttg aggaggaaac tgaggcacgg 99060
agggtgacag aacttatgta aaggcacggg ggagagaggc acatggtagg catttgatga 99120
attataggtg gtggatggaa tgaggcagac ccaggcatct atctcctcca ggttgttatt 99180
catcagtgag ggccgggatt gtatcttatt tgtctttcca tccccactcc tagcacggct 99240
tctgattgag ggcttccaca gacctctgtg gcagggagag gagaggcagg gggattccct 99300
gtaggctgca atgccgaaca gctcctggaa ggctctctga gggtgtgcag gctgagagag 99360
gtggcttctg ggctggagac tgcaaagaga ggaggtcact gccttcaccg tgtagcattt 99420
gcaggacatg aatgactcac cgtaattcag ctcctgaagg caccaagtag ctgagtggtc 99480
aggatgattc attcattcat tcaacaaacg ttttctgagt gcctgttaca tgctaagcat 99540
taagaatgca ggtatgcaaa cacagcctct gtccccctgg agcttccaga gcagtggagg 99600
agatggaggg caaagagcta gcaatgcggt ttggtttgag ttgcccagaa gtctgtactg 99660
agtgccacgg ggtaaccaag tctagtggca cagtgtgaag gctacaagag ggggagatgt 99720
tttgcaggat ttgaaggatg aaatgaattt gcagataacc agacaaagaa aggtgcatga 99780
ggactggggg aaggaaagca tcaggggcag tggggtatgt acgggcagga gctgtcaaag 99840
ggcgtcagtc atgtgtttga ggatgggtaa cagatgcagt aggaaagaca gtggtaccag 99900
cagggagggc cttgaaagct attctgagga ctgtgaattg catcttgtat ttgtcaggga 99960
atcaccatgc tgggagctct gctaggagct cagagttcca tggagaaggt gggcaaagag 100020
aggcccatca ctcatgttta ctgagccttg actatttcgt ggtgctaagc acttcttggg 100080
ccttggttta ttgtctgtct tataaggcag gtactgtgat catccccatt ttatacacga 100140
gtaaactgag acttgggata ctgacataag tttttcccaa ggtcataaaa ctggtactag 100200
tggagtcagg acttgtcttt tttgtttttt aatggtcacc tttactaaag ctgaagtgta 100260
tgggtttttc acggatgggg tacaaaattc aaaaggctca aaaagtccca agtgaggttg 100320
ctcttctttt tttttttttt tgggatggat tctcgctctg ttgcccaggc tggagtgtag 100380
tgggatgatc ttggctcact gcaacctctg cctcctgggt tcaagcgatt ctcctgtctc 100440
agcctcctga gtagctggga ctacaggcac atgccaccac gtctggctaa tttttttgta 100500
ttttttagca gagacagggt ttcaccatgt tggtcaggct ggtcttgaac tcctgacctc 100560
97/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
gtgatctgcc caccttggcc tccctccctc cccagaggtg actactctta cactttcttg 100620
tgttttttat tttctagaga ctttgcctgt ttgttttgtg agaggtgttt tatatagaca 100680
taagcacaaa aagcaagaca agacaagtgc ctgttaacta caaacatggg ctttgggaag 100740
agccagtgtg ggtttagatc ttgacttttt ctgagagcct gacaagtgtc accattaaat 100800
gctggtttgg acaaagggtg ggcgggcttg gagggtggga tgaggatggc agggggtagg 100860
gacgtggaca tcaagaggtc tgtgtgcaca agtgtgactg tgtgggcctg gactgggggt 100920
gaggtgatca gatggggaca ggaaatgggg actgcagagg cctggtgaga gacagagcag 100980
ggacgaggca ggggagagcg gctgctgcgg ggctgtcata gccggcaggc gtttggcagg,101040
gcagaaggca cagtaagagg aagagaggca gcctgcgggc ttggcttggg acagcctctc 101100
taaggctcgt gctgactctc gagcagttcc agctcagcag gccatgcaca cgaaccagga 101160
agctgggtgg actgggctgg gaaggaggcc atgggctcag gagcccggga gatctggtcc 101220
cagtgcccag tggggattct gggcaagcca attcctctcc aggcatctgt gcgggtcagc 101280
gccacacgga agcccctcgt ccctgttgat cttcactgta gagggagagg cagggaaagg 101340
cttgggagat gccgggctgg gatgggctag gggcttggaa tgcctgccca gaggttttca 101400
gggcggcatc tcagcaagtg tccacagtgt gcagagctct cccaggcagg atgggcacct 101460
atacatgcat gcatatgtgt actttacatg ttatatgtaa tacaatgtaa tacatgttat 101520
tttgctcggt tcccacttcc ccttttagaa gccagttgat atataatgag ttggtgtcct 101580
cccattcttt ttgatgcatt gaggatccta agtctgtgcc ccagtcccca tagtctgttc 101640
acttcctggc ttcctggaag aacaaaatgt ccccgcctcc tctcgttctt tccctgcccc 101700
actcctagaa tcagctgttt ttctaaggag cccaggtttt cttccctgag aaatgctatt 101760
tgggtggggg agagggaggg aagcaacaag ctgtggggga agagcctcga tctgggcaac 101820
ccctttgctc ttgtgacctc gagcaagtcc ctcggggcat taggggacca gttatgtcct 101880
ttctagactc acctgaggcc aagaagatgt gggaaacatc catcctgtgt gcctgcggtc 101940
tggaaaggca cagccccagc tctgcccctg tgtggctgtg tgattctggg tttcttaacc 102000
tctctgagcc tcagagtccc catctgtgag ataggaataa catgaggctt tttttttttt 102060
tttttttttt ttttaagaca gggtcttact ctcttgccca ggctgaagtg caatgacatg 102120
atcatagctc attgcaacct tgaactcctg ggttcaagtg atcctcccga ctcagcctct 102180
caaagtgcta ggattacagg catgagccac tgcatctggc acgtggacat ttctgactta 102240
tctcaactag ggaaggtact caataaatgc taattccctt cttcctcccc ttaattattt 102300
98/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
gacttcagta ccccaggaaa tgaggactgg gatattggat ggtttgggag aggaggaaag 102360
aggtgtccag ggaaaaggaa gaaattggga aatagaagac cacggacaaa taaaagagga 102420
ggggttaatt cagaataggg aagacgggcc aggcgcaggg gctcacacct gtaatcccag 102480
cactttggga agccgagaca ggcggatcac gaggtcagga gttcgagacc agccttgcca 102540
atatggtgaa accccgtctc tactaaaaat acaaaaatta cctgggcgtg gtggcactca 102600
actgtagtcc cagctgctca ggaggctgag gcagaagaat cgcttgaacc tgggaggcgg 102660
aggttgcagt gagctgagat cgtgtcactg cactccagcc tgggcaacag agcaagactc 102720
catctcaaaa ataaaaaaaa agaaaagaaa agaatagaga agatgatttt aatcatcaga 102780
gctttccaat aaaggcaggc tctggctgct tgggggaggt tgagagcctc ctgtcattag 102840
aggtatgcaa gtagaggctg agggattgtg agccacacag atgtgtttgt gaggactcgc 102900
aatggccagg aggtagattc cttcactcag caaactttgg gagagggctg tccttgcctg 102960
gtcctgtaat ggggcaggga agccaaggtg aataggacac catccctggc cccagggagc 103020
gcccagccca ggaaataagc aaatcgctga gatcctttta ctctgcagtt ctgtgctttg 103080
aagcatccaa gccttggagg gagttggctg gggattttca gtgtgcgcct tttggtattg 103140
atccactgaa gttggagctg gctggggaat ggcaggagga cgccgcagtg ttattagtgc 103200
ggaggacacg ctgtaatctg tcagtgtcac cccggttgca gctggccagg aaccatcctg 103260
ctgttaacgc ctcccttccc agcagccatg gagcacacaa cttgtacagc acctgccagt 103320
gcctccacct ctccttgtag gagggagagt gtggatattt attctttttc tgcatctccc 103380
tagcatgagt cctcgtctcc aatcacacta atttattcag tgttttccaa cacaccttgg 103440
gcattcctac ctctgtacct tcagttacca gaattcccta ccagcggtgg tcactcctgt 103500
ccattcatcc atccacctgt ccatccatcc aatcatccat ccatccaccc acctatccat 103560
tcaatcatcc atccattcat ccgtcatcca tccatccccc cattcatcca ttcaatcatc 103620
catccatcca ttcatccatc cacccaccca ccttccatcc attcaacttt gcaatccgct 103680
tcagttcaat tcaattcaat tcacctttat tcaactcata aggttactgg gctttgccat 103740
gtaccacaca catgtgataa gtgaggcatg cctctgccct caaggagccc atgggaagaa 103800
tcctccccat tctccatggc cagctttgca tctcacctct gttaatcctt tgccatgccc 103860
ttcagcagaa gcaacggact ctgaagggct gtcctgtgag gagagttcag ttctggcttt 103920
catgaattgc agaggacaga gctcagacaa ggagagaggc aaagggtggg gaggaggtga 103980
gagtgagatg agctagtggg acggggattt tggctttgtg gagggagctg cttccagtta 104040
gctgtgagta ctcagcagtg tattggggga tgaagggaaa gagaaggggg caaggaaacc 104100
99/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
actattggag aagtgggtta gtgtggcggt gaggaggtga gctctgcagc caatggacta 104160
cctggcttat tgtctcagct ccaccatatt cctgctgtgt gaacctgggc acatatctta 104220
acatctctga gcctccatgt cctcatttgt aaaatgagga taataagacc tatctcacaa 104280
tgttgccttt agcattaaca catgcagtgc ttaaattaat gcgtggcaca aagggagagc 104340
ttaatagatt ccagctttgg ttgtgactac tcctattacg taccagctac tatgccagga 104400
gctttcattc cagtgtgtcc tctgagctaa ccctatgcgg ggattattga acccattttg 104460
cagatgagga aatgaagacc gacggaagct atctcttgag ctcgtcatgc agctggcgaa 104520
gggtggagca gggcttcaaa tgcagacctt tccaactcca ttgtccctgc tctcctgcgt 104580
gccctttcct gccttttctc aaggggtgag tgctctgaga tgcaaagatt ggaagacttc 104640
catcccagct tctgcctagg gcactctttt ggccttctct agttgtagcc ctgaattgtt 104700
aattactgtt tcatgtatgt tttctctgct ccccagagac catgagatca agaaaaaaga 104760
ttttcttctc cacggcaact gaagtgttga ctttgacagt gaaagctaca gagtgtatga 104820
tgtttccctt tttgccttgc ttgccaggaa gcttgtgctt tttgtcaaac tgcttacttc 104880
ccctttccat ggttttggtc ttctaccttt gacagacttt tattcataag tcttactgta 104940
agctgttcta ctcatagaat aagctgaata aatagaaatt gaattgaatg gaaaaggatg 105000
ggttacaaat tacaagtaaa taattcattt tatatttaat ttaatttatt tatttacttt 105060
tgagatggaa tactgctgtc acccaggctg gagtgcaatg tcgtgatctc actgcaacct 105120
gcgcctcctg agtttaagtg attctcccgc ctcagcctcc caagtagctg ggattacagg 105180
tgcccatgcc tggctaattt ttgtattttt agtagagatg gggtttcacc atgttggcca 105240
ggctggtctc gaactcctga cctcaggtga tccatccgcc ttggcctccc gagtgctggg 105300
attacagatg tgagccactg tgcccggcct gcaagtaaat aattcaaata aaatcacgag 105360
cttcaggaaa gaaaaatgcc tttcttatat cgggccattg ccacagtgtt tagccctgag 105420
ccctggttct ggctgggtga agtttgcatg gaaagcccag tggtgatttt ccctgttgtg 105480
tctggatcag tggctctcct tgcacctaga atataactca aaggccttcc ctttggatta 105540
gagcagcagt ccccgacctt tttggcacca gggatcagtt tcatggaaga caatttttcc 105600
acatactggg tgggaaactg tttctcctca catcatcagg cattagttag agtctcataa 105660
ggaacaggca acctagatct ctctcatgca cagttcacag taggactcat cctcctgtga 105720
gtatctaatg ctgccgctga tgtgacagga ggtggagctc aggtggtaat tctccatcac 105780
ccgctgctca cctcctgctg tgtggccctg gtccaaggcc cagggattgg ggaccccggg 105840
100/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
attagaggac tgacccctgc ccacctcttc caccttatcc tgtgtaactt gtccccttgc 105900
tcacccagga taactactgg agtcatcttt gagatgttct cacaagccag gttctttccc 105960
tgcttcagaa aagaggcttt gtggctgggc gtggtggctc acacctgtaa tcccagcact 106020
ttgggaggcc gaggcaggcg aaccacctga ggtcaggagt tcgagaccag cctgaccaac 106080
atagagaaac ccggtcttta ctaaaaatac aaaattagct gggagtagtg gcacaagcct 106140
gtaataccag ctactcgggg aggctgaggc aggagaatca cttgaacccg ggaggcagag 106200
gtggtggtga gctgagatca tgccattgct ctccagcctg ggcaacaaga gcaaaaacta 106260
cgtctcaaaa aaaaaaaaaa aaaagaaaaa gaggctttgc atgtgccgtt ccctctgcct 106320
ggagccctct gctctctccc atcccctgct tctgcctggc tcatcattcc tacgcttcaa 106380
atttctgctg aaagtcagca tcttagggag gcctcccctg actgctctgt ttaaaggggt 106440
tgtggtagct ggtctgcaaa gacaactccc agtgcttcct ggcctctcct gtgtatgctg 106500
ctgttcccat caagaaacag actctatttc tcctcctcct ggaagtgggc cgggcgttgg 106560
gcctggcttt ggccaatgga atgtggcaga ggtaatttac tgaggcttcc gaggtgaggc 106620
cttcagatga ctggcagctt ctccttcctg ccacctggaa cccagctggt atgctgtggg 106680
aagcccatat cacatagaga gacacagcgg gagaaatggg gtgttcagct caacagccca 106740
gttgaacccc cagccaacag tcagcatgga ttccagccat gtgcgtgagc cagcctgggt 106800
gctgcagccc aggtgagccc ctgaatgact gcaggcccag ctaacatcat acggaacaga 106860
agaaccaccc aactgagccc acagaactgt gggagataat aaaatggtat tgctgtttta 106920
agccactgaa tttccagtca tctaaagaga ggttaatccc tgataaattt ctctctttct 106980
ctctctctct cttttttttt ttttttagag agacaagttc tcactacgtt gcccagactg 107040
gagtgcagtg actgttcaca agtgcaatca tagtgcactg cagcctcgaa ctcctagtct 107100
caagcatccc tcctgcctca gcctcctggg tagctgatat tctaaaaatc attgccccaa 107160
tgcacttact tcatagcatt cacaataatc tataattata taattatttg attcttaact 107220
tgctaatttt cccttttttc tttttctttt tcttttcttt tctttttttt tttttttgag 107280
acagtctcgc tctgttgccc aggctggagt gcagtggcat ggtcttggct cactgcaatc 107340
tccacctctt gcattcaagc aattttcctg cctcagcctc ccgagtagct gggattacag 107400
gcatgcgcca tcatgcccgg ctaatttttt gtatttttag tagagatggg gtttcaccac 107460
gttggccagg ctggtttcaa actcctgact tcatgataca tctgcctcag cctcccaaag 107520
tactggaatt acaggcgtga gccaccgcac ctggccaatt ttccctttct tcctatagca 107580
catgagttac agaaggctgg gaccatgttt gtcttgattg cagctatccc cagcattaag 107640
101/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
cacagtgaat ggcatgtggt gggagctgaa agaatgaaag aatgaatgaa tgaatgaatg 107700
aatgaatgca aggcatcgga gtggtcttga agtgttccta agagccagtg taagtctctg 107760
tggctgcagc ccaggctgat atagcaccag aaaggagatg ggtatggcct aagtctcagt 107820
tctctggggc tttcacgact cagaactgta caacactccc tgacaccacc tctataaccc 107880
agatctccac acccctgcca ggaagaatca cccttttcct tctccttgcc cttctgtatc 107940
ctgcacagct ctccattagg ggacccgaca ggtctccgcg catgctcgtg tgtatagatg 108000
atggaagcag gacagaataa tgggtatgaa tgagggctct ggatccagag acccccacct 108060
ttgaacccca gtccaccaca ttctaaggat atcttggtgc catggctaca gatattgagt 108120
gttcactcac ataggaagtg ctgtgtaagt gtgagcttac attacaattg ccatgtgcca 108180
ggcactactc tcacgtcttg aattcattta cttcatacaa ccttataagg tggttgctat 108240
tatcattccc ctcttacaga tgaggcaact gacgtgtgga taatttgccc aaagttgcgg 108300
atctgaaccc tgccaatgtg gctacagagc ccaccttctt cttttttttt tttgagacgg 108360
ggtctctctc tgttgcccag gttggagcgc agtgatgcaa tcatggctca ctgcagcctt 108420
gaactcctgg gctcaagtga ctcttccatc tcatcctccc aagtagctag gactgaaggc 108480
gtgcaccacc atgcccagct aatttttgta ttttttgtag agacagggtt tcaccatgtt 108540 .
gcccagcctg gtctcaaact cctgagctgg cgtgatccac ccagcttggc ctcctaaagt 108600
tctgggacta cagccgtgag ccaccgtgcc tggtccagag cccaccttct taaccctcat 108660
actgcctctc tcgttctcaa ggtagaaccc tcgttctgcc tccctgagcc tcagttttca 108720
tacctataaa tgggataata atgcctgttt aatagggcta tgataccatg atctggcagt 108780
gcctgacaca ttgtagaatc tcaataaatc ccaatttgct gtggcaagat agatgaacag 108840
acttccaaac caaggagggc tttgaagctt tactgtgagg gtgctagaga accactgaaa 108900
gttttcgagt aagacaatga catagtgaag ctgtggctta gctccagtcc taccttttcc 108960
cgcctctgtc cccccaacaa ttagctctat gctgcctgag gttggtatct gagtttcaca 109020
tccctgtctt acctccccgt gaggtgctga gatttgaact gtttcaggat cgtgatagtt 109080
catcccgggc ctggaatgaa tggggtggga gggatgttct tgatcttgtg ggactcatct 109140
caaagggctg cctcagagat cccatctggg gccccatttc tgtctccacc tccagcccta 109200
ctgactgaca gaggtgcctg ggtttcatat gactgacttc gtattcccct tggaatccct 109260
tctgcagcat agtggatgag gtgagacaga ggctggtaac tcggtggaag agagaggagg 109320
gagaaaaaac aagggagcca gaacaggaga gagtgggaga cagggggaca gagagagaga 109380
102/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
gtggtggaga gagggcgagc cagagtgagg gaaagatggg ctcactgctt cagggcgggg 109440
tgcacctggt gacagaaatg ggccacctga ccttgtgctg tgttcccttg ttctgacaga 109500
tatggtgagg ccatctgacc ttgtgctgtg ttcccttgtt ctgatggatg ttgtgagtct 109560
gtgtgggtgc acaagcatgc acatgtggtc tgtgtgtcca catagatgcg agcgtctgtg 109620
acatagcatg caccctgtct gctggcctgt gcatggaagt gcacagatgg gtctccaagg 109680
acctagggac taagcatgtg gagaaccatg tgcagtgcct atgtacgtcc tcagccccag 109740
cgtcacctcc tccatgtgcc tcacccccta ttcgttcacc ctcctccccc tgtggtggca 109800
ttatcacctt tcttggtcag tctctgctta cctgtccctg tctctgcctc tattgagagc 109860
ttcctgcagg aaagtccaca tccttgtcat ccctgtactc ttggcagcaa gatcaaggct 109920
tgctggggca ggtgatcaat aaaggctgat gactgattga gtatatttgt gtgaatggat 109980
ctacttccag aagcgtgtgt gggtgtgtat gtgtgtgtgt gcacgcacat gtgcacacat 110040
ggaaacatgt atgtggccat acacaaatgc acatgcactg tggggtgtgg atgtgtctct 110100
gagatgtcca tgaatgagcc tctgggcaca caccatgccc acagattgat gcagtgatat 110160
gctggcaaat gtttaacaac cggctcttca ttgaaaaaaa gaatgctgtt gggccgggcg 110220
aagtggctca ccctgtaatc ccagcacttt gggagtctaa ggtgggcgga tcatgaggtc 110280
aagagatcga gaccatcctg gccaacatgg tgaaacccca tctctactaa aaatacaaaa 110340
attagctggg tgtggtggcg cacacctgtg gtcccagcta cttgggaggc tgaggcggga 110400
gaatcacttg aacctgggag gcggaggtag cagtgagcca agatctcatc actgcactcc 110460
agcttggtga cagagtgaga ctctgtctca aaaaaaaaaa aaaaagaaaa gaaaagaaaa 110520
ggaaaaataa gccctgatta gcagcatttg cccattgctg tagtgtaaat gttcccacca 110580
tggccgactt caagttgctg ctgtggcgtc atggaatatg gagttagctg ggaagagatg 110640
cacataactg gctcacatga gcccacagga gttggcttca gtacacggaa gtattcatgt 110700
ctgtgactgc ccagcccatg atgggcaggg gaggcagtgc aaagttcccc tggtgatggt 110760
aatgcttctt tccagagctg tgccctgggg gagcaggcag ttgctggctg ccagccagct 110820
ttcaccaagc ggccttagaa gtcagtctaa accaatactc cttgttaggc aggtctaggc 110880
gctcaccaac acagcagcac cttccctcac tccctgcaga ggctttgaag tttttggatt 110940
tggtgaagtc agcatgactg caaggaggaa ttgctaagcc tgaagcatga atggaagagg 111000
gggaaggagg aacgcttcaa acctccatct gaggcaggtg gccagggatg ctggaaggtc 111060
tggaggccct gggccttgtg cctgcttgaa gccgattcac tgtgtaagcc tggacacatc 111120
gcttgccctt gctggcctcc acctgtgact tccgtgaagg gagaggtctt ctgagctccg 111180
103/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
tggcctctac ctgaccctct gggagttggt ccttaaactg cgctctgagt gttaaaatct 111240
acattcaaaa ggcagagaga ggctgtgttg gccttaaaca agagcaagag gggaccctgc 111300
cctggccctc ctcagaccag gccctttccc acatggtgag gaattcacag gccaaggcga 111360
tgtgctcacc ccaagcccta ccctttgcta gacactcgtc tgatgcctgc tgctgtagaa 111420
tttctgctcc aagagtcctg ccgtgctggc ttccagggct ggctgccatc tgtcctcctg 111480
aggacccatg tcctcctgcc ttaagcagtg gttttgggaa agctgggtgt gcaggctggg 111540
atgtgtgccc actttgtggg agatgccctg aacgtgctga gtggagctgg aagtgggaaa 111600
ggaggagggg tgggtcatgg gcagggagct gtggtcttgg gttccagggt gggcttgccc 111660
catgctgcta ctttgaggag cagaatgcag aggaggttga gaattctaaa ttcaaaccta 111720
acattttagt ttgtcacaag gacatatttg ccaggacaga ggatagacca tatttttaaa 111780
ttttatttta tattttattt taattttttt tgagatagag tctcgctctg tcacccaggc 111840
tggagtgcag tggcgcgatc tcggctcact gtaacctctg cctcccgggt tcaagcaatt 111900
ctctgcctca gtctaccgag tagctgggat tgcaggcgcc caccaccacg ctcggctaat 111960
ttttgtgttt ttagtagaga cgggatttca tcatctcggc caggccggtc ttgaactcct 112020
gacctcatga tccaccttcc tcggcctccc aaagtgctgg gattacaggg gtgagccacc 112080
tcgcctggct gatagaccat tttttaaggt cgttagttcg atgtgcagct gttaaatctt 112140
cagacttaag ttatggagag tgagcctccc tttctactct tgccctggac cccacaagtg 112200
ttaggggtga gcctggagag agagataatt gagattggtg ggggcttggt ggtgtggccc 112260
cagcagactg aggctgagtt gaacagggag ttttgaacat tggacccttc tagagtagac 112320
ttttccgggc cacgtcatac agggcttacc ttctcttagg tctgtgcggt gtgtaggtgt 112380
catctgcttg ccatctcctt tctctggagc cccaggagag ctgtacagtg agtatgcttc 112440
cccaacacat cttagatagc actgttatct tagacagctg ttttggggca tgacaggtca 112500
tccttccaat ggggcctttc tctgatgtca aaggtcaaat cctcctgtta gcattccatc 112560
ttgtctttct catctcttca agttaagaga gtcccaggga ccctccccat tcttctgcca 112620
ctccatggct ctcctcttcc tgagaagcac ccctctgcag ggagccccct gagtaaactg 112680
gtagggtcat gtccattcca aactgcacaa tttcacgggg gaaaatggaa accctggagt 112740
gtaactggga tgttgagtgg ggctgcttta ttctaaaaga taaaactcaa ggacgtcatg 112800
ctctctgtct tcaaatatct gaggggctgt catgctgaaa agggaaggga tttattcagt 112860
gttgttggag tgtgaaggaa gaggtggatt aaaattcagt gtgcagagaa gacttttgcc 112920
104/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
aaagagtgct gcttagcact ggctggtgct atctttggag ggggtgagcc cgctgtcact 112980
ggaggcgtgc aagtatccct aaaggatatt taatagggaa ctcatgatct agagagtggg 113040
gggacaccct actgtacagc atctaaacct ctcatcccca ataatctgta gctttaggat 113100
tgttttaaat aggatgccag gagttgggaa aggaattaaa gaaattcact gaagtgagga 113160
ccaagctata aaaaaaaaaa atctttattt catgtaccag gatttttttt ttcagttttc 113220
tgctttttaa aatttttttt ctgttaacag tctgaaaaaa aaaaaaagga ctcaccaaga 113280
aaataaatgg aggttagttt cttgaactgg tctgagctgg acatgagcaa tcatccacac 113340
ccctgggcag caacgccctt gcagttccgg tcctggctcc ttccctccgg accccctagc 113400
cccttctcag ccatggcgat gtcaccccac accccagtgg ctttcttcaa gcacacccag 113460
aacccaggcc ttgcgccatg gaaagaagca ctgatcgcct tcccagacgc tctgccagaa 113520
ttcggagaac tggagctagt ttttctcttc agacagtgct cgcttgggtg cggttttctt 113580
ggggaccctc ccttctccct tcgctctcat ccttgatccc tttaggtctg gaatctggtg 113640
ggatggcggg caagattggg gtgggagagg ggtagagttc agtttctgcc cagactgagg 113700
gcaacttggt tgttgttacc acaccttgaa ttgtctccca ttgttctgcc ccagggccca 113760
tgacctcccc ctgtacttct gggctgggct ggccgatgtt ctgccccttg ctgacctggg 113820
aaaataactt tcctttccca ggcaaaagac aggaaaggca ggtgagatgt gcaagctcaa 113880
aaagccttac tagccattct ctagaactcc ccagagagct caacctcagg aaatgccggt 113940
gtcaagaaaa atgcaaaccg ggggagactc gcaggcagag gcaggggggc ctcaccttga 114000
ccttcagtca cctgggagta acttgcagac tgttctgaaa tttccagctc aggaaagctg 114060
ttggatttct gtcagtctga actggccctt gtcactctgg ggaagaaagg ggagaaacac 114120
aggatgccct tgacctttag tctgtggtgc aagtttaact tttggggttg gtccttacac 114180
tgggatggaa ctgctaaaat tttcctctcc attccctcag ccttgagccc tcccagtaaa 114240
cctcagagga tcctcttttt cacagacccc caaagacact ggggaagccc tggtggcaga 114300
gctcttctcc caaggaagcc tctttaactc tccatgatcg cagcaagggg acacaaagtg 114360
aagaagggct ttggggaccc ctgcgtcttt cccctctttg cctgaacagc tttatgtttg 114420
ctcacatgtg tgtatttttg ctttgacatt ggatgtgggg gcaggtgttc ggggagcaca 114480
gtgaggaggt atatggtgtg tgtgtgtgtg tgtgtctgag aggctgactg atgatgagcc 114540
tgggggcttg gtggcagctg tcctggtcat ccctggcata tcctcggggc aggtggcaga 114600
tcttaagtca cagatacata gagcaagaat gggcctttag tgcttctctg ggtcaatcca 114660
catgcttaca tggggggaaa attaaggccc agagaggcca tgcagcaagg aattccggaa 114720
105/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
tccagtcctg gattctagac gggtgccctt cccatgcatg cgagtggtgt gtgtgtgtgt 114780
gtgggtatgt gtgcgtgtgt gggtatgtgt gcatgtgtgt gttcatgtgt atgctctgtt 114840
gggaggttgt gaatgaacac aaaggccagt gtggagttgt tgtcgtccat ggctttggag 114900
ggcatgagtc aatttccttt gagccacgcc cctggccgtg tatgggatgg aagggttgag 114960
actgagtgtg tccctgtgag tgactgcagt gctgggctaa gtggactgtg tatgtgtgtg 115020
tgaacgtgcc tgtgtgcgtg tggggtgtgt ggtctctttc tttgttggat tctgtcttcc 115080
cccattcgca gcaccttcct tgtctgagga agccaccttt ccatcacaga gaccccctgc 115140
agctcactgg gaccttccgc tactccctcc aaccttcaag cccagctctc acctctcaca 115200
acggttttgc tttgtttttg taaatggatt tgtatattcg ttttctgttt tttttttctt 115260
tacaagttcc ctgctaaagt ttaagtcccc caccccgccc cattttttgt tttcacagtt 115320
taaagctgga aaagaattaa aagaaaaata ctatctgatt ttcttgcaag taaatccact 115380
tattttgtat ttacatttat ttatagtctg tggttttttt attaaaaaaa aatcaccact 115440
tgtttttcct ttttcttttg taaaaagaag cctttttgca gtgtcattgt tgaacccgct 115500
gggccccaag ggggcatcag tgagtccaag gacccccaaa gggtcaatga acccccttcc 115560
caggggactg gggggcttat gagtcagggg gtccaccatc gccccagggt catcaggtgg 115620
ccctgaggtg aggggtgagg agggagagct gtttcatgtc ccccgggggg gggggtggca 115680
tctcctgacc ccaaggacag gagcttgggg acatgacccc aagaggctca ccctgaggat 115740
tccggggttt ccggcatett ggtaagccac cggcagcctc ccctctcctt ccctttcctc 115800
aaggcctagg aagtcatcac agtgggttaa ggagcattaa ggactgggaa cctggggcca 115860
ggcaagcccc aagtgtaccc ccctccaggc accctaacgg agaggaggga caagggctcg 115920
gtcacctgga ggcctacgat tgccccatca~atgctgggcg gagccggctc gagctctgag 115980
ccttcctgga gttcctgggg cacccaccca ggggctccag ggacctggca gtgactgcag 116040
gctcacctgg ccccagggcc cctgagtctc gccccccaat ctcccaggga ggcagggccc 116100
gctgggggtt aaagggaaca gaaaagtaac tctccccgag ttaaaaaaaa aaaaaaaaag 116160
taacataaac cctgaaaaat acaaaggaca tcccctttcc tttctgttct catttttttt 116220
ttttttgctt taatgttatc ttggttccct tttatttttt catttaaatt gatttttatt 116280
aaatgttaaa ataatggtac atgggaaatc atgcattttc ttttagattt attttctatt 116340
tttaattttt tatccctctc gctttttttt aaagtttgtt ttcttccctc gtttatattt 116400
tcccacattt cctgttgttt tgcttctttg ttcctcttat attttgttct tttttttaaa 116460
106/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
atttacttgt tatgtttttt ctcttttttt gtgtgtgtgt gtttttttgt tttttgtttt 116520
tttgtttttt ttgttttttg tttttgcttt tggaaggtct cccagcggag ggtctgggtc 116580
tccccgcccc gccccgcccc cggggaccgc gccctcctcc cgcggtcttc tggcgaggcc 116640
cgcggtcttt atacgggggt ggtccggcgg ttggctgtgt tggagtggag agagtccttg 116700
ttctccttct ggatacagtt gtgaacctgg aggaagctgt tatccctgtc ggagttgtag 116760
gtggcggtgg gcgtggtggc ggccttcagg gggtccctgc tgagcgtgta catggagatc 116820
tccgtggacg gcagggtgtt gaagcccttg atgcccacgg gggaggcgtc cctggagtgt 116880
gagggctccg tggagcgcga gctggagcgg ctgcggcgct ggtagcggta gcggtagctg 116940
gggatgcggg tgatggcaga ggcctggagg tagtccgtgg cgcgggccgt ggcccgcagc 117000
tgtttgtgcc ggtcgataaa catgtgcacc gccagcaccc cgaccatctc ggcgatgatg 117060
aaggacaggg ccccgaagta gaaggaccag ccgtatgagt aactattctt tttggagtcg 117120
ctcttggagg ggtctccggc attggcagat atgtacacta tgatgccaat gatgttactc 117180
agacctgcgg ggcgcagggt ggcggggtgg gggatcagag agaaggacgt tagtttctca 117240
ggaagtcggc cacagggcag ccgtaaagga cggggacagc tgtgtgggcc ttccccggtc 117300
ccgcgccttc atgaacaggt ggggcggtgt agatggacat ccgcaagctt ccccttaaca 117360
ttttatcttt ccattcagag agagccacaa gggaagcgct aatggaaaca gacatgggca 117420
gggcgggaga agggaggcat ttcacaaggc gctgagtaac taataataga tattgttcat 117480
tgagccttct ctacctgctt tcactgcttg gtgcttctca agcagggcac agatgaggaa 117540
acaagcacag agaggttaag gaacttgctt aaggctgcac agggcttcaa agctggtgta 117600
gcagcgggtg aaggcgggct gatggagcca ggctggcctg cgttcaaagc cttcgcaagt 117660
taaccttggt ttgagtttcc agatctgtag aatgggagta aggttaagcc ttactcttta 117720
gggccacgga gagggttaaa tgggtgaata catgtgagta ctcttagatg ttggtggttc 117780
cttttttttt ttttaagata cagtcttgct ctgtcaccca ggctggagtg cagtggtgtg 117840
atcacagctc actgcagtct caaactcctg ggatcaagcg atcctcccac cttagcctct 117900
ctagtagctg ggattatgta tgcgtcacca tgcccagctg attaaaataa aaaaatttct 117960
gtagagacgc ggtcttgagg cctcgctgtg ttgcccaggc tggtctcgga ctcctgagct 118020
caagtgatcc tcctgtctca gcctcccaaa gtgctgggat tgcaggcgtg agccactgca 118080
cccggcctga tgttggtcat tcttattaaa tggctcaggc tacacccagg ttctttttct 118140
ggcatctgaa gtgagtgtga ctcatctgtc atgtaactgg gctcagacat ctggatgtgg 118200
gtgcctgcct gctcccacct gagtagaaca gtgaggggag agtccaccct tggtttccaa 118260
107/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
ggtgaagctg agtatcccat aggggttgga acagcgaggc acttgggtgc cctctctcca 118320
gcctcctcat gggtttactt gcaccgggaa gggaaagggt aagtggcaat tggccaagta 118380
ccctgagagg aagcgggcat ttgggccttt tctcaagtgg tgggaagaag atggggtgtg 118440
gggatgctcc tggaggattt ggtacaggct cgggagttgc tacaggacag gagccccccc 118500
accaccttcc tcccctgcaa cacgacctag tgcaagtctt ggagatttcc tctcctctct 118560
ccccatctct ctctgccagg ccctcgtggc ccctgagcac ccacacccca gccttcttcc 118620
cagtggcagg actggatcag tggctgttac ctgcagacac gaagaagatg ccggcactca 118680
ggatgatgtt gtgtcgagtt ttgtagaact cgctggctgc gatgcagagg ccacccatga 118790
aaagcagaat cacactcagg attgggaaaa tgctggaggc cctcacggcc cctgtggaac 118800
acagagggtc agggagaaag agaacggcat ggctgtgaga ctgaggcaca cagaggcagg 118860
tgggagagca gccccgaggc gctgggggtt tatggacaca gccttagagg agaggttgct 118920
ttgcaatcct agggagggag agacagcgag caggccactg cccagctcac agccctgcag 118980
gagctcccca ctgcctccag ggccaaactc cagcacaccg tcaggcacac agggccctgt 119040
gtgacttggc ctctgcccac ttccagctcc cacggctccc agtcctcatg ttctctctcg 119100
tcccaccaca tcaaacttcc cacgacatgt catttcatgc tgctgacttt tgaaatacag 119160
agcttcctac tggaatgtct ttcctattct tcactcagca aactcttctt catccttcaa 119220
aacccagctc gaagtcccct cttctgtaaa gccttccctg acttccttag gcaaagttat 119280
gagctccctc gtctgcactt tggggccctt gggcacgctg agaggcagtg tggtatagtg 119340
gttaggtgga accacgtggg ttggatttga gtctggctgc agcatttatt agctgtgcaa 119400
tagaaaaagt atctcacctc tgtgtgcctc agtttcctca tctgtaaagc agggatggta 119460
ataatgccaa gctcctaaga ttgttgtgag gattaaatga gttgattcag gcaatgcact 119520
tagataagtt tctggtgtct ataataaaca ttcaatgcat gatattataa taaatatttg 119580
tgtatacata tgcttccacc atgaaccatg ggtcgtgaga caaggactgt ggctttacaa 119640
agaaaaagtt tcttgtcttt atcctctctg ttcaacgaca cagtagtctg ccaatagaag 119700
ctcattaagt gaataaatgt ggggtcgtgg tccagaagga aggaacaggc acattgcaaa 119760
gaaaacaaag taagaagaga aaeccctcta gataaggact gacaaacagg accggagaag 119820
aaaagaatat ggtaatgaaa agggagaaac agaaggtgag ggccagggct cctacagttg 119880
ggggtggatg ggggaaaagg gggacaggtg gctaagggca gaggtcgggg ctacatgtgt 119940
ttgtgggggg agcagcacct gaatgaggac ccagaggtgt tggggagccc ttcacaaagt 120000
108/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
gtctttgcga agtaaaacat ttttttttta atccaaattc aaataggcag tgagtgacct 120060
caggacccag ctccgtgtcc tgggagccat gggctaggca ggaggcagag ctggcttgag 120120
gcaggggtga gggaaaatat gtcttcttta ttattattat tttttgagac ggagtcttcc 120180
cctgtcaccc aggctggagt gcagtggtgc aatctcggct cactgcaact tctgcctcct 120240
gggttcaagt gattctcctg cctcagcctc ccaagtagct gggactacag gcgtgtacca 120300
ccatgcttgg ctaatttttg tacttttagt agagatgggg tttcactatg ttggccaggc 120360
tggtctcaaa ctcttgacct catgatctgc ccaccttggc ctcccaaagt gctgggatta 120420
caggcttgag ccaccgtgcc tggccaaaga tgtcttcttt aaatggtgct taagtggttt 120480
ctaaggaagt tgagtcctga taattacagg accctttggc caagcccagg gattggtcag 120540
ggaggttggt tttggagggg aatgtgccag gagcggagct tcctcttatc cccatccccg 120600
tccccaccct tttgggtggg agtgtgttca agaaggatct gtgagaagag aatttctcta 120660
tatagaactg tagggatttt tctttttctt ttttaaaatt tatttttatt tttatttttt 120720
gagatggagt cttgctctgt tgcccaggct ggagtgtagt ggtgtgatct cggctcactg 120780
cagcctccac ctcccaggtt caagcgattc tcctgcctca gcctcccaag taggtgggac 120840
tacaggtgtg cgccatcaca cctggctagt ttttgtattt ttagtagaga cggggtttcg 120900
ctatgttggc caggctggtc ttgaactcct gacctcaagt gatctgcccg cctcggcctc 120960
ccaaagtgct gggattacag gcgttaaaag gggattttag gcagtttgct gagatgtgtg 121020
tgatgtgaaa actcttcttc tgtcctcacc atggatctgc agcatagtct acactgctca 121080
caaatgggtg agtgggttat ttggggggga cctgaagaag ggcagggctc ttggggcaaa 121140
actgagctgc atatagggaa gcaggggtgg gaggatgggg gcttggggtg gctgggctac 121200
tctgcagcct cagcaccctc cttctcttgg gcgggatggg gctgctcctc cacagacccc 121260
agggaggtgt tctctccttg caaatcattg ctaagacaac acgctgtatc cctaacctga 121320
tcccccagcc caaacacacc cacatccaca cccacgcgtg acagacatgc atgactaaaa 121380
agccacctta actctcatct ttataagcac atgaggatgg tgagagctta ctgaaaaccc 121440
aggagaagag agagaatatt tgttaaacac ccattcggtg ttgggtcttg agcaggtacc 121500
taacatatat gatataattt catcctcata acagtccggc agggtgtgtt tttttgcccc 121560
aatttacaga caagaaaatt gaggttcaga gagagaaact cccctgccac ccagctagtg 121620
aaccaggatt catatccaga ccagctcaac ttttggagca ccctgtagtc tccctatgtg 121680
gcttccaagg agcccaggaa gggtgagtgc cacagggcct ggagaactgg gtttgggtcc 121740
cacctgtgcc actcacttgc tgtgtggcta aggcgggtgc tcacttcctc tgtttttccc 121800
109/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
ctgtgtaaca tggggtatgg cctgttagat ggtttctttt tgtttgtttg ttttagatac 121860
agagtcttgc tctatacccc aggctggagt gcagtggcgt gatcttgact cactgcaacc 121920
tccgtcttcg gggttcaagc aattctcctg cctcagcctc ccaagtagct gggattatag 121980
gcgcccgcca ccatgtccgg ctaatttttg tatttttagt agagatgggt tttcgccatg 122040
ttggccaggc tggtctcaaa ctcatgacct caggtgatcc accggcctcg gccttccaaa 122100
gtgctgggat tacaggcctg agccaccgcg cccggccgtt agatagtttc taatagctct 122160
gccctttcca tgtggacatg gtcctggcca gccacaaagg ggaatgacag aagagagaag 122220
gaaagaaaga aagaggtcgg tgtggcttcc gaggcgcagc agcagcagct cagaggaaca 122280
ggcagaagaa aggctctggc cttccccctc caagaaagtg gggtcttact acccacagga 122340
tgcctgcagg tcgccgaccc aattgtgccc tcacagcaaa tggactcaca gcagcccagg 122400
gcttgatttt tccagttgag ccccatctgc tgtgggaacc cggatgcccc agctcagccc 122460
tcctgccagc agggggaggg agcgtcggct gcggagggag ctgggatgca tgcgtgtggg 122520
cagccagagg ccaggcatgt gtggacaaga tggagggcgg cgggagagca gggaggggtc 122580
tgctgtgttg cagccagcaa agagcaatgt ggaggaatca gaacggcttc agaagccacc 122640
aaggcagcgt atgacatgct ctaaataatg accaccagcg gggaatacaa acagaagcct 122700
cttcggcaca gaagagccag ccccaagctc tggcctttcg tggaagaggc ctctttgccc 122760
agaaagaagg caacaggccg ggcgcggtgg ctcacgcctg taatcccagc actttgggag 122820
gcagaggtgg gtggatcacc tgaggtcagg agttcgagac cagcctggct aacatggtga 122880
aaccccgtct ctactgaaaa aaacacaaaa attagccggg catggtggtg cgtgtcagta 122940
gtctcagcta ctgggggtgc tgaggcagga agatagcttc aacttggga.g gcggaggttg 123000
cagtgagctg agatcgcgcc actgcacccc agcctgggca acagagcaag actccatctc 123060
aaaaaaaaaa aaaaaaaaaa aggcaacagt gggcaaccag caaatagcac catgcttagg 123120
ccactagact tggcagggcc cagatccagg tgggaaggaa gctggtttag gagcaagcag 123180
ggacttctac attggagacg tttcttgaag gaggtatttc tggctgggta gtgtcacaaa 123240
cggaatgggg attttggagt tagtcacact tgactttgaa tcctcgcttt gtcagttatc 123300
aacagtgtga cccttgggca agggtcatta ctgctctgag cctcagtttc cccatcctgt 123360
gaaatgggaa tagtaaaaat aatatttagc ttataggaat gttgtaaggc cttgctgctg 123420
caagtgtggc ctgaggccca gcggcattgg catctgatta gaaaggcagc cctgccaggc 123480
atggtggctc atgcctgtaa tcccagcact ttgggatgct gaggtgagcg gatcacatga 123540
110/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
agtcaggagt tcgagaccaa cctggccagc atggcgaaac cttgcttcta ctaaaaatac 123600
aaaaattagc cgggcgtgac ggtaagtgcc tgtaatctca gctacttggg aggctgaggc 123660
aggagaaccg cttgaacccg ggaggcagag gttgcagtaa actgagattt cgccactgca 123720
ctctagcctg ggtgacggag cgaggttcca tctcagaaaa aaagaaaaaa gaaatgccgc 123780
ccctcagctc tttcccccaa ctgagtcata atctccattt taatgagatc cccagagcaa 123840
gatttgcatg catatgaaag tttgagaagt gctgttataa gaattaaatt ggggctgggc 123900
tcggtggctc acacetgtaa tcccagcact ttgggaggcc gaggctggtg gatcacttga 123960
ggtcaggagt tcaagaccag cctagccaat atgatgaaac ctcgtctcta ccaaaaataa 124020
aaaaattagc tgggcatggt ggtgcacacc catagcccca gctacttggg gggctgaggc 124080
aggagaatcg cttgaacgcg ggaggcagag gttgcagtga gccaggatct caccactgca 124140
ctccagcctg ggcgtcacag caagattctg tctcaaaaac aaaaaaaaaa aaaaaaagaa 124200
ttaaattggg tcctaccttt tactgtgtct cacactagaa gttgcacagt aaaaggtagc 124260
aatttttatt tctgaggtcc ctcttcccaa aacatcagtc caggcataac ttccctataa 124320
attgtcctca cttcctacaa agccaagcat ggtcttgttg ccaaaatcta tcacaagagt 124380
caggaaatat ctgatttatt taatgaacaa atatttactg gtctcctatg agtaagcata 124440
tggcacttca cattacctga caacatttat ggagcccctc ccctgtacca ggccttgttc 124500
taagagcggt gtaaacctca taccagcccc atgaagccat gggctttggc ttcaaggaga 124560
ttacacacgc ctaaagctga cactggcaaa cttgttctgt gaagggaaag acagcaaata 124620
ttttcatctt tgctggccat atggtctcag ttgcaatttc ttaactttgc agttgtagca 124680
cataaacagc cataaacaat atgtaaacaa atgaacgtgg ttgtcttcca ataaaacttt 124740
atttacaaaa tcactttggg aggccgaggg ggctggatca cttgaggtca ggagttcgag 124800
accagcatgg ccaatatggc gaaaccccat ctctactaaa aatacaaaaa ttagcccggc 124860
gtggtggcgc atgcctgtag tcccagctac tcgggagccc gaggcaggag aatcgtttga 124920
acccaggagg cagaagttgc agtgagctga gatcaagcca ctgcactcta gcctgggcag 124980
tgggtgacag agtgagtgag actccatctc aaaaaaaaaa aaaaaatcag gtggtgggct 125040
ggatgggctg gatttggcct gctagtcata cttggccagc tgtggccaag agtatactct 125100
atactgggga aaaggccacg tggtccagag cagggagatg ctttgctcta ggctagctgt 125160
gaatccagtg agcaaatatg gactgagtgc ccaccgctgt gctagacctg ggcttggcat 125220
gagagacatg aggggtccaa aacaggcctg gttcatgtct ttctagagct tatactctca 125280
tgaaggacat gtatgccatc agataatcac acagcctgga taacgtgcta tgaaagaaaa 125340
111/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
gtacctatat ggcaccatga gggtatgtga caggctaatg tcacatgtag acaactaatg 125400
tccatagaga gcttagagta tgccgaggac tgttttgagc actgcacata cacaaactcg 125460
ttagttctca ttacaactct gtgaagtaag tacttcatat tatttttatt ttttaaattt 125520
attttagttc tacttattgc attatcttaa gcagcatata atagtatggc ctctgaaatg 125580
tgatagacct ggattcaaat ccaatgcttt tgttttttac tttttaatta ttattattat 125640
ttttttgaga cagagtcttg ctctgtcacc caggctggag agcagtggcg tgatctcggc 125700
tcactgtaac ctctgcctcc tgggtttgag tgattcttgt gtctcagcct cccaagtagc 125760
ttagattaca ggccatgtgc catcacacct ggctaatttt tgtattttta gtagagacgg 125820
ggtttcacca tgttggccag cctggtctcg aacttctggc ctcaaatgat atgcctgcct 125880
cagcctccca aagtgccggg agtgcaggcg tgagccacca cacatggcct atataggtat 125940
tttaattatc cccactctac agagaccaaa ctgaagcaag gagaggttaa gccatttgtt 126000
caagatttgt gaatccaggc agtctgactc tagggtctgt gtgtctaacc actgcattcc 126060
cttcttttca ggctctacac tttgctgccc ttcaaagcat cctctgagct tatgtgggga 126120
tcaggacagg tctccctgag gaagtggtgg tagagctgac ctctggcgaa taaggagcag 126180
ctgattaggc acaatgaagg cagggctgtg ggagagagag cagcaggagc cgaaggtgga 126240
ggaggcatgg ctccttcaga gacctggaag aaggctggat cacgaggagc cagtggaaga 126300
gtgtggggag cactgaaggg aggagccagt ggaggagtgt ggggagcacc taaggagagg 126360
aggcaggcgg gtctgggcca cgtggggcct catgagttga gctaaagagc ttagctttat 126420
cccaagagca atgggaaact ttaaagggct tagaacaggc agggctgtca tgatctgatt 126480
tgcatcttaa gaagcaaacg gattacgaag gggtcaaggg tggctccagg gaagcagtga 126540
gaaggctact gcagctgatc ggagaggagt gatgccggtg cttgggccag ggtaggtaca 126600
aagggcatgg acagaggcag atgtgtctga gagatgttta ggaggtgaat tgaagcttga 126660
tggatggata tgggtagtga agagggtggc gttgaggtta acttctaggt ttcagacttg 126720
ccagctgggt ggaaaaaacc acttaggggg actgggagag gacccagcct agcagtgagt 126780
agagagtagg ggaggagcct gggcgaggtg gctcacgcct gtaatcccag cactttggaa 126840
ggctgaggcc ggtggatcac ctgaggtcag gagttcgaaa ccagcctggc caacatggtg 126900
aaaccccatc tctactaaaa aaatacaaaa ttagccaggg gtggtggcgc atccctgtaa 126960
acccagctac ttgggaagct gaggcaggag aattgcttga acctgggagg tggaggttgc 127020
cgtgcaccaa aattgtgcca ttgcactcca gcctgggcaa caagagcgga actctgtctc 127080
112/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
aacaaaacaa aacaaaacca aaacaaaaca aaacaaacaa aaaaagagac tagaggagga 127140
agatc 127145
<2l0> 27
<211> 2406
<212> DNA
<213> Human
<400> 27
agtttactct acatcatagc agagaaaatg gacaaaacac agctgttttg catgtaggag 60
aatactaaccctgcacagattgtgatggtgatgtggaatatactaaagcctagaacgcac120
ctcctctgcatgactaatatgttctgcacaagacatgaaggcacagacagcactgtcttt180
cttcctcattctcataacatctctgagtggatctcaaggcatattccctttggctttctt240
catttatgttcctatgaatgaacaaatcgtcattggaagacttgatgaagatataattct300
cccttcttcatttgagaggggatccgaagtcgtaatacactggaagtatcaagatagcta360
taaggttcacagttactacaaaggcagtgaccatttggaaagccaagatcccagatatgc420
aaacaggacatcccttttctataatgagattcaaaatgggaatgcgtcgctatttttcag480
aagagtaagccttctggacgaaggaatttacacctgctatgtaggaacagcaattcaagt540
gattacaaacaaagtggtgctaaaggtgggagtttttctcacacccgtgatgaagtatga600
aaagaggaacacaaacagcttcttaatatgcagcgtgttaagtgtttatcctcgtccaat660
tatcacgtggaaaatggacaacacacctatctctgaaaacaacatggaagaaacagggtc720
tttggattctttttctattaacagcccactgaatattacaggatcaaattcatcttatga780
atgtacaattgaaaattcactgctgaagcaaacatggacagggcgctggacgatgaaaga840
tggccttcataaaatgcaaagtgaacacgtttcactctcatgtcaacctgtaaatgatta900
tttttcaccaaaccaagacttcaaagttacttggtccagaatgaaaagtgggactttctc960
tgtcctggcttactatctgagctcctcacaaaatacaattatcaatgaatcccgattctc1020
atggaacaaagagctgataaaccagagtgacttctctatgaatttgatggatcttaatct1080
ttcagacagtggggaatatttatgcaatatttcttcggatgaatatactttacttaccat1140
ccacacagtgcatgtagaaccgagccaagaaacagcttcccataacaaaggcttatggat1200
tttggtgccc tctgcgattt tggcagcttt tctgctgatt tggagcgtaa aatgttgcag 1260
agcccagcta gaagccagga ggagcagaca ccctgctgat ggagcccaac aagaaagatg 1320
ttgtgtccct cctggtgagc gctgtcccag tgcacccgat aatggcgaag aaaatgtgcc 1380
tctttcagga aaagtatagg aaatgagaga agactgtgac aactcatgac ctgcatcctt 1440
113/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
aatatccagtgacttcatctcccctttcttcaccacaattccaggcaatggcctgtcgga1500
ccagacaattctaccactgcaaagagttgtaaccattttctggtatcacatttatttttc1560
aagacatacttttcaagacatcattcactgacccactacctgcattgagtataaatgcct1620
ggatgttaaggattccaatttaactttgaaaagaactgtctcattcatttacatttctgt1680
tacagtcagcccaggaggttacagtgagctctccactaagaatctggaagaaatgcatca1740
ctaggggttgattcccaatctgatcaactgataatgggtgagagagcaggtaagagccaa1800
agtcaccttagtggaaaggttaaaaaccagagcctggaaaccaagatgattgatttgaca1860
aggtattttagtctagttttatatgaacggttgtatcagggtaaccaactcgatttggga1920
tgaatcttagggcaccaaagactaagacagtatctttaagattgctagggaaaagggccc1980
tatgtgtcaggcctctgagcccaagccaagcatcgcatcccctgtgatttgcacgtatac2040
atccagatggcctaaagtaactgaagatccacaaaagaagtaaaaatagccttaactgat2100
gacattccaccattgtgatttgttcctgccccaccctaactgatcaatgtactttgtaat2160
ctcccccacccttaagaaggtactttgtaatcttccccacccttaagaaggttctttgta2220
attctccccacccttgagaatgtactttgtgagatccaccctgcccacaaaacattgctc2280
ttaacttcaccgcctaacccaaaacctataagaactaatgataatccatcacccttcgct2340
gactctcttttcggactcagcccacctgcacccaggtgaaataaacagctttattgctca2400
~aaaaa 2406
<210>
28
<211>
530
<212>
DNA
<213>
Human
<400>
28
tgtttttcacacactggatgtttattattagaaaatagcttctatcagctgtcagtacca60
aacaagttgaaaggagcgagcttctcaccatatttttttttctccttaatgatatttaaa120
taaacagctcactgtgtgagctcacgccctttttccctttaaaaactgaataattaaatg180
aagtttagtacaaaacattcttcaaatatgacttgttctgcatctgttatgctgtctcct240
tgagtaatggacgcgaaagagatgaaaaagaccactcaggctaccaaagtaccccaaaga300
atccatacgagaaactgagaaacaaactaactcaaataagacccaaccaaaccaagaaac360
cagtttttacgttgactttttgattttgattatcatctaagtttaatatatatatatatg420
tgtgtgtgtttgaaatagtaataaaaaaggaagaattgaattgcatccgtagcaggacaa480
ccttcctcat acgttaaaga ggtgttcaga aaattccata cagtatctgc 530
114/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
<210> 29
<211> 1785
<212> DNA
<213> Human
<400>
29
gggggaattatgttgatgactattctctctattctctctctctctctttttttttttttg 60
gagatagagtcttgctctgtcacccaggctggatcttggctcgctgcagcctctgcctcc 120
tgggttcaagcgattctcctgccttggcctctcgagtggctgggattgcaggcacctgcc 180
accgcgcccggctagtttttgtatttttggcagagatggggtttcgccgtgttggccagg 240
atggtctcgatctcttgacctcatggtctgcctgccttggcctcccaaagtgccggaatt 300
acaggcatgagccaccacacctggccactgttctcaaattgtattatggagttttttttt 360
ttttacaaaatatggatatattttaatttactcaaatgggaactactgataagcagttct 420
tatttttccagcataagcaaggctacaataaatatctttgaatatatgtactgatgcttt 480
ttgttttttgttgaagctatatcccaataagtgataagtacggtctaagagagaacatgt 540
tttttacaattttgattgatatcatattgggccacgcatggtggctcaggcctggcatcc 600
cggcactttgggaggttgaggtgggaggatagcttgagctcaggagttcaagaccagctt 660
gagcaacctggtgagacctcatctctactaaaaaaacaaaacaaacaaacacaaaattag 720
ctaggtgtggtggcatgtgccagtagtcccagctagttgggaggctgaggtggaaagatt 780
gcttgatcctgggaggttgaggctacagtgagctgtgatggtatcactgcactctatcct 840
ggacaacacagcaagaacctgcctcaaacaaatgtatttggttgatattgtatcagattt 900
cttctgaaaaacgttttaatggtttagactttcaccaagtgcaagaaactggcattttct 960
ttgtaactggcctggaatgttaccactcttttaaacttttgtcaagatgatcgtgagaaa 1020
tagtatctaattacttcaatttgcatttccctgactcctaatgaagttcagcatctcttc 1080
aaatctttattgggcatttggattttctcttcagtgaattgcttcatcatattctccatt 1140
tattctaaagttgtgttcctatttgtcgctttcaaatctagtttggtggaatccttgcat 1200
gttagaaaccttaaccctcgtaatatgtgttgtagatatttttccctcgcctatgagttg 1260
tctttcatccttgagcatgagttttagagtcagaagaacaacagtaggatttgaatcatg 1320
ttacgttattttctagttgtcgtattttttatttcttcagcctcttagaatcttagtttc 1380
ctttaaaatt gagataatag tatctacttt attcaaaaaa attttttggc tggacgcggt 1440
ggctcacgct tgtgatccca ccattttggg aggccaaggc aggcggatca cctgaggtca 1500
ggagtttgag accagcttgg ccaacgtggt gaaaacccat ctctactaaa aatacaaaaa 1560
115/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
ttagccaggt acagcggggc atgcctgtag tcccaggtac tcgggaggct gaggcaggag 1620
aatcacttga acccgggagg cagagatgag gtagtgagct gagatcgcac cactgcactc 1680
cggcctgagt ggtagggcga gactctgtct caaaaaaaaa attgtttttt catttatttg 1740
tttgttgaga ctccacttca aaaaataaaa aaaaaaaaaa aaaaa 1785
<210> 30
<211> 2653
<212> DNA
<213> Human
<400>
30
gaagttacaagagtagtagatgaacaactaaaggcgttgcttgagtccatggttgatgct 60
gctgagaatctttgtcccaatgtgatgaaaaaagcccacattcgacaagacttgattcat 120
gccagcaccgaaaagatttctattccacgtacctttgttaaaaatgtcctgttggagcag 180
tctggaattgatatccttaacaaaattagtgaagtaaaattgacagtggcctcgttcctg 240
tctgatagaattgtggatgaaatcctggatgcactctcacattgccatcataaactggct 300
gaccatttcagcagacgtggcaagacccttcctcaacaagaatccttagagatcgagctg 360
gctgaggagaggccagttaaacgttccatcatcacagtggaggagctaacagagatagag 420
cgtttggaagatctggatacctgtatgatgacccctaaatccaaaaggaagagtatccat 480
agccgaatgctgcggcctgtttctagggcttttgaaatggagtttgatctagataaagcg 540
ctggaagaggtaccaattcacatcgaagacccgcccttcccatccctcagacaggagaag 600
cggagctcgggatttatctctgagttgccctctgaagaggggaagaagctggaacacttt 660
accaagttaaggccaaaaaggaataagaagcagcaacccacccaagcagcggtctgtgct720
gccaacatagtctcacaagatggtgaacagaatggtctcatggggagagtggatgaaggt780
gtagatgaattttttaccaagaaggtgaccaaaatggattccaagaaatggtcaacaaga840
ggctcagagtcccatgagcttaatgaaggaggagatgaaaagaaaaagcgagattctcgg900
aaaagtagtggctttctcaatttaatcaaatcccggtccaaatccgagcgaccaccaacg960
atcttgatgacagaagaaccctcctcaccaaaaggggcagtcagaagtccacctgtggac1020
tgtcccaggaaggacacaaaggccgccgagcacaatggcaattctgaacggatagaggag1080
ataaaaacacctgactcctttgaagagagtcaaggggaagaaatagggaaggtggaacgg1140
agtgacagca agagcagccc acaggcaggg cggaggtatg gggtccaggt gatgggcagt 1200
ggtctgctgg cagagatgaa agccaagcaa gagaaccgct ttggtttggg aacaccagaa 1260
aagaatacca aagcagaacc caaagcggaa gcaggctcca ggtctcggag ctcatccagc 1320
116/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
acacctacgagcccgaagcccctcctgcagtcccccaaacccagtctggcagcacggccc1380
gtcatcccgcagaaaccaagaaccgcctcacggcctgatgacattccagactctccatct1440
agcccgaaagttgcccttcttccacctgtcctgaaaaaagttccttcagacaaagagaga1500
gatggccagagtagcccccagcccagccccaggacattttcacaggaagtttcaaggaga1560
agctggggccagcaggcccaggagtatcaagaacaaaagcaacggtcctccagtaaagat1620
ggccatcaaggcagcaaatctaatgactccggggaagaagcagaaaaagagtttattttt1680
gtgtaaaggtcacccacgcagaagtcttcctgtgcagggtgctttggtagccatcagaga1740
ggaaccaagggcaacatcttttcttcccaggcgttcttctctgggtgctttattctcttc1800
tttttctttatttcgcccccacccccatcccctgccttttttttttttttttttttgtat1860
agaaacagatccatttcttggtaatcaaag.cacatttgtttggtcttcctccaacccttt1920
gcatttgatttctaaacattccttcatatgcctttaatgaaagccagcaattatcccatg1980
ggccctacttgaatttatctgaggcagctacagattgccctgcaagatgagtttttggag2040
ataaatgaaataactggacacacactcacacaagtaacaccacagcagacctcggagtac2100
tgctaagtgtacctgtgtcaaatccgcacaggactcaatatagcaatttattcttgatgt2160
atgcaattgcacattgtaattatattaacagagcacactaataatttgtatagattatat2220
atattagatcttgggtatggtttttaccttctcccatggggaacttcttccttcctgatg2280
tggaattgtacatttaaagcttggtcggtgacctttgcataccatcaacgagcacagcta2340
agaacagagtgagagaggcccatggctgattttaccatgtgcccagattaatgtatatag2400
ttgattggaatgaggttttatgaatattcatgtttttgaaggcctttaatttctgtctgc2460
atattagcttttaatgtgtgattttaagagagaatactttgacacctgtaaaaatcaaaa2520
tactactctttataagacatttcacaaatattcacttacattacaggctggaagtatttt2580
attcatatgtatatttataccaataaaatgattttacaagtggaaaaaaaaaaaaaaaaa2640
aaaaaaaaaaaaa 2653
<210> 31
<211> 1379
<212> DNA
<2l3> Human
<400> 31
tgcaagatgc ccctgaagct gcgggggaag aagaaggcca agtccaagga gaccgccggg 60
ctggtggagg gcgagccgac gggcgcgggc ggcgggagcc tctcagcgtc ccgggctccc 120
gcacgcaggc tggtcttcca cgcgcagctg gcgcacggta gtgccacggg ccgagtggag 180
117/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
ggcttctcca gcatccagga gctctacgcc cagatcgcgg gcgcgtttga aatctcgccg 240
tcggagatct tatattgcac tttaaacaca cctaaaattg acatggaaag actcttagga 300
ggacaactaggactagaagatttcatatttgcccatgtgaaaggaatcgaaaaagaagtg360
aatgtgtataaatctgaggattcacttggtctcaccattacagataatggtgttggctat420
gcttttataaagagaattaaagatggtggtgttattgactcagttaaaacaatctgtgtt480
ggggatcatattgaatccataaatggagaaaatattgttgggtggcgtcactatgatgtt540
gctaagaagttaaaggaattaaaaaaggaggaactctttactatgaagttaatagaacct600
aagaaggcatttgaaatagagctgaggtcaaaggctggaaagtcatcaggagaaaaaatt660
ggttgtggaagggcaacacttcgcctgagatcaaaaggtcctgccaccgtggaagaaatg720
ccttctgaaaccaaagcaaaggcaattgaaaagattgatgatgttcttgagttgtacatg780
ggaattcgagatattgatttagccaccacaatgtttgaagctggaaaggacaaagtaaat840
ccagatgaatttgctgtggcacttgacgaaactcttggagactttgcgttcccagacgaa900
tttgtctttgatgtttggggagtcattggtgatgccaaacgaagaggattatgatgtgta960
cactccatctctgaagaaacaacccatcgttcttttttttctcttttttaaaaagtccta1020
taagatctgtttttggacacctttactaactctggtttaatttcatgtgtatggaatata1080
ttctttgaaatataattttggtaattttgatttctgggcactttttaacattgctgatgt1140
agtatgcttaagagaaatgacctaaataaggatcaattgtaatattcattcaaaaggttt1200
ttaaaagtaagttttaaggagtatttctcgacagatgattttcttctccattaataccca1260
tgctttgtttttcacatataaatagatgatttcaatagctttgtagttttttttcaaaat1320
cttaatgtaaactaggattggagtatgatttacctcatagtatcttcactgtgttatcc 1379
<210> 32
<211> 585
<212> DNA
<213> Human
<400> 32
tttttttttt ttttaaaaaa gagcatttta ttttaataaa gaataaaaga gatcaatata 60
ctgttttaat ggatacaaaa ataaatattc attcagcata ttaaagatat gtgctttgac 120
attcatttga attggagatt caagcctatt gttatcttat gaacacttca gcaaacagga 180
ctgccattct taaaaatata atgctttgtt ggacaaaagg gacaagccac gtcccctggt 240
cctctcctct attcgcctgt gaactccatc cacacgtaaa ggacctctgg gtctgactgt 300
cccctccaca ggcatggtgc tgggaaaagg aaacaggcat atctggcttt tcagatttta 360
118/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
aaccggaaac tctcacagtc acaaatccac catgagactt gggagattgg atgagctgtc 420
tcccaaaccc taacaccttc caccttctca aaatgaaggc tgccctttca ctgggaggtt 480
ctgaatgcgg gatggtgctg actcaggctg ggcacaaagg agaaaggagg acatggaaaa 540
tccgacaatt caaagtacaa atatttcaaa cacatgtgaa aacca 585
<210> 33
<211> 1964
<212> DNA
<213> Human
<400>
33
tgatgacaacaatggaagcagtggagtccccggagtccctggccgccgttgcttacctgc60
tgaaccttgtcctgaagcgtgttcccagccctgtgcttattaagaagttctctgatacct120
ccaaagccttcatggatatcatgtcagctcaggccagcagcggctccacctctgtcctcc180
gatgggtcctttcctgcctggccacccttctgcggaagcaagacctggaggcctggggct240
accccgtgacccttcaggtgtaccatgggctgctgagcttcacggtgcatcccaagccca300
agatccggaaggctgcccagcatggagtatgctcagtcctcaagggcagtgaattcatgt360
ttgaaaaggcccctgcccatcatcctgctgccatttccactgccaagttctgcatccagg420
agattgagaagtctggaggctccaaggaggccaccaccacgctgcacatgctgacgctgc480
tgaaggacctgctgccctgcttcccggaaggcctggtgaagagctgcagtgagactctcc540
tcagggtcatgaccttgagccatgtgctggtgacagcctgtgccatgcaggcctttcaca600
gcctcttccacgccaggcctggcctgagcaccctgtcagcagagctcaacgcccagatca660
tcacggccctgtacgactatgttcccagtgagaatgatttacaacccctgctagcctggc720
ttaaggtcatggagaaagcccacatcaacctggtgaggttgcagtgggacctggggctag780
gccacctccctcgcttttttggaactgcggtgacctgcctcctttccccacacttgcaag840
tgctgactgctgctacgcagagcctcaaggagatcctgaaggaatgcgtggctccccaca900
tggctgacattggctccgtgacctcctcggcctcaggccctgcccaatctgttgccaaga960
tgttcagggcagtggaggagggcctgacgtacaaattccatgcggcctggagctccgtgt1020
tgcagctgctgtgtgtcttcttcgaggcgtgtgggagacaggccgaccctgtgatgagga1080
agtgcctccagtccctgtgtgacctgcgcctctcccctcatttcccccacacggcggctc1140
ttgaccaggcagtgggggctgcggtgaccagtatgggacctgaggtggtgctgcaggctg1200
tgcctttggaaattgatggctctgaggagactctggatttcccacggagctggctgctgc1260
ctgtcatccgagaccatgttcaggaaacgcgacttggtttttttcaccacctacttcttg1320
119/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
cccctggctaacaccctgaagagcaaagccatggacctggctcaggcaggcagcacagtg1380
gaatctaagatctacgacacactccagtggcagatgtggacactcctgcctgggttctgc1440
acaaggcctacagatgtggccatctccttcaaagggctggcacggacgctgggcatggcc1500
atcagcgagcgtccagacctgagggtcaccgtgtgccaggccctgcgcaccctcatcacc1560
aagggctgccaggcagaggctgaccgtgctgaagtgagtcgctttgccaagaactttctg1620
ccgatcctcttcaacctgtatgggcagcccgtggcagccggggacactccagcccctcgc1680
cgggctgtgctggaaaccatcagaacttacctcaccatcactgacactcagttggtgaac1740
agtctcctggaaaaagccagtgagaaggtgctcgaccctgccagctctgactttaccaga1800
ttgtctgtcctggacctggtcgtggccttggctccgtgtgctgacgaagctgccatcagt1860
aagctatactccaccatccggccctacctagattgctaacaaatcagaaatatgacaatt1920
aatgattaaagactgtgattgccaccaaaaaaaaaaaaaaaaaa 1964
<210> 34
<211> 2599
<212> DNA
<213> Human
<400>
34
aaatccgagcctcgcgtgggctcctggcccccgacggacaccaccaggcccacggagccc 60
accatgccgcgcccggcccccgcgcgccgcctcccgggactcctcctgctgctctggccg 120
ctgctgctgctgccctccgccgcccccgaccccgtggcccgcccgggcttccggaggctg 180
gagacccgaggtcccgggggcagccctggacgccgcccctctcctgcggctcccgacggc 240
gcgcccgcttccgggaccagcgagcctggccgcgcccgcggtgcaggtgtttgcaagagc 300
agacccttggacctggtgtttatcattgatagttctcgtagcgtacggcccctggaattc 360
accaaagtgaaaacttttgtctcccggataatcgacactctggacattgggccagccgac 420
acgcgggtggcagtggtgaactatgctagcactgtgaagatcgagttccaactccaggcc 480
tacacagataagcagtccctgaagcaggctgtgggtcgaatcacacccttgtcaacaggc 540
accatgtcaggcctagccatccagacagcaatggacgaagccttcacagtggaggcaggg 600
gctcgagagccctcttctaacatccctaaggtggccatcattgttacagatgggaggccc 660
caggaccaggtgaatgaagtggcggctcgggcccaagcatctggtat,tgagctctatgct 720
gtgggcgtggaccgggcagacatggcgtccctcaagatgatggccagtgagcccctagag 780
gagcatgttttctacgtggagacctatggggtcattgagaaactttcctctagattccag 840
gaaaccttctgtgcgctggacccctgtgtgcttggaacacaccagtgccagcacgtctgc-900
120/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
atcagtgatggggaaggcaagcaccactgtgagtgtagccaaggatacaccttgaatgcc960
gacaagaaaacgtgttcagctcttgataggtgtgctcttaacacccacggatgtgagcac1020
atctgtgtgaatgacagaagtggctcttatcattgtgagtgctatgaaggttataccttg1080
aatgaagacaggaaaacttgttcagctcaagataaatgtgctttgggtacccatgggtgt1140
cagcacatttgtgtgaatgacagaacagggtcccatcattgtgaatgctatgagggctac1200
actctgaatgcagataaaaaaacatgttcagtccgtgacaagtgtgccctaggctctcat1260
ggttgccagcacatttgtgtgagtgatggggccgcatcctaccactgtgattgctatcct1320
ggctacaccttaaatgaggacaagaaaacatgttcagccactgaggaagcacgaagactt1380
gtttccactgaagatgcttgtggatgtgaagctacactggcattccaggacaaggtcagc1440
tcgtatcttcaaagactgaacactaaacttgatgacattttggagaagttgaaaataaat1500
gaatatggacaaatacatcgttaaattgctccaatttctcacctgaaaatgtggacagct1560
tggtgtacttaatactcatgcattcttttgcacacctgttattgccaatgttcctgctaa1620
taatttgccattatctgtattaatgcttgaatattactggataaattgtatgaagatctt1680
ctgcagaatcagcatgatttttccaaggaaatacatatgcagatacttattaagagcaaa1740
ctttagtgtctctaagttatgactgtgaaatgattggtaggaaatagaatgaaaagttta1800
gtgtttctttatctactaattgagccatttaatttttaaatgtttatattagataaccat1860
attcacaatggaaactttaggtctagtttcttttgatagtatttataatataaatcaatc1920
ttattactgagagtgcaaattgtacaaggtatttacacatacaacttcatataactgaga1980
tgaatgtaattttgaactgtttaacactttttgttttttgcttattttgttggagtatta2040
ttgaagatgtgatcaatagattgtaatacacatatctaaaaatagttaacacagatcaag2100
tgaacattacattgccatttttaattcattctggtctttgaaagaaatgtactactaaag2160
agcactagttgtgaatttagggtgttaaactttttaccaagtacaaaaatcccaaattca2220
ctttattattttgcttcaggatccaagtgacaaagttatatatttataaaattgctataa2280
atcgacaaaatctaatgttgtctttttaatgttagtgatccacctgcctcagcctcccaa2340
agtgctgggattacaggcttgaaagtctaacttttttttacttatatatttgatacatat2400
aattcttttggctttgaaacttgcaactttgagaacaaaacagtcctttaaattttgcac2460
tgctcaattctgtttttcgtttgcattgtctttaatataataaaagttattacctttaca2520
tattatcatgtctatttttgatgactcatcaattttgtctattaaagatatttctttaaa2580
ttaaaaaaaa aaaaaaaaa 2599
121/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
<210> 35
<211> 3060
<212> DNA
<213> Human
<400>
35
tccggaaggaggcgaaccctgaggcgggcccggcaagccttccctgcggccggcagagcc 60
caacgactagtgggactccgcgggggcgggggtagctggagcctggctctggcctggcag 120
gagccgagcttgttccggaagaagccgagcggacgggggccagcctcagcgtcccgggag 180
tgaggcgatagctgcggcggcgacagcgcgggccgggatgaaccgcgacggctgaggcag 240
cggaggtgccggctgcgcgggccccagtgagactccctcgaagcggcagcccaccgttcg 300
gggctttgcctcgagccgagccctgcccccgcgagcctcccggacccctttgtgcggccg 360
gaggcggcggcgggaacggccatggcggccaacatgtaccgggtgggagattacgtctat 420
tttgagaactcttccagcaatccttacctggttagacggattgaggagctcaacaagact 480;
gcaaatggaaatgtggaggcaaaggttgtctgtcttttccggcgcagggacatttctagt 540
agcctcaacagcctggctgatagtaatgccagggagtttgaagaggaatcaaagcagcca 600
ggggtgtctgagcagcagcgccatcaactgaagcaccgggaactttttctttctcggcaa 660
tttgaatcattaccagccacccacatacgggggaaatgcagtgtgaccctcttgaatgag 720
acagatatcttgagccagtacctggaaaaggaggactgctttttttactcactggtgttt 780
gaccccgtgcagaagacacttctcgctgatcagggcgagattagagttggttgcaaatac 840
caagctgagatcccagatcgcctagtagagggagaatctgataatcggaaccagcagaag 900
atggagatgaaggtctgggacccagacaaccctctcacagaccggcagatcgaccagttt 960
cttgtggtggcccgagctgtgggaacctttgcaagagccctagattgtagcagctccatt 1020
cggcagccaagcttgcacatgagtgcagctgctgcctcccgagatatcactctgtttcac 1080
gccatggataccttgcaaaggaacggctacgacctggctaaggccatgtcgaccctggta 1140
ccccagggaggcccggtgctgtgtcgggatgagatggaggaatggtcagcctcagaggcc,1200
atgctatttgaggaggccctagagaagtatgggaaggacttcaatgatattcgccaggat 1260
tttctaccctggaagtcacttgccagcatagtccagttttattacatgtggaaaaccaca 1320
gaccggtatattcagcagaaaaggttgaaagctgctgaagcagacagcaaactgaaacag 1380
gtctacattcccacctacactaagccaaaccctaaccagatcatttctgtgggttcaaaa 1440
cctggcatgaatggggctggatttcagaagggcctgacttgtgagagttgccacaccaca 1500
cagtctgctcagtggtatgcctggggcccacctaacatgcagtgccgcctctgtgcttcc 1560
tgttggatctactggaagaagtatgggggactgaagaccccaactcagcttgagggggcc 1620
122/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
actcggggca ccacggagcc acactcaagg ggtcatttat ccagacctga agctcaaagt 1680
ctctctcctt acacaaccag cgccaacagg gccaagctac tggctaagaa cagacaaact 1740
ttcctgcttc agaccacaaa gctgacccgt cttgccagac gcatgtgcag ggacctatta 1800
cagccaagga gggccgcccg acggccttat gctcctatca atgccaatgc catcaaagca 1860
gagtgctcca ttcgacttcc taaggccgcc aagactccat tgaagattca ccctctggtg 1920
cggctgcccc tggcaactat cgtcaaagat ctggtggccc aggcacccct gaaaccaaaa 1980
acacctcggg gtaccaagac accgatcaac agaaaccagc tgtcccagaa ccggggactg 2040
gggggcatta tggtgaaacg ggcctatgag actatggcag gggcaggggt tcctttctct 2100
gccaatggaa ggcctctggc ttcagggatt cgttcaagct cacagccagc agccaagcgt 2160
cagaaactaa acccagctga tgcccccaat cctgtggtgt ttgtggccac aaaggatacc 2220
agggccctac ggaaggctct gacccatctg gaaatgcggc gagctgctcg ccgacccaac 2280
ttgcccctga aggtgaagcc aacgctgatt gcagtgcggc cccctgtccc tctacctgca 2340
ccctcacatc ctgccagcac caatgagcct attgtcctgg aggactgagc acctgtgggg 2400
aagggaggtg ggctgagagg tagagggtgg atgcccaggg cacccaaacc tcccttccct 2460
ttcgtgtcga agggagtgag gagtgaatta aggaagagag caagtgagtg tgtgtccctg 2520
gaggggttgg gcgccctctg gtgttaccac ctcgagactt gtctcatgcc tccatgcttg 2580
ccgatggagg acagactgca ggaacttggc ccatgtggga acctagcctg ttttgggggg 2640
taggacccac agatgtcttg gacagttttg gggggagggt tttttaattt tttaaaagtt 2700
ttgcctccct ttgtgaaagg ggatggggag gggaagagta aacagataac aggtggtggt 2760
acctggttgg gggagggggg cgtgcactgc catgtctttt tttttttttt tttttttttt 2820
tttcctaatt gggggtttct ctttctgtcc ggtgtccgga ctttcctaat tggagtttga 2880
ggcccctaag ctggcatcaa ccccaggcca cgctcgctct ttccttccct cccctccccc 2940
tctgcctttt gtacgccagt tctcagaaat aaagatcttt tgtccgtttt tttaacctcg 3000
gattctgtaa ttggttctta tagtaacaaa taaaaagctg ttttcttcag cttctcctgg 3060
<210> 36
<211> 15720
<212> DNA
<213> Human
<400> 36
caacccacac cgcccctgcc agccaccatg gggctgccac tagcccgcct ggcggctgtg 60
tgcctggccc tgtctttggc agggggctcg gagctccaga cagagggcag aacccgatac 120
123/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
cacggccgcaacgtctgcagcacctggggcaacttccactacaagaccttcgacggggac 180
gtcttccgcttccccggcctctgcgactacaacttcgcctccgactgccgaggctcctac 240
aaggaatttgctgtgcacctgaagcggggtccgggccaggctgaggcccccgccggggtg 300
gagtccatcctgctgaccatcaaggatgacaccatctacctcacccgccacctggctgtg 360
cttaacggggccgtggtcagcaccccgcactacagccccgggctgctcattgagaagagc 420
gatgcctacaccaaagtctactcccgcgccggcctcaccctcatgtggaaccgggaggat 480
gcactcatgctggagctggacactaagttccggaaccacacctgtggcctctgcggggac 540
tacaacggcctgcagagctattcagaattcctctctgacggcgtgctcttcagtcccctg 600
gagtttgggaacatgcagaagatcaaccagcccgatgtggtgtgtgaggatcccgaggag 660
gaggtggcccccgcatcctgctccgagcaccgcgccgagtgtgagaggctgctgaccgcc 720
gaggccttcgcggactgtcaggacctggtgccgctggagccgtatctgcgcgcctgccag 780
caggaccgctgccggtgcccgggcggtgacacctgcgtctgcagcaccgtggccgagttc 840
tcccgccagtgctcccacgccggcggccggcccgggaactggaggaccgccacgctctgc900
cccaagacctgccccgggaacctggtgtacctggagagcggctcgccctgcatggacacc960
tgctcacacctggaggtgagcagcctgtgcgaggagcaccgcatggacggctgtttctgc1020
ccagaaggcaccgtatatgacgacatcggggacagtggctgcgttcctgtgagccagtgc1080
cactgcaggctgcacggacacctgtacacaccgggccaggagatcaccaatgactgcgag1140
cagtgtgtctgtaacgctggccgctgggtgtgcaaagacctgccctgccccggcacctgt1200
gccctggaaggcggctcccacatcaccaccttcgatgggaagacgtacaccttccacggg1260
gactgctactatgtcctggccaagggtgaccacaacgattcctacgctctcctgggcgag1320
ctggccccctgtggctccacagacaagcagacctgcctgaagacggtggtgctgctggct1380
gacaagaagaagaatgcggtggtcttcaagtccgatggcagtgtactgctcaaccagctg1440
caggtgaacctgccccacgtgaccgcgagcttctctgtcttccgcccgtcttcctaccac1500
atcatggtgagcatggccattggcgtccggctgcaggtgcagctggccccagtcatgcaa1560
ctctttgtgacactggaccaggcctcccaggggcaggtgcagggcctctgcgggaacttc1620
aacggcctggaaggtgacgacttcaagacggccagcgggctggtggaggccacgggggcc1680
ggctttgccaacacctggaaggcacagtcaacctgccatgacaagctggactggttggac1740
gatccctgctccctgaacatcgagagcgccaactacgccgagcactggtgctccctcctg1800
aagaagacagagaccccctttggcaggtgccactcggctgtggaccctgctgagtattac1860
124/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
aagaggtgca aatatgacac gtgtaactgt cagaacaatg aggactgcct gtgcgccgcc 1920
ctgtcctcctacgcgcgcgcctgcaccgccaagggcgtcatgctgtggggctggcgggag1980
catgtctgcaacaaggatgtgggctcctgccccaactcgcaggtcttcctgtacaacctg2040
accacctgccagcagacctgccgctccctctccgaggccgacagccactgtctcgagggc2100
tttgcgcctgtggacggctgcggctgccctgaccacaccttcctggacgagaagggccgc2160
tgcgtacccctggccaagtgctcctgttaccaccgcggtctctacctggaggcgggggat2220
gtggtcgtcaggcaggaagaacgatgtgtgtgccgggatgggcggctgcactgtaggcag2280
atccggctgatcggccagagctgcacggccccaaagatccacatggactgcagcaacctg2340
actgcactggccacctcgaagccccgagccctcagctgccagacgctggccgccggctat2400
taccacacagagtgtgtcagtggctgtgtgtgccccgacgggctgatggatgacggccgg2460
ggtggctgcgtggtggagaaggaatgcccttgcgtccataacaacgacctgtattcttcc2520
ggcgccaagatcaaggtggactgcaatacctgcacctgcaagagaggacgctgggtgtgc2580
acccaggctgtgtgccatggcacctgctccatttacgggagtggccactacatcaccttt2640
gatgggaagtactacgactttgacggacactgctcctacgtggctgttcaggactactgc2700
ggccagaactcctcactgggctcattcagcatcatcaccgagaacgtcccctgtggcact2760
acgggcgtcacctgctccaaggccatcaagatcttcatggggaggacggagctgaagttg2820
gaagacaagcaccgtgtggtgatccagcgtgatgagggtcaccacgtggcctacaccacg2880
cgggaggtgggccagtacctggtggtggagtccagcacgggcatcatcgtcatctgggac2940
aagaggaccaccgtgttcatcaagctggctccctcctacaagggcaccgtgtgtggcctg3000
tgtgggaactttgaccaccgctccaacaacgacttcaccacgcgggaccacatggtggtg3060
agcagcgagctggacttcgggaacagctggaaggaggcccccacctgcccagatgtgagc3120
accaaccccgagccctgcagcctgaacccgcaccgccgctcctgggccgagaagcagtgc3180
agcatcctcaaaagcagcgtgttcagcatctgccacagcaaggtggaccccaagcccttc3240
tacgaggcctgtgtgcacgactcgtgctcctgtgacacgggtggggactgtgagtgcttc3300
tgctctgccgtggcctcctacgcccaggagtgtaccaaagagggggcctgcgtgttctgg3360
aggacgccggacctgtgccccatattctgcgactactacaaccctccgcatgagtgtgag3420
tggcactatgagccatgtgggaaccggagcttcgagacctgcaggaccatcaacggcatc3480
cactccaacatctccgtgtcctacctggagggctgctacccccggtgccccaaggacagg3540
cccatctatgaggaggatctgaagaagtgtgtcactgcagacaagtgtggctgctatgtc3600
gaggacacccactacccacctggagcatcggttcccaccgaggagacctgcaagtcctgc3660
125/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
gtgtgtacca actcctccca agtcgtctgc aggccggagg aaggaaagat tcttaaccag 3720
acccaggatg gcgccttctg ctactgggag atctgtggcc ccaacgggac ggtggagaag 3780
cacttcaaca tctgttccat tacgacacgc ccgtccaccc tgaccacctt caccaccatc 3840
accctcccca ccacccccac ctccttcacc actaccacca ccaccaccac cccgacctcc 3900
agcacagttt tatcaacaac tccgaagctg tgctgcctct ggtctgactg gatcaatgag 3960
gaccacccca gcagtggcag cgacgacggt gaccgagaac catttgatgg ggtctgcggg 4020
gcccctgagg acatcgagtg caggtcggtc aaggatcccc acctcagctt ggagcagcat 4080
ggccagaagg tgcagtgtga tgtctctgtt gggttcattt gcaagaatga agaccagttt 4140
ggaaatggac catttggact gtgttacgac tacaagatac gtgtcaattg ttgctggccc 4200
atggataagt gtatcaccac tcccagccct ccaactacca ctcccagccc tccaccaacc 4260
acgacgacca cccttccacc aaccaccacc cccagccctc caaccaccac cacaaccacc 4320
cctccaccaa ccaccacccc cagccctcca ataaccacca cgaccacccc tctaccaacc 4380
acc~actccca gccctccaat aagcaccaca accacccctc caccaaccac cactcccagc 4440
cctccaacca ccactcccag ccctccaacc accactccca gccctccaac aaccaccaca 4500
accacccctc caccaaccac cactcccagc cctccaatga ctacgcccat cactccacca 4560
gccagcacta ccacccttcc accaaccacc actcccagcc ctccaacaac caccacaacc 4620
acccctccac caaccaccac tcccagtcct ccaacgacta cgcccatcac tccaccaacc 4680
agcactacta cccttccacc aaccaccact cccagccctc caccaaccac cacaaccacc 4740
cctccaccaa ccaccactcc cagccctcca acaaccacca ctcccagtcc tccaacaatc 4800
accacaacca cccctccacc aaccaccact cccagccctc caacaacgac cacaaccacc 4860
cctccaccaa ccaccactcc cagccctcca acgactacac ccatcactcc accaaccagc 4920
actaccaccc ttccaccaac caccactccc agccctccac caaccaccac aaccacccct 4980
ccaccaacca ccactcccag ccctccaaca accaccactc ccagccctcc aataaccacc 5040
acaaccaccc ctccaccaac caccactccc agctctccaa taaccaccac tcccagccct 5100
ccaacaacca ccatgaccac cccttcacca accaccaccc ccagctctcc aataaccacc 5160
acaaccaccc .cttcctcaac taccactccc agccctccac caaccaccat gaccacccct 5220
tcaccaacca ccactcccag ccctccaaca accaccatga ccacccttcc accaaccacc 5280
acttccagcc ctctaacaac tactcctcta cctccatcaa taactcctcc tacattttca 5340
ccattctcaa cgacaacccc tactacccca tgcgtgcctc tctgcaattg gactggctgg 5400
126/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
ctggattctggaaaacccaactttcacaaaccaggtggagacacagaattgattggagac5460
gtctgtggaccaggctgggcagctaacatctcttgcagagccaccatgtatcctgatgtt5520
cccattggacagcttggacaaacagtggtgtgtgatgtctctgtggggctgatatgcaaa5580
aatgaagaccaaaagccaggtggggtcatccctatggccttctgcctcaactacgagatc5640
aacgttcagtgctgtgagtgtgtcacccaacccaccaccatgacaaccaccaccacagag5700
aacccaactccgccaaccacgacacccatcaccaccaccactacggtgaccccaacccca5760
acacccaccggcacacagaccccaaccacgacacccatcaccaccaccactacggtgacc5820
ccaaccccaacacccaccggcacacagaccccaaccacgacacccatcaccaccaccact5880
acggtgaccccaaccccaacacccaccggcacacagaccccaaccacgacacccatcacc5940
accaccactacggtgaccccaaccccaacacccaccggcacacagaccccaaccacgaca6000
cccatcaccaccaccactacggtgaccccaaccccaacacccaccggcacacagacccca6060
accacgacacccatcaccaccaccactacggtgaccccaaccccaacacccaccggcaca6120
cagaccccaaccacgacacccatcaccaccaccactacggtgaccccaaccccaacaccc6180
accggcacacagaccccaaccacgacacccatcaccaccaccactacggtgaccccaacc6240
ccaacacccaccggcacacagaccccaaccacgacacccatcaccaccaccactacggtg6300
accccaaccccaacacccaccggcacacagaccccaaccacgacacccatcaccaccacc6360
actacggtgaccccaaccccaacacccaccggcacacagaccccaaccacgacacccatc6420
accaccaccactacggtgaccccaaccccaacacccaccggcacacagaccccaaccacg6480
acacccatcaccaccaccactacggtgaccccaaccccaacacccaccggcacacagacc6540
ccaaccacgacacccatcaccaccaccactacggtgaccccaaccccaacacccaccggc6600
acacagaccccaaccacgacacccatcaccaccaccactacggtgaccccaaccccaaca6660
cccaccggcacacagaccccaaccacgacacccatcaccaccaccactacggtgacccca6720
accccaacacccaccggcacacagaccccaaccacgacacccatcaccaccaccactacg6780
gtgaccccaaccccaacacccaccggcacacagaccccaaccacgacacccatcaccacc6840
accactacggtgaccccaaccccaacacccaccggcacacagaccccaaccacgacaccc6900
atcaccaccaccactacggtgaccccaaccccaacacccaccggcacacagaccccaacc6960
acgacacccatcaccaccaccactacggtgaccccaaccccaacacccaccggcacacag7020
accccaaccacgacacccatcaccaccaccactacggtgaccccaaccccaacacccacc7080
ggcacacagaccccaaccacgacacccatcaccaccaccactacggtgaccccaacccca7140
acacccaccggcacacagaccccaaccacgacacccatcaccaccaccactacggtgacc7200
127/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
ccaaccccaa cacccaccgg cacacagacc ccaaccacga cacccatcac caccaccact 7260
acggtgaccc caaccccaac acccaccggc acacagaccc caaccacgac acccatcacc 7320
accaccacta cggtgacccc aaccccaaca cccaccggca cacagacccc aaccacgaca 7380
cccatcacca ccaccactac ggtgacccca accccaacac ccaccggcac acagacccca 7440
accacgacac ccatcaccac caccactacg gtgaccccaa ccccaacacc caccggcaca 7500
cagaccccaa ccacgacacc catcaccacc accactacgg tgaccccaac cccaacaccc 7560
accggcacac agaccccaac cacgacaccc atcaccacca ccactacggt gaccccaacc 7620
ccaacaccca ccggcacaca gaccccaacc acgacaccca tcaccaccac cactacggtg 7680
accccaaccc caacacccac cggcacacag accccaacca cgacacccat caccaccacc 7740
actacggtga ccccaacccc aacacccacc ggcacacaga ccccaaccac gacacccatc 7800
accaccacca ctacggtgac cccaacccca acacccaccg gcacacagac cccaaccacg 7860
acacccatca ccaccaccac tacggtgacc ccaaccccaa cacccaccgg cacacagacc 7920
ccaaccacga cacccatcac caccaccact acggtgaccc caaccccaac acccaccggc 7980
acacagaccc caaccacgac acccatcacc accaccacta cggtgacccc aaccccaaca 8040
cccaccggca cacagacccc aaccacgaca cccatcacca ccaccactac ggtgacccca 8100
accccaacac ccaccggcac acagacccca accacgacac ccatcaccac caccactacg 8160
gtgaccccaa ccccaacacc caccggcaca cagaccccaa ccacgacacc catcaccacc 8220
accactacgg tgaccccaac cccaacaccc accggcacac agaccccaac cacgacaccc 8280
atcaccacca ccactacggt gaccccaacc ccaacaccca ccggcacaca gaccccaacc 8340
acgacaccca tcaccaccac cactacggtg accccaaccc caacacccac cggcacacag 8400
accccaacca cgacacccat caccaccacc actacggtga ccccaacccc aacacccacc 8460
ggcacacaga ccccaaccac gacacccatc accaccacca ctacggtgac cccaacccca 8520
acacccaccg gcacacagac cccaaccacg acacccatca ccaccaccac tacggtgacc 8580
ccaaccccaa cacccaccgg cacacagacc ccaaccacga cacccatcac caccaccact 8040
acggtgaccc caaccccaac acccaccggc acacagaccc caaccacgac acccatcacc 8700
accaccacta cggtgacccc aaccccaaca cccaccggca cacagacccc aaccacgaca 8760
cccatcacca ccaccactac ggtgacccca accccaacac ccaccggcac acagacccca 8820
accacgacac ccatcaccac caccactacg gtgaccccaa ccccaacacc caccggcaca 8880
cagaccccaa ccacgacacc catcaccacc accactacgg tgaccccaac cccaacaccc 8940
128/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
accggcacac agaccccaac cacgacaccc atcaccacca ccactacggt gaccccaacc 9000
ccaacaccca ccggcacaca gaccccaacc acgacaccca tcaccaccac cactacggtg 9060
accccaaccc caacacccac cggcacacag accccaacca cgacacccat caccaccacc 9120
actacggtga ccccaacccc aacacccacc ggcacacaga ccccaaccac gacacccatc 9180
accaccacca ctacggtgac cccaacccca acacccaccg gcacacagac cccaaccacg 9240
acacccatca ccaccaccac tacggtgacc ccaaccccaa cacccaccgg cacacagacc 9300
ccaaccacga cacccatcac caccaccact acggtgaccc caaccccaac acccaccggc 9360
acacagaccc caaccacgac acccatcacc accaccacta cggtgacccc aaccccaaca 9420
cccaccggca cacagacccc aaccacgaca cccatcacca ccaccactac ggtgacccca 9480
accccaacac ccaccggcac acagacccca accacgacac ccatcaccac caccactacg 9540
gtgaccccaa ccccaacacc caccggcaca cagaccccaa ccacgacacc catcaccacc 9600
accactacgg tgaccccaac cccaacaccc accggcacac agaccccaac cacgacaccc 9660
atcaccacca ccactacggt gaccccaacc ccaacaccca ccggcacaca gaccccaacc 9720
acgacaccca tcaccaccac cactacggtg accccaaccc caacacccac cggcacacag 9780
accccaacca cgacacccat caccaccacc actacggtga ccccaacccc aacacccacc 9840
ggcacacaga ccccaaccac gacacccatc accaccacca ctacggtgac cccaacccca 9900
acacccaccg gcacacagac cccaaccacg acacccatca ccaccaccac tacggtgacc 9960
ccaaccccaa cacccaccgg cacacagacc ccaaccacga cacccatcac caccaccact 10020
acggtgaccc caaccccaac acccaccggc acacagaccc caaccacgac acccatcacc 10080
accaccacta cggtgacccc aaccccaaca cccaccggca cacagacccc aaccacgaca 10140
cccatcacca ccaccactac ggtgacccca accccaacac ccaccggcac acagacccca 10200
accacgacac ccatcaccac caccactacg gtgaccccaa ccccaacacc caccggcaca 10260
cagaccccaa ccacgacacc catcaccacc accactacgg tgaccccaac cccaacaccc 10320
accggcacac agaccccaac cacgacaccc atcaccacca ccactacggt gaccccaacc 10380
ccaacaccca ccggcacaca gaccccaacc acgacaccca tcaccaccac cactacggtg 10440
accccaaccc caacacccac cggcacacag accccaacca cgacacccat caccaccacc 10500
actacggtga ccccaacccc aacacccacc ggcacacaga ccccaaccac gacacccatc 10560
accaccacca ctacggtgac cccaacccca acacccaccg gcacacagac cccaaccacg 10620
acacccatca ccaccaccac tacggtgacc ccaaccccaa cacccaccgg cacacagacc 10680
ccaaccacga cacccatcac caccaccact acggtgaccc caaccccaac acccaccggc 10740
129/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
acacagaccc caaccacgac acccatcacc accaccacta cggtgacccc aaccccaaca 10800
cccaccggca cacagacccc aaccacgaca cccatcacca ccaccactac ggtgacccca 10860
accccaacac ccaccggcac acagacccca accacgacac ccatcaccac caccactacg 10920
gtgaccccaa ccccaacacc caccggcaca cagaccccaa ccacgacacc catcaccacc 10980
accactacgg tgaccccaac cccaacaccc accggcacac agaccccaac cacgacaccc 11040
atcaccacca ccactacggt gaccccaacc ccaacaccca ccggcacaca gaccccaacc 11100
acgacaccca tcaccaccac cactacggtg accccaaccc caacacccac cggcacacag 11160
accccaacca cgacacccat caccaccacc actacggtga ccccaacccc aacacccacc 11220
ggcacacaga ccccaaccac gacacccatc accaccacca ctacggtgac cccaacccca 11280
acacccaccg gcacacagac cccaaccacg acacccatca ccaccaccac tacggtgacc 11340
ccaaccccaa cacccaccgg cacacagacc ccaaccacga cacccatcac caccaccact 11400
acggtgaccc caaccccaac acccaccggc acacagaccc caaccacgac acccatcacc 11460
accaccacta cggtgacccc aaccccaaca cccaccggca cacagacccc aaccacgaca 11520
cccatcacca ccaccactac ggtgacccca accccaacac ccaccggcac acagacccca 11580
accacgacac ccatcaccac caccactacg gtgaccccaa ccccaacacc caccggcaca 11640
cagaccccaa ccacgacacc catcaccacc accactacgg tgaccccaac cccaacaccc 11700
accggcacac agaccccaac cacgacaccc atcaccacca ccactacggt gaccccaacc 11760
ccaacaccca ccggcacaca gaccccaacc acgacaccca tcaccaccac cactacggtg 11820
accccaaccc caacacccac cggcacacag accccaacca cgacacccat caccaccacc 11880
actacggtga ccccaacccc aacacccacc ggcacacaga ccccaaccac gacacccatc 11940
accaccacca ctacggtgac cccaacccca acacccaccg gcacacagac cccaaccacg 12000
acacccatca ccaccaccac tacggtgacc ccaaccccaa cacccaccgg cacacagacc 12060
ccaaccacga cacccatcac caccaccact acggtgaccc caaccccaac acccaccggc 12120
acacagaccc caaccacgac acccatcacc accaccacta cggtgacccc aaccccaaca 12180
cccaccggca cacagacccc aaccacgaca cccatcacca ccaccactac ggtgacccca 12240
accccaacac ccaccggcac acagacccca accacgacac ccatcaccac caccactacg 12300
gtgaccccaa ccccaacacc.caccggcaca cagaccccaa ccacgacacc catcaccacc 12360
accactacgg tgaccccaac cccaacaccc accggcacac agaccccaac cacgacaccc 12420
atcaccacca ccactacggt gaccccaacc ccaacaccca ccggcacaca gaccccaacc 12480
130/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
acgacaccca tcaccaccac cactacggtg accccaaccc caacacccac cggcacacag 12540
accccaacca cgacacccat caccaccacc actacggtga ccccaacccc aacacccacc 12600
ggcacacaga ccgggccccc cacccacaca agcacagcac cgattgctga gttgaccaca 12660
tCCaatCCtC CgCCtgagtC CtCaaCCCCt CagaCCtCtC ggtccacctc ttCCCCtCtC 12720
acggagtcaa ccacccttct gagtacccta ccacctgcca ttgagatgac cagcacggcc 12780
ccaccctcca cacccacggc acccacgacc acgagcggag gccacacact gtctccaccg 12840
cccagcacca ccacgtcccc tccaggcacc cccactcgcg gtaccacgac cgggtcatct 12900
tcagccccca cccccagcac tgtgcagacg accaccacca gtgcctggac cccaacgccg 12960
accccactct ccacacccag catcatcagg accacaggcc tgaggcccta cccttcctct 13020
gtgcttatct gctgtgtcct gaacgacacc tactacgcac caggtgagga ggtgtacaac 13080
ggcacatacg gagacacctg ttatttcgtc aactgctcac tgagctgtac gttggagttc 13140
tataactggt cctgcccatc cacgccctcc ccaacaccca cgccctccaa gtcgacgccc 13200
acgccttcca agccatcgtc cacgccctcc aagccgacgc ccggcaccaa gccccccgag 13260
tgcccagact ttgatcctcc cagacaggag aacgagactt ggtggctgtg cgactgcttc 13320
atggccacgt gcaagtacaa caacacggtg gagatcgtga aggtggagtg tgagccgccg 13380
cccatgccca cctgctccaa cggcctccaa cccgtgcgcg tcgaggaccc cgacggctgc 13440
tgctggcact gggagtgcga ctgctactgc acgggctggg gcgacccgca ctatgtcacc 13500
ttcgacggac tctactacag ctaccagggc aactgcacct acgtgctggt ggaggagatc 13560
agcccctccg tggacaactt cggagtttac atcgacaact accactgcga tcccaacgac 13620
aaggtgtcct gtccccgcac cctcatcgtg cgccacgaga cccaggaggt gctgatcaag 13680
accgtgcata tgatgcccat gcaggtgcag gtgcaggtga acaggcaggc ggtggcactg 13740
ccctacaaga agtacgggct ggaggtgtac cagtctggca tcaactacgt ggtggacatc 13800
cccgagctgg gtgtcctcgt ctcctacaat ggcctgtcct tctccgtcag gctgccctac 13860
caccggtttg gcaacaacac caagggccag tgtggcacct gcaccaacac cacctccgac 13920
gactgcattc tgcccagcgg ggagatcgtc tccaactgtg aggctgcggc tgaccagtgg 13980
ctggtgaacg acccctccaa gccacactgc ccccacagca gctccacgac caagcgcccg 14040
gccgtcactg tgcccggggg cggtaaaacg accccacaca aggactgcac cccatctccc 14100
ctctgccagc tcatcaagga cagcctgttt gcccagtgcc acgcactggt gcccccgcag 14160
cactactacg atgcctgcgt gttcgacagc tgcttcatgc cgggctcgag cctggagtgc 14220
gccagtctgc aggcctacgc agccctctgt gcccagcaga acatctgcct cgactggcgg 14280
i
131/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
aaccacacgc atggggcctg cttggtggag tgcccatctc acagggagta ccaggcctgt 14340
ggccctgcag aagagcccac gtgcaaatcc agctcctccc agcagaacaa cacagtcctg 14400
gtggaaggct gcttctgtcc tgagggcacc atgaactacg ctcctggctt tgatgtctgc 14460
gtgaagacct gcggctgtgt gggacctgac aatgtgccca gagagtttgg ggagcacttc 14520
gagttcgact gcaagaactg tgtctgcctg gagggtggaa gtggcatcat ctgccaaccc 14580
aagaggtgca gccagaagcc cgttacccac tgcgtggaag acggcaccta cctcgccacg 14640
gaggtcaacc ctgccgacac ctgctgcaac attaccgtct gcaagtgcaa caccagcctg 14700
tgcaaagaga agccctccgt gtgcccgctg ggattcgaag tgaagagcaa gatggtgcct 14760
ggaaggtgct gtcccttcta ctggtgtgag tccaaggggg tgtgtgttca cgggaatgct 14820
gagtaccagc ccggttctcc agtttattcc tccaagtgcc aggactgcgt gtgcacggac 14880
aaggtggaca acaacaccct gctcaacgtc atcgcctgca cccacgtgcc ctgcaacacc 14940
tcctgcagcc ctggcttcga actcatggag gcccccgggg agtgctgtaa gaagtgtgaa 15000
cagacgcact gtatcatcaa acggcccgac aaccagcacg tcatcctgaa gcccggggac 15060
ttcaagagcg acccgaagaa caactgcaca ttcttcagct gcgtgaagat ccacaaccag 15120
ctcatctcgt ccgtctccaa catcacctgc cccaactttg atgccagcat ttgcatcccg 15180
ggctccatca cattcatgcc caatggatgc tgcaagacct gcacccctcg caatgagacc 15240
agggtgccct gctccaccgt ccccgtcacc acggaggttt cgtacgccgg ctgcaccaag 15300
accgtcctca tgaatcattg ctccgggtcc tgcgggacat ttgtcatgta ctcggccaag 15360
gcccaggccc tggaccacag ctgctcctgc tgcaaagagg agaaaaccag ccagcgtgag 15420
gtggtcctga gctgccccaa tggcggctcg ctgacacaca cctacaccca catcgagagc 15480
tgccagtgcc aggacaccgt ctgcgggctc cccaccggca cctcccgccg ggcccggcgc 15540
tcccctaggc atctggggag cgggtgagcg gggtgggcac agcccccttc actgccctcg 15600
acagctttac ctcccccgga ccctctgagc ctcctaagct cggcttcctc tcttcagata 15660
tttattgtct gagtctttgt tcagtccttg ctttccaata ataaactcag ggggacatgc 15720
<210> 37
<211> 3941
<212> DNA
<213> Human
<400> 37
accatctact ccacagtcag ctcatccaca actgccatca cctcaccttt cactaccgca 60
gagactgggg tgacttccac accttcatcc ccatcttctc tgagtacaga catcccgacc 120
132/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
acatccctaagaactctcaccccattatctttgagcaccagcacttcattgactacaacc 180
acagaccttccctctatacccactgatatcagtagcttaccaaccccaatacacatcatt 240
tcatcttctccctccatccaaagtacagaaacctcatcccttgtgggcaccacctctccc 300
accatgtccactgtgagagcgaccctcagaagtactgagaacaccccaatcagttccttt 360
agcacaagtattgttgttacacctgaaaccccaacaacacaggcccctcctgtactgatg 420
tctgccactgggacccaaacatcccctgtacctactactgtcacctttggaagtatggat 480
tcctctacgtccactcttcatactcttactccatcaacagccttgagcaagatcatgtca 540
acatcacagtttcctattcctagcacacattcctccacccttcaaacaactccttcaatc 600
ccctctttgcaaacttcactcacatctacaagtgagttcactacagaatctttcactagg 660
ggaagtacgtctacaaatgcaatcttgacttcttttagtaccatcatctggtcctcaaca 720
cccactattatcatgtcctcttctccatcttctgccagcataactccagtgttcgctact 780
accattcattctgttccttcgtcaccatacattttcagtacagaaaatgtgggctccgct 840
tctatcacagcctttcctagtctctcttcctcttcaactaccagcacttctccaaccagc 900
tcctctctgaccacagctctcactgaaataacccccttttcttatatttcccttccctcc 960
accacaccctgtccaggaactataacaattaccatagtccctgcctcccccactgatcca 1020
tgtgttgaaatggatcccagcactgaagctacttctcctcccaccactccattaacagtc 1080
tttccctttactactgaaatggtcacctgtcctagctccatcagtatgcaaactactctt 1140
gctacacatatggacacttcttccatgacgccagaaagtgagtccagcatcatacctaat 1200
gcttccagttccactggcactgggactgtacccacaaacacagttttcacaagtactcga 1260
ctgcccaccagtgagacctggctgagcaacaactctgtgatccccacacctcttcctggc 1320
gtctctaccatcccgctcaccatgaaaccaagcagtagcctcccgaccatcctgaggact 1380
tcaagcaagtcaacacacccatccccacccaccgccaggacttcagagacatcagtggcc 1440
actacccagactcctaccacccttacaacgcgcaggacaactcccatcacttcttggatg 1500
accacacagtccacgttgaccaccactgcaggcacctgtgacaatggtggcacctgggaa 1560
cagggccagtgtgcttgccttccggggttttctggggaccgctgtcagctccagaccaga 1620
tgccagaacgggggccagtgggatggcctcaagtgccagtgccccagcaccttctatggt 1680
tccagttgtgagtttgctgtggaacaggtggatctagatgtagtggagaccgaggtgggc 1740
atggaagtgtctgtggatcagcagttctcgccggacctcaatgacaacacttcccaggcc 1800
tacagggatttcaacaagaccttctggaatcagatgcagaagatttttgcagacatgcag 1860
133/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
ggcttcacct tcaagggtgt ggagatcctg tccctgagga atggcagcat cgtggtggac 1920
tacctggtcc tgctggagat gcccttcagc ccccagctgg agagcgagta tgagcaggtg 1980
aagaccacgc tgaaggaggg gctccagaac gccagccagg atgcgaacag ctgccaggac 2040
tcccagaccctgtgttttaagcctgactccatcaaggtgaacaacaacagcaagacagag2100
ctgaccccggaagccatctgccgccgcgccgctcccacgggctatgaagagttctacttc2160
cctctggtggaggccacccggctccgctgtgtcaccaaatgcacgtcgggcgtggacaac2220
gccatcgactgtcaccagggccagtgcgttctagagacgagcggtcccgcgtgtcgctgc2280
tactccaccgacacgcactggttctctggcccgcgctgcgaggtggccgtccactggagg2340
gcgctggtcgggggcctgacggccggcgccgcgctgctggtgctgctgctgctggcgctg2400
ggcgtccgggcggtgcgctccggatggtggggcggccagcgccgaggccggtcctgggac2460
caggacaggaaatggttcgagacctgggatgaggaagtcgtgggcactttttcaaactgg2520
ggtttcgaggacgacggaacagacaaggatacaaatttccatgtggccttggagaacgtg2580
gacaccactatgaaggtgcacatcaagagacccgagatgacctcgtcctcagtgtgagcc2640
ctgcggggccccttcaccaceccctccgccctgccccggacacaagggtctgcattgcgt2700
ccatttcaagaggtggccccaggacgcgggcagcccaggctcctgctgttcttgggcaag2760
atgagactgttcccccaaatcccatccttctccttccaacttggctgaaacccacctgga2820
gacgcagttcacgtccaggctcttccactgtggaatcttgggcaagtcagtaacgagcct2880
cagtttcctcacctgcaaaacgggtacagcattcctgtatgatagctcacgccgttgttg2940
tgaaaaccacatagacttggtcaattctcggtcctactctgccctcccgtctcagccctc3000
gtgttgccattgcctctctcggatcctccaatcctcacgtccttcacctggtctctggcc3060
ctggttcttattttctctcaattccctactgcctgtttcttactttgaacctggaggcag3120
cctgcagccccatcccatctcctgccctctcotgatctaactccctgctgcatctcttgc3180
tctcattccttagacgtcctccccttttgaccccgttccttcatccatcctgcaccccag3240
tcccccagccctaaatcctccctcctctcctcacatcctggtccctagcaaggtatagat3300
agcctctgtgtcttaggataccccgggtgctgttccctcggtcaccctgttgcccagttc3360
cccgtttctcttgctctcattccttgtatcttctccccttctgagcccgtccattcatcg3420
gttctgcccccgactcccccagccctaaataccccagctcctaattcccccctcaccccg3480
ttgctcaattccccgtttctcttgctctcattccttgtatcttctccccttctgagcctg3540
tccattcatc ggtggttctg cccctactcc eccagcccta aataccccag ctgctgttcc 3600
tccccatcac ccagccaccg gattctccat tcaccccttt ctctcacccc tggagccccg 3660
134/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
tgggtggggg cagggcatga gttccccagt ccccaaggaa aggcagcccc ctcagtctcc 3720
ctcctcctca ttcccttcca tctccctccc ctctgccttt taaacccatc ccctccgatt 3780
cccctcctcc cccctctctc cctggtgtca actcgattcc tgcggtaact ctgagccctg 3840
aaatcctcag tctccttggc ggggaagatt ggctttgggg acaggaagtc ggcacatctc 3900
caggtctcca tgtgcacaat atagagttta ttgtaaaaag c 3941
<210> 38
<21l> 5992
<212> DNA
<213> Human
<400> 38
aaattgctgt gaccgcagca tctctaggaa gacgctttat tcctgaagga cactgactgt 60
cacttgggaa ccaagaagcc ctctgcagtc atgagctctg acgcagaaat ggccattttt 120
ggagaagcagctccctacctccggaaaccagagaaggagagaatcgaggctcaaaatcgt180
ccattcgattccaagaaagcctgctttgtagcggataataaggaaatgtatgtgaaaggc240
atgatccagactagggaaaatgacaaagtcatagtcaagaccctcgatgaccggatgctc300
actctgaacaatgaccaggtcttccccatgaaccctcccaaatttgacaagatcgaggac360
atggccatgatgactcacctgcatgaacctgctgttctgtacaacctcaaagagcgctat420
gcagcctggatgatctacacctactcaggcctcttctgtgtcaccgtcaacccctacaag480
tggctgccggtgtacaagcccgaggtggtggctgcctacagaggcaaaaagcgccaggag540
gccccgccccacatcttctccatctctgacaatgcctatcagttcatgctgactgatcga600
gacaaccagtctatcctcatcaccggagaatccggggctgggaagactgtgaacaccaag660
cgtgtcatccagtattttgcaacaattgcagttaccggggacaagaagaaggagacacag720
ccaggcaaaatgcagggaaccctagaggatcagatcatccaggccaacccactgetggag780
gcctttggaaatgccaagactgtgaggaatgacaactcctcaagatttgggaagttcatt840
cggattcattttggagccacaggaaagctggcatcggcagacatcgaaacttatctgtta900
gaaaaatccagagtgacgtttcaattatccagtgagagaagctatcatattttctaccaa960
attatgtcaaacaagaagccagaactaattgacctgcttctgatctccaccaaccccttc1020
gacttcccct tcgtgagcca aggagaggtc acggtagcca gtatcgatga cagtgaagaa 1080
ctgctggcga cagataatgc cattgacatc ctgggcttca gctcagagga gaaagtcggg 1140
atctacaaac tgacgggagc cgtgatgcat tatgggaaca tgaagttcaa gcagaagcag 1200
cgtgaggagc aggcggagcc agacggcacc gaagtggctg acaaagccgg atacctgatg 1260
135/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
ggactgaattctgcagaaatgctgaagggcctgtgctgtccaagggtgaaggttggcaat1320
1
gaatatgtcactaaagggcaaaatgtccagcaggtgaccaattcggtgggtgctctggcc1380
aaagccgtctacgagaagatgttcctgtggatggtcacccgcatcaaccagcagttggac1440
accaagcagcccaggcagtacttcatcggggtcttggacattgctggctttgagatcttt1500
gatttcaacagcctggagcagctgtgcatcaacttcaccaatgagaaactgcaacagttt1560
ttcaaccaccacatgttcgtgctggagcaggaagagtacaagaaggaaggcatcgagtgg1620
gagttcattgacttcggaatggacctggctgcctgcatcgagctcatcgagaagcctatg1680
ggcatcttctccatcctggaagaggagtgcatgttccccaaggcaacagacacctccttc1740
aagaacaagctgtatgaccagcatcttggaaaatccaacaacttccagaagcccaagcct1800
gccaaaggcaaggctgaggctcacttctcgctggtgcactatgccggcaccgtggactac1860
aacatcgccggctggctggacaaaaacaaggaccccctgaatgagactgtggtggggctg1920
taccagaagtcttcgctgaagcttctctccttccttttttccaactatgctggtgcagag1980
acaggtgactccggaggaagcaagaagggcgggaagaagaagggctcctctttccagacc2040
gtgtcggccgtgttcagggaaaatttaaacaaattgatgactaacttaaggagcacccac2100
cctcactttgtacgatgtctgattcccaatgagaccaagactcctggtgtgatggaccac2160
tacttggtcatgcaccagctgcgctgtaacggggtcctcgagggcatccggatttgcagg2220
aagggattccccagccggatcctctatgctgacttcaagcagcggtaccggatcctcaat2280
gccagtgctatccctgaagggcagttcattgacagcaaaaatgcctcagagaagctcctc2340
aactccatcgatgtggaccgggagcagttcaggttcggcaacaccaaggtgtttttcaaa2400
gctgggctcctgggacttttggaggagatgagagatgagaagctggtgacgctgatgaca2460
agcacgcaggcggtgtgcagggggtacctgatgcgggtggagttcaagaagatgatggag2520
aggagggactccatcttctgcatccaatacaacatccgctcttttatgaacgtcaagcac2580
tggccctggatgaacctgttcttcaaaatcaagcccctgctgaagagtgcagaggccgag2640
aaggagatggccaccatgaaggaagactttgagaggaccaaggaagaactggcccgatct2700
gaggctcgccggaaggagctggaggagaaaatggtctccctcctgcaggagaagaatgac2760
ctccaattgcaggtccagtctgaaacagaaaatctgatggacgctgaggaacggtgtgaa2820
ggactcatcaaaagcaagatcctactggaagcaaaagtcaaggagctgacggagagattg2880
gaagaggaagaggagatgaattctgaattggttgccaagaagaggaatctggaagataaa2940
tgctcctctctcaagagagacattgatgatctggagctgaccttgacgaaagttgaaaag3000
136/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
gagaagcatg ccacagagaa caaggtaaag aatctttccg aagaaatgac agcacttgaa 3060
gaaaacattt ccaaattgac caaagaaaag aaatctctac aggaggccca tcagcaaaca 3120
ctggatgatc ttcaggtgga agaagataaa gtcaatggtc taatcaaaat aaatgccaag 3180
cttgaacagc aaacagatga tcttgagggt tccttagagc aggagaagaa actgcgggcg 3240
gacttggaaa gggcgaagag gaagctggaa ggagatctga aaatgtccca ggaatccatt 3300
atggatctag aaaatgaaaa gcagcaaata gaagagaaat tgaaaaagaa ggagtttgaa 3360
ctcagtcagt tacaagccag aatagatgac gaacaagtcc acagtttgca gtttcaaaag 3420
aagattaaag agctgcaagc ccgcatagaa gagctggagg aggaaattga agcggaacac 3480
acgctcagag ccaagattga gaagcagcgc tcagatctgg ccagggaact ggaggagatc 3540
agcgagaggc tggaagaagc cagtggggcc acttcagccc agattgagat gaacaagaag 3600
agggaggctg agttccagaa aatgcgcagg gacctggagg aggccaccct gcagcacgaa 3660
gccacagcag ccaccctgag gaagaagcaa gcagatagtg tggccgagct tggggagcag 3720
attgacaacc tgcagcgggt gaagcagaag ctggagaagg agaagagcga gctgaagatg 3780
gagatcgacg acatggccag caacatcgag gctctctcca agtcaaagag taacatagaa 3840
agaacgtgcc ggacggtaga agatcaattt agtgaaatca aagccaagga cgagcaacag 3900
acacagttga tccatgatct gaacatgcag aaagcaagac tgcagaccca aaatggggag 3960
ctgagccacc gagtggaaga gaaggagtct ctgatttcac agctgaccaa aagcaagcag 4020
gccctcaccc agcagctgga ggagcttaag aggcaaatgg aagaagaaac caaggccaag 4080
aacgccatgg cgcacgccct gcagtcctcc cgccacgact gtgacctgct gcgggaacag 4140
tatgaggagg agcaggaagc caaggccgag ctgcagaggg cgctgtccaa ggccaacagt 4200
gaggttgccc agtggaagac caaatacgag acggacgcca ttcagcgcac agaagagctg 4260
gaggaggcca agaaaaaact ggcccagagg ctccaggaag cagaggagaa gacggagacg 4320
gcgaactcca agtgcgcatc gttggagaaa accaagcaga ggctgcaggg agaggtggag 4380
gatctgatgc gggatctgga gcgctcccac accgcctgtg ccacactgga caagaagcag 4440
aggaacttcg acaaggtcct tgcagagtgg aagcaaaagc tggacgaaag ccaggctgag 4500
ctggaagctg ctcagaagga gtccaggtca ctcagcactg aactcttcaa gatgaggaat 4560
gcctatgagg aggtggtgga ccagttagag acactgaggc gagagaacaa aaatctgcaa 4620
gaagagattt ccgacttaac tgagcagatt gcagaaactg gcaagaatct tcaggaagcg 4680
gaaaagacca agaagctagt ggagcaggaa aagtcagatc tgcaggtcgc cttagaagaa 4740
gtggagggtt ccttggaaca cgaggagagc aagatcttgc gcgtgcagct agagctgagc 4800
137/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
caggtgaaatccgagctagaccgcaaggtcattgagaaggatgaagaaatcgagcagcta4860
aaaagaaacagccagcgggcagcagaggccctgcagagcgtgctggatgctgaaatccgc4920
agccggaacgacgccctgaggctaaagaagaagatggagggagaccttaatgagatggag4980
attcagctgggccactccaaccgccagatggcagagacccagaggcatctgcgcacggtc5040
cagggccagctcaaggactcccagctgcatctcgatgacgccctgaggagcaatgaggac5100
ctcaaggagcagctggccatcgtggagcgcaggaatggcctcctgctggaggagctggag5160
gaaatgaaggtggccctggaacagacggagcggacccgcaggctgtcagagcaggagctg5220
ctggacgccagcgaccgcgtgcagctcctgcactcccagaacacaagcctgataaatacc5280
aagaaaaaactggaggctgacatagctcagtgccaggcagaggtggagaactcgatccag5340
gagtccaggaacgcagaggagaaggccaagaaggccatcacggatgctgccatgatggct5400
gaggagctaaagaaggaacaggacaccagcgcccacctggagcggatgaagaagaacctg5460
gagcagacggtgaaggacctgcagcaccgtctagatgaggctgaacaactggcgctgaag5520
ggcgggaagaagcagatccagaaactggagaaccgggtgcgggagctggaaaatgagctt5580
gatgtggaacagaagaggggagctgaagccctgaagggagcccacaagtacgaacgcaaa5640
gtcaaggagatgacttaccaggctgaggaggaccgcaagaatatccttaggctccaggac5700
ctggtggacaagctgcaggccaaagtgaagtcttacaagaggcaggctgaggaggcggag5760
gagcaggccaacacgcagctgtccagatgccggagagtccagcatgagctagaggaggcc5820
gcggagagggcggacatcgctgagtcccaggtcaacaagctgagggccaagagccgagac5880
gtgggcagccagaagatggaagaatgaggctcacctgatgctcgttgccatgggacacct5940
ccgagagagtggagggaaaatgtgtgagaaataaattctcctaaatactcgg 5992
<210> 39
<211> 661
<2l2> DNA
<213> Human
<400> 39
ggagtggcag ccggagtctg aactgtcctg ggggaccaag caggagctta agatgggcaa 60
gacctggggc cctgggcaga cgcatcaaag caggcagaag caggcatggc cagcaggaag 120
accaagaaga aggaaggggg tgccctccgg gcccagagag cctcatccaa tgtcttctcc 180
aactttgagc agactcagat ccaggagttc aaggaggcat tcacactcat ggatcagaac 240
cgagatggct tcattgacaa ggaggacctg aaggacacct atgcctccct gggcaagacc 300
aacgtcaagg acgacgagct ggacgccatg ctcaaagagg cctcggggcc catcaacttc 360
138/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
accatgtttc tgaacctgtt tggggagaag ctgagcggta ccgacgccga ggagaccatt 420
cttaacgcct tcaagatgct ggacccggac gggaaaggga aaatcaacaa ggagtacatc 480
aagcgtctgc tgatgtccca ggctgacaag atgacggcgg aagaggtgga ccagatgttc 540
cagttcgcct ccatcgatgt ggcgggcaac ctggactaca aggcgctcag ctacgtgatc 600
acccacgggg aggagaagga ggagtgagac cca.gccgggt caataaacct ggacgcttgg 660
a 661
<210> 40
<211> 5749
<212> DNA
<2l3> Human
<400>
40
cgcgggagccaacttcaggctgctcagaggaagcccgtgcagtcagtcacctgggtgcaa60
gagcgttgctgcctcgggctctcccgctgcagggagagcggcactcgctggcctggatgt120
ggttggatttaggggggctccgcagcaggggtttcgtggcggtggcaagcgctgcaacag180
gtagacggcgagagacggaccccggccgaggcagggatggagaccaaaggctaccacagt240
ctccctgaaggtctagatatggaaagacggtggggtcaagtttctcaggctgtggagcgt300
tcttccctgggacctacagagaggaccgatgagaataactacatggagattgtcaacgta360
agctgtgtttccggtgctattccaaacaacagtactcaaggaagcagcaaagaaaaacaa420
gaactactcccttgccttcagcaagacaataatcggcctgggattttaacatctgatatt480
aaaactgagctggaatctaaggaactttcagcaactgtagctgagtccatgggtttatat540
atggattctgtaagagatgctgactattcctatgagcagcagaaccaacaaggaagcatg600
agtccagctaagatttatcagaatgttgaacagctggtgaaattttacaaaggaaatggc660
catcgtccttccactctaagttgtgtgaacacgcccttgagatcatttatgtctgactct720
gggagctccgtgaatggtggcgtcatgcgcgccattgttaaaagccctatcatgtgtcat780
'
gagaaaagcccgtctgtttgcagccctctgaacatgacatcttcggtttgcagccctgct840
ggaatcaactctgtgtcctccaccacagccagctttggcagttttccagtgcacagccca900
atcacccagggaactcctctgacatgctcccctaatgctgaaaatcgaggctccaggtcg960
cacagccctgcacatgctagcaatgtgggctctcctctctcaagtccgttaagtagcatg1020
aaatcctcaa tttccagccc tccaagtcac tgcagtgtaa aatctccagt ctccagtccc 1080
aataatgtca ctctgagatc ctctgtgtct agccctgcaa atattaacaa ctcaaggtgc 1140
tctgtttcca gcccttcgaa cactaataac agatccacgc tttccagtcc ggcagccagt 1200
139/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
actgtgggat ctatctgtag ccctgtaaac aatgccttca gctacactgc ttctggcacc 1260
tctgctggat ccagtacatt gegggatgtg gttcccagtc cagacacgca ggagaaaggt 1320
gctcaagagg tcccttttcc taagactgag gaagtagaga gtgccatctc aaatggtgtg 1380
actggccagc ttaatattgt ccagtacata aaaccagaac cagatggagc ttttagcagc 1440
tcatgtctag gaggaaatag caaaataaat tcggattctt cattctcagt accaataaag 1500
caagaatcaa ccaagcattc atgttcaggc acctctttta aagggaatcc aacagtaaac 1560
ccgtttccat ttatggatgg ctcgtatttt tcctttatgg atgataaaga ctattattcc 1620
ctatcaggaa ttttaggacc acctgtgccc ggctttgatg gtaactgtga aggcagcgga 1680
ttcccagtgg gtattaaaca agaaccagat gacgggagct attacccaga ggccagcatc 1740
ccttcctctg ctattgttgg ggtgaattca ggtggacagt ccttccacta caggattggt 1800
gctcaaggta caatatcttt atcacgatcg gctagagacc aatctttcca acacctgagt 1860
tcctttcctc ctgtcaatac tttagtggag tcatggaaat cacacggcga cctgtcgtct 1920
agaagaagtg atgggtatcc ggtcttagaa;tacattccag aaaatgtatc aagctctact 1980
ttacgaagtg tttctactgg atcttcaaga ccttcaaaaa tatgtttggt gtgtggggat 2040
gaggcttcag gatgccatta tggggtagtc acctgtggca gctgcaaagt tttcttcaaa 2100
agagcagtgg aagggcaaca caactattta tgtgctggaa gaaatgattg catcattgat 2160
aagattcgac gaaagaattg tcctgcttgc agacttcaga aatgtcttca agctggaatg 2220
aatttaggag cacgaaagtc aaagaagttg ggaaagttaa aagggattca cgaggagcag 2280
ccacagcagc agcagccccc acccccaccc ccacccccgc aaagcccaga ggaagggaca 2340
acgtacatcg ctcctgcaaa agaaccctcg gtcaacacag cactggttcc tcagctctcc 2400
acaatctcac gagcgctcac accttccccc gttatggtcc ttgaaaacat tgaacctgaa 2460
attgtatatg caggctatga cagctcaaaa ccagatacag ccgaaaatct gctctccacg 2520
ctcaaccgct tagcaggcaa acagatgatc caagtcgtga agtgggcaaa ggtacttcca 2580
ggatttaaaa acttgcctct tgaggaccaa attaccctaa tccagtattc ttggatgtgt 2640
ctatcatcat ttgccttgag ctggagatcg tacaaacata cgaacagcca atttctctat 2700
tttgcaccag acctagtctt taatgaagag aagatgcatc agtctgccat gtatgaacta 2760
tgccagggga tgcaccaaat cagccttcag ttcgttcgac tgcagctcac ctttgaagaa 2820
tacaccatca tgaaagtttt gctgctacta agcacaattc caaaggatgg cctcaaaagc 2880
caggctgcat ttgaagaaat gaggacaaat tacatcaaag aactgaggaa gatggtaact 2940
140/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
aagtgtcccaacaattctgggcagagctggcagaggttctaccaactgaccaagctgctg3000
gactccatgcatgacctggtgagcgacctgctggaattctgcttctacaccttccgagag3060
tcccatgcgctgaaggtagagttccccgcaatgctggtggagatcatcagcgaccagctg3120
cccaaggtggagtcggggaacgccaagccgctctacttccaccggaagtgactgcccgct3180
gcccagaagaactttgccttaagtttccctgtgttgttccacacccagaaggacccaaga3240
aaacctgtttttaacatgtgatggttgattcacacttgttcaacagtttctcaagtttaa3300
agtcatgtcagaggtttggagccgggaaagctgtttttccgtggatttggcgagaccaga3360
gcagtctgaaggattccccacctccaatcccccagcgcttagaaacatgttcctgttcct3420
cgggatgaaaagccatatctagtcaataactctgattttgatattttcacagatggaaga3480
agttttaactatgccgtgtagtttctggtatcgttcgcttgttttaaaagggttcaagga3540
ctaacgaacgttttaaagcttacccttggtttgcacataaaacgtatagtcaatatgggg3600
cattaatattcttttgttattaaaaaaacacaaaaaaataataaaaaaatatatacagat3660
tcctgttgtgtaataacagaactcgtggcgtggggcagcagctgcctctgagccctcgct3720
cgtccacggtcttctgcatcactggtatacacactcgttagcgtccatttcttatttaat3780
tagaatggataagatgatgttaaatgccttggtttgatttctagtatctattgtgttggc3840
tttacaaataattttttgcagtcttttgctgtgctgtacattactgtatgtataaattat3900
gaaggacctgaaataaggtataaggatcttttgtaaatgagacacatacaaaaaaaatct3960
ttaatggttaataggatgaatgggaaagtatttttgaaagaattctattttgctggagac4020
tatttaagtactatctttgtctaaacaa~ggtaatttttttttgtaaagtgcaatgtcctg4080
catgcataatgaaccgtttacagtgtatttaagaaagggaaagctgtgccttttttagct4140
tcatatctaatttaccattattttacagtctctgttgtaaataaccacactgaaacctct4200
tcggttgtcttgaaacctttctactttttctgtactttttgttttgttcttggtctcccg4260
cttggggcatttgtgggactccagcacgttttctggcttctgcttcatcctgctccatcg4320
gggaatgacacactgcggtgtctgcagctcctggaaggtgtcatttgacaacacatgtgg4380
gagaggaggtccttggagtgctgcagctttgggaaagcctgcctcgtttcccttttcctc4440
tagaagcagaaccagctctacgagagtgagactgggaacttgatggctcagagagcatct4500
tttcctcccattttagaaaatcagattttctcctgtgggaaaaaaaaattccatgcactc4560
tctctctgttaaagatcagctattcccttctgatcttggaaagaggttctgcactcctgg4620
aaccggtcacaggaacgcacagatcatggcaggatgcgctgggacggcccatcttggcaa4680
ggttcagtctgaatggcatggagaccgggagatagaggggttttagatttttaaaaggta4740
141/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
ggttttaaaaataagttttatacataaacagttttggagaaaaattacagatcatataag4800
r
caagacagtggcactaaaatgtttaattcattaatctgtttgtttggcactgatgcaatg4860
tatggcttttctcttgccccaaatcacaaacatatgtatctttggggaaactaacaatat4920
gattgcactaaataaactactttgaatagaggccaaattaatcttttaaaaatgatgata4980
atcatcaggtttactcagtgaaatcatattaattattttccaaaatctaaaagctgtagc5040
tggagaagcc catggccacg aggaagcagc aattaattag atcaacactt ttctccaggg 5100
ttcaccatgc aggcaacatt accttgtctt tcaaaagaca cctgccttag tgcaagggga 5160
aacctgtgaaagctgcactcagagggaggagtctttcttacataatttgcaatttcagga5220
atttaatttataggcagatctttaaatacagtcaacttacggtgcacagtaatatgaaag5280
ccacactttgaaggtaataaatacacagcatgcagactgggagttgctagcaaacaaatg5340
gcttacttacaaaagcagcttttagttcagacttagtttttataaaatgagaattctgac5400
ttacttaaccaggtttgggatggagatggtctgcatcagctttttgtattaacaaagtta5460
ctggctctttgtgtgtctccaggtaactttgcttgattaaacagcaaagccatattctaa5520
attcactgttgaatgcctgtcccagtccaaattgtctgtctgctcttatttttgtaccat5580
attgctcttaaaaatcttggtttggtacagttcataattcaccaaaaagttcatataatt5640
taaagaaacactaaattagtttaaaatgaagcaatttatatctttatgcaaaaacatatg5700
tctgtctttgcaaaggactgtaagcagattacaataaatcctttacttt 5749
<210> 41
<211> 2306
<212> DNA
<213> Human
<400>
41
tcatcatccaagtttgtagttcatttaaaaatacaacattaaacacattttgctaggatg 60
tcaaatagtcacagttctaagtagttggaaacaaaattgacgcatgttaatctatgcaaa 120
gagaaaggaaaggatgaggtgatgtattgactcaaggttcattcttgctgcaattgaaca 180
tcctcaagagttgggatggaaatggtgatttttacatgtgtcctggaaagatattaaagt 240
aattcaaatcttccccaaaggggaaaggaagagagtgatactgacctttttaagtcatag 300
accaaagtctgctgtagaacaaatatgggaggacaaagaatcgcaaattcttcaaatgac 360
tattatcagtattattaacatgcgatgccacaggtatgaaagtcttgccttatttcacaa 420
ttttaaaaggtagctgtgcagatgtggatcaacatttgtttaaaataaagtattaatact 480
ttaaagtcaaataagatatagtgtttacattctttaggtcctgaggggcagggggatctg 540
142/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
tgatataacaaaatagcaaaagcggtaatttccttaatgttatttttctgattggtaatt600
atttttaacagtacttaattattctatgtcgtgagacactaaaatcaaaaacgggaatct660
catttagactttaatttttttgagattatcggcggcacaatcactttgtagaaactgtaa720
aaaataaaagtatctcctagtcccttaattttttcataaatatttctggcttttgagtag780
tgtatttatattgtatatcatactttcaactgtagacaattatgatgctaatttattgtt840
tcttggtttcacctttgtataagatatagccaagactgaagaaaccaaatatatgtgttt900
actgtagcatgtcttcaaattagtggaacttagttcagggacatagaagagtcttaatga960
attaaaatcattcacttgattaaatgtctgtaaatcttcatcattcctactgtagtttat1020
ttaatatctattgtaaattatgtgacttgtagcttcctctggttttcaagtaaactcaac1080
aaggtggagtcttacctggttttcctttccaagcattgtaaattgtataccaaagatatt1140
agttattacttctgtgtgtacaaagaggattattttattatgtttattaatcacctctaa1200
tactcatccacatgaagggtacacattaggtaagctgggcgttgactcatgcgcagtctc1260
agtcacccgtgttatcttcgtggctcaaaggacaatgcaaaatcgccgatcagagctcat1320
acccaaagcattacagagaacagcagcatcattgccctccccagctgaaaaacaagttgg1380
ctagaagatacatggagaggaatggtgtggtcaacagttaatgaaacggttctatcatgc1440
atgtgtaatgtggatggagacaattataagatttgactataactatttggagggtcttta1500
acattgccaaaaaaacaaatatgttgatttttattttattttattttttattttaagagg1560
cgggatcttgatctcacatgttgcccaggctggccttgaactcctgggctcaagcattcc1620
tcctgcctcagcctcccccatagctgggactaggggtgcatgccagcatacctggctacg1680
ttgactcttaaaatctatgttctcttattttaaagatacagtgctccccactgaaaatta1740
aacctaaaaaatgtcacatattggtatgttgttaacctggtagattaaatcatgagaatg1800
attagaaagacgggcaacacagcgggttacatccacactgctgatcacaccaacgacagg1860
agctgataag caagaaagcg tcacagccag cgtctgttca cccaaggttg acaagtgaag 1920
tttctctaat gttgattgtt agccgatttg taacctggca tttacttagc aactgcctta 1980
tcaattacag gatttgccgg taaaagcaga ctcaaatata aaggtttttg gcttaacttg 2040
gtttattata gttgctctat gtttgtaaac agacaatctc taatgtctga ttatttgtat 2100
cacagatctg cagctgcctt ggacttgaat ccatgcaatg tttagagtgt gaagtcagtt 2160
acttgttgat gttttcttac tgtatcaatg aaatacatat tgtcatgtca gttcttgcca 2220
ggaacttctc aacaaaatgg aatttttttt ttcagtattt caataaatat tgatatgccc 2280
143/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
agcctgataa aaaaaaaaaa aaaaaa 2306
<210> 42
<211> 7609
<212> DNA
<213> Human
<400>
42
atctaccaccttaaaaccctgatctagaaaaaatatatattcatgataggaagttataac 60
taagaaaatttatttgcctcttaatgctcctgaatgaaagaaattatccctttgttcttt 120
gggaggacttgtgtatctgagattgttgtaataatcagtcattttattaaaaccttgaca 180
tgatcaccagggaggaaaaatagagcaatagtcaaaacctgtgtgttagtccaagatgac 240
ttctgaagaaatgacagcttctgttctcatacctgtgactcagagaaaagtggtttctgc 300
ccagtcggctgcagatgaaagtagtgaaaaggtctcagacatcaatatttcaaaagcaca 360
tactgtcagacgaagtggggagacttctcataccatctcacaactgaacaaacttaaaga 420
agaaccttctggaagcaacttgccaaagattctctcaatagcgagggagaaaatagtgag 480
tgatgagaacagtaatgaaaaatgttgggagaaaatcatgccagattctgcgaaaaacct 540
taacattaactgcaacaacatattgagaaaccatcagcatggccttcctcagagacaatt 600
ttatgaaatgtacaactctgttgctgaggaagacttgtgtttagaaactggaattccttc 660
tccactggaaagaaaggtgttccctggaattcaactggaactagacagaccttccatggg 720
cattagtcctttaggaaatcagtcagtgatcatagagacaggcagagcacaccctgacag 780
cagaagggcagtatttcattttcattatgaagttgacagaagaatgtcagacactttctg 840
taccctatcagaaaacttaattttagacgattgtggaaattgtgtaccactacctggggg 900
tgaggagaagcaaaagaaaaactatgtggcatatacctgtaaactgatggaattggccaa960
aaattgtgataataagaatgagcagctgcagtgtgatcattgtgacaccttgaatgataa1020
atacttttgctttgaaggctcttgtgagaaggttgacatggtatattcaggtgatagctt1080
ttgtaggaaagactttactgacagtcaagctgccaagacctttttgagccattttgagga1140
cttccctgataattgtgatgatgtagaagaagacgcttttaaaagcaaaaaggagcgatc1200
cactttgttagtcaggagattctgtaaaaatgacagagaagttaagaaatctgtgtatac1260
tggaacaagagcaattgtgagaactctgccttctggccacattgggctgactgcatggag1320
ttacatagatcagaagagaaatggtcccttactgccttgtgggagagtaatggaaccccc1380
gtcaacagtggagataaggcaagatgggagccaacgtctgtcagaagcccagtggtatcc1440
tatctacaatgcagtgagaagagaagaaacagaaaatacagttggatctctactccattt1500
144/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
cctcaccaag ctcccagcct ccgagacagc ccatggaagg ataagcgttg gtccatgctt 1560
aaagcaatgt gtccgagaca ctgtatgtga gtatcgcgcc accctccaaa ggacttcaat 1620
atcgcagtac atcaccggtt ctctcctaga agcaaccacg tctttgggag caagaagtgg 1680
ccttctcagt acttttggag gatccactgg acgaatgatg ctgaaagaac gccagccagg 1740
cccctctgtg gccaattcca atgccctccc ttcaagttca gctgggatca gcaaggagct 1800
gatcgatctg cagcctctca tccagttccc agaggaagtc gccagcatcc tgatggagca 1860
agagcagact atttaccgca gggtcttgcc agtcgactac ctttgcttct taacacggga 1920
cttgggcact cctgaatgcc agagctcctt gccctgcctc aaagcatcca tctcagcgtc 1980
gattcttacc actcagaatg gagagcacaa tgcccttgaa gatctggtga tgaggtttaa 2040
tgaggtgagc tcctgggtga catggctgat cctcacggca ggctccatgg aggagaagcg 2100
agaagtcttt tcatatttgg tgcatgtggc caaatgctgc tggaacatgg gcaactacaa 2160
cgctgtcatg gagttcttgg ctggcctcag gtcaagaaaa gttttaaaaa tgtggcagtt 2220
catggaccag tctgatattg agaccatgag gagcctgaag gatgctatgg cccagcatga 2280
gtcctcttgt gagtacagaa aggtggtgac acgtgccctg cacatccctg gctgtaaggt 2340
ggttccattc tgtggggtgt ttctgaagga gctctgtgaa gtgcttgacg gcgcctccgg 2400
tctcatgaag ctttgcccgc ggtacaattc ccaagaagaa actttagagt ttgtagcaga 2460
ttacagtgga caagataatt tcttacaacg agtgggacaa aatggcttaa agaattcgga 2520
gaaggagtcc actgtcaaca gcatctttca ggtcatccgg agctgcaatc gaagtctgga 2580
gacagacgag gaggacagcc ccagtgaagg gaacagctcc aggaaaagct ccttgaagga 2640
taaaagccga tggcagttta taattggaga tttgttggat tcagacaatg acatctttga 2700
gcaatccaaa gaatacgact ctcatggttc agaggactca cagaaggcct tcgaccatgg 2760
gacggagctc atcccttggt acgtgctgtc catccaagcc gatgtgcacc agttcctgct 2820
gcagggggcc acggtcatcc actacgacca ggacacacac ctctctgccc gctgcttcct 2880
ccagcttcag cccgacaata gcaccttgac ctgggtaaag cccacaactg cctccccagc 2940
cagcagtaaa gcaaaacttg gtgtacttaa taacacagct gagcctggaa aattcccact 3000
actgggtaat gctggattaa gtagcctgac ggaaggggtc ttggatcttt ttgcagtgaa 3060
ggctgtatac atgggccacc ctggcattga tatacacact gtgtgtgttc agaacaaact 3120
gggtagcatg ttcctgtcag agactggtgt gacattgctc tatgggcttc agaccacaga 3180
caacagatta ttgcacttcg tggcaccaaa gcacacagct aaaatgctct tcagcggatt 3240
attggaactc actagagctg tgagaaagat gaggaaattc cctgaccaaa gacagcagtg 3300
145/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
gctgcggaaa cagtacgtca gcctttatca ggaggatgga cggtatgaag gcccaacttt 3360
ggctcacgct gtggagttgt ttggtggcag acggtggagt gctcgaaacc ccagccccgg 3420
aacatcagca aagaatgctg agaagcccaa tatgcagaga aacaataccc tgggcataag 3480
cactaccaag aaaaagaaga aaatcctcat gaggggtgag agtggagagg taactgacga 3540
tgagatggcaacccgaaaggccaagatgcacaaagagtgtcgaagccggagtggttctga3600
tcctcaagacattaatgaacaagaagaatcagaggtgaatgccatcgctaaccctccaaa3660
ccccctcccttccagaagagcccactctttgaccacagctgggtcccccaacttggctgc3720
cgggacgtcatctcccatcaggccagtgtcctcccctgtgctgtcttcttcaaacaagag3780
cccatccagtgcttggagcagtagtagctggcacgggcggatcaaaggcggcatgaaggg3840
atttcagagcttcatggtttcagatagcaacatgagttttgttgaatttgttgagctgtt3900
caaatcattcagtgtcaggagccgcaaggacctgaaggatctgtttgatgtctatgcagt3960
gccctgcaaccgatctggctccgagtcagccccactctacaccaacctgacaattgatga4020
aaacaccagcgatcttcagcctgacctagatctgttgaccagaaatgtctcggatttggg4080
gttgttcattaagagtaaacagcagctatcggacaaccagaggcagatatctgatgccat4140
tgctgctgcaagcattgtgacaaatggcactgggattgagagcacatctctgggcatttt4200
tggggtgggcatacttcagctcaacgatttcctcgtgaattgccaaggagaacactgcac4260
ttatgatgaaatcctcagcatcatccagaagttcgagcctagcatcagtatgtgtcatca4320
gggactaatgtcatttgaagggtttgccaggtttctgatggataaagaaaattttgcctc4380
aaaaaatgatgagtcacaggagaacattaaagaactgcagctacccctctcatactatta4440
catcgaatcttcgcacaatacctacctcacgggccatcagctcaaaggagaatcctcggt4500
agaactctacagccaggtccttttgcaaggctgtcgaagtgtagaattggactgctggga4560
cggagacgatgggatgcccatcatttatcatggacatacgccgacaaccaagatcccctt4620
caaggaagtggttgaagccattgatcgcagtgccttcatcaactctgacctgccaatcat4680
catatcgattgagaaccactgttcattgcctcagcaacgaaaaatggcagaaattttcaa4740
gactgtgtttggagaaaagctggtgactaaattcttatttgagactgatttctcagatga4800
tccaatgcttccttcacctgaccaactcagaaagaaagttcttcttaaaaacaagaagct4860
aaaagcccatcagacgccagtggatatcttaaagcaaaaggctcatcagttagcatctat4920
gcaagtgcaggcttataatggtgggaatgccaacccccgacctgccaataatgaggaaga4980
ggaagatgaggaggacgaatatgattatgactatgaatccctttctgatgacaacattct5040
146/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
ggaagacaga cctgaaaata aatcatgtaa tgacaagctt cagtttgaat ataatgaaga 5100
aatcccaaag aggataaaga aagcagataa ctctgcttgc aacaaaggaa aggtttatga 5160
tatggaactg ggagaagaat tttatcttga tcagaataaa aaggaaagca gacagattgc 5220
accagagctt tctgaccttg taatctatcg tcaagcagta aaatttccag gactgtcaac 5280
tctaaatgca tctggctcta gcagaggaaa agaaaggaaa agcaggaagt ccatttttgg 5340
caacaatccg ggcagaatga gcccagggga gacagcatca tttaacaaaa catctggaaa 5400
aagttcctgt gaaggcattc gacagacctg ggaggaatct tcttcccccc tcaacccaac 5460
cacgtccctc agtgctatca ttagaactcc caaatgttat catatctcgt cgctgaatga 5520
aaatgccgcc aaacgtctgt gtcgcaggta ttctcagaaa ctgatccagc acaccgcctg 5580
tcagctgctg agaacttacc ctgctgccac ccgcatcgac tcttccaacc cgaaccccct 5640
catgttctgg ctccatggga tacagcttgt ggcactcaac taccagactg atgatctccc 5700
tttacattta aatgctgcaa tgtttgaggc aaatggtggt tgtggttatg tattgaaacc 5760
tccagttctg tgggacaaga actgccccat gtatcagaag ttttctccac tagaaagaga 5820
tctggacagc atggatcctg cagtctattc tttaactatt gtctctggtc agaatgtgtg 5880
ccccagtaat agcatgggaa gcccgtgcat tgaagtcgac gtcctgggca tgcctctgga 5940
cagctgccat ttccgcacaa agcccatcca tcgaaacacc ctgaacccca tgtggaacga 6000
gcagtttctg ttccgcgttc acttcgaaga tcttgtattt cttcgttttg cagttgtgga 6060
aaacaatagt tcagcggtaa ctgctcagag aatcattcca ctgaaagctt taaaacgagg. 6120
atatcgacat cttcagctgc gaaaccttca caatgaagtc ttggagattt ctagtttatt 6180
cattaacagc agaaggatgg aagaaaattc ctctggcaat accatgtcag cctcttcgat 6240
gtttaataca gaagaaagaa aatgtttgca gactcacaga gtcacggtgc atggggtccc 6300
agggccagag ccctttaccg ttttcactat taatggaggc accaaggcaa agcagcttct 6360
gcagcaaatt ctgacaaatg aacaagacat caaacctgtt accacagact attttttgat 6420
ggaagaaaaa tattttatat ctaaagaaaa gaatgaatgt aggaaacaac cattccagag 6480
agccattggt ccagaagagg agatcatgca aattttaagc agctggtttc cagaagaggg 6540
atacatgggc aggattgtct taaaaaccca gcaggaaaac ctagaagaga aaaacattgt 6600
tcaagatgac aaagaggtga tcttgagctc agaggaggag agtttctttg tccaagtgca 6660
tgatgtttct ccagagcaac ctcgaacagt catcaaagca ccccgcgtca gcactgcaca 6720
ggatgtcatt cagcagacct tatgcaaagc caaatattcc tacagcatcc tgagcaaccc 6780
caatccaagc gactatgtgc ttttggaaga ggtggtgaaa gacactacca acaagaagac 6840
147/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
taccacacca aagtcctctc agcgggtcct tctggatcag gagtgtgtgt ttcaagccca 6900
aagcaagtgg aaaggtgcag gaaaattcat ccttaagcta aaggagcagg tgcaggcatc 6960
tcgagaagat aaaaagaaag gcatttcttt cgcaagtgaa ctcaagaagc tcaccaagtc 7020
aactaaacag ccccgaggac ttacatcacc ttctcagctc ttgacctcag aaagtatcca 7080
aaccaaggaggagaaacctgtgggtggcttgtctccagtgacacaatggattaccgacag7140
tgactaagggcagcatgtttaacccaggtggagatctttaagcaagaagttaaagagtga7200
acatggtggaaaaaatataattattttcatcagacttaaactggaaattgatgatttctg7260
aactgaagccttcacacatgtgagatccatgctgaggagaagcaaaatggcacagggcta7320
gttgccaccaaccaatttactgatgaatgaagcccaggggactgccattttataaatgtc7380
agcagttggaaaaatcgtcacgaattgacttagagcaagggtcagcaagcttgtctgtaa7440
agggccaaacagtaaatattttagggctgggggccataaaatatgttgcaaccacccaat7500
tctgccattgtagtgcaaaagcagccatagacaacacatacatgaacgaacgtggctgta7560
ttccaataaaactttatttatggacactgaaaaaaaaaaaaaaaaaaaa 7609
<210> 43
<211> 1922
<212> DNA
<213> Human
<400>
43
gcacgagaatgtccctgagacccagaagggcctgcgctcagctgctctggcaccccgctg60
cagggatggcctcctgggctaagggcaggagctacctggcgcctggtttgctgcagggcc120
aagtggccatcgtcaccggcggggccacgggcatcggaaaagccatcgtgaaggagctcc180
tggagctggggagtaatgtggtcattgcatcccgtaagttggagagattgaagtctgcgg240
cagatgaactgcaggccaacctacctcccacaaagcaggcacgagtcattcccatacaat300
gcaacatccggaatgaggaggaggtgaataatttggtcaaatctaccttagatacttttg360
gtaagatcaatttcttggtgaacaatggaggaggccagtttctttcccctgctgaacaca420
tcagttctaagggatggcacgctgtgcttgagaccaacctgacgggtaccttctacatgt480
gcaaagcagtttacagctcctggatgaaagagcatggaggatctatcgtcaatatcattg540
tccctactaaagctggatttccattagctgtgcattctggagctgcaagagcaggtgttt600
acaacctcaccaaatctttagctttggaatgggcctgcagtggaatacggatcaattgtg660
ttgcccctggagttatttattcccagactgctgtggagaactatggttcctggggacaaa720
gcttctttgaagggtcttttcagaaaatccccgctaaacgaattggtgttcctgaggagg780
148/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
tctcctctgtggtctgcttcctactgtctcctgcagcttccttcatcactggacagtcag840
tggatgtggatgggggccggagtctctatactcactcgtatgaggtaccagatcatgaca900
actggcccaagggagcaggggacctttctgttgtcaaaaagatgaaggagacctttaagg960
agaaagctaagctctgagctgaggaaacaaggtgtcctccatcccccagtgccttcacat1020
cttgaggatatgcttctgtactttttaaaagcttatagttggtatggaaaacatttttct1080
tatttttaagtgttattaattatatctatggaaaaactattcctgaaatatatacagtct1140
tatgtcccaatcagagtcttttaacctatgatttaaaaatgtataagtaacagaaattaa1200
catattttaatgactttactttttatttctaagaaaagtatttgaaaaatggaataattt1260
taaatcaatgataattctagggatcatgaactcccagaagattttattatttaattgtaa1320
aggtagaggccggacgcagtggctcacgcctgtaattccagcactttgggaggccgaggt1380
gggcgggtcagttgaggtcaggagttcaagaccaggctggccaacatggtaaaaccctgt1440
ctctactgaaaaacaacaaaaacaaaaacacaaattagtcgggtgtggtggcacacacct1500
gtagtcccaggtacttgggaggctgaggcaggaggatcgcttgaacccaggaagcagagg1560
ttgcagtgagctgagatcgtgctactgcagtccagcctgggctacagagtgagactgcat1620
ctcaaaaaaaacccmaaaaaacaaaaacaaacaacaacaacaaaattataaaggtagaaa1680
ataaatctaaattgtgtcgtaattaagattattaaaatgagaattatacaatgacttatt1740
tttggtggcaaatactttaggagcaataatgccttatggtaattattgatgtatagtttt1800
ttttgtttatgaagtcaaatttgtataaatttttttaattcaaaggaaaagttttatgtg1860
attttaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa1920
1922
as
<210> 44
<211> 1182 '
<212> DNA
<213> Human
<400> 44
aggacaccag gcacagagat ccaaactatt atatcaaatc caatccctaa aatggaagaa 60
gccaaaagcc aaagtttgga ggaagacttt gaaggacagg ccacacatac aggacccaaa 120
ggagtaataa atgattggag aaagtttaaa ttagagagtc aagacagtga ttcaattcca 180
cctagcaaga aggagattct caggcaaatg tcttctcctc agagtaggaa tggcaaagat 240
tcaaaggaac gagtcagcag aaagatgagc attcaagaat atgaactaat ccataaagag 300
aaagaggatg aaaactgcct tcgtaaatac cgtagacagt gtatgcagga tatgcaccag 360
149/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
aagctgagttttgggcctagatatgggtttgtgtatgagctggaaactggaaagcaattc420
ctagaaacaattgaaaaggaactgaagatcaccacaattgttgttcacatttatgaagat480
ggtattaagggttgtgatgctctaaacagtagtttaacatgccttgcagcagaataccct540
atagttaagttttgtaaaataaaagcttcgaatacaggtgctggggaccgcttttcctta600
gatgtacttcctacactgctcatctataaaggtggggaactcataagcaattttattagt660
gttgctgaacagtttgctgaagaattttttgctggggatgtggagtctttcctaaatgaa720
tatgggttactacctgaaagagaggtacatgtcctagagcataccaaaatagaagaagaa780
gatgttgaatgaagattcactatgtcaatatctcatgtttatcctttaggtattggatga840
tggttttggtagtatctatattgcttttgtgaacacagagtatgggcacggctatgctaa900
cttgacaaaaatgactgatgcaacaatcgagttattagcatttcatagtattagttactc960
aaattgatacaatgcttgactacaaaacaaagctgtcttcagcaacattattagtagaca1020
aagaggatgtggataatattatgacatttttcaaaaatccctttcaagttatgttttgtc1080
ttttttactccattttccctcatcactgttattatttggacttttcaaattacattattc1140
attataattttctttgtgtaataaaaatgaaatctcatgaag 1182
<210> 45
<211> 3160
<212> DNA
<213> Human
<400> 45
cctcccctcg cccggcgcgg tcccgtccgc ctctcgctcg cctcccgcct cccctcggtc 60
ttccgaggcgcccgggctcccggcgcggcggcggagggggcgggcaggccggcgggcggt 120
gatgtggcaggactctttatgcgctgcggcaggatacgcgctcggcgctgggacgcgact 180
gcgctcagttctctcctctcggaagctgcagccatgatggaagtttgagagttgagccgc 240
tgtgaggcgaggccgggctcaggcgagggagatgagagacggcggcggccgcggcccgga 300
gcccctctcagcgcctgtgagcagccgcgggggcagcgccctcggggagccggccggcct 360
gcggcggcggcagcggcggcgtttctcgcctcctcttcgtcttttctaaccgtgcagcct 420
cttcctcggcttctcctgaaagggaaggtggaagccgtgggctcgggcgggagccggctg 480
aggcgcggcggcggcggcggcggcacctcccgctcctggagcgggggggagaagcggcgg 540
cggcggcggccgcggcggctgcagctccagggagggggtctgagtcgcctgtcaccattt 600
ccagggctgggaacgccggagagttggtctctccccttctactgcctccaacacggcggc 660
ggcggcggcg gcacatccag ggacccgggc cggttttaaa cctcccgtcc gccgccgccg 720
150/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
caccccccgtggcccgggctccggaggccgccggcggaggcagccgttcggaggattatt780
cgtcttctccccattccgctgccgccgctgccaggcctctggctgctgaggagaagcagg840
cccagtcgctgcaaccatccagcagccgccgcagcagccattacccggctgcggtccaga900
gccaagcggcggcagagcgaggggcatcagctaccgccaagtccagagccatttccatcc960
tgcagaagaagccccgccaccagcagcttctgccatctctctcctcctttttcttcagcc1020
acaggctcccagacatgacagccatcatcaaagagatcgttagcagaaacaaaaggagat1080
atcaagaggatggattcgacttagacttgacctatatttatccaaacattattgctatgg1140
gatttcctgcagaaagacttgaaggcgtatacaggaacaatattgatgatgtagtaaggt1200
ttttggattcaaagcataaaaaccattacaagatatacaatctttgtgctgaaagacatt1260
atgacaccgccaaatttaattgcagagttgcacaatatccttttgaagaccataacccac1320
cacagctagaacttatcaaacccttttgtgaagatcttgaccaatggctaagtgaagatg1380
acaatcatgttgcagcaattcactgtaaagctggaaagggacgaactggtgtaatgatat1440
gtgcatatttattacatcggggcaaatttttaaaggcacaagaggccctagatttctatg1500
gggaagtaaggaccagagacaaaaagggagtaactattcccagtcagaggcgctatgtgt1560
attattatagctacctgttaaagaatcatctggattatagaccagtggcactgttgtttc1620
acaagatgatgtttgaaactattccaatgttcagtggcggaacttgcaatcctcagtttg1680
tggtctgccagctaaaggtgaagatatattcctccaattcaggacccacacgacgggaag1740
acaagttcatgtactttgagttccctcagccgttacctgtgtgtggtgatatcaaagtag1800
agttcttccacaaacagaacaagatgctaaaaaaggacaaaatgtttcacttttgggtaa1860
atacattcttcataccaggaccagaggaaacctcagaaaaagtagaaaatggaagtctat1920
gtgatcaagaaatcgatagcatttgcagtatagagcgtgcagataatgacaaggaatatc1980
tagtacttactttaacaaaaaatgatcttgacaaagcaaataaagacaaagccaaccgat2040
acttttctccaaattttaaggtgaagctgtacttcacaaaaacagtagaggagccgtcaa2100
atccagaggctagcagttcaacttctgtaacaccagatgttagtgacaatgaacctgatc2160
attatagatattctgacaccactgactctgatccagagaatgaaccttttgatgaagatc2220
agcatacacaaattacaaaagtctgaatttttttttatcaagagggataaaacaccatga2280
aaataaacttgaataaactgaaaatggacctttttttttttaatggcaataggacattgt2340
gtcagattaccagttataggaacaattctcttttcctgaccaatcttgttttaccctata2400
catccacagggttttgacacttgttgtccagttgaaaaaaggttgtgtagctgtgtcatg2460
151/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
tatatacctt tttgtgtcaa aaggacattt aaaattcaat taggattaat aaagatggca 2520
ctttcccgtt ttattccagt tttataaaaa gtggagacag actgatgtgt atacgtagga 2580
attttttccttttgtgttctgtcaccaactgaagtggctaaagagctttgtgatatactg2640
gttcacatcctacccctttgcacttgtggcaacagataagtttgcagttggctaagagag2700
gtttccgaaaggttttgctaccattctaatgcatgtattcgggttagggcaatggagggg2760
aatgctcagaaaggaaataattttatgctggactctggaccatataccatctccagctat2820
ttacacacacctttctttagcatgctacagttattaatctggacattcgaggaattggcc2880
gctgtcactgcttgttgtttgcgcatttttttttaaagcatattggtgctagaaaaggca2940
gctaaaggaagtgaatctgtattggggtacaggaatgaaccttctgcaacatcttaagat3000
ccacaaatgaagggatataaaaataatgtcataggtaagaaacacagcaacaatgactta3060
accatataaatgtggaggctatcaacaaagaatgggcttgaaacattataaaaattgaca3120
atgatttattaaatatgttttctcaattgtaaaaaaaaaa 3160
<210> 46
<211> 1224
<212> DNA
<213> Human
<400> 46
gggcaggaag acggcgctgc ccggaggagc ggggcgggcg ggcgcgcggg ggagcgggcg 60
gcgggcgggagccaggcccgggcgggggcgggggcggcggggccagaagaggcggcgggc 120
cgcgctccggccggtctgcggcgttggccttggctttggctttggcggcggcggtggaga 180
agatgctgcagtccctggccggcagctcgtgcgtgcgcctggtggagcggcaccgctcgg 240
cctggtgcttcggcttcctggtgctgggctacttgctctacctggtcttcggcgcagtgg 300
tcttctcctcggtggagctgccctatgaggacctgctgcgccaggagctgcgcaagctga 360
agcgacgcttcttggaggagcacgagtgcctgtctgagcagcagctggagcagttcctgg 420
gccgggtgctggaggccagcaactacggcgtgtcggtgctcagcaacgcctcgggcaact 480
ggaactgggacttcacctccgcgctcttcttcgccagcaccgtgctctccaccacaggtt 540
atggccacaccgtgcccttgtcagatggaggtaaggccttctgcatcatctactccgtca 600
ttggcattcccttcaccctcctgttcctgacggctgtggtccagcgcatcaccgtgcacg 660
tcacccgcag gccggtcctc tacttccaca tccgctgggg cttctccaag caggtggtgg 720
ccatcgtcca tgccgtgctc cttgggtttg tcactgtgtc ctgcttcttc ttcatcccgg 780
ccgctgtctt ctcagtcctg gaggatgact ggaacttcct ggaatccttt tatttttgtt 840
152/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
ttatttccct gagcaccatt ggcctggggg attatgtgcc tggggaaggc tacaatcaaa 900
aattcagaga gctctataag attgggatca cgtgttacct gctacttggc cttattgcca 960
tgttggtagt tctggaaacc ttctgtgaac tccatgagct gaaaaaattc agaaaaatgt 1020
tctatgtgaa gaaggacaag gacgaggatc aggtgcacat catagagcat gaccaactgt 1080
ccttctcctc gatcacagac caggcagctg gcatgaaaga ggaccagaag caaaatgagc 1140
cttttgtggc cacccagtca tctgcctgcg tggatggccc tgcaaaccat tgagcgtagg 1200
atttgttgca ttatgctaga gcac 1224
<210> 47
<21l> 4465
<212> DNA
<213> Human
<400>
47
caattgtcatacgacttgcagtgagcgtcaggagcacgtccaggaactcctcagcagcgc60
ctccttcagctccacagccagacgccctcagacagcaaagcctacccccgcgccgcgccc120
tgcccgccgctcggatgctcgcccgcgccctgctgctgtgcgcggtcctggcgctcagcc180
atacagcaaatccttgctgttcccacccatgtcaaaaccgaggtgtatgtatgagtgtgg240
gatttgaccagtataagtgcgattgtacccggacaggattctatggagaaaactgctcaa300
caccggaatttttgacaagaataaaattatttctgaaacccactccaaacacagtgcact360
acatacttacccacttcaagggattttggaacgttgtgaataacattcccttccttcgaa420
atgcaattatgagttatgtcttgacatccagatcacatttgattgacagtccaccaactt480
acaatgctgactatggctacaaaagctgggaagccttctctaacctctcctattatacta540
gagcccttcctcctgtgcctgatgattgcccgactcccttgggtgtcaaaggtaaaaagc600
agcttcctgattcaaatgagattgtggaaaaattgcttctaagaagaaagttcatccctg660
atccccagggctcaaacatgatgtttgcattctttgcccagcacttcacgcatcagtttt720
tcaagacagatcataagcgagggccagctttcaccaacgggctgggccatggggtggact780
taaatcatatttacggtgaaactctggctagacagcgtaaactgcgccttttcaaggatg840
gaaaaatgaaatatcagataattgatggagagatgtatcctcccacagtcaaagatactc900
aggcagagatgatctaccctcctcaagtccctgagcatctacggtttgctgtggggcagg960
aggtctttggtctggtgcctggtctgatgatgtatgccacaatctggctgcgggaacaca1020
acagagtatgcgatgtgcttaaacaggagcatcctgaatggggtgatgagcagttgttcc1080
agacaagcaggctaatactgataggagagactattaagattgtgattgaagattatgtgc1140
153/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
aacacttgag tggctatcac ttcaaactga aatttgaccc agaactactt ttcaacaaac 1200
aattccagta ccaaaatcgt attgctgctg aatttaacac cctctatcac tggcatcccc 1260
ttctgcctga cacctttcaa attcatgacc agaaatacaa ctatcaacag tttatctaca 1320
acaactctatattgctggaacatggaattacccagtttgttgaatcattcaccaggcaaa1380
ttgctggcagggttgctggtggtaggaatgttccacccgcagtacagaaagtatcacagg1440
cttccattgaccagagcaggcagatgaaataccagtcttttaatgagtaccgcaaacgct1500
ttatgctgaagccctatgaatcatttgaagaacttacaggagaaaaggaaatgtctgcag1560
agttggaagcactctatggtgacatcgatgctgtggagctgtatcctgcccttctggtag1620
aaaagcctcggccagatgccatctttggtgaaaccatggtagaagttggagcaccattct1680
ccttgaaaggacttatgggtaatgttatatgttctcctgcctactggaagccaagcactt1740
ttggtggagaagtgggttttcaaatcatcaacactgcctcaattcagtctctcatctgca1800
ataacgtgaagggctgtccctttacttcattcagtgttccagatccagagctcattaaaa1860
cagtcaccatcaatgcaagttcttcccgctccggactagatgatatcaatcccacagtac1920
tactaaaagaacgttcgactgaactgtagaagtctaatgatcatatttatttatttatat1980
gaaccatgtctattaatttaattatttaataatatttatattaaactccttatgttactt2040
aacatcttctgtaacagaagtcagtactcctgttgcggagaaaggagtcatacttgtgaa2100
gacttttatgtcactactctaaagattttgctgttgctgttaagtttggaaaacagtttt2160
tattctgttttataaaccagagagaaatgagttttgacgtctttttacttgaatttcaac2220
ttatattataagaacgaaagtaaagatgtttgaatacttaaacactatcacaagatggca2280
aaatgctgaaagtttttacactgtcgatgtttccaatgcatcttccatgatgcattagaa2340
gtaactaatgtttgaaattttaaagtacttttggttatttttctgtcatcaaacaaaaac2400
aggtatcagtgcattattaaatgaatatttaaattagacattaccagtaatttcatgtct2460
actttttaaaatcagcaatgaaacaataatttgaaatttctaaattcatagggtagaatc2520
acctgtaaaagcttgtttgatttcttaaagttattaaacttgtacatataccaaaaagaa2580
gctgtcttggatttaaatctgtaaaatcagatgaaattttactacaattgcttgttaaaa2640
tattttataagtgatgttcctttttcaccaagagtataaacctttttagtgtgactgtta2700
aaacttccttttaaatcaaaatgccaaatttattaaggtggtggagccactgcagtgtta2760
tctcaaaataagaatattttgttgagatattccagaatttgtttatatggctggtaacat2820
gtaaaatcta tatcagcaaa agggtctacc tttaaaataa gcaataacaa agaagaaaac 2880
caaattattg ttcaaattta ggtttaaact tttgaagcaa actttttttt atccttgtgc 2940
154/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
actgcaggcctggtactcagattttgctatgaggttaatgaagtaccaagctgtgcttga3000
ataacgatatgttttctcagattttctgttgtacagtttaatttagcagtccatatcaca3060
ttgcaaaagtagcaatgacctcataaaatacctcttcaaaatgcttaaattcatttcaca3120
cattaattttatctcagtcttgaagccaattcagtaggtgcattggaatcaagcctggct3180
acctgcatgctgttccttttcttttcttcttttagccattttgctaagagacacagtctt3240
ctcatcacttcgtttctcctattttgttttactagttttaagatcagagttcactttctt3300
tggactctgcctatattttcttacctgaacttttgcaagttttcaggtaaacctcagctc3360
aggactgctatttagctcctcttaagaagattaaaagagaaaaaaaaaggcccttttaaa3420
aatagtatacacttattttaagtgaaaagcagagaattttatttatagctaattttagct3480
atctgtaaccaagatggatgcaaagaggctagtgcctcagagagaactgtacggggtttg3540
tgactggaaaaagttacgttcccattctaattaatgccctttcttatttaaaaacaaaac3600
caaatgatat ctaagtagtt ctcagcaata ataataatga cgataatact tcttttccac 3660
atctcattgtcactgacatttaatggtactgtatattacttaatttattgaagattatta3720
'tttatgtcttattaggacactatggttataaactgtgtttaagcctacaatcattgattt3780
ttttttgttatgtcacaatcagtatattttctttggggttacctctctgaatattatgta3840
aacaatccaaagaaatgattgtattaagatttgtgaataaatttttagaaatctgattgg3900
catattgagatatttaaggttgaatgtttgtccttaggataggcctatgtgctagcccac3960
aaagaatattgtctcattagcctgaatgtgccataagactgaccttttaaaatgttttga4020
gggatctgtggatgcttcgttaatttgttcagccacaatttattgagaaaatattctgtg4080
tcaagcactgtgggttttaatatttttaaatcaaacgctgattacagataatagtattta4140
tataaataattgaaaaaaattttcttttgggaagagggagaaaatgaaataaatatcatt4200
aaagataactcaggagaatcttctttacaattttacgtttagaatgtttaaggttaagaa4260
agaaatagtcaatatgcttgtataaaacactgttcactgttttttttaaaaaaaaaactt4320
gatttgttattaacattgatctgctgacaa.aacctgggaatttgggttgtgtatgcgaat4380
gtttcagtgcctcagacaaatgtgtatttaacttatgtaaaagataagtctggaaataaa4440
tgtctgtttatttttgtactattta 4465
<210> 48
<211> 631
<212> DNA
<213> Human
155/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
<400>
48
caatacagctaaggaattatcccttgtaaataccacagacccgccctggagccaggccaa 60
gctggactgcataaagattggtatggccttagctcttagccaaacaccttcctgacacca 120
tgagggccagcagcttcttgatcgtggtggtgttcctcatcgctgggacgctggttctag 180
aggcagctgtcacgggagttcctgttaaaggtcaagacactgtcaaaggccgtgttccat 240
tcaatggacaagatcccgttaaaggacaagtttcagttaaaggtcaagataaagtcaaag 300
cgcaagagccagtcaaaggtccagtctccactaagcctggctcctgccccattatcttga 360
tccggtgcgccatgttgaatccccctaaccgctgcttgaaagatactgactgcccaggaa 420
tcaagaagtgctgtgaaggctcttgcgggatggcctgtttcgttccccagtgaagggagc 480
cggtccttgctgcacctgtgccgtccccagagctacaggccccatctggtcctaagtccc 540
tgctgcccttccccttcccacactgtccattcttcctcccattcaggatgcccacggctg 600
gagctgcctctctcatccactttccaataaa 631
<210> 49
<211> 701
<2l2> DNA
<2l3> Human
<220>
<221> misc_feature
<222> (464)..(464)
<223> n is a, c, g, 0r t
<400>
49
tttttttttcgcataaatattgcttttattacaagaaagaagagaccacctctgaagtaa 60
ggcacaacacaattccattgtcactgtggcagaagtccctgttgctcatccctttgatct 120
cagccaagactgtggtccacgggcctaaggcacttgagcttttccctcaactgaagtgta 180
gggggtgcctgagagctgagcctcgtgggagtgtccatggtctctggacctgcatcgaag 240
ttcatgtgtttccactggtgctgaagatgaacatcaagaattactagacatgtaaaagtg 300
tctttaagtgtctttcctcctgagtccacctttggcaatggtccccaaagcctggcccct 360
tagagatgcagctccagatcctggccaccctcagggttcaaagagactggcccaggggta 420
cacaattgctggaatattctctgcgagtcatgcacacgtgcggnggtgaggtgcagttat 480
atggtgacacacacagtgttactgtgagctctcagggtgcacagagggcaggtgacaagg 540
gcatcagctaatctgtcccacctggtccagcccatccagttcaggggcatcaagggggct 600
gaggccccggtagccactgtagaccctgtgactatcactgacacegtcactgggctccat 660
tgggcaaatgtagtccgcgattcatcgaacttcttttttct 701
156/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
<210> 50
<211> 602
<212> DNA
<2l3> Human
<400>
50
atttagaaatgtaaacatttatttaaaagtaggtagcaagttaaaaatgaatacttgcct 60
gaaatcataaaacataatcaagttctttttaaaacagttaatttttttcctataatttac 120
tttcatcgaaagtatattatctttgtttaacatgctagatagaagcaatttagcaacata 180
aaatatattagctatagtatgttcaaaagaatgagaaatataaattcagagatgagacca 240
tcattttttgcagttaaaaaaaaatgttgattctggtgcaacatacactgattatccagg 300
ttttacattttagggctgaaaccctgaggaacctgctggtgactgtttagcactgagcag 360
agttcagtgtgcatgcgcttccagagttaaaagctaaagcagactgagaaacaaaaaacc 420
aacatctttgcatttctgagttttcacttgtaatcataggttttcccaaattattagaat 480
gtctataccttagctgttttactagaatgatttatgctagtatagtcacttgtttagaag 540
tcggaaaaagatcattttttctttttagaaattactaagctctgttgtactacagctgat 600
cc 602
<210> 51
<211> 1653
<212> DNA
<213> Human
<400>
51
acgtccggggaggggccaggtgagcggcagacccggcacgcaggtgggggccggcggggt 60
ccgtggccagagctgcagagagacaaggcggcggcggctgctgtgctgggtgcagtgagg 120
1
aagaggccctcggtggtgcccatggctggccaggatcctgcgctgagcacgagtcacccg 180
ttctacgacgtggccagacatggcattctgcaggtggcaggggatgaccgctttggaaga 240
cgtgttgtcacgttcagctgctgccggatgccgccctcccacgagctggaccaccagcgg 300
ctgctggagtatttgaagtacacactggaccaatacgttgagaacgattataccatcgtc 360
tatttccactacgggctgaacagccggaacaagccttccctgggctggctccagagcgca 420
tacaaggagttcgataggaaagacggggatctcactatgtggcccaggctggtctcgaac 480
tccaagctcaagcgatcctcccacctcagcctcccaaagtactgggattacaggtacaag 540
aagaacttgaaggccctctacgtggtgcaccccaccagcttcatcaaggtcctgtggaac 600
atcttgaagcccctcatcagtcacaagtttgggaagaaagtcatctatttcaactacctg 660
157/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
agtgagctcc acgaacacct taaatacgac cagctggtca tccctcccga agttttgcgg 720
tacgatgaga agctccagag cctgcacgag ggccggacgc cgcctcctac caagacacca 780
ccgccgcggc ccccgctgcc cacacagcag tttggcgtca gtctgcaata cctcaaagac 840
aaaaatcaag gcgaactcat cccccctgtg ctgaggttca cagtgacgta cctgagagag 900
aaaggcctgcgcaccgagggcctgttccggagatccgccagcgtgcagaccgtccgcgag960
atccagaggctctacaaccaagggaagcccgtgaactttgacgactacggggacattcac1020
atccctgccgtgatcctgaagaccttcctgcgagagctgccccagccgcttctgaccttc1080
caggcctacgagcagattctcgggatcacctgtgtggagagcagcctgcgtgtcactggc1140
tgccgccagatcttacggagcctcccagagcacaactacgtcgtcctccgctacctcatg1200
ggctttctgcatgcggtgtcccgggagagcatcttcaacaaaatgaacagctctaacctg1260
gcctgtgtcttcgggctgaatttgatctggccatcccagggggtctcctccctgagtgcc1320
cttgtgcccctgaacatgttcactgaactgctgatcgagtactatgaaaagatcttcagc1380
accccggaggcacctggggagcacggcctggcaccatgggaacaggggag cagggcagcc1440
cctttgcaggaggctgtgccacggacacaagccacgggcctcaccaagcc taccctacct1500
ccgagtcccctgatggcagccagaagacgtctctagtgttgcgaacactc tgtatgtttc1560
gagctacctcccacacctgtctgtgcacttgtatgttttgtaaacttggc atctgtaaaa1620
ataaccagccattagatgaattcagaaccttct 1653
<210> 52
<211> 846
<212> DNA
<213> Human
<400>
52
gtataaggtccacaccccgggagctgagtgattgcagaaactggccttccatctctctca 60
gacaccaagctgcagatccaggcttttctgggaaagtgaggccaccatggctctggagaa 120
gtctcttgtccggctccttctgcttgtcctgatactgctggtgctgggctgggtccagcc 180
ttccctgggcaaggaatcccgggccaagaaattccagcggcagcatatggactcagacag 240
ttcccccagcagcagctccacctactgtaaccaaatgatgaggcgccggaatatgacaca 300
ggggcggtgcaaaccagtgaacacctttgtgcacgagcccctggtagatgtccagaatgt 360
ctgtttccaggaaaaggtcacctgcaagaacgggcagggcaactgctacaagagcaactc 420
cagcatgcacatcacagactgccgcctgacaaacggctccaggtaccccaactgtgcata 480
ccggaccagc ccgaaggaga gacacatcat tgtggcctgt gaagggagcc catatgtgcc 540
158/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
agtccacttt gatgcttctg tggaggactc tacctaaggt cagagcagcg agatacccca 600
cctccctcaacctcatcctctccacagctgcctcttccctcttccttccctgctgtgaaa660
gaagtaactacagttagggctcctattcaacacacacatgcttccctttcctgagtccca720
tccctgcgtgattttgggggtgaagagtgggttgtgaggtgggccccatgttaacccctc780
cactctttctttcaataaaacgcagttgcaaacaataaaaaaaaaaaaaaaaaaaaaaaa840
aaaaaa 846
<210> 53
<2l1> 2566
<212> DNA
<213> Human
<400> 53
ggcacgagtt gtgctcctcg cttgcctgtt ccttttccac gcattttcca ggataactgt 60
gactccaggcccgcaatggatgccctgcaactagcaaattcggcttttgccgttgatctg120
ttcaaacaactatgtgaaaaggagccactgggcaatgtcctcttctctccaatctgtctc180
tccacctctctgtcacttgctcaagtgggtgctaaaggtgacactgcaaatgaaattgga240
caggttcttcattttgaaaatgtcaaagatataccctttggatttcaaacagtaacatcg300
gatgtaaacaaacttagttccttttactcactgaaactaatcaagcggctctacgtagac360
aaatctctgaatctttctacagagttcatcagctctacgaagagaccctatgcaaaggaa420
ttggaaactgttgacttcaaagataaattggaagaaacgaaaggtcagatcaacaactca480
attaaggatctcacagatggccactttgagaacattttagctgacaacagtgtgaacgac540
cagaccaaaatccttgtggttaatgctgcctactttgttggcaagtggatgaagaaattt600
cctgaatcagaaacaaaagaatgtcctttcagactcaacaagacagacaccaaaccagtg660
cagatgatgaacatggaggccacgttctgtatgggaaacattgacagtatcaattgtaag720
atcatagagcttccttttcaaaataagcatctcagcatgttcatcctactacccaaggat780
gtggaggatgagtccacaggcttggagaagattgaaaaacaactcaactcagagtcactg840
tcacagtggactaatcccagcaccatggccaatgccaaggtcaaactctccattccaaaa900
tttaaggtggaaaagatgattgatcccaaggcttgtctggaaaatctagggctgaaacat960
atcttcagtgaagacacatctgatttctctggaatgtcagagaccaagggagtggcccta1020
tcaaatgttatccacaaagtgtgcttagaaataactgaagatggtggggattccatagag1080
gtgccaggagcacggatcctgcagcacaaggatgaattgaatgctgaccatccctttatt1140
tacatcatcaggcacaacaaaactcgaaacatcattttctttggcaaattctgttctcct1200
159/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
taagtggcatagcccatgttaagtcctccctgacttttctgtggatgccgatttctgtaa1260
actctgcatccagagattcattttctagatacaataaattgctaatgttgctggatcagg1320
aagccgccagtacttgtcatatgtagccttcacacagatagacctttttttttttccaat1380
tctatcttttgtttccttttttcccataagacaatgacatacgcttttaatgaaaaggaa1440
tcacgttagaggaaaaatatttattcattatttgtcaaattgtccggggtagttggcaga1500
aatacagtcttccacaaagaaaattcctataaggaagatttggaagctcttcttcccagc1560
actatgctttccttctttgggatagagaatgttccagacattctcgcttccctgaaagac1620
tgaagaaagtgtagtgcatgggacccacgaaactgccctggctccagtgaaacttgggca1680
catgctcaggctactataggtccagaagtccttatgttaagccctggcaggcaggtgttt1740
attaaaattctgaattttggggattttcaaaagataatattttacatacactgtatgtta1800
tagaacttcatggatcagatctggggcagcaacctataaatcaacaccttaatatgctgc1860
aacaaaatgtagaatattcagacaaaatggatacataaagactaagtagcccataagggg1920
tcaaaatttgctgccaaatgcgtatgccaccaacttacaaaaacacttcgttcgcagagc1980
ttttcagattgtggaatgttggataaggaattatagacctctagtagctgaaatgcaaga2040
ccccaagaggaagttcagatcttaatataaattcactttcatttttgatagctgtcccat2100
ctggtcatgtggttggcactagactggtggcaggggcttctagctgactcgcacagggat2160
tctcacaatagccgatatcagaatttgtgttgaaggaacttgtctcttcatctaatatga2220
tagcgggaaaaggagaggaaactactgcctttagaaaatataagtaaagtgattaaagtg2280
ctcacgttaccttgacacatagtttttcagtctatgggtttagttactttagatggcaag2340
catgtaacttatattaatagtaatttgtaaagttgggtggataagctatccctgttgccg2400
gttcatggattacttctctataaaaaatatatatttaccaaaaaattttgtgacattcct2460
tctcccatctcttccttgacatgcattgtaaataggttcttcttgttctgagattcaata2520
ttgaatttctcctatgctattgacaataaaatattattgaactacc 2566
<210> 54
<211> 555
<212> DNA
<213> Human
<220>
<221> misc_feature
<222> (9). (10)
<223> n is a, c, g, or t
<400> 54
160/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
tttttattnn ttcagttctg ggtctataga aacccagggg gattttcatt tgctacaaca 60
gattcccttctaataaaatgcactggcaaggtgaccagtgagtgacccaatgtctggttg 120
ggaaatctctctctgaacttcttgctgttggacctaaaatgtggatgtaaattggatcac 180
agctggtttggcattgaaaaaaatacatacacaacaaacaattacaacttctttatatgg 240
cagtttttactgggtgtctaatactctctttactgtctcaagtggaagtccaaacaaatt 300
tcatttttgtagtaaaaaatctttatttccaaaatgatttgttagccaaaagaactataa 360
accacctaacaagactttggtaagaaagagacttgatgcttcttataaattccccattgc 420
aaacaaaaaataacaatccaacaagagtcatgttacccattcttagccattaacctggtt 480
ttaagtctccaaaatcaggattttaaaatgtacccaactgggaccaaatacaaacatgag 540
acactagggtggctt 555
<210> 55
<211> 1984
<212> DNA
<213> Human
<400>
55
ggatccagagatttagattttttataagctttcctgccaccgaaacgggtgtttgggacc 60
tcacgaggccctgttcattcttcgtcgctgcgctccccactctgtactggatgcatttac 120
tgacgttgttgtctccgtccccagagtatgaacccccaaggtgactcatgcagctgtggg 180
tgcccggcatacagcatggtgactggaatggatgagcacccaataaacatttgttgcagg 240
aatgcaggaggacgggcaggccagcaagcaggctgcctggtttttcccacatgggctttt 300
ctgggaaagaagagcttctatttttggaaagggctgctatgattgagaaaagttcatggc 360
agcaaaaaaaggacagacgtcgggagggaaacactcctagttctcccagacaacacattt 420
tttaaaaagactccttcatctctttaataataacggtaacgacaatgacaatgatgatta 480
cttatgagtgcggctagtgccagccactgtgttgtcactgggcgagtaatgatctcattg 540
gatcttcacggtgggcgtgcggggctccagggacagcctgcgttcctgggctggctgggt 6,00
gcagctctcttttcaggagagaaagctctcttggaggagctggaaaggtgcccgactcca 660
gccatgctggcgctactgtgttcctgcctgctcctggcagccggtgcctcggacgcctgg 720
acgggcgaggactcggcggagcccaactctgactcggcggagtggatccgagacatgtac 780
gccaaggtcacggagatctggcaggaggtcatgcagcggcgggacgacgacggcacgctc 840
cacgccgcctgccaggtgcagccgtcggccacgctggacgccgcgcagccccgggtgacc 900
ggcgtcgtcctcttccggcagcttgcgccccgcgccaagctcgacgccttcttcgccctg 960
161/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
gagggcttcccgaccgagccgaacagctccagccgcgccatccacgtgcaccagttcggg1020
gacctgagccagggctgcgagtccaccgggccccactacaacccgctggccgtgccgcac1080
ccgcagcacccgggcgacttcggcaacttcgcggtccgcgacggcagcctctggaggtac1140
cgcgccggcctggccgcctcgctcgcgggcccgcactccatcgtgggccgggccgtggtc1200
gtccacgctggcgaggacgacctgggccgcggcggcaaccaggccagcgtggagaacggg1260
aacgcgggccggcggctggcetgctgcgtggtgggcgtgtgcgggcccgggctctgggag1320
cgccaggcgcgggagcactcagagcgcaagaagcggcggcgcgagagcgagtgcaaggcc1380
gcctgagcgcggcccccacccggcggcggccagggacccccgaggcccccctctgccttt1440
gagcttctcctctgctccaacagacaccttccactctgaggtctcaccttcgcctctgct1500
gaagtctccccgcagccctctccacccagaggtctccctataccgagacccaccatcctt1560
ccatcctgaggaccgccccaaccctcggagccccccactcagtaggtctgaaggcctcca1620
tttgtaccgaaacaccccgctcacgctgacagcctcctaggctccctgaggtacctttcc1680
acccagaccctccttccccaccccataagccctgagactcccgcctttgacctgacgatc1740
ttcccccttcccgccttcaggttcctcctaggcgctcagaggccgctctg'gggggttgcc1800
tcgagtccccccacccctccccacccaccaccgctcccgcggcaagccagcccgtgcaac1860
ggaagccaggccaactgccccgcgtcttcagctgtttcgcatccaccgccaccccactga1920
gagctgctcctttgggggaatgtttggcaacctttgtgttacagattaaaaattcagcaa1980
ttca 1984
<210> 56
<211> 1621
<212> DNA
<213> Human
<400>
56
ggcacgaggggacagctcctgcctcccgcagggcccacctgtgtcccccagcgccgctcc60
acccagcaggcctgagcccctctctgctgccagacaccccctgctgcccactctcctgct120
gctcgggttctgaggcacagcttgtcacaccgaggcggattctctttctctttctctttc180
tcttctggcccacagccgcagcaatggcgctgagttcctctgctggagttcatcctgcta240
gctgggttcccgagctgccggtctgagcctgaggcatggagcctcctggagactgggggc300
ctcctccctggagatccacccccagaaccgacgtcttgaggctggtgctgtatctcacct360
tcctgggagc cccctgctac gccccagctc tgccgtcctg caaggaggac gagtacccag 420
tgggctccga gtgctgcccc aagtgcagtc caggttatcg tgtgaaggag gcctgcgggg 480
162/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
agctgacgggcacagtgtgtgaaccctgccctccaggcacctacattgcccacctcaatg540
gcctaagcaagtgtctgcagtgccaaatgtgtgacccagccatgggcctgcgcgcgagcc600
ggaactgctccaggacagagaacgccgtgtgtggctgcagcccaggccacttctgcatcg660
tccaggacggggaccactgcgccgcgtgccgcgcttacgccacctccagcccgggccaga720
gggtgcagaagggaggcaccgagagtcaggacaccctgtgtcagaactgccccccgggga780
ccttctctcccaatgggaccctggaggaatgtcagcaccagaccaagtgcagctggctgg840
tgacgaaggccggagctgggaccagcagctcccactgggtatggtggtttctctcaggga900
gcctcgtcatcgtcattgtttgctccacagttggcctaatcatatgtgtgaaaagaagaa960
agccaaggggtgatgtagtcaaggtgatcgtctccgtccagcggaaaagacaggaggcag1020
aaggtgaggccacagtcattgaggccctgcaggcccctccggacgtcaccacggtggccg1080
tggaggagacaataccctcattcacggggaggagcccaaaccactgacccacagactctg1140
caccccgacgccagagatacctggagcgacggctgctgaaagaggctgtccacctggcga1200
aaccaccggagcccggaggcttgggggctccgccctgggctggcttccgtctcctccagt1260
ggagggagaggtggggcccctgctggggtagagctggggacgccacgtgccattcccatg1320
ggccagtgagggcctggggcctctgttctgctgtggcctgagctccccagagtcctgagg1380
aggagcgccagttgcccctcgctcacagaccacacacccagccctcctgggccagcccag1440
agggcccttcagaccccagctgtctgcgcgtctgactcttgtggcctcagcaggacaggc1500
cccgggcactgcctcacagccaaggctggactgggttggctgcagtgtggtgtttagtgg1560
ataccacatcggaagtgattttctaaattggatttgaattcggaaaaaaaaaaaaaaaaa1620
a 1621
<210> 57
<211> 2755
<212> DNA
<213> Human
<400>
57
cctacccgcgcgcaggccaagttgctgaatcaatggagccctccccaacccgggcgttcc60
ccagcgaggcttccttcccatcctcctgaccaccggggcttttcgtgagctcgtctctga120
tctcgcgcaagagtgacacacaggtgttcaaagacgcttctggggagtgagggaagcggt180
ttacgagtgacttggctggagcctcaggggcgggcactggcacggaacacaccctgaggc240
cagccctggctgcccaggcggagctgcctcttctcccgcgggttggtggacccgctcagt300
acggagttggggaagctctttcacttcggaggattgctcaacaaccatgctgggcatctg360
163/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
gaccctcctacctctggttcttacgtctgttgctagattatcgtccaaaagtgttaatgc420
ccaagtgactgacatcaactccaagggattggaattgaggaagactgttactacagttga480
gactcagaacttggaaggcctgcatcatgatggccaattctgccataagccctgtcctcc540
aggtgaaaggaaagctagggactgcacagtcaatggggatgaaccagactgcgtgccctg600
ccaagaagggaaggagtacacagacaaagcccatttttcttccaaatgcagaagatgtag660
attgtgtgatgaaggacatggcttagaagtggaaataaactgcacccggacccagaatac720
caagtgcagatgtaaaccaaactttttttgtaactctactgtatgtgaacactgtgaccc780
ttgcaccaaatgtgaacatggaatcatcaaggaatgcacactcaccagcaacaccaagtg840
caaagaggaaggatccagatctaacttggggtggctttgtcttcttcttttgccaattcc900
actaattgtttgggtgaagagaaaggaagtacagaaaacatgcagaaagcacagaaagga960
aaaccaaggttctcatgaatctccaaccttaaatcctgaaacagtggcaataaatttatc1020
tgatgttgacttgagtaaatatatcaccactattgctggagtcatgacactaagtcaagt1080
taaaggctttgttcgaaagaatggtgtcaatgaagccaaaatagatgagatcaagaatga1140
caatgtccaagacacagcagaacagaaagttcaactgcttcgtaattggcatcaacttca1200
tggaaagaaagaagcgtatgacacattgattaaagatctcaaaaaagccaatctttgtac1260
tcttgcagagaaaattcagactatcatcctcaaggacattactagtgactcagaaaattc1320
aaacttcagaaatgaaatccaaagcttggtctagagtgaaaaacaacaaattcagttctg1380
agtatatgcaattagtgtttgaaaagattcttaatagctggctgtaaatactgcttggtt1440
ttttactgggtacattttatcatttattagcgctgaagagccaacatatttgtagatttt1500
taatatctcatgattctgcctccaaggatgtttaaaatctagttgggaaaacaaacttca1560
tcaagagtaaatgcagtggcatgctaagtacccaaataggagtgtatgcagaggatgaaa1620
gattaagattatgctctggcatctaacatatgattctgtagtatgaatgtaatcagtgta1680
tgttagtacaaatgtctatccacaggctaaccccactctatgaatcaatagaagaagcta1740
tgaccttttgctgaaatatcagttactgaacaggcaggccactttgcctctaaattacct1800
ctgataattctagagattttaccatatttctaaactttgtttataactctgagaagatca1860
tatttatgtaaagtatatgtatttgagtgcagaatttaaataaggctctacctcaaagac1920
ctttgcacagtttattggtgtcatattatacaatatttcaattgtgaattcacatagaaa1980
acattaaattataatgtttgactattatatatgtgtatgcattttactggctcaaaacta2040
cctacttctttctcaggcatcaaaagcattttgagcaggagagtattactagagctttgc2100
cacctctccatttttgccttggtgctcatcttaatggcctaatgcacccccaaacatgga2160
164/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
aatatcaccaaaaaatacttaatagtccaccaaaaggcaagactgcccttagaaattcta2220
gcctggtttggagatactaactgctctcagagaaagtagctttgtgacatgtcatgaacc2280
catgtttgcaatcaaagatgataaaatagattcttatttttcccccacccccgaaaatgt2340
tcaataatgtcccatgtaaaacctgctacaaatggcagcttatacatagcaatggtaaaa2400
tcatcatctggatttaggaattgctcttgtcatacccccaagtttctaagatttaagatt2460
ctccttactactatcctacgtttaaatatctttgaaagtttgtattaaatgtgaatttta2520
agaaataatatttatatttctgtaaatgtaaactgtgaagatagttataaactgaagcag2580
atacctggaaccacctaaagaacttccatttatggaggatttttttgccccttgtgtttg2640
gaattataaaatataggtaaaagtacgtaattaaataatgtttttggtaaaaaaaaaaaa2700
aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaa 2755
<210> 58
<211> 2553
<212> DNA
<213> Human
<400>
58
ctaaaggccttgcacaacatcagagagttcatactggagagaaccttacacatttcacga60
gtatggaaagacctttgctcaaaattcagcccttgtaatgcataaggcaattcatactgg120
aaagaaaccttacacatgtaatgaatgtggcaaggtttttagtagaaaagcacaccttgc180
atgtcatcatagacttcatactgtctaaggtttctaatcaacaatcaaaccttgcacaac240
atcagagagtttatactggagagaaaccttacaagtgtaatgagtggggcaaagccttaa300
gtgggaagtcgtcacttttttatcatcaagcaatccatggtgtagggaaactttgcaaat360
gtaatgattgtcacaaagtcttcagtaatgctacaaccattgcaaatcactggagaatcc420
ataatgaagacagatcttacaagtgtaataaatgtggtaaaattttcagacatcgatcat480
atcttgcagtttatcagcgaactcatactggagagaaaccttacaaatatcatgactgtg540
gcaaggtcttcagtcaagcttcatcctatgcaaaacataggagaattcatacaggagaga600
aacctcacaagtgtgatgattgtggcaaagtcttgacttcacgttcacacctcattagac660
atcagagaatccatactggacagaaatcttacaaatgtcttaagtgtggcaaggtcttca720
gtctgtgggcactccatgcagaacatcagaaaattcatttttgagataactgttccaaat780
acagtgactatagaagatcataaagctttaattgacattagagccaaataggcattgact840
tgagattgagttgacttaaccttgagtttaagaattaatttacattaaagtgtttatgtt900
aagaagattgggccaggtgggattacaggcgcgagcaccgcgcccggcccctaagttaat960
165/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
atttcaaacaatcgaaggtaaaacaacatattgtgttgggccacctgtactgaacgctga1020
atcgtttttcctcttaagttgaaaatggttttaatgcaaagcgcctttttttgagcaggt1080
agagtcacgcatccggcaggcggggcgagctcccctctgtctggggcagggtgggggaga1140
ggggcagggacctcggtaaaggggtggagtggcgcgctggttgccgcgggcactggcaat1200
tagaagggattattaaactaagcaaggtcctgggttgtttgagtggataatggaaactga1260
aaggtgacgtgcaaaactgcctattactcccaggagtggaggataatttcatatttcatg1320
gaaataaactcagggcccggagcggtggctcacacctgtaatcccagcactttgagaggc1380
caaggagggaggatcgcttaagcccaggaattcgaaatcagcctaggcaacatagtaaga1440
cctcatctctactaaaaataaaaaaaaacagccaggtgtgttagtccacacctgtggtcc1500
cagctgcctcagcttcccgagtagctgggattacaggtatgaaccactatgcccggctaa1560
ctttgttttttttttttagaaattaaaccttttttcagcttaatgacccaggggtgtatt1620
tttgaaggacttgggagctctctttgaaaggcaaacaacaagggaaacagtacctttatc1680
tcagtaggaaattaaataattcaaacatcaaataacttcaatttaaggctatggactttg1740
agataattctgagccttgagaggaatgtggtcaggcaacctgagtccagtggaatgcagg1800
tgcaacttctaagagttttcctgtaagtaattaagaagactaagtagccccagagataag1860
acctcctcggatcattgtcccttcttatgtagtgataaagtaaccttccttgaagtgtat1920
ctatccgtaatcaatcaagttgctgcagcctatgcactggcccagaataaaaaacgtggt1980
gattctgctaaagcttctctgtctttccctgtgtgtgaaatcttaacgtctctacttggg2040
aacgctgatcccattcatttagagttgatgtttccacgtggctatttccaagctttgcct2100
tcaaataaattctgtacttaatcatatattctaaattttattatttactgctgacatcag2160
tttctgtcggattgtaggagcctcaccagagagggcccctgtcgccatgttgtaaaactc2220
acacttgccaaaagttgtgggttagggtttctccccctccctcaggatgacgctagttag2280
ctgacacagatggtcacctccattaccaagtagagtcaggatgaactatgtgtgactgtt2340
caactatgtgtcctcttccctgaggactgattagtgtttatcttgaaaacatgtccttaa2400
tgggttgtatagaacactgaagcatctgatttcaaactcttagctcttttcctctatttc2460
ccatcacattctggtctaaggcttatttattaataaaatgatttttatttctttaaacaa2520
aaaaaactttagagcacactggggtaccggatc 2553
<210> 59
<211> 452
< 212 > DI~iA
166/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
<213>
Human
<400>
59
gcggccgcgttgatccacagggcgctgttcagaaagcccaggaaagcaaagagccagtga60
agcctggggggctggctgtcagatgtggcaaaaaaggtcactgaagccaaggctgtgcct120
gcgatcaccaccacgacccagacgggaacgaggccgcctatctcatagacaccataggtc180
cccgactgcagggtcaggaccacaaccagggggctgataaccagatgcagacagttgagg240
ggccgtttccagttctggtcatccttgtccgggtccacgacggggactgtgaggagcagc300
aggaactccacaggcagcttgaacaccttgagggctttccagtatgctgatttccttctc360
cacttcatgtaatccaggggattgagggcccggaccaggatctgagccgtggtctcctgg420
tagaagaacagcggccggtactcatcaccgto 452
<210> 60
<211> 1130
<2l2> DNA
<213> Human
<400>
60
ggcccttagagtcttggttgccaaacagatttgcagatcaaggagaacccaggagtttca60
aagaagcgctagtaaggtctctgagatccttgcactagctacatcctcagggtaggagga120
agatggcttccagaagcatgcggctgctcctattgctgagctgcctggccaaaacaggag180
tcctgggtgatatcatcatgagacccagctgtgctcctggatggttttaccacaagtcca240
attgctatggttacttcaggaagctgaggaactggtctgatgccgagctcgagtgtcagt300
cttacggaaacggagcccacctggcatctatcctgagtttaaaggaagccagcaccatag360
cagagtacataagtggctatcagagaagccagccgatatggattggcctgcacgacccac420
agaagaggcagcagtggcagtggattgatggggccatgtatctgtacagatcctggtctg480
gcaagtccatgggtgggaacaagcactgtgctgagatgagctccaataacaactttttaa540
cttggagcag caacgaatgc aacaagcgcc aacacttcct gtgcaagtac cgaccataga 600
gcaagaatca agattctgct aactcctgca cagccccgtc ctcttccttt ctgctagcct 660
ggctaaatctgctcattatttcagaggggaaacctagcaaactaagagtgataagggccc720
tactacactggcttttttaggcttagagacagaaactttagcattggcccagtagtggct780
tctagctctaaatgtttgccccgccatccctttccacagtatccttcttccctcctcccc840
tgtctctggctgtctcgagcagtctagaagagtgcatctccagcctatgaaacagctggg900
tctttggccataagaagtaaagatttgaagacagaaggaagaaactcaggagtaagcttc960
tagaccccttcagcttctacacccttctgccctctctccattgcctgcaccccaccccag1020
167/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
ccactcaact cctgcttgtt tttcctttgg ccataggaag gtttaccagt agaatccttg 1080
ctaggttgat gtgggccata cattccttta ataaaccatt gtgtacataa 1130
<210> 61
<211> 3323
<212> DNA
<213> Human
<400>
61
tgcttcataaaatttacctaagcaagtggtcttgcttgcctcaaatccaagcagtcttga60
acacttggaggcaattaatgagtatatcttagtcaaaagaattgttggagctttttatta120
aagctgcagtttcagttctgcttttggggaattgtgctatgaaagcagctgccaaaataa180
gctcatttattttcttcaatcccactcagtgctcagtcactatattctgtttcctttttt240
tttttcaagttgcatatttggtttccccttatgattgggaaagatgaattttcagcagaa300
aacagtgtttgttcactttcaaagagtgatagtttctaaaacatttagagcaataaatat360
tcatcagaggtaccaagtaagccagcagaagagttaagggttagagaaatcccttatttc420
atgtcttgactctaaaatgatcaaagtacttttccttgtaatgtggatttcttcttatgc480
ggatatgcaaaaacttcagttatacgtagtaatgctagcaggtaattttagtggacattt540
tataacaactgtcactttgttttgccacatgtagagtttgttcagctattttccagatat600
ctccccacaaaaggaggcaaagggtaccagcttttcaatgagcattacctattacttggc660
aaagatgatgaagactctattaatagttcatttgataaatgttgacataaccaacaatag720
agattaggaagttagttttaagaaatcaatagcatatagacattaccctcatggagtttg780
tattctactacttgaactgattgtagctataaaagcatagttagatagctgaatagttag840
atcataagcaaagaaggccagaacacatctcttatcaagaaatcaatgaatagtttatct900
catttttaaagcaactttatccttctttaattccttcctttcttctagtgcaaaactact960
taataaggttggtgtttaggttagtgttcacaccattcctcatctggtgtgaattacctt1020
ctctttctttactatttactaccaacctagtacatgtgttgactgaattcttttcaaaca1080
atgttgagttatcatggtgcacctaataaattaacaccacagattacagcatccttgctg1140
attttctcagcaaagccagattagatggaaataaacaaagaaaatgatcctagagtgaat1200
ttttctagaaaatatctattatgaaccatgctgtttaaagtattagcttgaaggtgatgg1260
atccagctattcagaaaataactttcatataaccatgattttgcacagtatgaggtctta1320
aatgtgtggaaagagataaattttttatcattaccacaaaccccttttaaagattcaaag1380
gtggaagaaagtgatttattttttctcttcagcatacatatataaaagacttgtcagatg1440
168/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
tttaatttggggaggttgataatgaaacatatcaacagagtatagtagttatagtagtgt1500
ttgtgggtaaataatttcctggggtcagacatatataaacatatttgcttcaaaatgata1560
aaggcatgaaatcagtcttaaaaattgaaatgggggtgatgggggagaaaaagaagaaca1620
aatttgaagtgccctttcaaatctgctggatacaagtattgaagttttaagtcatcttat1680
tctgtctgaaagtgtatttttcattctacaatagacccaatcaacaagacgtataacttg1740
agttgcatgatgttcagtttatgtaatctactgttgggatggtaagaattgatgtaggct1800
gtggtgtaagaatgaattaaaatatagtttcactggcttttctctacatatccactatca1860
caatggctaggtttcctgttgctcactgttggattctggagaaaaatttaatgaaagatg1920
atatcagagg aagaataagt ggaggtagag aagaaaggag tgatagagga ggggaaaaaa 1980
acaaaacata tttttgtgtt atccaaagga gctttttcct tattctgtca agcattgaga 2040
tcttcttcag ctttcaatgt agttgctaaa tacaaataat gctactaggt agtgactaaa 2100
tatagcaaac acttcatcag atattagaat taggtcacac tattgaggtt ataatctgaa 2160
ggttgtgtta catagaaacc actttagatt attatcaact tgggctaggc tttattttat 2220
aatagcatag taagtaatat ctattgtgtc atttcttcaa ccattttatt ctaagatcca 2280
tgaagcttct tgaggccaaa taaaataata agtttagaca agaagtagat tgtgactttt 2340
tttcccttag agatactatt tactatctcc tatcctgata ggtggaaggt ttactgaatt 2400
ggaaattggt tgactattag tttttaacta aaatgtgcaa taacacattg cagtttcctc 2460
aaactagttt cctatgatca ttaaactcat tctcagggtt aagaaaggaa tgtaaatttc 2520
tgcctcaatt tgtacttcat caataagttt ttgaagagtg cagattttta gtcaggtctt 2580
aaaaataaac tcacaaatct ggatgcattt ctaaattctg caaatgtttc ctggggtgac 2640
ttaacaagga ataatcccac aatataccta gctacctaat acatggagct ggggctcaac 2700
ccactgtttt taaggatttg cgcttacttg tggctgagga aaaataagta gttcgaggaa 2760
gtagttttta aatgtgagct tatagataga aacagaatat caacttaatt atgaaattgt 2820
tagaacctgt tctcttgtat ctgaatctga ttgcaattac tattgtactg atagactcca 2880
gccattgcaa gtctcagata tcttagctgt gtagtgattc ttgaaattct ttttaagaaa 2940
aattgagtag aaagaaataa accctttgta aatgaggctt ggcttttgtg aaagatcatc 3000
cgcaggctat gttaaaagga ttttagctca ctaaaagtgt aataatggaa atgtggaaaa 3060
tatcgtaggt aaaggaaact acctcatgct ctgaaggttt tgtagaagca caattaaaca 3120
tctaaaatgg ctttgttaca ccagagccat ctggtgtgaa gaactctata tttgtatgtt 3180
169/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
gagagggcat ggaataattg tattttgctg gcaatagaca cattctttat tatttgcaga 3240
ttcctcatca aatctgtaat tatgcacagt ttctgttatc aataaaacaa aagaatcctg 3300
ttaaaaaaaa aaaaaaaaaa aaa 3323
<210> 62
<211> 737
<212> DNA
<213> Human
<400>
62
gggaatgccctaacaacacccatgcttgtgttgctgggagctgacattcaagaaaagtgc60
attaaaaattccttgagaaggcatattcttttgagagccgtaaatgaaaagtgcattcac120
ggagaacatgctcctttgttgtgagaggaaagaaaggactgttgttgcctttaaggaaca180
ggtttcccagttccccggaatgtcagggtcacatgaggaatgggtgagcacttagggcca240
agattgtcgtgtgcttggcccggcagcttctctctaagtgacctctccagcatcactctg300
tgccagtgctcatatctgaggccacttgagtgtcacgaggcagagcctggaaacattagc360
tttggaaaccgttccttcctttttatgtggaggaaagtaaggtttcacaagacacctaag420
ctggacatggtgatgtgccacttggatagttcccaaaagcagaaagcagcaggacatccc480
agtaccccacttctccgtgccgtgtactttcagggaggttctcgaaagctagcttcttta540
ccgatgatttgtctatgtactggttatggtggaaaaccttgcatttattacctggtccta600
tctcagagtcttctattcagcattcaatatgacttctaatgcttctaattggactgtatg660
gacagagaaccggtttgtcattcacgggccgcggatataatcagagcctggaatccgcca720
aaaggtcggtgccggat 737
<210> 63
<211> 3780
<212> DNA
<213> Human
<400> 63
tactggacaa acatttcctc caaggacaca gctctctgcc tccatgtcac cacctttgaa , 60
ggactgactg attccctcgg ctggtgccag tgcctgctcc tgccatgggg cccgcgggga 120
gcctgctggg cagcggacag atgcagatca ccctgtgggg aagtctggca gctgtcgcca 180
ttttcttcgt catcaccttc ctcatcttcc cgtgctctag ttgtgacagg gaaaagaagc 240
cgcgacagca tagtggggac catgagaacc tgatgaacgt gccttcagac aaggagatgt 300
tcagccgttc agttactagc ctggcaacag atgctcctgc cagcagtgag cagaatgggg 360
cactcaccaa tggggacatt ctttcagagg acagtactct gacctgcatg cagcattacg 420
170/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
aggaagtccagacatcggcctcggatctgctggattcccaggacagcacagggaaaccaa480
aatgtcatcagagtcgggagctgcccagaatccctcccgagagcgcagtggataccatgc540
tcacggcgagaagtgtggacggggaccaggggctggggatggaagggccctatgaagtgc600
tcaaggacagctcctcccaagaaaacatggtggaggactgcttgtatgaaactgtgaagg660
agatcaaggaggtggctgcagctgcacacctggagaaaggccacagtggcaaggcaaaat720
ctacttctgcctcgaaagagctcccagggccccagactgaaggcaaagctgagtttgctg780
aatatgcctcggtggacagaaacaaaaaatgtcgtcaaagtgttaatgtagagagtatcc840
ttggaaattcatgtgatccagaagaggaggccccaccacctgtccctgttaagcttctgg900
acgagaatgaaaaccttcaggagaaggaagggggagaggcggaagagagtgccacagaca960
cgaccagtgaaactaacaagagatttagctcattgtcatacaagtctcgggaagaagacc1020
ccactctcacagaagaagagatctcagctatgtactcatcagtaaataaacctggacagt1080
tagtgaataaatcggggcagtcgcttacagttccggagtccacctacacctccattcaag1140
gggacccacagaggtcaccctcctcctgtaatgatctctatgctactgttaaagacttcg1200
aaaaaactccaaacagcacacttccaccagcagggaggcccagcgaggagccagagcctg1260
attatgaagcgatacagactctcaacagagaggaagaaaaggccaccctggggaccaatg1320
gccaccacggtctcgtcccaaaggagaacgactacgagagcataagtgacttgcagcaag1380
gcagagatattaccaggctctagcaacccagaagacaaccctgggtagcctgtgatcagt1440
gtctggagacgtttcttctgtggaagagaagaagtgacacaaacctatacttcatatgct1500
gctttagtcacctgaagatggttggagaggccctgtcgactgttctcccagttgttcagt1560
ttctgagacagagaggtacggactaggctgcacctgagtgtgcccctgcctgccagatgg1620
acaggtacacccaagcacatctccctgctgcaccctcaccacccacaaaagatcccagct1680
gtcagtggtctcatctcattagtgaggaaagccaagctgtatggaaaagctgcactcacc1740
aaggaccacaatgcccccggcctaaagtactgccattcagaaaagcaggtttttcttcct1800
ctctttccttttctctgtctgctactgactttaaggctttttcccccttgaaatgtccag1860
attcctgtggttcatcccaaggaaattttcacacaaagcttggcctttgccctcaatata1920
ggtgttttaggatggtgacaaaccatggctgctgctttctgcccagctcgccagtcctcc1980
ccaaagagttgcgcatcagcacctggggatctggaccctgcgggtgaagggatggggagg2040
gacgtccctggagtctcttctgtctttgttccttcttattttggcattcgatatcagcag2100
cctctccccaaagtacttgaagtcagttttagatgctttattttatttttctagtcaaaa2160
171/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
acgtgtttcccccagtgtttgaaaactcgtccgaatcttttcagtattttccatgagtat2220
tgtggtacttctagacttgtttaagcccagaactcattccttcaaaacagagagccttaa2280
tctttatgttgggacacagaccacatatttggacggcagccatgcatccatcgctgaagg2340
gctgtggacatgaatgtgtatttcccatggtctccgctgcccacaccaacagtgtggcat2400
ctcataagttaactgctaccctaaggtaatctaagattaaaatgtaaacatttatttttg2460
ttatgtaagtttataagatgttttatgttcaatgcctaatttctcaaaagtgccagaaaa2520
aaatgtatattagctattttgattttatgtacaatgatttatactctccttttgaaaaga2580
taccataaagcacataagctagatcactacaaggagctgttatcttttttctaatcaagt2640
gtttaaaacactgatggtttttaaagactcacctttttaaatggtacttggagctcctga2700
ttcaaattacctagaccccctagagaaataaatggaatatacataaataatcattttcag2760
tggtttatggtgggcaatattgcaatatttgaaatggtaaaaatggaaagaagaacaaaa2820
tatgatgagaggtggctgtgaattataaacctcataaaagtgtcataattccattaaggt2880
ttaattatattttttcagaaaacagtgatgaattctgtagtccagtgcttgccaatgcaa2940
attgcctattggaatcttcttcctatattttacaaacatcagtggctgaaatagctcaga3000
gtaagagctcagcctggtttgaatttaatcatctctttagatcttataaggccagcatta3060
ggaaacttgttcacttttcattttcaaaggagcctagttgaagtgctattatgagtgtgg3120
gctatggaaagacagcttttcctacactgataaagaaaaaaaatgaggaaattatttcat3180
ccccttgtgacatctgtgactttttggatttaataatcttgctgtttttcctctttatga3240
caaagaatataattgggaggatgaagtgtcttaaaaattgtagagaccagctcactggaa3300
tgtttttccatccctgtattcatggcttgactttgtgactgctctacactgcatgtctga3360
cattgcagagtgagctatgttgaggtaaactggttggttgtcattattttgcaatcagcc3420
tggtctctcccatgaagatgtcgtgtgcataagcacaatcatcactgattagaagatcac3480
agcagaatacccttggattagagagaagttcgtaccttgcatttctctgaattctagtct3540
ctcataagcactgctttgctggatgattttcactgctttgtgttaatgactttgagcgat3600
ctctcacatgatggggttctttagtacatggtaacagccatgtcatcttacacacctagc3660
attgtgaatgctgtagtgacatcctttataggcaccttacagctcaaaacttttgtttca3720
tttcatgccttacttatcaaaaaggcaggaaagtaggtatgatctctaaagtaaaaaaaa3780
<210> 64
<211> 437
<212> DNA
<213> Human
172/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
<400> 64
gtgatggtgg gtttttgttt tattttttat aaaacacttg cactcaagaa catacaaaca 60
gtggccaccaatccccacccctggggctccggggagcaccatggcttgtttgtggctgtt120
ttcctctgtcccttccctggcatctggtgccagagggcaggtgcgggggtcctggggcggl80
gtggaatttgtacagcactttcatggggagatggtcacaagaaaggaaaccaggacaaga240
taaggactaagtctagggcacccacaaagatggcagacgaagcccatgaaagggcctgcg300
acagagtgaagagacggatgggcctgcgttggcctcagctagctctggaggctctgtggg360
ggaggggcaggtgggccttgcagtcaggattcggtaattacactttgctcacgggtagca420
ccttcggagtcctcctg 437
<210> 65
<211> 566
<212> DNA
<213> Human
<400> 65
tacgttttat caactgccaa gatcctttat tttttccagg ccccttcctg cccactccac 60
atcggggcagctccagcataagggagatgacatgatgaaggggctaagagtagggcctgg120
ccagcatccactgagggcccaaccagggaacagttgctagccgctctcttccatgcagct180
ggagcactagcaaggccttccagaggctcccagggcgacctccacatcactcccgcttgt240
ctctgccctccagggtgctccgggcctcctctccctgtgtaccctagaggtgtgagggcc300
acagtcctcctcaggtgaacctccctccccaagcccagggccctagcacaggctgcagtt360
ggacggcttcgagctgcggctctgggcctgctgccgctggtattctgcctcactggctga420
cagtgcttgtgctaaagctaggtcttcttcctcctgacaacttggaaactggggtttggg480
ttctgccagggacatttccagggcccctgcagagttcatcctcactcaggccatttgcaa540
gaatcactgg aggggctgtc agaagg 566
<210> 66
<211> 566
<212> DNA
<213> Human
<400> 66
ttttttttga gcaaagagct ttttattcaa agaaagaggc aaattgcacc caatctctct 60
ccctgtaaga tctcatctgg ttttgacatc agttgcaatg ctttcagtct gaggctaagc 120
aaaatgttat gctgtgaatg gtcaccacag agagaccact gtgttgctgg tgtggggagg 180
cgaggctcag ggttggacag gttaattacc tacataaccc tggctgtggc ccagcccagc 240
173/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
acctcccaaaacagggactgacatggctgaggtctaccttggagatggggtcagtgaaga300
ggggaggcagggtcagcctctgtgcaagtaaaatgccccctcaccccagccttcctttcc360
agagcaaccaatctgaaaacagaattgcctttggggctggtgttgtacctctgctttcag420
gccaagatggattccctagaagaggagtttgaagcccaatgtgcaaggacatttctcaag480
ggccatgtggttttgcagacactgctgtcctcaggcctgaactcaccatggaaacccatg540
tcagcaaacagtgaccagcaaatcct 566
<210> 67
<2l1> 3510
<212> DNA
<213> Human
<400>
67
agaagccgttcagatgtgagaactgcaatgagcgcttccagtacaagtaccagctgcggt60
cacacatgagcatccacattggccacaagcagttcatgtgccaatggtgcggcaaggact120
tcaacatgaagcagtacttcgatgagcacatgaagacccacacaggagagaagccgtaca180
tctgcgagatctgtggcaagagcttcaccagccggcccaacatgaagcggcaccggcgca240
cgcacacgggcgagaagccgtacccgtgcgacgtgtgtggccagcgcttccgcttctcca300
acatgctcaaggcccacaaggagaagtgcttccgcgtcagccacaccctggccggcgacg360
gcgtccccgctgccccaggcctgcccccaacccagccccaggcgcacgcactgcccctgc420
tcccggggctgccccagaccctgccgcccccgccccacctgccgcccccgcctccgctct480
tccccaccactgccagccccggcgggaggatgaacgccaacaactagctgccgagctgca540
cccgtgcacccgctggggcctggagtcagggcccactccaggagggacccactgccttcc600
cggggagcacagtagtgcgggcctgggccctgctccacctccagaagtggctggatgtac660
cctgcctgaggccccgacgaggaggggtatgcaggctggcaggccccagagctggtggag720
ggcatctcactcccaagtgccccccctttctgtgactccttgaagcctttactttttttt780
ttttttggaagtgaaggaaaaagaaactatttacagcactcccctccaggtgaggggggt840
gctgggggtctgcagcagaaagaaaggggcctgggcagcaggtgtggccagtccctctgc900
caaggcctgtgccagaggggttggccagttggagcctgggtcagcctcagcagcctatcc960
ccatgtcctctatgcccctaatttgcttcctcatcttggagggtttggggagaagttggc1020
gtgccacccccacaacccctgaggaggtgtagacccagtctgagagccgcaagcactgag1080
gcagggcctgagactggacctgggtgagcgtggggggtggagggtggcgaggtgcggaga1140
ctgcagaccagtgcttcactgtgtggagtggggcaggcaggggctggaccccagggactt1200
174/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
gccttcccca cccactctgc tgccagcagg cccagggatc cctgacctgc accaggtggc 1260
accaagggtc ctgagtcctg gagatgtccc cagaagctgc tgtgcctcac agcgctgtga 1320
gccagaccct ccttgggcag acaggctgac tggcagcacc agctttgggg gcagagtcct 1380
aggatgaggc ttgggcagtg ctggtagggt ttcaaggtgc tattagtggg gcaggggcag 1440
ggcggctgct cacagagcac cccagttcct caccagctac tctggccata tatcccacac 1500
cagaaggaac aagtgtggct gtgtccatct ctgctccccc aaaggcccgc tctaggcctt 1560
atCCtCCCtC taggtCCtgC cacaacctgt ccctggctgg ctccagcgtc ctcgtccctc 1620
ctgggcctgt gcaccggtgg gtggggcgcc catagcactg ccggtaaagg agcctgcatg 1680
ttcaggcccc tcgggggatt ggggggactg gggaggcgca gcctagaccc aattgcttgc 1740,
ccccatgagg ctagcactaa taggaaaccc ttttttgttg tcatttaatg tctttattcc 1800
tgcctttaat atggggagga aggttccata agctacatgt ttcctagtta agctctttcc 1860
tattgtgttt atacagtttt gtttgttata ctctttgcac cttaaacccc caccactccc 1920
cgacactatt gccttcccag catggctgga gtgggaagag gcttgggccc cgggggaatg 1980
gttaggggga ctgaacccct ctgaccttat gaggcccatg gcactggggc agggagctgg 2040
ggacatttta atcatcaata aacgaagcac tttattctgt acagatttgg gcaggcccaa 2100
ggtgcccgag tgatctgagg atttataatc caagccacac caccctggtt gttctctggg 2160
cttggagggt acagtgccag cagcttcctt gcccaattga tgttggagct gtagacgtac 2220
gctcaggcgc tcctgctgtc ctgggggaga gaaggttcgc ccctccccga ggaagaaggc 2280
ttctggtcag gacccccacc ccaaggctgg ggactccagg ctcctgcttt actgtagctc 2340
tttttcttcc ttgcactcct tgatctttgg gcttccgtga tgtcctcagg gtccccccct 2400
ccctgttgct atttttaatc tctagtccca gtgcctggca gctctttgga gctggctcac 2460
attttcccaa aaaaaagttg atctctccca gtgggctgta ggcagggtcc tccatgggtt 2520
tccaaccccc atcactggca ccaggatctc ccacaggcac tggtggtgtc atcacctgct 2580
ggccccacta cagcctgagt aggcctgagt ggccgtggcc aggctgagac ctgtcaggcc 2640
atactgacaa gcagaggtca gagacactgg tggggagctg gcaatgaaac cctgtcctgg 2700
gacatgggtt tcatgttctt gtacacttcc cctctgggat caggtgaggg gtccagacag 2760
ctgaccagac agcttgacag ctggtcaaga cggtcacggg agctctaggt gggcacaacc 2820
aacccctctc ctgggaggcc cctgccccac tggggatagg agcctgtgtc cctggtgcta 2880
agcactctct tcacttgggc cattgttggt gggggctcct ttccggccag accacaaggc 2940
175/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
cagaagcaat aatggcacct cagcagttcc agtatggata ggggttactg ttttactagc 3000
ttttacatct ttttatttaa aacaaaacaa cacaaaaaaa caatgtgccc ccagatgtca 3060
gaatgaggcgactagggcaccatactcactttccagggctgggggaagggggacgcagga3120
tcatcccctcccaaggagatctgtgggggtcccaccgtccatctggacttctcagcctgt3180
ttggctagaactcaggcctggagtctgggtctgccccctccccggctccttggggctctc3240
tggtctcaggccagctggcgatgggtggctagagtgatgaactcaagccctgtggccaca3300
gttctgggagccttcaaccctggctcatgctgccatagtctccacggtgcccttcacaga3360
gggcttggtagtggcagaatggccatgcccaggtgtgtgttgagaccattgacaactgct3420
cgtgtacaggcaccccacagccccagagcatggggcacagcaggcatgcgagtgagagga3480
tgaaggggaataaagtcagtacaactcgtg 3510
<210> 68
<211> 2800
<212> DNA
<213> Human
<400>
68 ggggcactgaggcctccccacctcagaacaacagcggcagtagttctcct60
gcctcccccc
gtcttcaccttccgccacccgcttctgtcatctggtggcccccagtccccactccgagga120
tccacaggctccctgaagtcttccccgtccatgtcccatatggaggccctgggcaaggcc180
tggaaccggcagctcagccgtcccctctcccaggctgtgtcattcagcaccccctttggc240
ctggacagcgacgtggatgtcgtcatgggagaccctgtgctcctccgctctgtgagctcg300
gacagcctgggccccccgcgtcccgcgccggccaggacccccacccagccacccccggag360
cctggtgacctgcccaccatcgaggaagctctgcagatcatccacagtgccgagccccgg420
ctcctcccagatggggcggccgacggcagcttctacctccactcccctgaggggccctcc480
aagccatccctggcctccccctacctgcccgaggggacctccaaaccactgtccgacagg540
cccaccaaagcaccagtgtacatgccacaccccgagaccccctcgaaaccatctccctgt600
ctggtgggggaggcatcgaaaccgccagccccatccgaggggtccccgaaggcggtggct660
tcgtccccagcagccaccaactccgaggtgaaaatgaccagctttgcagaacgcaagaaa720
cagctggtgaaggcagaggctgaggccggagcggggtcccccacgtccactccggccccg780
ccggaggccctgagctcggagatgagtgagctcagcgcccggctggaggagaaacgcaga840
gccatcgaggctcagaagcgacggattgaggccatattcgccaagcaccgccagcggctg900
ggcaaaagcgccttcctgcaggtgcagccgcgggaagcctctggggaggcggaagcagag960
176/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
gcggaggagg ccgattccgg tccagtccct ggtggggagc ggcccgcagg cgagggccag 1020
ggtgagccaa cctcacggcc caaggcagtg accttctcgc cagacctggg cccggtgccc 1080
cacgaggggc tgggggaata caatcgagcg gtcagcaagc tgagtgccgc cttgagctcg 1140
ctgcagcggg acatgcagag gctcacggac cagcagcagc ggctcctggc cccgcccgag 1200
gcccccggat ccgccccacc acctgctgcg tgggtcatcc ctggccccac gacggggccc 1260
aaagctgcat cccccagccc cgcccggcga gtcccggcca cccggcgcag ccctgggccc 1320
~gggcccagcc agtcaccccg cagcccgaaa cacacgcggc cagcggagct gcggctggca 1380
cccttgacca gggtgcttac gccaccccac gacgtagaca gcctccccca cctgcgcaag 1440
ttctcgccga gccaggtgcc cgtgcagacg cgctcttcca tcctcctggc ggaggagacg 1500
ccccccgagg agccagccgc ccggccgggc ctcatcgaga tcccgctggg cagcctggca 1560
gatcccgccg ccgaggacga gggagacggg agccccgctg gtgctgagga ttccttggag 1620
gaggaggcgt cttcggaggg ggagccccgg gtggggctgg ggttcttcta caaggatgaa 1680
gacaagcctg aggacgagat ggcccaaaag cgggccagcc tgctggagcg gcagcagcgg 1740
cgagcagagg aggcgcggcg gcgcaagcag tggcaggagg tggagaagga acagcggagg ; 1800
gaggaggccg cgaggctggc ccaagaggag gccccgggcc cagccccgct tgtgtccgca 1860
gtcccgatgg cgactccagc ccctgctgcc cgggctccag ccgaggagga ggtgggcccc 1920
cggaaggggg acttcacgcg gcaggagtac gagcgccggg cccagctgaa gctgatggac 1980
gacctcgata aggtgctgcg gccccgggct gcggggtccg ggggtccagg tcggggcggg 2040
cggagggcca cccggcctcg ctcgggttgc tgtgacgact cagccctggc acgaagccca 2100
gcccgcggcc tgctgggctc tcggctgagc aaaatctatt cccagtccac cctgtcactg 2160
tccactgtgg ccaacgaggc ccacaataac ctcggggtga agaggcccac gtctcgggct 2220
ccctccccgt caggtctcat gtccccaagc cgcctgcctg gaagccgcga acgggactgg 2280
gaaaatggca gcaatgcctc ctccccagcg tcagtgcccg agtacacagg tccacggctg 2340
tacaaagaac ccagcgccaa gtccaacaag ttcatcatcc acaatgccct atcacactgc 2400
tgcctggcgg gcaaggtgaa cgaaccgcag aagaatcgca ttctggagga aattgagaaa 2460
agcaaggcca accacttcct gatcctcttt cgcgactcga gctgccagtt ccgggcgctc 2520
tacacgctgt cgggggagac agaggagctg tcgcggctgg cagggtatgg gccccggacc 2580
gtcacgcccg ccatggtgga aggcatctac aagtacaact cggaccgcaa gcgcttcacc 2640
cagatccccg ccaagaccat gtccatgagc gtcgatgcct tcaccatcca gggacacctc 2700
tggcagggca agaaacccac cactcccaag aagggcggcg gcacccccaa atagccccac 2760
177/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
ccgggcggtc cacgggccgg gccctgtgtg ctgcggccgc 2800
<210> 69
<211> 1634
<212> DNA
<2l3> Human
<400> 69
aaaggtaaga gcactttatt cttatttgaa ccacactgta ttgttgatta ccgagtgtga 60
aggtagtatg ttcagagtct tgttttatgc ctttgtagct gtgttgccag catttgaagg 120
taactcctcc acataagcgg caggaaaatg gccttttttc ccattcaaag atccaaacca 180
ccatccttct tcttttttct cgtgtataat cacaatgtca cccttttcca aattcaactc 240
atcatcttgcctggcttgaaaagaatacaaggccttgcaaagtctgctgctgagctgggc300
tgcaccaggggctggagttgaagaacctggattgctctgcccaccagaagatgccttgct360
cacaatattctctaatctcttcattaaaaaaggccgagatattttcacatagctatgagt420
atgctccttttccctccacctgaagatggaattactacaaggatggctgggttgaggtct480
ttgctcaagttctgctaacattgatgacagtttgtaggagttcgcttccaaaaggtctag540
tttcaaattgttctcatccattaacgctgctgtgtctttctggctctttgcatcagagaa600
ggaggaggtgctggagtacgttttaagcattcgttccaggccttccttgtcttttgaggc660
tttttcaatgtctctctgcagtctcaataattttggttttagtaaagactttcgtctctc720
tttatccattgcactgttaggatcttcttcaaagtaatccgttaacaggaactcagattt780
gttttctgtagataaaattgcagtttcttccattacagcctggatatctttttcaatgtc840
aatcttgctgatggcacagtgaatctgcgtgtggcatgtggtcagggtttggccaaaaag900
agaaatatgttggctgtactggtttaagttattgcataaaagttgaattctttccttctc960
cagctccagaatgctctggtagcagttctctagtgtgttttcccatttcagtctggtaga1020
ataacccgccatgtttttttggtagtaattttcatcttccttttccaacttttcagttga1080
ttttgtcagtttattgaggagcttccgcttctccttctcagtcatagattgcttggagct1140
ttctacaagctggaaaagtgcttcatgtttcttggtactaaccattaatttcttcttggc1200
cttaatttgctgattccagttgctaatgacaagatttgctgtcttttcaacttcattgtc1260
aagtgattttctcttcttctcttgtacatttaggacttgataagtcggttttattgcttc1320
caattcaattgctttgccaagtttttgatgcaggtccgctgtggatttcattccctctga1380
ggcccaggcccaggcactgctaacacaactttttctcgtgttctgtaatgctttgctcag1440
cttgcttgccagtttctgaagtcctttggcatagctaatttccaggtttgccctttgctg1500
178/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
aagaacagat gtgacctgtt tgcagaaatt ctctccattt tgagaaaact cctttaggtt 1560
cttgtatact ttattatacg gacaatctgt cagtgggtcc ctcatgttga aatgtgtctg 1620
gcttttgtcc tttc 1634
<210> 70
<211> 774
<212> DNA
<213> Human
<220>
<221> misc_feature
<222> (465)..(465)
<223> n is a, c, g, or t
<220>
<221> misc_feature
<222> (509)..(509)
<223> n is a, c, g, or t
<220>
<221> misc_feature
<222> (617)..(617)
<223> n is a, c, g, or t
<220>
<221> misc_feature
<222> (636)..(636)
<223> n is a, c, g, or t
<220>
<221> misc_feature
<222> (667)..(667)
<223> n is a, c, g, or t
<220>
<221> misc_feature
<222> (693)..(693)
<223> n is a, c, g, or t
<220>
<221> misc_feature
<222> (740)..(740)
<223> n is a, c, g, or t
<220>
<221> misc_feature
<222> (762) . . (762)
<223> n is a, c, g, or t
<400> 70
accaaaccaa atcattttat tgtgcaattt ccttctacca gaaaattact aaaaatataa 60
atattaactc tctaaaaaat actcagaata gatctgtaat cttcctcctc ctcctccgaa 120
179/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
ctggagccaatcttcttctttaaacgctgatggattgcatacatgtatgtcttccatatc180
agccacatacacaacattcagatacacttccctctgtgcagggggatacaccagcctcct240
gccaggttctggaagctcaccttataatctaccaggataaagctgtgtgctgagtaggag300
gttatggtggggttggggagtaacaaggagataaaagaccttgtggtcccaacttcctta360
tgtggacagagaagataggtcctttactcctcctcattaccctgccctctcatggactgg420
gctaactgaaggccaagctcccagagaagctggactcactgtgtnggattactgagggtg480
tggctgccaggctacagtcacaggaaggncagactgttgagatggacatggaaaccaggt540
gaggcttggatggaaagctggtctgggccaagggctctggcaggatgagtagtaagctgt600
ttcctggctgggctttnggcagcccctagaccctangcaccaggtactatgtgcagcatc660
ttaaganccagacaccagtcttcagagagcctnccgaggtagccgcaacattcctgcagc720
aggggacgggcaggttgtangcagttagattggagccaggtnccatggcactgt 774
<210> 71
<211> 578
<212> DNA
<213> Human
<400> 71
tttttttttt tttttttaca tgcaatacca caaatttatt ataatacaca gggaaaaaca 60
aactcaaactttgacaacatccacagaatgttccagtctttaaaaagttagcagaaataa120
agggtaatggaaagaatataatctcgtaattttatacttaaggctgtaaatggcaaagtc180
ccatagatatttaaaaatctatatttgtatttatttataatatagatataggccctcaag240
gattcatagagatttatgtaataaactagattttggtactatttattttgttgttgttgt300
tgcttgttaggtaagcaaacccaaacaaattaagtcctgaaaagtgggatgaaatcccaa360
aggaactctatgagaccacacagaactcttttaataaatatggcccatacaaattccata420
tccagtgaaaatcattttgatccacaatcatgttgatgtttctatggaggatacttctag480
cagctgtgatttcttttgtagcattctggctctccacttctattcatataattgagtatg540
tgttttattacatgttagcttataggcaagttaaacat 578
<210> 72
<211> 475
<212> DNA
<213> Human
<220>
<221> misc_feature
<222> (285)..(285)
180/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
<223> n is a, c, g, or t
<220>
<221> misc_feature
<222> (361)..(361)
<223> n is a, c, g, or t
<400>
72
gggtttgcacagtttattaagataatcaatcaatttcttaagttattcctttgttaacca60
gacagcatctctggagagaaaatgcactctctgtgtagatacataaaaatacatcagtca120
ttttgcccctcctggatgtgaacggaatctcccctcctcacctccacagagggagctcaa180
gccccagggaaccttcccctccccttttatgcattaccaggggagtggcaggggcagccc240
ccaactgtggagtgcattcaggtctgaggggggaggaaggctcanaggggcatctcccca300
gcaccctgccacagtgctggcttctggggtgtttgttcagcggcctgctgggctgcccca360
ngctgggggctcccccagctccccgtgcatcctggcttgttccacggagccctgagccaa420
gtctttgtctggctcatgttcctctcacaacatcccacaggcaggggtgagcctg 475
<210> 73
<211> 512 '
<212> DNA
<213> Human
<400> 73
catgtaaaactgacttttattacaattaaaaaagaacaaagacaatttgataagtgcctt60
taattacaacatacctgctatttacatgtaatcatacttttatatatagcttgaataagt120
tttattacatgtaaactataagatattacaagttaaactccagtcttttctggatattca180
attgaaatactactggcagaaacatacagaaaacaaatacccatttcagttcctcaggta240
ccattactggttgaatgatcaagatctggccacagaagagaagtggaaatatgcatcaaa300
acaaaacttattcttaacatgactaacagtattgttatttaaaccctaaacataattaat360
aattggatcattaaaaacacatcttcaatttatatagcacctttcttccgaagagttgaa420
agcattcgtgcttatctctattatttcgtttgtccccataacatctctatgaggtaggca480
atggttagta tcattatccc cattttgtat at 512
<210> 74
<211> 668
<212> DNA
<213> Human
<400> 74
tttcaaaacc agcaaaaatt aaatttaatt gggctcaagt ctgggcagtt tgtccttcct 60
caggaccagc cgtcagcagt ccctgacgaa agcaccccat tctctccaca gacagctggt 120
181/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
tccaaaaggaccctctgaggctggtcttccgggtaggatgtgctgtgggagggttctgtt180
tccgaggaggagaggcgcgacacagcgtgcaaggacctgcagcaccttccacgcagcacc240
ccctgctcctcctcctcagcccctgccgggctctgactcctaaagtaaggcaggagcttc300
ttcaggcccctggctgaggaagagccacagccaccctaaaatggcttcgggggcatgcag360
ccctccatctccagcagctctggccatccctcgtatttgttggtgtctgggctgttcttt420
aagaactgctcaaaggggctgttacccctgaggtctttggctcctatgaagacccagctg480
tcccggaagcccagttgttttgcgtaggaactccccaagtcagagaagagtttcctgctt540
tcatcgatcattttggtcgctggatcgtcgtaggaggccaccaacaccagtgcaccccgc600
ggaaatatcttatggaatttcactaggtgcataacttctcctaagtgcatgtcaaatgcc660
tgctggcg 668
<210> 75
<211> 568
<212> DNA
<213> Human
<400>
75
aaggaataaggtgaatttttattaagtgaaaaaaatcaataacaatataggaatgatcac60
atctatacaaatacattgctacatttctacatataaaatgtataggaaaaagtctgaaag120
aatgcacaccaaattattctgtttttaggaaaagcagtaggattggtcagggcatggaat180
gtcggctaagtgaagtgagatttaaaatttttattctacatgattttctagtgttgggaa240
tttttgacagtgagcatacatgcacttattacttgcataattctgaaaactattttaaaa300
acaacagagaatatatgaaagtctattggtgtatacagcattaatagtagtgaaagttta360
acagaaaagatctgaaaatctcccaaagttatatagaaacagatctagctgacacactgt420
gtacctagaaatgattttggatctcttcacagagacccctatcccaccaacctccaatcc480
tcccaccatacattgatccctttctatctgcttggatcattagctgtaaatttaacttcg540
aaaaacaaagtacgtttaatcattgtac 568
<210> 76
<211> 491
<212> DNA
<213> Human
<220>
<221> misc_feature
<222> (371)..(371)
<223> n is a, c, g, or t
182/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
<220>
<221> misc_feature
<222> (394)..(394)
<223> n is a, c, g, or t
<400> 76
ttagattgaa gaaaacataa cgtttaattc tcagaaacaa atgcaagcct cggtccaagt 60
cttccttcccaaacctttgtcatttagggattgagaagctgagttgggtgaaaggttgaa120
tagaaaacaaaaaggaaagctagaaacacgctgagctcatggagatgcagcttcttctgt180
agctcctaaaggcccagctgaggtatcatctaatgagaattctctctatgccaggcactg240
cgctaagattttcacatcattaaccaatgtgagttttaggcaaccccgaagcaggcagtc300
tgttcatcccaattgcagctgaggaaacaggggtgaggtgaggccaagcagctgggccca360
agggtcccctncctgggtaagtgggcacagctgncagccctgccagggtggggtcctgct420
aaccaagccggcgttttcttgtcaccatgccgtattcgccttcccgtactatcaaaatgt480
acttatccaat 491
<210>
77
<211>
2437
<212>
DNA
<213>
Human
<400>
77
tcggatccactagtaacggccgccagtgtgctggaattcgcggccggtcgacccaccacc 60
atgaggtcctgcctgtggagatgcaggcacctgagccaaggcgtccagtggtccttgctt 120
ctggctgtcctggtcttctttctcttcgccttgccctcttttattaaggagcctcaaaca 180
aagccttccaggcatcaacgcacagagaacattaaagaaaggtctctacagtccctggca 240
aagcctaagtcccaggcacccacaagggcaaggaggacaaccatctatgcagagccagtg 300
ccagagaacaatgccctcaacacacaaacccagcccaaggcccacaccaccggagacaga 360
ggaaaggaggccaaccaggcaccgccggaggagcaggacaaggtgccccacacagcacag 420
agggcagcatggaagagcccagaaaaagagaaaaccatggtgaacacactgtcacccaga 480
gggcaagatgcagggatggcctctggcaggacagaggcacaatcatggaagagccaggac 540
acaaagacgacccaaggaaatgggggccagaccaggaagctgacggcctccaggacggtg 600
tcagagaagcaccagggcaaagcggcaaccacagccaagacgctcattcccaaaagtcag 660
cacagaatgctggctcccacaggagcagtgtcaacaaggacgagacagaaaggagtgacc 720
acagcagtcatcccacctaaggagaagaaacctcaggccaccccaccccctgcccctttc 780
cagagccccacgacgcagagaaaccaaagactgaaggccgccaacttcaaatctgagcct 840
183/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
cggtgggatt ttgaggaaaa atacagcttc gaaataggag gccttcagac gacttgccct 900
gactctgtga agatcaaagc ctccaagtcg ctgtggctcc agaaactctt tctgcccaac 960
ctcactctct tcctggactc cagacacttc aaccagagtg agtgggaccg cctggaacac 1020
tttgcaccac cctttggctt catggagctc aactactcct tggtgcagaa ggtcgtgaca 1080
cgcttccctc cagtgcccca gcagcagctg ctcctggcca gcctccccgc tgggagcctc 1140
cggtgcatca cctgtgccgt ggtgggcaac gggggcatcc tgaacaactc ccacatgggc 1200
caggagatag acagtcacga ctacgtgttc cgattgagcg gagctctcat taaaggctac 1260
gaacaggatg tggggactcg gacatccttc tacggcttta ccgccttctc cctgacccag 1320
tcactcctta tattgggcaa tcggggtttc aagaacgtgc ctcttgggaa ggacgtccgc 1380
tacttgcact tcctggaagg cacccgggac tatgagtggc tggaagcact gcttatgaat 1440
cagacggtga tgtcaaaaaa ccttttctgg ttcaggcaca gaccccagga agcttttcgg 1500
gaagccctgc acatggacag gtacctgttg ctgcacccag actttctccg atacatgaag 1560
aacaggtttc tgaggtctaa gaccctggat ggtgcccact ggaggatata ccgccccacc 1620
actggggccc tcctgctgct cactgccctt cagctctgtg accaggtgag tgcttatggc 1680
ttcatcactg agggccatga gcgcttttct gatcactact atgatacatc atggaagcgg 1740
ctgatctttt acataaacca tgacttcaag ctggagagag aagtctggaa gcggctacac 1800
gatgaaggga taatccggct gtaccagcgt cctggtcccg gaactgccaa agccaagaac 1860
tgaccggggc cagggctgcc atggtctcct tgcctgctcc aaggcacagg atacagtggg 1920
aatcttgaga ctctttggcc atttcccatg gctcagacta agctccaagc ccttcaggag 1980
ttccaaggga acacttgaac catggacaag actctctcaa gatggcaaat ggctaattga 2040
ggttctgaag ttcttcagta cattgctgta ggtcctgagg ccagggattt ttaattaaat 2100
ggggtgatgg gtggccaata ccacaattcc tgctgaaaaa cactcttcca gtccaaaagc 2160
ttcttgatac agaaaaaaga gcctggattt acagaaacat atagatctgg tttgaattcc 2220
aggatcgagt ttacagttgt gaaatcttga aggtattact taacttcact acagattgtc 2280
tagaagacct ttctaggagt tatctgattc tagaagggtc tatacttgtc cttgtcttta 2340
agctatttga caactctacg tgttgtagaa mactgataat aatacaaatg attgttgtcc 2400
atggaaaggc aaataaattt tctacagtga aaaaaaa 2437
<210> 78
<211> 582
<212> DNA
184/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
<213> Human
<400>
78 aattattatttatttcaataagactattgcgaggcattaaaaaaactaaa60
ttccagatca
tagtaatattacaaaatctatatacttgcacatttagtatttgtcaatgtgccagaggtt120
ttcttcatgaaatttgacttctttgaagtgaaggcttttttctatcatctcttatagctc180
tgactgaataagtcttaatgctttcttcatgttttctatcaataggggtaaatcccgagg240
cttatatgtgtacaatctgttagagtatcttccagctatgtcagctctaactgttaaaga300
agggtctacaaacatgattctaggcacatattgcccatcaggtgataaattcttatcagt360
ggtttcatgcataaggtttagcatgatgaacttattctgagccatttcttgtatttcttc420
attttgggcaaatactttctttagtgcttgagagtattgacaatcctccaggtgatgaat480
aaccattaatggcttcttacttttttgagcataaaagagaccttgctcataagtttgtac540
ccaagagatggcatctacccatcctcttgagagtgactgagg 582
<210> 79
<211> 511
<2l2> DNA
<213> Human
<400> 79
ttgaaagcct ttacatttat tgaagagcgg acatatgttt gcaaatcaca gtgtgcatgg 60
gcatgcatta catggttcat aatgctattc caattaggct tttcatagtg ccttctcata 120
acgtcctttaaaaaaaataataactgaaagggaaaagaaagtgtcaattgcaattacatt180
tacaaaaccaaactgctgctttcaattagagtgaatctgtgcttcgctactcagatatac240
acatgtagattttccaaggcccatgcacacacttctgtaggggcagaaattttctatgaa300
taatggctttagcaacccgaatagtatctctaaacattgacaagcttggggaacagggca360
acaagtgcaatgaacaatacaatttctaacgtttgtcccagtcaacataccactttgccc420
tggagatatttaacacagcatttcatttttggaatgataagggataattcatctaattaa480
gggtattatacagaatatacctataaaagac 5ll
<210> 80
<211> 987
<212> DNA
<213> Human
<400> 80
gtgatgatcg acatttgaat ctctttgccc tttccaacgg ctatggcatc aggttctaaa 60
ataagctcgt aatttttcct gttattttaa taatatggaa atattagcat agtgtttctt 120
185/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
ttgatagtga tagactataa tccatattta aattttatag.agaagaaatt ttattgtact 180
gtgatgtaga tatttattat ccaggtaagg atttgcccgg tgtgtatttt ttacaattga 240
gacattttac tttaatcttt aacaaaaaat gcattaaaaa cacactcaaa aaaaaacaaa 300
aaaaaaaaaaaaagacaacccaaacggggggggaaaaaagaggtgattggcaccctttat 360
cacgaaaatcttcctgcgggcggccctctaataaccagtcttctggaacaactgtgccca 420
aaccgaggtgtcgctctttaaaataggcgtggtctcccaccatatctaacactcaaatgg 480
cgccgcctcttctcaaaagaacccacaaatatgtgtgccgaccaagagttaaaaaacccg 540
ccttgcgttggacggggcggacattatcttggattggcaccaacactattaaaagaggcg 600
atgcgacacccaaccccgattaattggcagcagacagaaatcctttctcaactagtatag 660
aaaactgttgtggccctccaccacacaaaaggacgaatcctacccaactaatgtattagc720
tcctctccagtgtgaacaatatactaatctggatgcgcccacacccaagctggttagcta780
acacaaacaccagggagggaagacacacgcattttgtaacacaaatagatctaatattag840
actcgtgccgtataacatcggacactaatctctagcaccagcgggcgtcgactgtaatta900
tgtcccgccactgctgctgttcgtcggcatgttatcatgccccacgctctctgtgatcct960
acacgagagggatcaccccacgcttat 98~
<210> 81
<211> 483
<212> DNA
<213> Human
<400>
8l
ctgttcaaaaaaggttttatccaaaaaagttaatcaagacaagcaacagatactgcaaag 60
cattatatacagcaccatagtccaggggccaaagaaatcaggaggggctgggcagtagag 120
gaattccatatattaatgaatgtgagattaagtatagagtgaagacattaacacacaatt 180
ctaatttctgttaggcagaatgctcccctaccctgatgccacagcctttcacgtttccta 240
aaccctagtaacctctgatctccatctgcctcatcaacacgtcaccaccctttgctcttc 300
ttccaattagtcacatgttggctgaatttatttcactccagtactttaggaccttgacag 360
acaaatcgattacaaggtcaattcccaggatttcttcagggtgtgttcaggagtgcagat ~
420
gttctttggatgacctttctactaaattagacctctgaaggagaaagctacttgccagag 480
get 483
<210> 82
<211> 552
<212> DNA
186/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
<213>
Human
<400>
82
tttttttaccacctagaaataaacattatattttcctctgatatgtaggtaagaacttca 60
aatataagacataatttaaaagtttataattgacatagtcagggattataaataatatca 120
cacaaaataagctcttaatgcaagaaatgaatctccaggatagatcatactaatctatcc 180
aatccagccctctgttctgaaagcagcacatgaaaaggcagagaaagaaaaataatctct 240
acgacctggcctgttaaacatgtatttatttcctgagtaactattaggtgctagctgtaa 300
tgggctattcagtggaggacagtggtcaaagcctcttatgatgtatggcagatgccagaa 360
agatatgaaagatgtgatggtacaaaaaaggaagttggagtcacatccagccacaggact 420
aactaagcctctttggggcaggagactttggaagtgttgaaggagagtagaatctattca 480
gaaagaaacaactgggggcaggtccttccagtctgaatgaagattaactaggcgtaatgt 540
aactggcatcat 552
<210> 83
<211> 505
<212> DNA
<213> Human
<400> 83
gactgtagaaggaaagcattttattgcaaataactaatagttacaaaagcactttttaaa 60
tgttattattagatgttaagccgaaaatctagaaactaacatttacccaggttacaaaat 120
aagagcttcatatttttcaaagtctctaagggtaaggtacatccccagataaaatgagta 180
taggccagtctcctttggctttgtggattctttccaaaaattttccagactatttagctt 240
tccttgtgtagttacagctcaaattagaaactgaagaaacagcaagtggccaggcagggt 300
agaaagcaaataaactgagctacctgtgcctttttccaaatcagtatatgtgcttggctc 360
ctgaaaaaaaaaattctgatatgtaggcattctcattacttagtgagatattagtgaaga 420
cctttcaacgtataacacacagtaactgttgcatagttttaataaacacttgaattttcc 480
aggaatgtga ctgctgtgta aatca 505
<210> 84
<2l1> 671
<212> DNA
<213> Human
<400> 84
gcggccgcgg ctgcggcggc agcagcactg gctgggtctg gctgcacagc aatggggctg 60
atcatgtgct ccactgtgtg gattttgcca tcttcaatca ttttaggggc tggagctgct 120
187/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
ggaaacatggaatactgagccccaatggcagggatggctactgtaccaggtttaatggca 180
actgggttgacggtagggatttccaaattcggcaccagttcatatcctttttcttgctgc 240
tttcctttcccttcatgatatcggctatatataccacggccagcagaatatcccccgagg 300
taggaacccctaggccctggggctctgttgccagctgcacctcgccctcggcctcttatg 360
ctgcctgctttcacaaagtagtccctgttgggcccaatgagcgcgttgtaggggtagccg 420
tagtaggccagtgtgtaggggtcgcaggagtacacgtagctgggctgctgcgctgcctca 480
gccgcgccgccgcccctggctgccttctggtagcgcgagtactgctccttgtccacgggc 540
ttggccagcgtgacctccaggcacgagccctccagctcagtgccggttgagttgttcatg 600
gcatgcacggcatcctcgcggctggtgaagtgcacggaggcgtaggtccggatcttcttg 660
acgcgctcca c 671
<210> 85
<211> 563
<212> DNA
<213> Human
<400> 85
tttttttttt atatctgtta taagcttttt cttttttaga atttaagctt atgagtttat 60
ctacgcccactatattcataattacagttttatatctgcatacaaaagctatgtaaaaat 120
ccatttttcccaaatatacaaattttttttggatagtttaaaacattttgatcacagatt 180
tcaacagagttttaggctgaaaaaaatatcaccatctagcaatatcacttaacactgttt 240
gcaaaacacaaatcttccaatgactgtaaatctttttctattctgtagtatttttctgat 300
tctcagggcatgaaaacattatgggaaaaaaaaggattttctacgaagaaagcatggaga 360
actaatttggctctatggtcaaattaaaaatgccaagttaataagggagaaccaaaagaa 420
agaagtggcataatgtcacatcagctcattcatgccctgataatttctgtatcaacaata 480
catatgtaaagtgtctccttttgtcttacattgtgctccataatttacatgagtattatc 540
tgcatcctgaggaggacagattt 563
<210> 86
<211> 545
<212> DNA
<213> Human
<400> 86
ttattaggga ttcctgccac cttattaaca tataaaacaa tctggatgtt gacatagaaa 60
tgcaaatttc actatacaaa ggtaaggctc caagcacagt aacatggccc ccatatcttt 120
agtatttcaa tgaaataaac ttattgggga ttcaccccga gttgtgttta taaatattag 180
188/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
acaaaccaca aaatatattc caaatacata acattttaca atatttttca agcacagaca 240
aatacatact ttactttacc tacattgttt tcatgatcca acttgcatta gcactaaagg 300
caatattgtg tgtgtatatg tatttgccat atgtgtgtgt gtattatata tatttattta 360
tatccacaaa tgtacactca gtggcattta tggaaaattt aaccctttca ggctgtgggt 420
tttacccacc atagtatctg agagggagaa gaaccaataa tacatctcaa attcctcaat 480
tagggcaaaa taagcacaat tatgcatgag gggcatatat gttgtgtcta ttcaaagaca 540
cacat 545
<210> 87
<211> 464
<212> DNA
<213> Human
<220>
<221> misc_feature
<222> (28)..(28)
<223> n is a, c, g, or t
<220>
<221> misc_feature
<222> (276)..(276)
<223> n is a, c, g, or t
<220>
<221> misc_feature
<222> (422)..(422)
<223> n is a, c, g, or t
<220>
<221> misc_feature
<222> (463)..(463)
<223> n is a, c, g, or t
<400> 87
gcagcgtttg tccctgggca tgtgatgngg agtcctgggc acatcgagat gctttacttc 60
tttctttcga cctcttaaaa aactaaacca agccaaacca caaaggaaat ctgcacaact 120
taagagaaac ttgaaaggga tcgtgtaact actagtttgt actaagtttt tttcaagaaa 180
gggaaacaaa tttatatata tatatatata tatatatatg tgcaatatat ttttacactg 240
tgtgattaac attagggagt actgagtgca tcactntatc agtgtgacgg gtgatgtcca 300
cgtcatggct gttctgactc tgaaagccac ttctgctgat gtctaaaccg cactcaccgc 360
ggacgtccgg ggttgtggtg gccctgctgt gcctcctgca ggtgagaggt gtggtgttgc 420
cngttggact tgctgttgag cctggttgca aacctgtagt gana 464
189/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
<210> 88
<211> 611
<212> DNA
<2l3> Human
<400>
88
tttgctaaaaatttaccaaaatagtttgaacacataaaaatatttttaaaaaaacagaac60
caaaaacccagcataaatttagttgtataggcattggttagaggacactgttttcactaa120
ggattatattcaacaactttctcttgagttgttactaaaattctgattctgaaccttata180
gcttataatggtgccaactattagaaatgggaaaatctaattcagtccaatgtaacatgt240
attatgatataatagatgaagggtatgtctacactataataaaaaataaacatatttttg300
gttatttaaagaccatcttcctaacctgtaactaaaataactgtatttgatttaaactta360
tttaagtgcagtgaattatggaaagctaacttaaaggtttgaataatcaattatgagtaa420
ggaacacctg ttgacagccc cgtgaccctt cagaaccagg catttgctga aaaaaagaaa 480
tcactagcat tgaatatagc ccttagtcac gtgagagatt aacttcatga gcaacccagc 540
atgtagagga tgaggtggac tttcccagcc acccactcct tgaggggaca gtagtattca 600
tagtgaaact g 611
<210> 89
<211> 515
<2l2> DNA
<213> Human
<400> 89
tttaacagta aaatttattt ttatttttgc atattctcaa atacacattt acaatagtat 60
cacacttcct atatgaattc ttcatagtta ttttaagtat tttacaattt gtacagagga 120
agggacatac aatatctaat aggctatttt tcaaccaaat aataatttat gtccttgtaa 180
gattttgtac ctctttaaaa ctttcaactt caacatccac ttttttagct ttgctaatca 240
aattaagaattaaaaccagcctgcaaataataacagtatataacattaagcacaatttca300
tttctttctttatacaaatgttctatatttacttgaccaaatgcttaattaccttttaaa360
ggtttcaataccgtggttaaaaacaaaacaactgtgtatacctccagactatatgaaaaa420
tatgaaatatgtaaagtgtcacgttttttaccttagtttatttttaaaagataaatagct480
aactatctgtattaattttaaagaatgttttaaaa 515
<210> 90
<211> 535
<212> DNA
<213> Human
190/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
<220>
<221> misc_feature
<222> (422)..(422)
<223> n is a, c, g, or t
<220>
<221> misc_feature
<222> (424)..(424)
<223> n is a, c, g, or t
<400>
90
gaattctccttaatagttatgtgcaaacaggatgctcgaccctaagtgaattttagtgca 60
gcctcaggccaatcttggtcctgggagtgggcagggttcccagaagaacgagtctggttt 120
ctgaggctgtagaagggagccggaagcccctcaacttgatcacggtgagaacacagggag 180
cctttggagaagctattcagccactgtagttaagagctcctgttctgatccagggagacc 240
tgggttcaagtcctgactcagccacttcctagttgtgtgagtttcagaaaaaaaatcact 300
tcacctcttagaacgcaatttcagcttctgtaacaatctctaggttaggagggagtgggg 360
cgggtgagggcggggaggggagaggaaaaaaaaacacaacaatctctatgtggtttaagg 420
gnangggggttaaatgagatgatcatgacaatgcctatagaagtgctgggagtatgaaag 480
ctggaacagccctgtgagctttgtgtcgttgtccgatttttgataagggcaaata 535
<210> 91
<211> 535
<212> DNA
<213> Human
<220>
<221> misc_feature
<222> (97) .(97)
<223> n is a, c, g, or't
<220>
<221> misc_feature
<222> (322)..(322)
<223> n is a, c, g, or t
<400>
91
tttttttttttttttttacaatttaaacaagaggattcactggtttgaaaaaaaggtttg60
aaaatcaggaaagctaaacaaaagtcattttacatantggagaaactgagacccatatgt120
gtaaatggcttcccaaggtcacagtggtgtcagtggcagagctggtactgtaccaggctg180
cctggatcatagactgatgtttttgccaagaccagccgaaatgttcctctcaggaggtgg240
caggtgggggtggagtgccaggaaggcactgtccaaagaagtgggttaaggtcacagcct300
191/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
cccggctccc aaggaccccc tngagaacag ttgctttgga aaggtcactc agatgtgaac 360
cagaggcttg aggttttgga gtggaaaggg gcagggtaag gaagaataga gtaggaggag 420
ggcgggggac agggattcat cctccaggtt cctcacaccc ccactgggag cagcgccccc 480
accccaagca cctgatttca aagtctcccc tccactgaag ggaggggcaa aggga 535
<210> 92
<211> 548
<212> DNA
<213> Human
<400>
92
accttcttaactatgagattattacaaatatatttttacaaatacaaaaaactgaagtac 60
agagaggctaagttaatttctccaaggtcccacagcaagtaactgcagaagggcaaagca 120
aaaataggacaacacatgtaggcaataccaagcagttcttgtggcagcaactggaaacct 180
tttggagacaccattctgcatttcgttgtagtcatacacaaaaccctagttatgtatcca 240
tgcttctttctcataatgccaaagtggcactattctaatttactaacaaggttttctaaa 300
aactacccaaattattgaggtgtttttgctcacttcttcccattagaataaatgtagaca 360
ataagaaacgcatgagggatgacatagtcctccatcaaatctgtcctttcacacaagaga 420
tggcatggtgtagtgtagcagaatcatgagctgccaggaaattatgaattctgattcctc 480
cagctgagtctttgaaaaagtccagatgagaaacacttccatcctgatgctgaagcaagg 540
agaatgtc 548
<210> 93
<211> 481
<212> DNA
<213> Human
<400>
93
tttacattgttattaccactttatttatttcctgatatcgactagataattacatgtccc60
atcactctcccacatgggccatacaatggcttgagctgcatcattttgtaaattcctcaa120
gcttctctactggtacacatattaccctagcctatgtttctgagatgccttagtgaaagt180
tgattttctttctatgtcttctcagggaaaacgacttctgctttcacacttactggagat240
gggagatgagtggcactggcaattcacaccctgaaccttcagcttcacaacaaaatcgtt300
tgtgaggccaaaggaatcaagacagcagagctcaaagcagggccagaaggtgcagggggg360
accacattggcgggtctcgctcagggacacgatggcgtcattgtaacagcactgctccaa420
ggggttgtagatcttgtctccacacctgggtgccggctggcacagccatggttctgagcc480
481
192/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
<2l0> 94
<211> 4021
<212> DNA
<213> Human
<400>
94
taacgaacgtgtgagagatctacttcggcggaagtcatctaaaaccttcaatttgagagt60
ccgtgagcatcccaaagaaggcccttatgttgaggatttatccaaacatttagtacagaa120
ttatggtgacgtagaagaacttatggatgcgggcaatatcaaccggaccaccgcagcgac180
tgggatgaacgacgtcagtagcaggtctcatgccatcttcaccatcaagttcactcaggc240
taaatttgattctgaaatgccatgtgaaaccgtcagtaagatccacttggttgatcttgc300
cggaagtgagcgtgcagatgccaccggagccaccggggttaggctaaaggaagggggaaa360
tattaacaagtcccttgtgactctggggaacgtcatttctgccttagctgatttatctca420
ggatgctgcaaatactcttgcaaagaagaagcaagttttcgtgccttacagggattctgt480
gttgacttggttgttaaaagatagccttggaggaaactctaaaactatcatgattgccac540
catttcacctgctgatgtcaattatggagaaaccctaagtactcttcgctatgcaaatag600
agceaaaaacatcatcaacaagcctaccattaatgaggatgccaacgtcaaacttatccg660
tgagctgcgagctgaaatagccagactgaaaacgctgcttgctcaagggaatcagattgc720
cctcttagactcccccacagctttaagtatggaggaaaaacttcagcagaatgaagcaag780
agttcaagaattgaccaaggaatggacaaataagtggaatgaaacccaaaatattttgaa840
agaacaaactctagccctcaggaaagaagggattggagttgttttggattctgaactgcc900
tcatttgattggcatcgatgatgaccttttgagtactggaatcatcttatatcatttaaa960
ggaaggtcagacatacgttggtagagacgatgcttccacggagcaagatattgttcttca1020
tggccttgacttqgagagtgagcattgcatctttgaaaatatcggggggacagtgactct1080
gatacccctgagtgggtcccagtgctctgtgaatggtgttcagatcgtggaggccacaca1140
tctaaatcaaggtgctgtgattctcttgggaagaaccaatatgtttcgctttaaccatcc1200
aaaggaagccgccaagctcagggagaagaggaagagtggccttctgtcctccttcagctt1260
gtccatgaccgacctctcgaagtcccgtgagaacctgtctgcagtcatgttgtataaccc1320
cggacttgaatttgagaggcaacagcgtgaagaacttgaaaaattagaaagtaaaaggaa1380
actcatagaagaaatggaggaaaagcagaaatcagacaaggctgaactggagcggatgca1440
gcaggaggtg gagacccagc gcaaggagac agaaatcgtg cagctccaga ttcgcaagca 1500
ggaggagagc ctcaaacgcc gcagcttcca catcgagaac aagctaaagg atttacttgc 1560
193/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
ggagaaggaaaaatttgaagaggagaggctgagggaacagcaggaaatcgagctgcagaa 1620
gaagagacaagaagaagagacctttctccgcgtccaagaagaactccaacgactcaaaga 1680
actcaacaacaacgagaaggctgagaagtttcagatatttcaagaactggaccagctcca 1790
aaaggaaaaagatgaacagtatgccaagcttgaactggaaaaaaagagactagaggagca 1800
ggagaaggagcaggtcatgctcgtggcccatctggaagagcagctccgagagaagcagga 1860
gatgatccagctcctgcggcgtggggaggtacagtgggtggaagaggagaagagggacct 1920
ggaaggcattcgggaatccctcctgcgggtgaaggaggctcgtgccggaggggatgaaga 1980
tggcgaggagttagaaaaggctcaactgcgtttcttcgaattcaagagaaggcagcttgt 2040
caagctagtgaacttggagaaggacctggttcagcagaaagacatcctgaaaaaagaagt 2100
ccaagaagaacaggagatcctagagtgtttaaaatgtgaacatgacaaagaatctagatt 2160
gttggaaaaacatgatgagagtgtcacagatgtcacggaagtgcctcaagatttcgagaa 2220
aataaagccagtggagtacaggctgcaatataaagaacgccagctacagtacctcctgca 2280
gaatcacttgccaactctgttggaagaaaagcagagagcatttgaaattcttgacagagg 2340
ccctctcagcttagacaacactctttatcaagtagaaaaggaaatggaagaaaaagaaga 2400
acagcttgcacagtaccaggccaatgcaaaccagctgcaaaagctccaagccacctttga 2460
attcactgccaacattgcacgtcaggaggaaaaagtgaggaaaaaggaaaaggagatttt 2520
ggagtccagagagaagcagcagagagaggcgctggagcgggccctggccaggctggagag 2580
gagacattctgcgctgcagaggcactccaccctgggcacggagattgaagagcagaggca 2640
gaaacttgccagtctgaacagtggcagcagagagcagtcagggctccaggctagcctgga 2700
ggctgagcaggaagccctggagaaggaccaggagaggttagaatatgaaatccagcagct 2760
gaaacagaagatttatgaggtcgatggtgttcaaaaagatcatcatgggaccctggaagg 2820
gaaggtggcttcttccagcttgccagtcagtgctgaaaaatcacacctggttcccctcat 2880
ggatgccaggatcaatgcttacattgaagaagaagtccaaagacgccttcaggatttgca 2940
tcgtgtgattagtgaaggctgcagtacatctgcagacacgatgaaggataatgagaaact 3000
tcacaatggcaccattcaacgtaaactaaaatatgagctgtgtcgtgacctcctgtgtgt 3060
cctgatgccagagcctgatgccgctgcctgcgctaatcatcccttgctccagcaagatct 3120
ggttcagctttctcttgattggaaaacagaaatccctgatttagttttgccaaatggagt 3180
tcaggtgtcatccaaattccagactaccttggttgacatgatttactttcttcatggaaa 3240
tatggaagtcaatgtcccttccctggcagaagttcagttactgctctacacaacagtgaa 3300
194/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
agtcatgggtgactctggccatgaccagtgccagtcgctagtccttctgaacacccacat3360
tgcactggtgaaggaagactgtgttttttatccacgcattcgatctcgaaacatacctcc3420
tccgggtgcacaatttgatgtgatcaaatgccatgctttaagtgaattcaggtgtgttgt3480
tgttccagaaaagaaaaatgtgtcaacagtagaactagtcttcttacagaaactcaaacc3540
ttcagtgggttccagaaatagtccacctgagcaccttcaggaagccccaaatgtccagtt3600
gttcaccaccccattgtatcttcaaggcagtcagaatgtcgcacctgaggtctggaaact3660
tactttcaattctcaagatgaggctctttggctaatctcacatttgacaagactctaagg3720
aggagacttttaaagatgcactacatgttttttgagatcattaataaaataagcattgtg3780
aaaacagtcaaggcaatatgaatatctccgtgtagctaattgaattggaactggaaaaat3840
gcagacctctaaaattgaaaatgtaactattttaaatatctacaataaaataaaaacagc3900
taatagcagagccccaatgaaatatctttatcatcaccttgcttcattttcttgaaactc3960
aggcttgtaaatttgtgcctgcttcattatttgtgaggtgattaaagcatttctgattgt4020
t 4021
<210>
95
<211>
2917
<212>
DNA
<213>
Human
<400>
95
tgtcagtaccacacctgttacgaggtttcctgagagtagcaccccttccataccatctgt60
ttacaccagcatgtctatgaccactgcctctgaaggcagttcatctcctacaactcttga120
aggcaccaccaccatgcctatgtcaactacgagtgaaagaagcactttattgacaactgt180
cctcatcagccctatatctgtgatgagtccttctgaggccagcacactttcaacacctcc240
tggtgataccagcacacctttgctcacctctaccaaagccggttcattctccatacctgc300
tgaagtcactaccatacgtatttcaattaccagtgaaagaagcactccattaacaactct360
ccttgtcagcaccacacttccaactagctttcctggggccagcatagcttcgacacctcc420
tcttgacacaagcacaacttttaccccttctactgacactgcctcaactcccacaattcc480
tgtagccaccaccatatctgtatcagtgatcacagaaggaagcacacctgggacaaccat540
ttttattcccagcactcctgtcaccagttctactggtgatgtctttcctgcaacaactgg600
tgctgtatctacccctgtgataacttccactgaactaaacacaccatcaacctccagtag660
tagtaccaccacatctttttcaactactaaggaatttacaacacccgcaatgactactgc720
agctcccctcacatatgtgaccatgtctactgcccccagcacacccagaacaaccagcag780
195/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
aggctgcact acttctgcat caacgctttc tgcaaccagt acacctcaca cctctacttc 840
tgtcaccacc cgtcctgtga ccccttcatc agaatccagc aggccgtcaa caattacttc 900
tcacaccatcccacctacatttcctcctgctcactccagtacacctccaacaacctctgc960
ctcctccacgactgtgaaccctgaggctgtcaccaccatgaccaccaggacaaaacccag1020
cacacggaccacttccttccccacggtgaccaccaccgctgtccccacgaatactacaat1080
taagagcaaccccacctcaactcctactgtgccaagaaccacaacatgctttggagatgg1140
gtgccagaatacggcctctcgctgcaagaatggaggcacctgggatgggctcaagtgcca1200
gtgtcccaacctctattatggggagttgtgtgaggaggtggtcagcagcattgacatagg1260
gccaccggagactatctctgcccaaatggaactgactgtgacagtgaccagtgtgaagtt1320
caccgaagagctaaaaaaccactcttcccaggaattccaggagttcaaacagacattcac1380
ggaacagatgaatattgtgtattccgggatccctgagtatgtcggggtgaacatcacaaa1440
gctacgtcttggcagtgtggtggtggagcatgacgtcctcctaagaaccaagtacacacc1500
agaatacaagacagtattggacaatgccaccgaagtagtgaaagggaaaatcacaaaagt1560
gaccacacagcaaataatgattaatgatatttgctcagacatgatgtgtttcaacaccac1620
tggcacccaagtgcaaaacattacggtgacccagtacgaccctgaagaggactgccggaa1680
gatggccaaggaatatggagactacttcgtagtggagtaccgggaccagaagccatactg1740
catcagcccctgtgagcctggcttcagtgtctccaagaactgtagcctcggcaagtgcca1800
gatgtctctaagtggacctcagtgcctctgcgtgaccacggaaactcactggtacagtgg1860
ggagacctgtaaccagggcacccagaagagtctggtgtacggcctcgtgggggcaggggt1920
cgtgctgatgctgatcatcctggtagctctcctgatgctcgttttccgctccaagagaga1980
ggtgaaacggcaaaagtacagattgtctcagttatacaagtggcaagaagaggacagtgg2040
accagctcctgggaccttccaaaacattggctttgacatctgccaagatgatgattccat2100
ccacctggagtccatctatagtaatttccagccctccttgagacacatagaccctgaaac2160
aaagatccgaattcagaggcctcaggtaatgacgacatcattttaaggcatggagctgag2220
aagtctgggagtgaggagatcccagtccggctaagcttggtggagcattttcccattgag2280
agccttccatgggaactcaatgttcccattgtaagtacaggaaacaagccccgtacttac2340
caaggagaaa gaggagagac agcagtgctg ggagattctc aaatagaaac ccgtggacgc 2400
tccaatgggc ttgtcatgat atcaggctag gctttcctgc tcatttttca aagacgctcc 2460
agatttgagg gtactctgac tgtaacatct atcaccccat tgatcgccag gattgatttg 2520
gttgatctgg ctgagcaggc gggtgtcccc gtcctccctc actgccccat atgtgtccct 2580
196/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
cctaaagctg catgctcagt tgaagaggac gagaggacga ccttctctga tagaggagga 2640
ccacgcttca gtcaaaggca tacaagtatc tatctggact tccctgctgg cacttccaaa 2700
caagctcaga gatgttcctc ccctcatctg cccgggttca gtaccatgga cagcgccctc 2760
gacccgctgt ttacaaccat gaccccttgg acactggact gcatgcactt tacatatcac 2820
aaaatgctct cataagaatt attgcatacc atcttcatga aaaacacctg tatttaaata 2880
tagggcattt accttttggt aaagaaaaaa aaaaaaa 2917
<210> 96
<2l1> 138251
<212> DI~7A
<213> Human
<400>
96
gatcaaaagatgctcatcaaaagctctgagctttcctgagtgctaacaggaaacatccag60
catcactggtctctccaaggctgcaggtgtctttgcccatagtgcctgttttgtgtcagg120
gaaagaatcaacctgggagccaagcccaggaatcaggatgaccaagacatactggacaag180
gaaggaacaaacccatccaaggacactcaaggacaaatcaagcaaatgaatttaagggag240
acctgctcatggtctgctttgctgctcagcatggctgggaggcacagtggaagatcatgc300
atccttcccctgggactcctctgccagagcctgagagctttctcctgcacacaggctagg360
ggtagggcagttggaattgatccatgccttctagctagactgtgggtcccctcagtcttg420
ggcatggtgacagcccagcatcagacagaggtcagtatcaaactagaaaatttaataaat480
gctgtcagatttgtagacccaagaaaatataaactgccaatcacggaggaaaaaaatctc540
tcaatgatcttatctttatatgattcccttgctgcctggagattgacatttccttgggga600
taatctggtcataggattggtgaaggtggaagggaggcaacctccgaaggtggggccctc660
tgctcacctgggacagggggggcctgaggtaggtgtctgtgtgggctgggcaggaggatg720
ggagcagtgcttctagatgtttccactttctcctcattagataataatgaatgggtgatt780
tccctagtcactgcagtgtgaggaaatctacaaaattaatttcacaatacactttacagg840
ataggtggagaaacacatgaagcacaactgcagtgggttataaaaaatggcctttcgagt900
tgagcagtaaattcgttcaagcagccattctgaaggacaaactggctctgtatttaacag960
gggcattccagcacttctctagctactgggttgacaatgactcaccaaagcctctggtag1020
ccaccacaggacgcccagagcacgttttaaagctgaacaccaaactgcggacttcgggag1080
taagtgaactgactggtttttattttgttttactgcttttaacattacagtgactgttac1140
aggttccagcaggataactgggtggaaatgagtttggtttcacttagtctctctaaagag1200
197/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
aaagcaagttggtagactaatacctaataaaagcaaagctgccaacaattgaaattgcct1260
gggctgctctgtgtgtcccacatgcatgggtgtgggtgccagtgtgtgtgcgtgtgtgca1320
tgcatgtgcatgtgtgttgggatagagtggcaagaaaatgggaaataataagaatgttca1380
gtccatagcccttcattataaaaaggtgagctgtaataaatactagtgccacatttagcc1440
aaaactttactccagccaaaggtgatattttcatgataacatcctgtgattgctttgttc1500
ttcgtcttttatgttcttcctagatgggctcagaacatacaagaattaagtacacatctt1560
attttccagtgataatgctaccggcaaattctgttgtttgtataaacatcagccatgttt1620
atataactaaactagtgttttgttttgtcaattcagcaagaaattagaccacatggtggc1680
ttaatgctgcattgatttggctatcaatttgttttcacttttctgcaaaatatttaatac1740
attattaaattgaattatgctgatgccacagttgttcttatctcaattgtcttaaaattc1800
atttaatttttttttcctttcgtttcattattcaaattttaacttcagttctcaacattt1860
tatctgatggaagagatggagtccattactaaggactccattgtgctccatcatgccaga1920
gttgtaaaatagatcttttaaaggaaatttactgtgatttttttctatttaagagcttcc1980
tctccagttgagcatgtaagaaaattataccaggagaatacagtaaactctatgaggcaa2040
gctataaacatgtaggattgtgattagggctggttctccttctagagacatggtaggatt2100
gcaatttcataccatccttgaagttagagagagccacttgactcatttagccaatgaact2160
gtgagcagaatgacatgtcacttccagcagaagctttaagaatctgagagacattcatac2220
gttttccatgtgctgtagccttatacccaaagcctgggtcccaagtgaccatgacaggca2280
gagctccctgttgagccacagagatttagagaatggctgttaacacagcataatccagcc2340
catcctgactaatctgatattaacatgtataataaagaattctatcaatgctgagggaag2400
atgattagttaaggtcctaggttgcaagtctcaaaacctcttctaaggattgtagacagg2460
aaattaaatgacttctagtccctagagttcccaatctcctaccatcccatcctaatatga2520
cagaagtaattcctgagttgcttctgaaaccagagcttccctcagaacccttagcctgcc2580
agatggcttcttggagagccctcactcacttttctccttctgctattgctgctcattcat2640
tccagcttttaaaaattcatctttatccaggaacctcgcttctagaaaagtcatacaggt2700
gcttccaggaggctacatgggcacccatatttttctagccactttcattagaccaatgca2760
gcagagaagaaaagcctcaataattattatgacatggcatgttaggataccaagtaaatt2820
gcatttgtaaaatgtgattttctgttggtgttcacttcggctctactgacatttggtaag2880
tattattgactgactgactaactaatgtggtcattagtcttcataaagaaaggctctcta2940
198/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
caaaaacggagggatgccctttttctggcatttaatacgtaagaaattgcctccgataga3000
aaccagagttgcctgattactatcagcacaggagaaatgtattaatgtgcctttctagta3060
acaggtttttagaaagtcaaatataaacaaatctgtctatttgtgtgtgtgcatgtggta3120
gtggggagggaagaaaaaaggagggggagagaaagagaaataagaaccaagtttattata3180
ctgtattcagggggaaaacattttcccaaggttctaacagaagagcaaagtgccactgtc3240
aatagcctcagtagtgttagggttgcttttatgtatttatttatttacttatttatttat3300
ttttcctttttttttcctttctctttttttcttcttttttttttttttggacagagtctc3360
acactgtcgcctgggctggagtgcattggcgcaatcttgactcactgcaacttctgcctc3420
ccaggttcaagtgattctcctgcctcagccgcccaagtagctgggattacaggtgtctgc3480
caccgtgcctagataatttttttatatttttagtagagatgaggtttcactatgttggcc3540
acgctggtctcaaactcctgacctcatgatccacccacgttggcctcccaaagtgctggg3600
attacaggcgtgagccaccgcccctggccaggattgcttttatagccagtcttcaggtgc3660
ccactgtaggaacaatgtcatttagccctcgggattattctgtgccaaatatggataatg3720
actaatattcaacacagatattctcagctcagaagagcaattagcaaattcataaattaa3780
gtgcttgcttcctttttagtcaaatacaaacatttgttaaaagatattattttgctttac3840
actttttctctcagaaataaacagatgcttgaattcccacagtgctgcttgagcctcaca3900
ccatgtcatcctgccaggcacccagatccagttctagagtttcacatgatcatgagtgtt3960
ggttaataagtcactgtgaactgggaggggagatttttcaggagtgccacagggctctcc4020
ctttaatcacatacactccctgctttcattggaaagtgtataatgatgtcagagtgcccc4080
agaatggagctagttggaagactgccgtcatagggatgccttagtgaattaatcaggttt4140
taatttctggctctcaactttgtagatgtaaaagttgatttatcaatatgtgagaaagga4200
tgaatctttctgaaggttatgtcatcacactcactaagcacacagagaataatgtctaga4260
atctgagtgccatgttatcaaattatactgagactcttgcagtcacacgggctgacatgt4320
aagcatcgcctgcctagtacagactctccctgcagatgaaattatatgggatgctaaatt4380
ataatcagaacaatgtttggtgagccaaaactacaacaagggaagctaattggatgaatt4440
tataaaaatatacctcagccaaaatagcttaattcagtctcccttatcataaggatactc4500
ttgcctaaag ggacagtaat attaaagaca ctaggaataa cctctgtact ttggacagta 4560
gacctgcata gcccattagg cctcaatgaa gtcttatgca agaccagaag ccaatttgcc 4620
attttaaggt gattctccat gtttctgctc taactgtgct tcacaatact caagacactg 4680
aatcaggatg tttcctggag tgcagggagc tgtccgtgtt actgagcagt tctcagcaac 4740
199/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
acaaagatcctactgactcctcatcagacttctttctcactggaattttacacctgggct4800
gttaacaccaggccaggtcaaattcaaaggagagaaaaaagctcattatgaagggtaaaa4860
tccaaaacactgtgcataaagatatgtgtgcacaatttttatacataaagatttcataaa4920
gccaaagcatcaggaaatgaaaagagatacagaaagaaaaatgatggtaaatgagacatt4980
aatttacccttctaatctctatcacagcaaaaaggtaattaaaaaatctatatgaggacc5040
aaaaaatacacaaagactatgtagcaaagcctatagcctgaaaaagtaaacattgaaatt5100
tgtatgtccataaaatgtttacaaaattcagtacatattacacaccccaccctaaaaaca5160
tctaagcaaa gtagagaatg tagaaatgct acagattata ttctctgatt atgacacaac 5220
aaaactagaa attacagcat ggaaatttaa aagctttctc ttaaataatt ctatgtcaaa 5280
aagaaatccaggccgggtacagtggctcatgcctgtaattccagtactttgggaggccaa5340
ggtgggcaggtcacttgaggtcaggagttcaagaccagcctcgtcaacatggcgacaccc5400
tgtctctactaaaaatacaaaaattagctgggcctggtggcgcatgcctgtaatcccagc5460
tacttaggaggctgaggcaggagaattccttgaacccagaaggtggaggttgcagtgagc5520
tgagattgcaccactgcactccagcctaggtgacacagcaagactctgtcaaaaaaaaaa5580
aaaaaagaaatccaaataaaatttccagaatatgtggaaaatagtgccaataaaaatatt5640
acacatgtgtaatcccagcattttgagatgccaaggtggcaggatcacttgagaccagga5700
gttcgcaaccagcctggacaacatagggagactccatctccacacacgccaaaaaaaaat5760
tttaaatagccaggtatagtggtacttcttgtaatcccatctacttgggaggctaaggtg5820
ggagaatcacccaacctcaggagttcagggcttcagcaagccatgatcatatcactgcac5880
tccagcctcagcaacagagcaagatcctatctcaaaaaaaaaaaaaaaatcacatgtggg5940
aaatagctatagcacaataaaaataaatgtattaagtatgaacaacaaaaaagctagtaa6000
aggttgaacaacaactatccttaggaaagtggaaataatgtgttaataaatatgaaagca6060
ggctaggcacggtgactcacatctgtaatcccagcactttgggaggctgaggcaggcaga6120
tcacctgaggtcaggagttccagaccagcctggccaacatggtgaaatcttgtctctcct6180
acaaatacaaaaactagccaggcttggttgcgcactcctgtaattccagctacttgggag6240
gctgaggcaggagaatctcttgaacctgagaggcagaggttgcagtgagccaagatcatg6300
ccactgcactccaactggggcaacagagtgacactccatctcaaaataaataaataagaa6360
agcagaaactaataaattagaaaacagaaacatagaactaatttataaatcaaagcacta6420
tgccttgaaaagagggagaaaaattgtgaattaaggaagggaagagatggttggagagga6480
200/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
ggtgggagaaggcagagataattgaaggagcaaaagcatctggagaagcaaagccactga6540
aagatgaacagggctctgaaagaaatgcttgattgctatcttttcaaatgactgcagttc6600
ccagtgacatcatttttctcctccctggaagtctgaggggcagttcacttatctactccc6660
CtCCCCtaCtcctcaccccacactcaaaacctgtctatgctcctttcattctcatatgac6720
agatttcagatggcattcttatttccctgatttctttttgagatagcttgcatttcccta6780
ctctatataaagccaccgtttatcaaatgcctacatggaccaagcagtccacaagggctt6840
cacagacagttttactaaactcatgccaaaactttcaggttttatagataaagatctata6900
ccttatagataaaggtatctataaggtatagataaaggtaaggtatctataccttataga6960
taaagaaattgaagcttatagagtttaagtaatgttcccaaagcctcgtggctagtaatt7020
caaacctaatttctgcctactccaaagtctatttttcctcatgatactatactgcctctc7080
catggataaagacagagatcacatattaataaaatttgcacaaagtcggcaaattgttga7140
aagggaaggctaagatgactaataaaatcaagagccagatgatctcaacaacctgaaata7200
actggctgacaaccaatttgaataactccctgcgggtgaagttcaaagtactatttgggg7260
tttttttttaagtttggctgggtgcagcggctcacgcctgtaatccaagcacttagggaa7320
gccaaggtgggtggatcatgaagtcaggagttgaagaccagcccggtcaacatggtgaaa7380
ccccatctctactaaaaataaaaaattagccgggcctgctggtggatgcctgtagtccca7440
gctacgcgggaggctaaggcaggagaatcgcttgaacccaggaggtggaggttgcaggga7500
gccgagatcgcaccactgcactccagcctgggtgacagggcgagattccgtctcaaaaaa7560
taaaataaaataaaataaaaaataaaagtttgatatattcagaatcagggaggtctgttg7620
ggtgcagttcatttgaaaaattcctcagcattttagtgatctgtatggtccctctatccg7680
tcagggtcctagcaggaaattgttgcactctcaaaggattaagcagaaagagtttaatga7740
agggtctctttccagggttaagggaactgctagggtttggatatttgaccactccaaact7800
catgttgaaatgtgatccccattgttggaggtgggacctaatgggaggtgttttggtcct7860
gagtgtggacctctcacgaatgtcttggtgccatccaagtgagatcttgctcgctctttt7920
tttctttttgagatgtagtttcactcttgctgcccaggttggaatgtagtggtgcgatct7980
tggctcactgcaacatccacctcacgggttcaacccattctcctgtgtcagcctccagag8040
tagctaggattacaggtacccaccactatgcccagctaatttttggtatttttagtagag8100
acggggtttcaccatgttggccaggctggtctcaaactcctgacctcaggtgatccacct8160
gcctcggcctcccaaagtgctgggattacaggcgtaagccaccgtgcctacctagttcta8220
gctctcttaattcccacaagagctggttgttaacaagagcctggtacaaacccctctctc8280
201/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
ttgccacgtg atctctgcac atgccagctt cccttcccct tctgccatga gtggaaacag 8340
actaaagccc tcaccagaag caaatggtgg caccatcctt cttgcacacc ttcagaactg 8400
tgaaccaaat aaacctctct tctttaaaat tattcagcct ctggtattcc tttataacaa 8460
cacacacaca cacacacaca cacacacaca cacgcaaaag cagactaaaa caggaactaa 8520
ttagaaatgg tgatgcaccg agggattggc accgaggctc cccaacagga actgaggcca 8580
tggatagaag gacacattca tgttattttt ttctaatggt taagtaatta tttgctctta 8640
ctctcaaaat ttctgccaag gcctcccatg gaccaaactc aactagaatc taggaagcag 8700
agaacctgag tgttgcattc agcagaagtc agcttcctag ggaatattgc aggaagggtg 8760
aaggtagaga atctggtggg gaagcaagca aatgcccatc acatgcactt tcctccaaca 8820
gagcgactca gatgctataa aacttgctaa cgcagtctca gggtctgatc acagtaacat 8880
acaatccagg ttttaatcat cagaaatcgc agtcctattg tcttctgcac agacccaaac 8940
acacttggag gtcatgttca atatgaatac ctcacagaga aggaaattta cacacgagaa 9000
gtacatctgc agaaagccag ctggcatgtc aaccattcga aaactcagga tgttcgggat 9060
aaagaagact caggaagaca agtatgaagc ataatctgtg acattattga tatcttcctg 9120
atatcaataa tattgatatc ttcctgatat caatattatt gatatcttcc tgaagaacat 9180 ,
aattcctgcc taccatcaac aagcatcaat actttctacc agctattctc aaccctcatc 9240
atcggaagag acagacactg actgtgtcaa agtattagtc ccatcattca gcaattaact 9300
ttagctcaat gcttcaaaaa ttcttcaggc cctgtgtaat ttcagctatg tacattaatg 9360
atgagtaccc atacaaccat tctgtttctt attttcagta ccatatttaa taaatatcag 9420
ttattcaata ctttatttag acattttgtt agattgtttt gaccaatgaa gtctaatcta 9480
aatgttctga gcatgttcaa agtaagctag gctaacctat aatttttggt gtgctaaatg 9540
catttttaac ttatgatatt ttcagtttac gggggtttgt tgggacataa cttcatcata 9600
catcaaggag catctgtata tgggatatag ttaaagcagt gatcagagga aaatctatag 9660
ccttaacaca tttattaata aaagtgtagg aattaaatta tcagctgaaa aatgtaaaaa 9720
gtatctaaaa gagtaagcag aaagtacaag aaagaaccca tagtagaaaa aagtgaaaat 9780
taataaaata agaagccaaa aaacagatca aatcagtaaa ccaaaaatct tgttctttaa 9840
acaaatcaac aaagttgaca aaaaattaga tcttttaatc atgaataaaa aaagagaaag 9900
cacaaaaatg aataaggaat ggtgagagaa ataactattg ataatcagca aataaaaaat 9960
cattaaaaac aatgttgttc acatctatga aaaacattga aagctagagg gaatgggtaa 10020
202/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
ttttccagaa aaatacaatt caccacaatt gacttcaaaa aaaaaaaaaa agaagtacag 10080
cacttatgtg agcaatttcc atagagaaat acagttgtca tggaattata acacacacac 10140
aaacactagg tttagatgtt ttcacagaga attccaccaa acctttagaa atcagatcat 10200
ccaaaggcaa attaacaacc ctcagccatt tgaggcaaaa tattacaatt gaggcaagat 10260
atactgtact gaaaacttga ggaaaaagca ggagagaaag ttcctttggg aaattcgaat 10320
actcaaaagt gcttacatac aatgaaaaat ttggaaatcc ataagcatgg ccaaggtggg 10380
acacatgctc agaaaaggcc tgagaagaca ctaataactc acctttagta attcctaggc 10440
tcacagcaag aaaaaatgaa ggctaaggca gaattatata tggctccact aagtgttgag 10500
ggagccccaa tacagagtca gtaagcaaag tctgggagat gtttttcata tttttttctt 10560
ttttggctcc ttgcagtcaa ggaaatcatt tttaaatcac taaatgctaa atgaacacaa 10620
gctaaaggaa ccgagccgcc ttcaaacatc aaacataaaa aagaatgcag atattacaaa 10680
accagtttac aaaagttact aaacaaataa aaactacatc ccacagtggg taacaaaaat 10740
aaccttgaag aagggaaaaa tttggtttcc agaataaaca cattataata tccaaaatgc 10800
ccagttttca acaaaaatta agaagcatgc aaataaacac aaaactatgg cccatttaca 10860
gaagaaataa atgagactct ccctgagtaa gcagatattg gaaatattcg acaaaaactt 10920
tatataactg tcttaaataa acttaaagag ctaaagaaac ccaagagaat gacatataaa 10980
taaataagaa atatgaattt tttaaaaggt acaaaaaaat tctgaggctg aaaagtacaa 11040
taactaatta aaaagttact ttttacttag ggttccaata gaagatttga gcagctggaa 11100
aaaagaatca gtgaacttga tagatcaagt gaaatgattc agtctgaaga gcaggaaaat 11160
gaaagaatga caacaaaaaa gaatagagcc taaagacctg tgtaacaaca tcaagaatgc 11220
ctacatacag aatcctggtg gggagtgagg ggcaggaaga ctatttgaag aaatgtgttt 11280
gaaagcttcc caaatttcac taaaaacaaa tatatacatt caaaaagctc agtgcacttc 11340
atcaaggaaa tatacaaaga tattcacacc aagacacact atgtttcaaa ttgtcaaaag 11400
gcaaagcgaa tgtttgaaag cagcaagaga aaggcaacgc gtcatttaca aaggatcctc 11460
aataagtttg acagcagata gtgcattata atccatggat gccagaagag cttaggaaaa 11520
aggcaatgca tcatttacaa aggatcctca gtaagtttga cagcagagag ctcattataa 11580
accatgggtg ccagaagagc ttagaatgac attttaaagt tctgaaagaa aaaaacactg 11640
tcaaccaaaa attctgtaac ttggaagatg ccccttcaag tattaaggat aaattacaca 11700
ttcccagatt aaaaaaaaaa gagagagaga aagagaaaga aagaaagaag agagagaaag 11760
aaagggagag aaagaaaaag aaagaaagaa agaaagaaaa agaaagaaag aaagaaagaa 11820
203/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
agaaagaaag aaagaaagaa aaagaaagaa aagaaagaaa gaaaagcaag caagctttaa 11880
aagttcatgt ttggtaggct gtacttcaag atacactttt aaaaaaaaag actccttcag 11940
atacaaacta aaaaacacta gaaagtaact caaaaccaca taaagaaata actccagtaa 12000
ggataactac ataggtaaat ataaaagcaa ttatcatatt ttttgtaagt ctttttaaat 12060
attctatatg ttttaaaaca aatgtgtaaa ataatgacta taaatctatg ttaatgaagc 12120
atgatgtata aagatgtggt ttgtgaaatt accaacataa agaaattcat aggaaactaa 12180
ataataatag agattttgta tactattgaa gttgtttcaa tttattctaa attgttccaa 12240
attaagaatg ttaattgtaa atccccatgg taaccactaa gttaatatct tttgaaaata 12300
cagaaaagga aagcagaggg taaacacagt gatatgctac aaaatagcaa ctaaacacaa 12360
aagaaggcga taattgagga aattaggaac aaaggaggta taagacatac agaaaacaaa 12420
agcaaaatgg taggagtaag cccctcttta tcagtaatta cattaaatac aaatgaatta 12480
aactctccaa tccaaagaaa cagattgaca gaatggattt ttaaaaaatg atccaactat 12540
attgtccacc agatactcac tttagatcaa aatacacaat gagttgaaat gaaaggatgg 12600
gagaaaatat tccatgtaag taataaccaa aggagatctg aggcaaatat acttatatca 12660
gacaaaatag actttaagtc aaaaactgtt acaaaataca aagaacagta tatattgatt 12720
tcaaaattaa acaagaagat ataacaatta taaatatatg tacaccaact aacagggctc 12780
caaaatatat aatgtaacca ttgagagaat taaagggaga gacagacaat tccacgaaaa 12840
ttgttgggca ttttaaaacc caactttaat aaaggacaaa acatccagag caaatatcaa 12900
gggaggaatt agaggatttg aataaaacta taagcaataa ctatagataa cacttctctc 12960
aaaaactgca gaatacacat tcttctcaag tgaacatgga acattctcca gcacagatga 13020
tatgttaggc cataagataa gctcaataaa cttaaaaaga ttgaaatcat gcaaagtatc 13080
ttcactgacc acaatggaat gaaataagat atcaataaca aaaggaaaac tagaaaattt 13140
acaaatattt ggaaattaaa caacacagta tttaccaacc aatgaatcaa agaacaaatc 13200
atgagggaaa ttagaaaatg tttagagacg attgaaaaca aagatataac aagatgggtg 13260
tgatatatca aaagcagtgc tcagagttgt aacacctaca ttttaaaaaa gaaacatgtc 13320
aaatcaataa ccaaacttta ctcaataaat cataaaagga agagcaaaca aaatccagag 13380
ctagcagaag gaaggaaata aagattagag cagagataaa tgaaattgag aattaaaaaa 13440
ttatacagag atcaacaaaa ctaaaagttg gttcttttaa aatatcaata aaattaatat 13500
acttttacat agactaagca aaacatctct attcagctga cttttttttt tacaagggag 13560
204/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
ccaacattat tcagtgggga ataatagctt tttcaacaaa aagtgctggg aatactgaat 13620
attcatatgc aaaaaaaatg aagctggacc cctacctcac attatataca aaatctagat 13680
tggatcaata atgtaaatat acgagtgaaa accatacatg cttagaagaa aacatggaaa 13740
taaaacattg ctgtggattg gcaatgcatt cttagataat acaccaaaaa tacaagcatg 13800
aaacaaacaa atgtagccaa aatgtaccag aatctgaaaa catgtattat ctataaagaa 13860
ttagagggga atttggtgaa agaaatatgg gagaatggga tattgctctg tgaatgcttt 13920
tgtgcataat tgtacatttt taattaagtt aatcttttac actctcaaag tgtgatatta 13980
agcaagcaaa gataagttat tacaagactc taaaaccgaa tgcaatgaga aacaagtgaa 14040
tccaaatata tttcaaatga atgaatgaca taatcaaact taaggggaaa ataataatta 14100
atctgattaa tttttgactg ttctcttatt tcaaattgac ttttgaacat actttgacta 14160
catactattg cttgaaaaaa taaaatatct gcaaaaaatt attaaatctt catgatagga 14220
ttttttcttt ttatattagt ataaatataa caattctgaa acaaatgtat gtgcattgta 14280
agattaagcc aatgagtaaa tattaatata tttgtattgc tagaacccca gattctcact 14340
gtgaaaggac agagatacag atatggaata agacaaggaa agaagcagcc cactgagtta 14400
cattagaatc agtattatca acataaataa gcaatgtgct ctctcacatg ctctttcctt 14460
ctcttaaaaa atatataata tgtacttatt atatattata tgcatagaca cacgtgtgtc 14520
tatacatatc ctacatgtac atattgagga ttaacaggtg ctagtagaaa atattaactt 14580
tctttgtatt aacaggtgtt agtagaaagt agtagtaggt gctaagataa aagccataat 14640
taaacctcct ggtgaatgaa cacaccatca cctacaatct taccaaaaat agaatcaagc 14700
acgtgtccta gtcaaacctc tggattcaac tgtcatttgg ataaaacgca aaggatagtg 14760
aaaatgtcga tcttcactga gagtctcacc agcaaaattc acagtgtgga caccaagtga 14820
caaaaatccc aaatttttca acaaatatat tgtatgggaa agaaaacttt gaaaagaaac 14880
ctgtatgtta gaaggcattt taaaaacacg acaaatgaaa acaaatgggc aagactaaat 14940
catagtgtct tggaatgcat gcatgaagga cacagccgtg aaaatgcaag gacgcctcta 15000
ctggaacagt catgtttatc gtcacttttc aggagaaagg tggctgcagt tgaggagagt 15060
cacatgcttc agggctggca aagtcctata tcttgactta tgtgatgatt acagggatgt 15120
ttacaaaaat caaactataa gtttgttttg tgccatgttt tgtattgtgt gtgtgtgtgt 15180
tttgtttttc aacttaaaaa taaataaaat caaaaccaag gcttcattat caagtagcac 15240
aaagtctcca atctataacc tcctttgtct ggatatctgc atttaactac cattgccaga 15300
gctaatcctg acaatgcatt catattttta acactgaaac acagtaaaca gggaaaattt 15360
205/439
CA 02512536 2005-06-30
WO 2004/063709 PCT/US2004/000368
tgctcctcta aaacagggca tcttcaggca atcagaacaa ctcagaaagt ttctgtctgt 15420
tgcataaaac tcccctgtgc aaagagttac acaaaatgct gtcatagtaa aggtagttaa 15480
ctaacggcac taattgttct tgggcagtgg ccaagtggaa cttcagagac ctggcattgc 15540
caaccagaaa tcaattgtca tgggaattgt ctcctggaat cactttggtt gtcccagggt 15600
aacgcaggga aagtggttaa tgggtcactt cggggtggca tcttcatcag taaatcacat 15660
ttactttctc ctactaagaa ttttattttt ggccatgaag ccaaaagtca gctcttaaat 15720
aacaagggaa gcaaataatc attgaataaa aatagcagaa agaaaaagct gtgcaaagaa 15780
atttatgttt ttaatttgtt atatatgtat atttttatca tactttaagt tctagggtac 15840
atgtgcacaa tgtgcaggaa taaaatttat gtttttaaaa tttattctac attatgaatt 15900
ctacattaga aaaataaacc atagcctcat cacaggcact taaatacact gaagctgcca 15960
aaacaatcta tcgttttgcc tacgtactta tcaacttcct catagcaaac tgggagaaaa 16020
aagcaatgga atgaataaaa tgatagccac aaaaatcaag gtgggagaaa tacttattat 16080
atgtccataa aaaattttaa ttaatgcaaa gtattaacat caatgattgc agtaatacag 16140
atcttacaaa tgatagtttt agtctgaaca ggactatcca aaagttaatt ttctatagta 16200
acagttttta aataaaatat caattcctga aacacataaa atggtccatg agtatacaac 16260
gagtgaaaaa aaacaaattc agagcaaaga taaattaaga agtatctaat attcaaacat 16320
agtcaaagag agggagattt ctggataatc acttaaaccc atggttaaac ataaatgcac 16380
atatgttaat gtttactgaa taacttatct gtgccaagtg gtgtattaat gattcatttt 16440
tatttttcac taaatctttt ctctaaagtt ggtgtagcct gcaactaaat gcaagaaatc 16500
tgacctagga cctgcacttc ttaccatttt gctcatattt attccctgtg catttttgta 16560
acatgtatat gttatatata tagaaagaga gagaggcaga gatggaaagt aatttatgga 16620
gtttgatgtt atgtcagggt aattacatga ttatataatt aacaggtttc tttttaaatc 16680
agctatatca atagaaaaat aaatgtagga atcaagagac tcattctgtc catctgtgat 16740
agttccatca tgatactgca ttgtcaagtc attgctccaa aaatatggtt tagctcaaca 16800
ctgagtgact ataggaaacc agaaaccagg ctgggcgcta aagatgcaaa gatgaatgag 16860
acatcatctc tgccgtccaa aagcttactg tctagtggga gagttacaca cgtaaggaca 16920
gtaatctaat aagagctaat aagtgaaaac taagataaat taataataca agattacagg 16980
gaaggtttcc aaagtcaatg aggcctcaaa tgaatcttga aagtgtgcaa ggattaacca 17040
aatgaagaaa tgtgtaagtt tttcaaacaa aaaggaacag catgagcaaa tgcaaggagg 17100
206/439
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