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SECRETORY MOLECULES
TECHNICAL FIELD
The present invention relates to secretory molecules and to the use of these
sequences in the
diagnosis, study, prevention, and treatment of diseases associated with, as
well as effects of exogenous
compounds on, cell signaling and the expression of secretory molecules.
BACKGROUND OF THE INVENTION
Protein transport and secretion are essential for cellular function. Protein
transport is mediated
i o by a signal peptide located at the amino terminus of the protein to be
transported or secreted. The
signal peptide is comprised of about ten to twenty hydrophobic amino acids
which target the nascent
protein from the ribosome to a particular membrane bound compartment such as
the endoplasmic
reticulum (ER). Proteins targeted to the ER may either proceed through the
secretory pathway or
remain in any of the secretory organelles such as the ER, Golgi apparatus, or
lysosomes. Proteins that
~ transit through the secretory pathway are either secreted into the
extracellular space or retained in the
plasma membrane. Proteins that are retained in the plasma membrane contain one
or more
transmembrane domains, each comprised of about 20 hydrophobic amino acid
residues. Proteins that
are secreted from the cell are generally synthesized as inactive precursors
that are activated by post-
translational processing events during transit through the secretory pathway.
Such events include
2 o glycosylation, proteolysis, and removal of the signal peptide by a signal
peptidase. Other events that
may occur during protein transport include chaperone-dependent unfolding and
folding of the nascent
protein and interaction of the protein with a receptor or pore complex.
Examples of secretory proteins
with amino terminal signal peptides are discussed below and include proteins
with important roles in
cell-to-cell signaling. Such proteins include transmembrane receptors and cell
surface markers,
2 s extracellular matrix molecules, cytokines, hormones, growth and
differentiation factors, neuropeptides,
vasomediators, ion channels, transporters/pumps, and proteases. (Reviewed in
Alberts, B. et al. (1994)
Molecular Bioloey of The Cell, Garland Publishing, New York NY, pp. 557-560,
582-592.)
G-protein coupled receptors (GPCRs) comprise a superfamily of integral
membrane proteins
which transduce extracellular signals. Not all GPCRs contain N-terminal signal
peptides. GPCRs
3 o include receptors for biogenic amines such as dopamine, epinephrine,
histamine, glutamate
(metabotropic-type), acetylcholine (muscarinic-type), and serotonin; for lipid
mediators of inflammation
such as prostaglandins, platelet activating factor, and leukotrienes; for
peptide hormones such as
calcitonin, C5a anaphylatoxin, follicle stimulating hormone, gonadotropin
releasing hormone,
neurokinin, oxytocin, and thrombin; and for sensory signal mediators such as
retinal photopigments and
3 5 olfactory stimulatory molecules. The structure of these highly conserved
receptors consists of seven
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hydrophobic transmembrane regions, cysteine disulfide bridges between the
second and third
extracellular loops, an extracellular N-terminus, and a cytoplasmic C-
terminus. The N-terminus
interacts with ligands, the disulfide bridges interact with agonists and
antagonists, and the large third
intracellular loop interacts with G proteins to activate second messengers
such as cyclic AMP,
s phospholipase C, inositol triphosphate, or ion channels. (Reviewed in
Watson, S. and Arkinstall, S.
(1994) The G-protein Linked Receptor Facts Book, Academic Press, San Diego CA,
pp. 2-6; and
Bolander, F.F. (1994) Molecular Endocrinolo~y, Academic Press, San Diego CA,
pp. 162-176.)
Other types of receptors include cell surface antigens identified on
leukocytic cells of the
immune system. These antigens have been identified using systematic,
monoclonal antibody (mAb)-
1 o based "shot gun" techniques. These techniques have resulted in the
production of hundreds of mAbs
directed against unknown cell surface leukocyte antigens. These antigens have
been grouped into
"clusters of differentiation" based on common immunocytochemical localization
patterns in various
differentiated and undifferentiated leukocytic cell types. Antigens in a given
cluster are presumed to~
identify a single cell surface protein and are assigned a "cluster of
differentiation" or "CD"
1 s designation. Some of the genes encoding proteins identified by CD antigens
have been cloned and
verified by standard molecular biology techniques. CD antigens have been
characterized as both
transmembrane proteins and cell surface proteins anchored to the plasma
membrane via covalent
attachment to fatty acid-containing glycolipids such as
glycosylphosphatdylinositol (GPI). (Reviewed
in Barclay, A.N. et al. (1995) The Leueocyte Ant yen Facts Book, Academic
Press, San Diego CApp:
20 17-20.)
Matrix proteins (MPs) are transmembrane and extracellular proteins which
functon in
formation, growth, remodeling, and maintenance of Issues and as important
mediators and regulators
of the inflammatory response. The expression and balance of MPs may be
perturbed by biochemical
changes that result from congenital, epigenetc, or infectous diseases. In
additon, MPs affect
2 s leukocyte migraton, proliferaton, differentaton, and actvaton in the
immune response. MPs are
frequently characterized by the presence of one or more domains which may
include collagen-like
domains, EGF-like domains, immunoglobulin-like domains, and fibronectn like
domains. In additon,
MPs may be heavily glycosylated and may contain an Arginine-Glycine-Aspartate
(RGD) tripeptde
motf which may play a role in adhesive interactons. MPs include extracellular
proteins such as
3 o fibronectn, collagen, galectn, vitronectn and its proteolytic derivative
somatomedin B; and cell
adhesion receptors such as cell adhesion molecules (CAMs), cadherins, and
integrins. (Reviewed in
Ayad, S. et al. (1994) The Extracellular Matrix Facts Book, Academic Press,
San Diego CA, pp. 2-16;
Ruoslaht, E. (1997) Kidney Int. 51:1413-1417; Sjaastad, M.D. and Nelson, W.J.
(1997) BioEssays
19:47-55.)
3 s Cytokines are secreted by hematopoietc cells in response to injury or
infection. Interleukins,
2
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neurotrophins, growth factors, interferons, and chemokines all define cytokine
families that work in
conjunction with cellular receptors to regulate cell proliferation and
differentiation. In addition,
cytokines effect activities such as leukocyte migration and function,
hematopoietic cell proliferation,
temperature regulation, acute response to infection, tissue remodeling, and
apoptosis.
Chemokines, in particular, are small chemoattractant cytokines involved in
inflammation,
leukocyte proliferation and migration, angiogenesis and angiostasis,
regulation of hematopoiesis, HIV
infectivity, and stimulation of cytokine secretion. Chemokines generally
contain 70-100 amino acids
and are subdivided into four subfamilies based on the presence of conserved
cysteine-based motifs.
(Canard, R. and Gearing, A. (1994) The Cvtokine Facts Book, Academic Press,
New York NY, pp.
l0 181-190, 210-213, 223-227.)
Growth and differentiation factors are secreted proteins which function in
intercellular
communication. Some factors require ongomerization or association with MPs for
activity. Complex
interactions among these factors and their receptors trigger intracellular
signal transduction pathways
that stimulate or inhibit cell division, cell differentiation, cell signaling,
and cell motility. Most growth
1 s and differentiation factors act on cells in their local environment
(paracrine signaling). There are three
broad classes of growth and differentiation factors. The first class includes
the large polypeptide
growth factors such as epidermal growth factor, fibroblast growth factor,
transforming growth factor,
insulin-like growth factor, and platelet-derived growth factor. The second
class includes the
hematopoietic growth factors such as the colony stimulating factors (CSFs).
Hematopoietic growth
2 o factors stimulate the proliferation and differentiation of blood cells
such as B-lymphocytes, T-
lymphocytes, erythrocytes, platelets, eosinophils, basophils, neutrophils,
macrophages, and their stem
cell precursors. The third class includes small peptide factors such as
bombesin, vasopressin, oxytocin,
endothenn, transferrin, angiotensin II, vasoactive intestinal peptide, and
bradykinin which function as
hormones to regulate cellular functions other than proliferation.
2 s Growth and differentiation factors play critical roles in neoplastic
transformation of cells in
vitro and in tumor progression in vivo. Inappropriate expression of growth
factors by tumor cells may
contribute to vascularization and metastasis of tumors. During hematopoiesis,
growth factor
misregulation can result in anemias, leukemias, and lymphomas. Certain growth
factors such as
interferon are cytotoxic to tumor cells both in vivo and in vitro. Moreover,
some growth factors and
3 o growth factor receptors are related both structurally and functionally to
oncoproteins. In addition,
growth factors affect transcriptional regulation of both proto-oncogenes and
oncosuppressor genes.
(Reviewed in Pimentel, E. (1994) Handbook of Growth Factors, CRC Press, Ann
Arbor MI, pp. 1-9.)
Proteolytic enzymes or proteases either activate or deactivate proteins by
hydrolyzing peptide
bonds. Proteases are found in the cytosol, in membrane-bound compartments, and
in the extracellular
3 5 space. The major famines are the zinc, serine, cysteine, thiol, and
carboxyl proteases.
3
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Ion channels, ion pumps, and transport proteins mediate the transport of
molecules across
cellular membranes. Transport can occur by a passive, concentration-dependent
mechanism or can be
linked to an energy source such as ATP hydrolysis. Symporters and antiporters
transport ions and
small molecules such as amino acids, glucose, and drugs. Symporters transport
molecules and ions
s unidirectionally, and antiporters transport molecules and ions
bidirectionally. Transporter
superfamilies include facilitative txansporters and active ATP-binding
cassette transporters which are
involved in multiple-drug resistance and the targeting of antigenic peptides
to MHC Class I molecules.
These transporters bind to a specific ion or other molecule and undergo a
conformational change in
order to transfer the ion or molecule across the membrane. (Reviewed in
Alberts, B. et al. (1994)
s o Molecular Biolo~y of The Cell, Garland Publishing, New York NY, pp. 523-
546.)
Ion channels are formed by txansmembrane proteins which create a lined
passageway across the
membrane through which water and ions, such as Na+, K+, Ca2+, and Cl-, enter
and exit the cell. For
example, chloride channels are involved.in the regulation of the membrane
electric potential as well as
absorption and secretion of ions across the membrane. Chloride channels also
regulate the internal pH
is of membrane-bound organelles.
Ion pumps are ATPases which actively maintain membrane gradients. Ion pumps
are classified
as P, V, or F according to their structure and function. All have one or more
binding sites for ATP in
their cytosolic domains. The P-class ion pumps include Ca2+ ATPase and Na+/K+
ATPase and function
in transporting H+, Nat, Kt, and Ca2~ ions. P-class pumps consist of two a and
two (3 transmembrane
2 o subunits. The V- and F-class ion pumps have similar structures but
transport only H+. F class H~
pumps mediate transport across the membranes of mitochondria and chloroplasts,
while V-class H+
pumps regulate acidity inside lysosomes, endosomes, and plant vacuoles.
A family of structurally related intrinsic membrane proteins known as
facilitative glucose
transporters catalyze the movement of glucose and other selected sugars across
the plasma membrane.
2 5 The proteins in this family contain a highly conserved, large
transmembrane domain comprised of 12
a-helices, and several weakly conserved, cytoplasmic and exoplasmic domains.
(Pessin, J.E. and Bell,
G.I. (1992) Annu. Rev. Physiol, 54:911-930.)
Amino acid transport is mediated by Nay dependent amino acid transporters.
These
transporters are involved in gastrointestinal and renal uptake of dietary and
cellular amino acids and in
s o neuronal reuptake of neurotransmitters. Transport of cationic amino acids
is mediated by the system
y+ family and the cationic amino acid transporter (CAT) family. Members of the
CAT family share a
high degree of sequence homology, and each contains 12-14 putative
transmembrane domains. (Ito, K.
and Groudine, M, (1997) J. Biol. Chem. 272:26780-26786.)
Hormones are secreted molecules that travel through the circulation and bind
to speciFic
3 s receptors on the surface of, or within, target cells. Although they have
diverse biochemical compositions
4
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and mechanisms of action, hormones can be grouped into two categories. One
category includes small
lipophilic hormones that diffuse through the plasma membrane of target cells,
bind to cytosolic or
nuclear receptors, and form a complex that alters gene expression. Examples of
these molecules
include retinoic acid, thyroxine, and the cholesterol-derived steroid hormones
such as progesterone,
s estrogen, testosterone, cortisol, and aldosterone. The second category
includes hydrophilic hormones
that function by binding to cell surface receptors that transduce signals
across the plasma membrane.
Examples of such hormones include amino acid derivatives such as
catecholamines and peptide
hormones such as glucagon, insulin, gastrin, secretin, cholecystokinin,
adrenocorticotropic hormone,
follicle stimulating hormone, luteinizing hormone, thyroid stimulating
hormone, and vasopressin. (See,
to for example, Lodish et al. (1995) Molecular Cell Biolo~y, Scientific
American Books Inc., New York
NY, pp. 856-864.)
Neuropeptides and vasomediators (NP/VM) comprise a large family of endogenous
signaling
molecules. Included in this family are neuropeptides and neuropeptide hormones
such as bombesin,
neuropeptide Y, neurotensin, neuromedin N, melanocortins, opioids, galanin,
somatostatin, tachykinins,
s s urotensin IT and related peptides involved in smooth muscle stimulation,
vasopressin, vasoactive
intestinal peptide, and circulatory system-borne signaling molecules such as
angiotensin, complement,
calcitonin, endothelins, formyl-methionyl peptides, glucagon, cholecystokinin
and gastrin. NP/VMs can
transduce signals directly, modulate the activity or release of other
neurotransmitters and hormones, and
act as catalytic enzymes in cascades. The effects of NP/VMs range from
extremely brief to long-
2 0 lasting. (Reviewed in Martin, C.R. et al. (1985) Endocrine Physiolo~y,
Oxford University Press, New
York, NY, pp. 57-62.)
The discovery of new secretory molecules satisfies a need in the art by
providing new
compositions which are useful in the diagnosis, study, prevention, and
treatment of diseases associated
with, as well as effects of exogenous compounds on, cell signaling and the
expression of secretory
2 5 molecules.
SUMMARY OF THE INVENTION
The present invention relates to nucleic acid sequences comprising human
polynucleotides
encoding secretory polypeptides that contain signal peptides and/or
txansmembrane domains. These
3 o human polynucleotides (sptm) as presented in the Sequence Listing uniquely
identify partial or full
length genes encoding structural, functional, and regulatory polypeptides
involved in cell signaling.
The invention provides an isolated polynucleotide comprising a polynucleotide
sequence
selected from the group consisting of a) a polynucleotide sequence selected
from the group consisting of
SEQ ID N0:1-79; b) a naturally occurring polynucleotide sequence having at
least 90% sequence
3 s identity to a polynucleotide sequence selected from the group consisting
of SEQ ID N0:1-79; c) a
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polynucleotide sequence complementary to a); d) a polynucleotide sequence
complementary to b); and
e) an RNA equivalent of a) through d). In one alternative, the polynucleotide
comprises a
polynucleotide sequence selected from the group consisting of SEQ ID NO:I-79.
In another alternative,
the polynucleotide comprises at least 60 contiguous nucleotides of a
polynucleotide sequence selected
s from the group consisting of a) a polynucleotide sequence selected from the
group consisting of SEQ ID
NO:1-79; b) a naturally occurring polynucleotide sequence having at least 90%
sequence identity to a
polynucleotide sequence selected from the group consisting of SEQ ID NO:1-79;
c) a polynucleotide
sequence complementary to a); d) a polynucleotide sequence complementary to
b); and e) an RNA
equivalent of a) through d). The invention further provides a composition for
the detection of
1 o expression of secretory polynucleotides comprising at least one isolated
polynucleotide comprising a
polynucleotide sequence selected from the group consisting of a) a
polynucleotide sequence selected
from the group consisting of SEQ ID N0:1-79; b) a naturally occurring
polynucleotide sequence having
at least 90% sequence identity to a polynucleotide sequence selected from the
group consisting of SEQ
. ID N0:1-79; c) a polynucleotide sequence complementary to a); d) a
polynucleotide sequence
1 s complementary to b); and e) an RNA equivalent of a) through d); and a
detectable label.
The invention also provides a method for detecting a target polynucleotide in
a sample, said
target polynucleotide comprising a polynucleotide sequence selected from the
group consisting of a) a
polynucleotide sequence selected from the group consisting of SEQ ID NO:l-79;
b) a naturally
occurring polynucleotide sequence having at least 90% sequence identity to a
polynucleotide sequence
2 o selected from the group consisting of SEQ ID N0:1-79; c) a polynucleotide
sequence complementary to
a); d) a polynucleotide sequence complementary to b); and e) an RNA equivalent
of a) through d). The
method comprises a) amplifying said target polynucleotide or a fragment
thereof using polymerase
chain reaction amplification, and b) detecting the presence or absence of said
amplified target
polynucleotide or fragment thereof, and, optionally, if present, the amount
thereof.
2 s The invention also provides a method fox detecting a target polynucleotide
in a sample, said
target polynucleotide comprising a polynucleotide sequence selected from the
group consisting of a) a
polynucleotide sequence selected from the group consisting of SEQ ID NO:I-79;
b) a naturally
occurring polynucleotide sequence having at least 90% sequence identity to a
polynucleotide sequence
selected from the group consisting of SEQ ID NO:1-79; c) a polynucleotide
sequence complementary to
3 o a); d) a polynucleotide sequence cpmplementary to b); and e) an RNA
equivalent of a) through d). The
method comprises a) hybridizing the sample with a probe comprising at least 20
contiguous nucleotides
comprising a sequence complementary to said target polynucleotide in the
sample, and which probe
specifically hybridizes to said target polynucleotide, under conditions
whereby a hybridization complex
is formed between said probe and said target polynucleotide, and b) detecting
the presence or absence of
3 s said hybridization complex, and, optionally, if present, the amount
thereof. In one alternative, the probe
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comprises at least 30 contiguous nucleotides. In another alternative, the
probe comprises at least 60
contiguous nucleotides.
The invention further provides a recombinant polynucleotide comprising a
promoter sequence
operably linked to an isolated polynucleotide comprising a polynucleotide
sequence selected from the
s group consisting of a) a polynucleotide sequence selected from the group
consisting of SEQ ID NO:1
79; b) a naturally occurring polynucleotide sequence having at least 90%
sequence identity to a
polynucleotide sequence selected from the group consisting of SEQ ID N0:1-79;
c) a polynucleotide
sequence complementary to a); d) a polynucleotide sequence complementary to
b); and e) an RNA
equivalent of a) through d). In one alternative, the invention provides a cell
transformed with the
1 o recombinant polynucleotide. In another alternative, the invention provides
a transgenic organism
comprising the recombinant polynucleotide. In a further alternative, the
invention provides a method
for producing a secretory polypeptide, the method comprising a) culturing a
cell under conditions
suitable for expression of the secretory polypeptide, wherein said cell is
transformed with the
recombinant polynucleotide, and b) recovering the secretory ~polypeptide so
expressed.
~. s The invention also provides a purified secretory polypeptide (SPTM)
encoded by at least one
polynucleotide comprising a polynucleotide sequence selected from the group
consisting of SEQ ID
NO:1-79. Additionally, the invention provides an isolated antibody which
specifically binds to the
secretory polypeptide. The invention further provides a method of identifying
a test compound which
specifically binds to the secretory polypeptide, the method comprising the
steps of a) providing a test
2 o compound; b) combining the secretory polypeptide with the test compound
for a sufficient time and
under suitable conditions for binding; and e) detecting binding of the
secretory polypeptide to the test
compound, thereby identifying the test compound which specifically binds the
secretory polypeptide.
The invention further provides a microarray wherein at least one element of
the microarray is
an isolated polynucleotide comprising at least 60 contiguous nucleotides of a
polynucleotide comprising
2 s a polynucleotide sequence selected from the group consisting of a) a
polynucleotide sequence selected
from the group consisting of SEQ ID NO:l-79; b) a naturally occurring
polynucleotide sequence having
at least 90% sequence identity to a polynucleotide sequence selected from the
group consisting of SEQ
ID N0:1-79; c) a polynucleotide sequence complementary to a); d) a
polynucleotide sequence
complementary to b); and e) an RNA equivalent of a) through d). The invention
also provides a method
3 o for generating a transcript image of a sample which contains
polynucleotides. The method comprises a)
labeling the polynucleotides of the sample, b) contacting the elements of the
microarray with the labeled
polynucleotides of the sample under conditions suitable for the formation of a
hybridization complex,
and c) quantifying the expression of the polynucleotides in the sample.
Additionally, the invention provides a method for screening a compound for
effectiveness in
3 s altering expression of a target polynucleotide, wherein said target
polynucleotide comprises a
7
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polynucleotide sequence selected from the group consisting of a) a
polynucleotide sequence selected
from the group consisting of SEQ ID NO:1-79; b) a naturally occurring
polynucleotide sequence having
at least 90% sequence identity to a polynucleotide sequence selected from the
group consisting of SEQ
ID NO:1-79; c) a polynucleotide sequence complementary to a); d) a
polynucleotide sequence
s complementary to b); and e) an RNA equivalent of a) through d). 'The method
comprises a) exposing a
sample comprising the target polynucleotide to a compound, and b) detecting
altered expression of the
target polynucleotide, and c) comparing the expression of the target
polynucleotide in the presence of
varying amounts of the compound and in the absence of the compound.
The invention further provides a method for assessing toxicity of a test
compound, said method
s o comprising a) treating a biological sample containing nucleic acids with
the test compound; b)
hybridizing the nucleic acids of the treated biological sample with a probe
comprising at least 20
contiguous nucleotides of a polynucleotide comprising a polynucleotide
sequence selected from the
group consisting of i) a polynucleotide sequence selected from the group
consisting of SEQ ID N0:1-
79; ii) a naturally occurring polynucleotide sequence having at least 90%
sequence identity to a
15 polynucleotide sequence selected from the group consisting of SEQ ID NO:1-
79; iii) a polynucleotide
sequence complementary to i), iv) a polynucleotide sequence complementary to
ii), and v) an RNA
equivalent of i)-iv). Hybridization occurs under conditions whereby a specific
hybridization complex
is formed between said probe and a target polynucleotide in the biological
sample, said target
polynucleotide comprising a polynucleotide sequence selected from the group
consisting of i) a
2 o polynucleotide sequence selected from the group consisting of SEQ ID N0:1-
79; ii) a naturally
occurring polynucleotide sequence having at least 90% sequence identity to a
polynucleotide
sequence selected from the group consisting of SEQ ID N0:1-79; iii) a
polynucleotide sequence
complementary to i), iv) a polynucleotide sequence complementary to ii), and
v) an RNA equivalent
of i)-iv), and alternatively, the target polynucleotide comprises a fragment
of a polynucleotide sequence
2 5 selected from the group consisting of i-v above; c) quantifying the amount
of hybridization complex;
and d) comparing the amount of hybridization complex in the treated biological
sample with the amount
of hybridization complex in an untreated biological sample, wherein a
difference in the amount of
hybridization complex in the treated biological sample is indicative of
toxicity of the test compound.
DESCRIPTION OF THE TABLES
3 o Table 1 shows the sequence identification numbers (SEQ ID NOa) and
template identification
numbers (template IDs) corresponding to the polynucleotides of the present
invention, along with
polynucleotide segments of each template sequence as defined by the indicated
"start" and "stop"
nucleotide positions. The reading frames of the polynucleotide segments are
shown, and the
polypeptides encoded by the polynucleotide segments constitute either signal
peptide (SP) or
3 5 transmembrane (T1VI) domains, as indicated. The membrane topology of the
encoded polypeptide
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sequence is indicated, the N-terminus (N) listed as being oriented to either
the cytosolic (in) or non-
cytosolic (out) side of the cell membrane or organelle.
Table 2 shows the sequence identification numbers (SEQ ID NOa) corresponding
to the
polynucleotides of the present invention, along with component sequence
identification numbers
s (component IDs) corresponding to each template. The component sequences,
wluch were used to
assemble the template sequences, are defined by the indicated "start" and
"stop" nucleotide positions
along each template.
Table 3 shows the tissue distribution profiles for the templates of the
invention.
Table 4 summarizes the bioinformatics tools which are useful for analysis of
the
1 o polynucleotides of the present invention. The first column of Table 4
lists analytical tools, programs,
and algorithms, the second column provides brief descriptions thereof, the
third column presents
appropriate references, all of which are incorporated by reference herein in
their entirety, and the fourth
column presents, where applicable, the scores, probability values, and other
parameters used to evaluate
the strength of a match between two sequences (the higher the score, the
greater the homology between
15 two seduences).
DETAILED DESCRIPTION OF THE INVENTION
Before the nucleic acid sequences and methods are presented, it is to be
understood that this
invention is not limited to the particular machines, methods, and materials
described. Although
2 o particular embodiments are described, machines, methods, and materials
similar or equivalent to these
embodiments may be used to practice the invention. The preferred machines,
methods, and materials
set forth are not intended to limit the scope of the invention which is
limited only by the appended
claims.
The singular forms "a", "an", and "the" include plural reference unless the
context clearly
2 5 dictates otherwise. All technical and scientific terms have the meanings
commonly understood by one
of ordinary skill in the art. All publications are incorporated by reference
for the purpose of describing
and disclosing the cell Lines, vectors, and methodologies which are presented
and which might be used in
connection with the invention. Nothing in the specification is to be construed
as an admission that the
invention is not entitled to antedate such disclosure by virtue of prior
invention.
Definitions
As used herein, the lower case "sptm" refers to a nucleic acid sequence, while
the upper case
"SPTM" refers to an amino acid sequence encoded by sptm. A "full-length" sptm
refers to a nucleic
acid sequence containing the entire coding region of a gene endogenously
expressed in human tissue.
3 5 "Adjuvants" are materials such as Freund's adjuvant, mineral gels
(aluminum hydroxide), and
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surface active substances (lysolecithin, pluronic polyols, polyanions,
peptides, oil emulsions, keyhole
limpet hemocyanin, and dinitrophenol) which may be administered to increase a
host's immunological
response.
"Allele" refers to an alternative form of a nucleic acid sequence, Alleles
result from a
s "mutation," a change or an alternative reading of the genetic code. Any
given gene may have none, one,
or many allelic forms. Mutations which give rise to alleles include deletions,
additions, or substitutions
of nucleotides. Each of these changes may occur alone, or in combination with
the others, one or more
times in a given nucleic acid sequence. The present invention encompasses
allelic sptm.
"Amino acid sequence" refers to a peptide, a polypeptide, or a protein of
either natural or
1 o synthetic origin. The amino acid sequence is not limited to the complete,
endogenous amino acid
sequence and may be a fragment, epitope, variant, or derivative of a protein
expressed by a nucleic acid
sequence.
"Amplification" refers to the production of additional copies of a sequence
and is carried out
using polymerase chain reaction (PCR) technologies well known in the art.
15 "Antibody" refers to intact molecules as well as to fragments thereof, such
as Fab, F(ab')2, and
Fv fragments, which are capable of binding the epitopic determinant.
Antibodies that bind SPTM
polypeptides can be prepared using intact polypeptides or using fragments
containing small peptides of
interest as the immunizing antigen. The polypeptide or peptide used to
immunize an animal (e.g., a
mouse, a rat, or a rabbit) can be derived from the translation of RNA, or
synthesized chemically, and
2 o can be conjugated to a carrier protein if desired. Commonly used carriers
that are chemically coupled
to peptides include bovine serum albumin, thyroglobulin, and keyhole limpet
hemocyanin (KLH). The
coupled peptide is then used to immunize the animal.
"Antisense sequence" refers to a sequence capable of specifically hybridizing
to a target
sequence. The antisense sequence may include DNA, RNA, or any nucleic acid
mimic or analog such
2 s as peptide nucleic acid (PNA); oligonucleotides having modified backbone
linkages such as
phosphorothioates, methylphosphonates, or benzylphosphonates; oligonucleotides
having modified
sugar groups such as 2'-methoxyethyl sugars or 2'-methoxyethoxy sugars; or
oligonucleotides having
modified bases such as 5-methyl cytosine, 2'-deoxyuracil, or 7-deaza-2'-
deoxyguanosine.
"Antisense sequence" refers to a sequence capable of specifically hybridizing
to a target
3 o sequence. The antisense sequence can be DNA, RNA, or any nucleic acid
mimic or analog.
"Antisense technology" refers to any technology which relies on the specific
hybridization of an
antisense sequence to a taxget sequence.
A "bin" is a portion of computer memory space used by a computer program for
storage of
data, and bounded in such a manner that data stored in a bin may be retrieved
by the program.
3 5 "Biologically active" refers to an amino acid sequence having a
structural, regulatory, or
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biochemical function of a naturally occurring amino acid sequence.
"Clone joining" is a process for combining gene bins based upon the bins'
containing sequence
information from the same clone. The sequences may assemble into a primary
gene transcript as well
as one or more splice variants.
s "Complementary" describes the relationship between two single-stranded
nucleic acid
sequences that anneal by base-pairing (5'-A-G-T-3' pairs with its complement
3'-T-GA-5').
A "component sequence" is a nucleic acid sequence selected by a computer
program such as
PHRED and used to assemble a consensus or template sequence from one or more
component
sequences.
~ o A "consensus sequence" or "template sequence" is a nucleic acid sequence
which has been
assembled from overlapping sequences, using a computer program for fragment
assembly such as the
GELVIEW fragment assembly system (Genetics Computer Group (GCG), Madison WI)
or using a
relational database management system (RDMS).
"Conservative amino acid substitutions" are those substitutions that, when
made, least interfere
s s with the properties of the original protein, i. e., the structure and
especially the function of the protein is
conserved and not significantly changed by such substitutions. The table below
shows amino acids
which may be substituted for an original amino acid in a protein and which are
regarded as conservative
substitutions.
2 o Original Residue Conservative Substitution
Ala Gly, Ser
Arg His, Lys
Asn Asp, Gln, His
Asp Asn, Glu
Cys Ala, Ser
Gln Asn, Glu, His
Glu Asp, Gln, His
Gly Ala
His Asn, Arg, Gln, Glu
3 o Ile Leu, Val
Leu Ile, Val
Lys Arg, Gln, Glu
Met Leu, Ile
Phe His, Met, Leu, Trp, Tyr
3 5 Ser Cys, Thr
Thr Ser, Val
Trp Phe, Tyr
Tyr His, Phe, Trp
Val Ile, Leu, Thr
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Conservative substitutions generally maintain (a) the structure of the
polypeptide backbone in
the area of the substitution, for example, as a beta sheet or alpha helical
conformation, (b) the charge or
hydrophobicity of the molecule at the target site, or (c) the bulk of the side
chain.
"Deletion" refers to a change in either a nucleic or amino acid sequence in
which at Ieast one
nucleotide or amino acid residue, respectively, is absent.
"Derivative" refers to the chemical modification of a nucleic acid sequence,
such as by
replacement of hydrogen by an alkyl, acyl, amino, hydroxyl, or other group.
The terms "element" and "array element" refer to a polynucleotide,
polypeptide, or other
chemical compound having a unique and defined position on a microaxray.
"E-value" refers to the statistical probability that a match between two
sequences occurred by
chance.
A "fragment" is a unique portion of sptm or SPTM which is identical in
sequence to but shorter
in length than the parent sequence. A fragment may comprise up to the entire
length of the defined
sequence, minus one nucleotide/amino acid residue. For example, a fragment may
comprise from 10 to
1000 contiguous amino acid residues or nucleotides. A fragment used as a
probe, pximer, antigen,
therapeutic molecule, or for other purposes, may be at least S, 10, 1S, 16,
20, 2S, 30, 40, 50, 60, 75,
100, 150, 2S0 or at least S00 contiguous amino acid residues ox nucleotides in
length. Fragments may
be preferentially selected from certain regions of a molecule. For example, a
polypeptide fragment may
comprise a certain length of contiguous amino acids selected from the first
2S0 or S00 amino acids (or
2 o first 25 % or SO%) of a polypeptide as shown in a certain defined
sequence. Clearly these lengths are
exemplary, and any length that is supported by the specification, including
the Sequence Listing and the
figures, may be encompassed by the present embodiments.
A fragment of sptm comprises a region of unique polynucleotide sequence that
specifically
identifies sptm, fox example, as distinct from any other sequence in the same
genome. A fragment of
2 s sptm is useful, for example, in hybridization and amplif canon
technologies and in analogous methods
that distinguish sptm from related polynucleotide sequences. The precise
length of a fragment of sptm
and the region of sptm to which the fragment corresponds are routinely
determinable by one of ordinary
skill in the art based on the intended purpose for the fragment.
A fragment of SPTM is encoded by a fragment of sptm. A fragment of SPTM
comprises a
3 o region of unique amino acid sequence that specifically identifies SPTM.
For example, a fragment of
SPTM is useful as an immunogenic peptide for the development of antibodies
that specifically
recognize SPTM. The precise length of a fragment of SPTM and the region of
SPTM to which the
fragment corresponds are routinely determinable by one of ordinary skill in
the art based on the intended
purpose for the fragment.
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A "full length" nucleotide sequence is one containing at least a start site
for translation to a
protein sequence, followed by an open reading frame and a stop site, and
encoding a "full length"
polypeptide.
"Hit" refers to a sequence whose annotation will be used to describe a given
template. Criteria
s for selecting the top hit are as follows: if the template has one or more
exact nucleic acid matches, the
top hit is the exact match with highest percent identity. If the template has
no exact matches but has
significant protein hits, the top hit is the protein hit with the lowest E-
value. If the template has no
significant protein hits, but does have significant non-exact nucleotide hits,
the top hit is the nucleotide
hit with the lowest E-value.
"Homology" refers to sequence similarity either between a reference nucleic
acid sequence and
at least a fragment of an sptm or between a reference amino acid sequence and
a fragment of an SPTM.
"Hybridization" refers to the process by which a strand of nucleotides anneals
with a
complementary strand through base pairing. Specific hybridization is an
indication that two nucleic
acid sequences share a high degree of identity. Specific hybridization
complexes form under defined
annealing conditions, and remain hybridized after the "washing" step. The
defined hybridization
conditions include the annealing conditions and the washing step(s), the
latter of which is particularly
important in determining the stringency of the hybridization process, with
more stringent conditions
allowing less non-specific binding, i.e., binding between pairs of nucleic
acid probes that are not
perfectly matched. Permissive conditions for annealing of nucleic acid
sequences are routinely
2 o determinable and may be consistent among hybridization experiments,
whereas wash conditions may be
varied among experiments to achieve the desired stringency.
Generally, stringency of hybridization is expressed with reference to the
temperature under
which the wash step is carried out. Generally, such wash temperatures are
selected to be about 5°C to
20°C lower than the thermal melting point (T,~ for the specific
sequence at a defined ionic strength and
2 s pH. The Tm is the temperature (under defined ionic strength and pH) at
which 50% of the target
sequence hybridizes to a perfectly matched probe. An equation for calculating
Tm and conditions for
nucleic acid hybridization is well known and can be found in Sambrook et al.,
1989, Molecular
Cloning: A Laboratory Manual, 2nd ed., vol. 1-3, Cold Spring Harbor Press,
Plainview NY; specifically
see volume 2, chapter 9.
3 o High stringency conditions for hybridization between polynucleotides of
the present invention
include wash conditions of 68°C in the presence of about 0.2 x SSC and
about 0.1 % SDS, for 1 hour.
Alternatively, temperatures of about 65°C, 60°C, or 55°C
may be used. SSC concentration may be
varied from about 0.2 to 2 x SSC, with SDS being present at about 0.1 %.
Typically, blocking reagents
are used to block non-specific hybridization. Such blocking reagents include,
for instance, denatured
3 s salmon sperm DNA at about 100-200 ~ g/znl. Useful variations on these
conditions will be readily
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apparent to those skilled in the art. Hybridization, particularly under high
stringency conditions, may
be suggestive of evolutionary similarity between the nucleotides. Such
similarity is strongly indicative
of a similar role for the nucleotides and their resultant proteins.
Other parameters, such as temperature, salt concentration, and detergent
concentration may be
s varied to achieve the desired stringency. Denaturants, such as formamide at
a concentration of about
35-50% vlv, may also be used under particular circumstances, such as RNA:DNA
hybridizations.
Appropriate hybridization conditions are routinely determinable by one of
ordinary skill in the art.
"Immunogenic" describes the potential for a natural, recombinant, or synthetic
peptide, epitope,
polypeptide, or protein to induce antibody production in appropriate animals,
cells, or cell lines.
"Insertion" or "addition" refers to a change in either a nucleic or amino acid
sequence in which
at least one nucleotide or residue, respectively, is added to the sequence.
"Labeling" refers to the covalent or noncovalent joining of a polynucleotide,
polypeptide, or
antibody with a reporter molecule capable of producing a detectable or
measurable signal.
"Microarray" is any arrangement of nucleic acids, amino acids, antibodies,
etc., on a substrate.
~ s The substrate may be a solid support such as beads, glass, paper,
nitrocellulose, nylon, or an
appropriate membrane.
"Linkers" are short stretches of nucleotide sequence which may be added to a
vector or an sptm
to create restriction endonuclease sites to facilitate cloning. "Polylinkers"
are engineered to incorporate
multiple restriction enzyme sites and to provide for the use of enzymes which
leave 5' or 3' overhangs
(e.g., BamHI, EcoRI, and HindIII) and those which provide blunt ends (e.g.,
EcoRV, SnaBI, and StuI).
"Naturally occurring" refers to an endogenous polynucleotide or polypeptide
that may be
isolated from viruses or prokaryotic or eukaryotic cells.
"Nucleic acid sequence" refers to the specific order of nucleotides joined by
phosphodiester
bonds in a linear, polymeric arrangement. Depending on the number of
nucleotides, the nucleic acid
sequence can be considered an oligomer, oligonucleotide, or polynucleotide.
The nucleic acid can be
DNA, RNA, or any nucleic acid analog, such as PNA, may be of genomic or
synthetic origin, may be
either double-stranded or single-stranded, and can represent either the sense
or antisense
(complementary) strand.
"Oligomer" refers to a nucleic acid sequence of at least about 6 nucleotides
and as many as
3 o about 60 nucleotides, preferably about 15 to 40 nucleotides, and most
preferably between about 20 and
nucleotides, that may be used in hybridization or amplification technologies.
Oligomers may be used
as, e.g., primers for PCR, and are usually chemically synthesized.
"Operably linked" refers to the situation in which a first nucleic acid
sequence is placed in a
functional relationship with the second nucleic acid sequence. For instance, a
promoter is operably
3 5 linked to a coding sequence if the promoter affects the transcription or
expression of the coding
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sequence. Generally, operably linked DNA sequences may be in close proximity
or contiguous and,
where necessary to join two protein coding regions, in the same reading frame.
"Peptide nucleic acid" (PNA) refers to a DNA mimic in which nucleotide bases
are attached to
a pseudopeptide backbone to increase stability. PNAs, also designated antigene
agents, can prevent
gene expression by targeting complementary messenger RNA.
The phrases "percent identity" and "% identity", as applied to polynucleotide
sequences, refer
to the percentage of residue matches between at least two polynucleotide
sequences aligned using a
standardized algorithm. Such an algorithm may insert, in a standardized and
reproducible way, gaps in
the sequences being compared in order to optimize alignment between two
sequences, and therefore
1 o achieve a more meaningful comparison of the two sequences.
Percent identity between polynucleotide sequences may be determined using the
default
parameters of the CLUSTAL V algorithm as incorporated into the MEGALIGN
version 3.12e sequence
alignment program. This program is part of the LASERGENE software package, a
suite of molecular
biological analysis programs (DNASTAR, Madison WI). CLUSTAL V is described in
Higgins, D. G.
and Sharp, P.M. (1989) CABIOS 5:151-153 and in Higgins, D.G. et al. (1992)
CABIOS 8:189-191.
For pairwise alignments of polynucleotide sequences, the default parameters
are set as follows:
Ktuple=2, gap penalty=5, window=4, and "diagonals saved"=4. The "weighted"
residue weight table is
selected as the default. Percent identity is reported by CLUSTAL V as the
"percent similarity" between
aligned polynucleotide sequence pairs.
2 o Alternatively, a suite of commonly used and freely available sequence
comparison algorithms is
provided by the National Center for Biotechnology Information (NCBI) Basic
Local Alignment Search
Tool (BLAST) (Altschul, S.F. et al. (1990) J. Mol. Biol. 215:403-410), which
is available from several
sources, including the NCBI, Bethesda, MD, and on the Internet at
http://www.ncbi.nlm.nih.gov/BLAST/. The BLAST software suite includes vaxious
sequence analysis
2 5 programs including "blastn," that is used to determine alignment between a
known polynucleotide
sequence and other sequences on a variety of databases. Also available is a
tool called "BLAST 2
Sequences" that is used for direct pairwise comparison of two nucleotide
sequences. "BLAST 2
Sequences" can be accessed and used interactively at
http:/lwww.ncbi.nlm.nih.gov/gorf/b12/. The
"BLAST 2 Sequences" tool can be used for both blastn and blastp (discussed
below). BLAST
3 o programs are commonly used with gap and other parameters set to default
settings. For example, to
compare two nucleotide sequences, one may use blastn with the "BLAST 2
Sequences" tool Version
2Ø9 (May-07-1999) set at default parameters. Such default parameters may be,
for example:
Matrix: BLOSUM62
Reward for rytatch: 1
35 Peftalty for ntisntatcla: -2
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Opera Gap: 5 and Extension Gap: 2 penalties
Gap x drop-off. 50
Expect: 10
Word Size: 1l
s Filter: on
Percent identity may be measured over the length of an entire defined
sequence, for example, as
defined by a particular SEQ ID number, or may be measured over a shorter
length, for example, over
the length of a fragment taken from a larger, defined sequence, for instance,
a fragment of at least 20, at
least 30, at least 40, at least 50, at least 70, at least 100, or at least 200
contiguous nucleotides. Such
lengths are exemplary only, and it is understood that any fragment length
supported by the sequences
shown herein, in figures or Sequence Listings, may be used to describe a
length over which percentage
identity may be measured.
Nucleic acid sequences that do not show a high degree of identity may
nevertheless encode
similar amino acid sequences due to the degeneracy of the genetic code. It is
understood that changes in
nucleic acid sequence can be made using this degeneracy to produce multiple
nucleic acid sequences
that all encode substantially the same protein.
The phrases "percent identity" and "% identity", as applied to polypeptide
sequences, refer to
the percentage of residue matches between at least two polypeptide sequences
aligned using a
standardized algorithm. Methods of polypeptide sequence alignment are well-
known. Some alignment
2 o methods take into account conservative amino acid substitutions. Such
conservative substitutions,
explained in more detail above, generally preserve the hydrophobicity and
acidity of the substituted
residue, thus preserving the structure (and therefore function) of the folded
polypeptide.
Percent identity between polypeptide sequences may be determined using the
default parameters
of the CLUSTAL V algorithm as incorporated into the MEGALIGN version 3.12e
sequence alignment
2 5 program (described and referenced above). For pairwise alignments of
polypeptide sequences using
CLUSTAL V, the default parameters are set as follows: Ktuple=1, gap penalty=3,
window=5, and
"diagonals saved"=5. The PAM250 matrix is selected as the default residue
weight table. As with
polynucleotide alignments, the percent identity is reported by CLUSTAL V as
the "percent similarity"
between aligned polypeptide sequence pairs.
3 o Alternatively the NCBI BLAST software suite may be used. For example, for
a pairwise
comparison of two polypeptide sequences, one may use the "BLAST 2 Sequences"
tool Version 2Ø9
(May-07-1999) with blastp set at default parameters. Such default parameters
may be, for example:
Matrix: BLOSUM62
Open Gap: 11 and Extension Gap: 1 penalty
3 5 Gap x drop-off.- 50
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Expect: 10
Word Size: 3
Filter-: on
Percent identity may be measured over the length of an entire defined
polypeptide sequence, for
s example, as defined by a particular SEQ ID number, or may be measured over a
shorter length, for
example, over the length of a fragment taken from a larger, defined
polypeptide sequence, for instance,
a fragment of at least 15, at least 20, at least 30, at least 40, at least 50,
at least 70 or at least 150
contiguous residues. Such lengths are exemplary only, and it is understood
that any fragment length
supported by the sequences shown herein, in figures ar Sequence Listings, may
be used to describe a
length over which percentage identity may be measured.
"Post-translational modification" of an SPTM may involve lipidation,
glycosylation,
phosphorylation, acetylation, racemization, proteolytic cleavage, and other
modifications known in the
art. These processes may occur synthetically or biochemically. Biochemical
modifications will vary by
cell type depending on the enzymatic milieu and the SPTM.
"Probe" refers to sptm or fragments thereof, which are used to detect
identical, allelic or related
nucleic acid sequences. Probes are isolated oligonucleotides or
polynucleotides attached to a detectable
label or reporter molecule. Typical labels include radioactive isotopes,
ligands, chemiluminescent
agents, and enzymes. "Primers" are short nucleic acids, usually DNA
oligonucleotides, which may be
annealed to a target polynucleotide by complementary base-pawing. The primer
may then be extended
2 o along the target DNA strand by a DNA polymerase enzyme. Primer pairs can
be used for amplification
(and identification) of a nucleic acid sequence, e.g., by the polymerase chain
reaction (PCR).
Probes and primers as used in the present invention typically comprise at
least 15 contiguous
nucleotides of a known sequence. In order to enhance specificity, longer
probes and primers may also
be employed, such as probes and primers that comprise at least 20, 30, 40, 50,
60, 70, 80, 90, 100, or
2 s at least 150 consecutive nucleotides of the disclosed nucleic acid
sequences. Probes and primers may
be considerably longer than these examples, and it is understood that any
length supported by the
specification, including the figures and Sequence Listing, may be used.
Methods for preparing and using probes and primers are described in the
references, for
example Sambrook et al., 1989, Molecular Cloning: A Laborator~Manual,
2°d ed., vol. 1-3, Cold
3 o Spring Harbor Press, Plainview NY; Ausubel et a1.,1987, Current Protocols
in Molecular Biolo~y,
Greene Publ. Assoc. & Wiley-Intersciences, New York NY; Innis et al., 1990,
PCR Protocols, A Guide
to Methods and Applications, Academic Press, San Diego CA. PCR primer pairs
can be derived from
a known sequence, for example, by using computer programs intended for that
purpose such as Primer
(Version 0.5, 1991, Whitehead Institute for Biomedical Research, Cambridge
MA).
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Oligonucleotides for use as primers are selected using software known in the
art for such
purpose. For example, OLIGO 4.06 software is useful for the selection of PCR
primer pairs of up to
100 nucleotides each, and for the analysis of oligonucleotides and larger
polynucleotides of up to 5,000
nucleotides from an input polynucleotide sequence of up to 32 kilobases.
Similar primer selection
s programs have incorporated additional features for expanded capabilities.
For example, the PrimOU
primer selection program (available to the public from the Genome Center at
University of Texas South
West Medical Center, Dallas TX) is capable of choosing specific primers from
megabase sequences
and is thus useful for designing primers on a genome-wide scope. The Primer3
primer selection
program (available to the public from the Whitehead Institute/MIT Center for
Genome Research,
1 o Cambridge MA) allows the user to input a "mispriming library," in which
sequences to avoid as primer
binding sites are user-specified. Primer3 is useful, in particular, for the
selection of oligonucleotides for
microarrays. (The source code for the latter two primer selection programs may
also be obtained from
their respective sources and modified to meet the user's specific needs.) The
PrimeGen program
(available to the public from the UK Human Genome Mapping Project Resource
Centre, Cambridge
15 UK) designs primers based on multiple sequence alignments, thereby allowing
selection of primers that
hybridize to either the most conserved or least conserved regions of aligned
nucleic acid sequences.
Hence, this program is useful for identification of both unique and conserved
oligonucleotides and
polynucleotide fragments. The oligonucleotides and polynucleotide fragments
identified by any of the
above selection methods are useful in hybridization technologies, for example,
as PCR or sequencing
2 o primers, microarray elements, or specific probes to identify fully or
partially complementary
polynucleotides in a sample of nucleic acids. Methods of oligonucleotide
selection are not limited to
those described above.
"Purified" refers to molecules, either polynucleotides or polypeptides that
are isolated or
separated from their natural environment and are at least 60% free, preferably
at least 75 % free, and
2 s most preferably at least 90% free from other compounds with which they are
naturally associated.
A "recombinant nucleic acid" is a sequence that is not naturally occurring or
has a sequence
that is made by an artifcial combination of two or more otherwise separated
segments of sequence.
This artificial combination is often accomplished by chemical synthesis or,
more commonly, by the
artificial manipulation of isolated segments of nucleic acids, e.g., by
genetic engineering techniques
3 o such as those described in Sambrook, supra. The term recombinant includes
nucleic acids that have
been altered solely by addition, substitution, or deletion of a portion of the
nucleic acid. Frequently, a
recombinant nucleic acid may include a nucleic acid sequence operably linked
to a promoter sequence.
Such a recombinant nucleic acid may be part of a vector that is used, for
example, to transform a cell.
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Alternatively, such recombinant nucleic acids may be part of a viral vector,
e.g., based on a
vaccinia virus, that could be use to vaccinate a mammal wherein the
recombinant nucleic acid is
expressed, inducing a protective immunological response in the mammal.
"Regulatory element" refers to a nucleic acid sequence from nontranslated
regions of a gene,
s and includes enhancers, promoters, introns, and 3' untranslated regions,
which interact with host
proteins to carry out or regulate transcription or translation.
"Reporter" molecules are chemical or biochemical moieties used for labeling a
nucleic acid, an
amino acid, or an antibody. They include radionuclides; enzymes; fluorescent,
chemiluminescent, or
chromogenic agents; substrates; cofactors; inhibitors; magnetic particles; and
other moieties known in
1 o the art.
An "RNA equivalent," in reference to a DNA sequence, is composed of the same
linear
sequence of nucleotides as the reference DNA sequence with the exception that
all occurrences of the
nitrogenous base thymine are replaced with uracil, and the sugar backbone is
composed of ribose
instead of deoxyribose.
15 "Sample" is used in its broadest sense. Samples may contain nucleic or
amino acids,
antibodies, or other materials, and may be derived from any source (e.g.,
bodily fluids including, but not
limited to, saliva, blood, and urine; chromosome(s), organelles, or membranes
isolated from a cell;
genomic DNA, RNA, or cDNA in solution or bound to a substrate; and cleared
cells or tissues or blots
or imprints from such cells or tissues).
2 0 "Specific binding" or ''specifically binding" refers to the interaction
between a protein or
peptide and its agonist, antibody, antagonist, or other binding partner. The
interaction is dependent
upon the presence of a particular structure of the protein, e.g., the
antigenic determinant or epitope,
recognized by the binding molecule. For example, if an antibody is specific
for epitope "A," the
presence of a polypeptide containing epitope A, or the presence of free
unlabeled A, in a reaction
2 s containing free labeled A and the antibody will reduce the amount of
labeled A that binds to the
antibody.
"Substitution" refers to the replacement of at least one nucleotide or amino
acid by a different
nucleotide or amino acid.
"Substrate" refers to any suitable rigid or semi-rigid support including,
e.g., membranes, filters,
3 o chips, slides, wafers, fibers, magnetic or nonmagnetic beads, gels,
tubing, plates, polymers,
microparticles or capillaries. The substrate can have a variety of surface
forms, such as wells,
trenches, pins, channels and pores, to which polynucleotides or polypeptides
are bound.
A "transcript image" refers to the collective pattern of gene expression by a
particular tissue or
cell type under given conditions at a given time.
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"Transformation" refers to a process by which exogenous DNA enters a recipient
cell.
Transformation may occur under natural or artificial conditions using various
methods well known in
the art.. Transformation may rely on any known method for the insertion of
foreign nucleic acid
sequences into a prokaryotic or eukaryotic host cell. The method is selected
based on the host cell being
transformed.
"Transformants" include stably transformed cells in which the inserted DNA is
capable of
replication either as an autonomously replicating plasmid or as part of the
host chromosome, as well as
cells which transiently express inserted DNA or RNA.
A "transgenic organism," as used herein, is any organism, including but not
limited to animals
1 o and plants, in which one or more of the cells of the organism contains
heterologous nucleic acid
introduced by way of human intervention, such as by transgenic techniques well
known in the art. The
nucleic acid is introduced into the cell, directly or indirectly by
introduction into a precursor of the cell,
by way of deliberate genetic manipulation, such as by microinjection or by
infection with a recombinant
virus., mhe term genetic manipulation does not include classical cross-
breeding, or in vitro fertilization,
but rather is directed to the introduction of a recombinant DNA molecule. The
transgenic organisms
contemplated in accordance with the present invention include bacteria,
cyanobacteria, fungi, and plants
and animals. The isolated DNA of the present invention can be introduced into
the host by methods
known in the art, for example infection, transfection, transformation or
transconjugation. Techniques
for transferring the DNA of the present invention into such organisms are
widely known arid provided in
2 o references such as Sambrook et al. (1989), supra.
A "variant" of a particular nucleic acid sequence is defined as a nucleic acid
sequence having at
least 25 % sequence identity to the particular nucleic acid sequence over a
certain length of one of the
nucleic acid sequences using blastn with the "BLAST 2 Sequences" tool Version
2Ø9 (May-07-1999)
set at default parameters. Such a pair of nucleic acids may show, for example,
at least 30%, at least
2s 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%
or even at least 98% or
greater sequence identity over a certain defined length. The variant may
result in "conservative" amino
acid changes which do not affect structural andlor chemical properties. A
variant may be described as,
for example, an "allelic" (as defined above), "splice," "species," or
"polymorphic" variant. A splice
variant may have significant identity to a reference molecule, but will
generally have a greater or lesser
3 o number of polynucleotides due to alternate splicing of exons during mRNA
processing. The
corresponding polypeptide may possess additional functional domains or lack
domains that are present
in the reference molecule. Species variants are polynucleotide sequences that
vary from one species to
another. The resulting polypeptides generally will have significant amino acid
identity relative to each
other. A polymorphic variant is a variation in the polynucleotide sequence of
a particular gene between
3 s individuals of a given species. Polymorphic variants also may encompass
"single nucleotide
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polymorphisms" (SNPs) in which the polynucleotide sequence varies by one base.
The presence of
SNPs may be indicative of, for example, a certain population, a disease state,
or a propensity for a
disease state.
In an alternative, variants of the polynucleotides of the present invention
may be generated
s through recombinant methods. One possible method is a DNA shuffling
technique such as
MOLECULARBREEDING (Maxygen Inc., Santa Clara CA; described in U.S. Patent
Number
5,837,458; Chang, C.-C. et al. (1999) Nat. Biotechnol. 17:793-797; Christians,
F.C. et al. (1999) Nat.
Biotechnol. 17:259-264; and Crameri, A. et al. (1996) Nat. Biotechnol. 14:315-
319) to alter or improve
the biological properties of SPTM, such as its biological or enzymatic
activity or its ability to bind to
~. o other molecules or compounds. DNA shuffling is a process by which a
library of gene variants is
produced using PCR-mediated recombination of gene fragments. The library is
then subjected to
selection or screening procedures that identify those gene variants with the
desired properties. These
preferred variants may then be pooled and further subjected to recursive
rounds of DNA shuffling and
selection/screening. Thus, genetic diversity is created through "artificial"
breeding and rapid molecular
s s evolution. For example, fragments of a single gene containing random point
mutations may be
recombined, screened, and then reshuffled until the desired properties are
optimized. Alternatively,
fragments of a given gene may be recombined with fragments of homologous genes
in the same gene
fanuly, either from the same or different species, thereby maximizing the
genetic diversityof multiple
naturally occurring genes in a directed and controllable manner.
2 o A "variant" of a particular polypeptide sequence is defined as a
polypeptide sequence having
at least 40% sequence identity to the particular polypeptide sequence over a
certain length of one of
the polypeptide sequences using blastp with the "BLAST 2 Sequences" tool
Version 2.0:9 (May-07
1999) set at default parameters. Such a pair of polypeptides may show, for
example, at least SO%, at
least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or at least
98% or greater sequence
2 s identity over a certain defined length of one of the polypeptides.
THE INVENTTON
In a particular embodiment, cDNA sequences derived from human tissues and cell
lines were
aligned based on nucleotide sequence identity and assembled into "consensus"
or "template" sequences
3 o which are designated by the template identification numbers (template IDs)
in column 2 of Table 1.
The sequence identification numbers (SEQ ID NOa) corresponding to the template
IDs are shown in
column 1. Segments of the template sequences are defined by the "start" and
"stop" nucleotide
positions listed in columns 3 and 4. These segments, when translated in the
reading frames indicated in
column 5, have similarity to signal peptide (SP) or transmembrane (TM) domain
consensus sequences,
3 s as indicated in column 6.
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The invention incorporates the nucleic acid sequences of these templates as
disclosed in the
Sequence Listing and the use of these sequences in the diagnosis and treatment
of disease states
characterized by defects in cell signaling. The invention further utilizes
these sequences in hybridization
and amplification technologies, and in particular, in technologies which
assess gene expression patterns
correlated with specific cells or tissues and their responses in vivo or in
vitro to pharmaceutical agents,
toxins, and other treatments. In this manner, the sequences of the present
invention are used to develop
a transcript image for a particular cell or tissue.
Derivation of Nucleic Acid Seauences
s o cDNA was isolated from libraries constructed using RNA derived from normal
and diseased
human tissues and cell lines. The human tissues and cell lines used for cDNA
library construction were
selected from a broad range of sources to provide a diverse population of
cDNAs representative of gene
transcription throughout the human body. Descriptions of the human tissues and
cell lines used for
cDNA library construction are provided in the LIFESEQ database (Incyte
Genomics, Inc. (Incyte), Palo
Alto CA). Human tissues were broadly selected from, for example,
cardiovascular, dermatologic,
endocrine, gastrointestinal, hematopoieticlimmune system, musculoskeletal,
neural, reproductive, and
urologic sources.
Cell lines used for cDNA library construction were derived from, for example,
leukemic cells,
teratocarcinomas, neuroepitheliomas, cervical carcinoma, lung fibroblasts, and
endothelial cells. Such
2 o cell lines include, for example, THP-1, Jurkat, HUVEC, hNT2, WI38, HeLa,
and other cell lines
commonly used and available from public depositories (American Type Culture
Collection, Manassas
VA). Prior to mRNA isolation, cell lines were untreated, treated with a
pharmaceutical agent such as
5'-aza-2'-deoxycytidine, treated with an activating agent such as
lipopolysaccharide in the case of
leukocytic cell lines, or, in the case of endothelial cell lines, subjected to
shear stress.
Seguencin~ of the cDNAs
Methods for DNA sequencing are well known in the art. Conventional enzymatic
methods
employ the HIenow fragment of DNA polymerise I, SEQUENASE DNA polymerise (U.S.
Biochemical Corporation, Cleveland OH), Taq polymerise (Applied Biosystems,
Foster City CA),
3 o thermostable T7 polymerise (Amersham Pharmacia Biotech, Inc. (Amersham
Pharmacia Biotech),
Piscataway NJ), or combinations of polymerises and proofreading exonucleases
such as those found in
the ELONGASE amplification system (Life Technologies Inc. (Life Technologies),
Gaithersburg MD),
to extend the nucleic acid sequence from an oligonucleotide primer annealed to
the DNA template of
interest. Methods have been developed for the use of both single-stranded and
double-stranded
3 5 templates. Chain termination reaction products may be electrophoresed on
urea-polyacrylamide gels
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and detected either by autoradiography (fox radioisotope-labeled nucleotides)
or by fluorescence (for
fluorophore-labeled nucleotides). Automated methods for mechanized reaction
preparation, sequencing,
and analysis using fluorescence detection methods have been developed.
Machines used to prepare
cDNAs for sequencing can include the MICROLAB 2200 liquid transfer system
(Hamilton Company
s (Hamilton), Reno N~, Peltier thermal cycler (PTC200; MJ Research, Inc. (MJ
Research), Watertown
MA), and ABI CATALYST 800 thermal cycler (Applied Biosystems). Sequencing can
be carried out
using, for example, the ABI 373 or 377 (Applied Biosystems) or MEGABACE 1000
(Molecular
Dynamics, Inc. (Molecular Dynamics), Sunnyvale CA) DNA sequencing systems, or
other automated
and manual sequencing systems well known in the art.
1 o The nucleotide sequences of the Sequence Listing have been prepared by
current, state-of the-
art, automated methods and, as such, may contain occasional sequencing errors
or unidentified
nucleotides. Such unidentified nucleotides are designated by an N. These
infrequent unidentified bases
do not represent a hindrance to practicing the invention for those skilled in
the art. Several methods '
employing standard recombinant techniques may be used to correct errors and
complete the missing
is sequence information. (See, e.g., those described in Ausubel, F.M. et al.
(1997) Short Protocols in
Molecular Bioloay, John Wiley & Sons, New York NY; and Sambrook, J. et al.
(1989) Molecular
Cloning, A Laboratory Manual, Cold Spring Harbor Press, Plainview NY.)
Assembly of cDNA Secauences ,
2 o Human polynucleotide sequences may be assembled using programs or
algorithms well known
in the art. Sequences to be assembled are related, wholly or in part, and may
be derived from a single
or many different transcripts. Assembly of the sequences can be performed
using such programs as
PHRAP (Phils Revised Assembly Program) and the GELVIEW fragment assembly
system (GCG), or
other methods known in the art.
z s Alternatively, cDNA sequences are used as "component" sequences that are
assembled into
"template" or "consensus" sequences as follows. Sequence chromatograms are
processed, verified, and
quality scores are obtained using PHRED. Raw sequences are edited using an
editing pathway known
as Block I (See, e.g., the LIFESEQ Assembled User Guide, Incyte Genomics, Palo
Alto, CA). A series
of BLAST comparisons is performed and low-information segments and repetitive
elements (e.g.,
3 o dinucleotide repeats, Alu repeats, etc.) are replaced by "n's", or masked,
to prevent spurious matches.
Mitochondria) and ribosomal RNA sequences are also removed. The processed
sequences are then
loaded into a relational database management system (RDMS) which assigns
edited sequences to
existing templates, if available. When additional sequences are added into the
RDMS, a process is
initiated which modifies existing templates or creates new templates from
works in progress (i.e.,
3 s nonfinal assembled sequences) containing queued sequences or the sequences
themselves. After the new
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sequences have been assigned to templates, the templates can be merged into
bins. If multiple templates
exist in one bin, the bin can be split and the templates reannotated.
Once gene bins have been generated based upon sequence alignments, bins are
"clone joined"
based upon clone information. Clone joining occurs when the 5' sequence of one
clone is present in one
bin and the 3' sequence from the same clone is present in a different bin,
indicating that the two bins
should be merged into a single bin. Only bins which share at least two
different clones are merged.
A resultant template sequence may contain either a partial or a full length
open reading frame,
or all or part of a genetic regulatory element. This variation is due in part
to the fact that the full length
cDNAs of many genes are several hundred, and sometimes several thousand, bases
in length. With
1 o current technology, cDNAs comprising the coding regions of large genes
cannot be cloned because of
vector limitations, incomplete reverse transcription of the mRNA, or
incomplete "second strand"
synthesis. Template sequences may be extended to include additional contiguous
sequences derived
from the parent RNA transcript using a variety of methods known to those of
skill in the art. Extension
may thus be used to achieve the full length coding sequence of a gene.
Analysis of the cDNA Sequences
The cDNA sequences are analyzed using a variety of programs and algorithms
which are well
known in the art. (See, e.g., Ausubel, 1997, supra, Chapter 7.7; Meyers, R.A.
(Ed.) (1995) Molecular
Biolo~y and Biotechnology, Wiley VCH, New York NY, pp. 856-853; and Table 4.)
These analyses
2 o comprise both reading frame determinations, e.g., based on triplet codon
periodicity for particular
organisms (Fickett, J.W. (1982) Nucleic Acids Res. 10:5303-5318); analyses of
potential start and stop
codons; and homology searches.
Computer programs known to those of skill in the art for performing computer-
assisted
searches for amino acid and nucleic acid sequence similarity, include, for
example, Basic Local
2s Alignment Search Tool (BLAST; Altschul, S.F. (1993) J. Mol. Evol. 36:290-
300; Altschul, S.F. et al.
(1990) J. Mol. Biol. 215:403-410). BLAST is especially useful in determining
exact matches and
comparing two sequence fragments of arbitrary but equal lengths, whose
alignment is locally maximal
and for which the alignment score meets or exceeds a threshold or cutoff score
set by the user (Karlin,
S. et al. (1988) Proc. Natl. Acid. Sci. USA 85:841-845). Using an appropriate
search tool (e.g.,
3 o BLAST or HMM), GenBank, SwissProt, BLOCKS, PFAM and other databases may be
searched for
sequences containing regions of homology to a query sptm or SPTM of the
present invention.
Other approaches to the identification, assembly, storage, and display of
nucleotide and
polypeptide sequences are provided in "Relational Database for Storing
Biomolecule Information,"
U.S.S.N. 081947,845, filed October 9, 1997; "Project-Based Full-Length
Biomolecular Sequence
3 5 Database," U.S,S.N. 08/811,758, filed March 6, 1997; and "Relational
Database and System for
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Storing Information Relating to Biomolecular Sequences," U.S.S.N. 09/034,807,
filed March 4, 1998,
all of which are incorporated by reference herein in their entirety.
Protein hierarchies can be assigned to the putative encoded polypeptide based
on, e.g., motif,
BLAST, or biological analysis. Methods for assigning these hierarchies are
described, for example, in
s "Database System Employing Protein Function Hierarchies for Viewing
Biomolecular Sequence Data,"
U.S.S.N. 08/812,290, filed March 6, 1997, incorporated herein by reference.
Human Secretory Seguences
The sptm of the present invention may be used for a variety of diagnostic and
therapeutic
purposes. For example, an sptm may be used to diagnose a particular condition,
disease, or disorder
1 o associated with cell signaling. Such conditions, diseases, and disorders
include, but are not limited to, a
cell proliferative disorder such as actinic keratosis, arteriosclerosis,
atherosclerosis, bursitis, cirrhosis,
hepatitis, mixed connective tissue disease (MCTD), myelofibrosis, paroxysmal
nocturnal
hemoglobinuria, polycythemia vera, psoriasis, primary thrombocythemia, and
cancers including
adenocarcinoma, leukemia, lymphoma, melanoma, myeloma, sarcoma,
teratocarcinoma, and, in
1 s particular, a cancer of the adrenal gland, bladder, bone, bone marrow,
brain, breast, cervix, gall
bladder, ganglia, gastrointestinal tract, heart, kidney, liver, lung, muscle,
ovary, pancreas, parathyroid,
penis, prostate, salivary glands, skin, spleen, testis, thymus, thyroid, and
uterus; an immune system
disorder such as such as inflammation, actinic keratosis, acquired
immunodeficiency syndrome
(AIDS), Addison's disease, adult respiratory distress syndrome, allergies,
ankylosing spondylitis,
2 o amyloidosis, anemia, arteriosclerosis, asthma, atherosclerosis, autoimmune
hemolytic anemia,
autoimmune thyroiditis, bronchitis, bursitis, cholecystitis, cirrhosis,
contact dermatitis, Crohn's
disease, atopic dermatitis, dermatomyositis, diabetes mellitus, emphysema,
erythroblastosis fetalis,
erythema nodosum, atrophic gastritis, glomerulonephritis, Goodpasture's
syndrome, gout, Graves'
disease, Hashimoto's thyroiditis, paroxysmal nocturnal hemoglobinuria,
hepatitis, hypereosinophilia,
2 5 irritable bowel syndrome, episodic lymphopenia with lymphocytotoxins,
mixed connective tissue
disease (MCTD), multiple sclerosis, myasthenia gravis, myocardial or
pericardial inflammation,
myelofibrosis, osteoarthritis, osteoporosis, pancreatitis, polycythemia vera,
polymyositis, psoriasis,
Reiter's syndrome, rheumatoid arthritis, scleroderma, Sjogren's syndrome,
systemic anaphylaxis,
systemic lupus erythematosus, systemic sclerosis, primary thrombocythemia,
thrombocytopenic
3 o purpura, ulcerative colitis, uveitis, Werner syndrome, complications of
cancer, hemodialysis, and
extracorporeal circulation, trauma, and hematopoietic cancer including
lymphoma, leukemia, and
myeloma; and a neurological disorder such as epilepsy, ischemic
cerebrovascular disease, stroke,
cerebral neoplasms, Alzheimer's disease, Pick's disease, Huntington's disease,
dementia, Parkinson's
disease and other extrapyramidal disorders, amyotrophic lateral sclerosis and
other motor neuron
3 5 disorders, progressive neural muscular atrophy, retinitis pigmentosa,
hereditary ataxias, multiple
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sclerosis and other demyelinating diseases, bacterial and viral meningitis,
brain abscess, subdural
empyema, epidural abscess, suppurative intracranial thrombophlebitis, myelitis
and radiculitis, viral
central nervous system disease, prion diseases including kuru, Creutzfeldt-
Jakob disease, and
Gerstmann-Straussler-Scheinker syndrome, fatal familial insomnia, nutritional
and metabolic diseases
s of the nervous system, neurofibromatosis, tuberous sclerosis,
cerebelloretinal hemangioblastomatosis,
encephalotrigeminal syndrome, mental retardation and other developmental
disorder of the central
nervous system, cerebral palsy, a neuroskeletal disorder, an autonomic nervous
system disorder, a
cranial nerve disorder, a spinal cord disease, muscular dystrophy and other
neuromuscular disorder, a
peripheral nervous system disorder, dermatomyositis and polymyositis,
inherited, metabolic, endocrine,
s o and toxic myopathy, myasthenia gravis, periodic paralysis, a mental
disorder including mood, anxiety,
and schizophrenic disorder, seasonal affective disorder (SAD), akathesia,
amnesia, catatonia, diabetic
neuropathy, tardive dyskinesia, dystonias, paranoid psychoses, postherpetic
neuralgia, and Tourette's
disorder. The sptm can be used to detect the presence of, or to quantify the
amount of, an sptm-related
polynucleotide in a sample. This information is then compared to information
obtained from appropriate
s s reference samples, and a diagnosis is established. Alternatively, a
polynucleotide complementary to a
given sptm can inhibit or inactivate a therapeutically relevant gene related
to the sptm.
Analysis of sptm Expression Patterns
The expression of sptm may be routinely assessed by hybridization-based
methods to
2 o determine, for example, the tissue-specificity, disease-specificity, or
developmental stage-specificity of
sptm expression. For example, the level of expression of sptm may be compared
among different cell
types or tissues, among diseased and normal cell types or tissues, among cell
types or tissues at
different developmental stages, or among cell types or tissues undergoing
various treatments. This type
of analysis is useful, for example, to assess the relative levels of sptm
expression in fully or partially
2 s differentiated cells or tissues, to determine if changes in sptm
expression levels are correlated with the
development or progression of specific disease states, and to assess the
response of a cell or tissue to a
specific therapy, for example, in pharmacological or toxicological studies.
Methods for the analysis of
sptm expression are based on hybridization and amplification technologies and
include membrane-based
procedures such as northern blot analysis, high-throughput procedures that
utilize, for example,
3 o microarrays, and PCR-based procedures.
Hybridization and Genetic Analysis
The sptm, their fragments, or complementary sequences, may be used to identify
the presence
of and/or to determine the degree of similarity between two (or more) nucleic
acid sequences. The sptm
a 5 may be hybridized to naturally occurring or recombinant nucleic acid
sequences under appropriately
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selected temperatures and salt concentrations. Hybridization with a probe
based on the nucleic acid
sequence of at least one of the sptm allows for the detection of nucleic acid
sequences, including
genomic sequences, which are identical or related to the sptm of the Sequence
Listing. Probes may be
selected from non-conserved or unique regions of at least one of the
polynucleotides of SEQ ID NO:1-
79 and tested for their ability to identify or amplify the target nucleic acid
sequence using standard
protocols.
Polynucleotide sequences that are capable of hybridizing, in particular, to
those shown in SEQ
ID NO:l-79 and fragments thereof, can be identified using various conditions
of stringency. (See, e.g.,
Wahl, G.M. and S.L. Berger (1987) Methods Enzymol. 152:399-407; Kimmel, A.R.
(1987) Methods
so Enzymol. 152:507-511.) Hybridization conditions are discussed in
"Definitions."
A probe for use in Southern or northern hybridization may be derived from a
fragment of an
sptm sequence, or its complement, that is up to several hundred nucleotides in
length and is either
single-stranded or double-stranded. Such probes may be hybridized in solution
to biological materials
such as plasmids, bacterial, yeast, or human artificial chromosomes, cleared
or sectioned tissues, or to
s s artificial substrates containing sptm. Microarrays are particularly
suitable for identifying the presence
of and detecting the level of expression for multiple genes of interest by
examining gene expression
correlated with, e.g., various stages of development, treatment with a drug or
compound, or disease
progression. An array analogous to a dot or slot blot may be used to arrange
and link polynucleotides
to the surface of a substrate using one or more of the following: mechanical
(vacuum), chemical,
2 o thermal, or UV bonding procedures. Such an array may contain any number of
sptm and may be
produced by hand or by using available devices, materials, and machines.
Microarrays may be prepared, used, and analyzed using methods known in the
art. (See, e.g.,
Brennan, T.M, et al. (1995) U.S. Patent No. 5,474,796; Schena, M. et al.
(1996) Proc. Natl. Acad. Sci.
USA 93:10614-10619; Baldeschweiler et al. (1995) PCT application W095/251116;
Shalom D. et al.
2s (1995) PCT application W095/35505; Heller, R.A. et al. (1997) Proc. Natl.
Acad. Sci. USA 94:2150-
2155; and Heller, M.J. et al. (1997) U.S. Patent No. 5,605,662.)
Probes may be labeled by either PCR or enzymatic techniques using a variety of
commercially
available reporter molecules. For example, commercial kits are available for
radioactive and
chemiluminescent labeling (Amersham Pharmacia Biotech) and for alkaline
phosphatase labeling (Life
3 o Technologies). Alternatively, sptm may be cloned into commercially
available vectors for the
production of RNA probes. Such probes may be transcribed in the presence of at
least one labeled
nucleotide (e.g., 32P-ATP, Amersham Pharmacia Biotech).
Additionally the polynucleotides of SEQ ID N0:1-79 or suitable fragments
thereof can be used
to isolate full length cDNA sequences utilizing hybridization and/or
amplification procedures well
a s known in the art, e.g., cDNA library screening, PCR amplification, etc.
The molecular cloning of such
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full length cDNA sequences may employ the method of cDNA library screening
with probes using the
hybridization, stringency, washing, and probing strategies described above and
in Ausubel, supra,
Chapters 3, 5, and 6. These procedures may also be employed with genomic
libraries to isolate
genomic sequences of sptm in order to analyze, e.g., regulatory elements.
Genetic Mapping
Gene identification and mapping are important in the investigation and
treatment of almost all
to conditions, diseases, and disorders. Cancer, cardiovascular disease,
Alzheimer's disease, arthritis,
diabetes, and mental illnesses are of particular interest. Each of these
conditions is more complex than
the single gene defects of sickle cell anemia or cystic fibrosis, with select
groups of genes being
predictive of predisposition for a particular condition, disease, or disorder.
For example;
cardiovascular disease may result from malfunctioning receptor molecules that
fail to clear cholesterol
s s from the bloodstream, and diabetes may result when a particular
individual's immune system is
activated by an infection and attacks the insulin-producing cells of the
pancreas. In some studies,
Alzheimer's disease has been linked to a gene on chromosome 21; other studies
predict a different gene
and location. Mapping of disease genes is a complex and reiterative process
and generally proceeds
from genetic linkage analysis to physical mapping.
2 o As a condition is noted among members of a family, a genetic linkage map
traces parts of
chromosomes that are inherited in the same pattexn as the condition.
Statistics link the inheritance of
particular conditions to particular regions of chromosomes, as defined by RFLP
or other markers.
(See, for example, Lander, E. S. and Botstein, D. (1986) Proc. Natl. Acad.
Sci. USA 83:7353-7357.)
Occasionally, genetic markers and their locations are known from previous
studies, More often,
2 s however, the markers are simply stretches of DNA that differ among
individuals. Examples of genetic
linkage maps can be found in various scientific journals or at the Online
Mendelian Inheritance in Man
(OMIM) World Wide Web site.
In another embodiment of the invention, sptm sequences may be used to generate
hybridization
probes useful in chromosomal mapping of naturally occurring genomic sequences.
Either coding or
3 o noncoding sequences of sptm may be used, and in some instances, noncoding
sequences may be
preferable over coding sequences. For example, conservation of an sptm coding
sequence among
members of a multi-gene family may potentially cause undesired cross
hybridization during
chromosomal mapping. The sequences may be mapped to a particular chromosome,
to a specific region
of a chromosome, or to artificial chromosome constructions, e.g., human
artificial chromosomes
35 (HACs), yeast artificial chromosomes (YACs), bacterial artificial
chromosomes (BACs), bacterial P1
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constructions, or single chromosome cDNA libraries. (See, e.g., Harrington,
J.J. et al. (1997) Nat.
Genet. 15:345-355; Price, C.M. (1993) Blood Rev. 7:127-134; and Trask, B.J.
(1991) Trends Genet.
7:149-154.)
Fluorescent in situ hybridization (FISH) may be correlated with other physical
chromosome
s mapping techniques and genetic map data. (See, e.g., Meyers, supra, pp. 965-
968.) Correlation
between the location of sptm on a physical chromosomal map and a specific
disorder, or a
predisposition to a specific disorder, may help define the region of DNA
associated with that disorder.
The sptm sequences may also be used to detect polymorphisms that are
genetically linked to the
inheritance of a particular condition, disease, or disorder.
~ o In situ hybridization of chromosomal preparations and genetic mapping
techniques, such as
linkage analysis using established chromosomal markers, may be used for
extending existing genetic
maps. Often the placement of a gene on the chromosome of another mammalian
species, such as
mouse, may reveal associated markers even if the number or arm of the
corresponding human
chromosome is not known. These new marker sequences can be mapped to human
chromosomes and
s s may provide valuable information to investigators sear ching for disease
genes using positaonal cloning
or other gene discovery techniques. Once a disease ox syndrome has been
crudely correlated by genetic
linkage with a particular genomic region, e.g., ataxia-telangiectasia to 11q22-
23, any sequences
mapping to that area may represent associated or regulatory. genes for further
investigation. (See, e.g.,
Gatti, R.A. et al. (1988) Nature 336:577-580.) The nucleotide sequences of the
subject invention may
2 o also be used to detect differences in chromosomal architecture due to
translocation, inversion, etc.,
among normal, carrier, or affected individuals.
Once a disease-associated gene is mapped to a chromosomal region, the gene
must be cloned in
order to identify mutations or other alterations (e.g., translocations or
inversions) that may be correlated
with disease. This process requires a physical map of the chromosomal region
containing the disease-
2 s gene of interest along with associated markers. A physical map is
necessary for determining the
nucleotide sequence of arid order of marker genes on a particular chromosomal
region. Physical
mapping techniques are well known in the art and require the generation of
overlapping sets of cloned
DNA fragments from a particular organelle, chromosome, or genome. These clones
are analyzed to
reconstruct and catalog their order. Once the position of a marker is
determined, the DNA from that
3 o region is obtained by consulting the catalog and selecting clones from
that region. The gene of interest
is located through positional cloning techniques using hybridization or
similar methods.
Diagnostic Uses
The sptm of the present invention may be used to design probes useful in
diagnostic assays.
3 5 Such assays, well known to those skilled in the art, may be used to detect
or confirm conditions,
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disorders, or diseases associated with abnormal levels of sptm expression.
Labeled probes developed
from sptm sequences are added to a sample under hybridizing conditions of
desired stringency. In some
instances, sptm, or fragments or oligonucleotides derived from sptm, may be
used as primers in
amplification steps prior to hybridization. The amount of hybridization
complex formed is quantified
s and compared with standards for that cell or tissue. If sptm expression
varies significantly from the
standard, the assay indicates the presence of the condition, disorder, or
disease. Qualitative or
quantitative diagnostic methods may include northern, dot blot, or other
membrane or dip-stick based
technologies or multiple-sample format technologies such as PCR, enzyme-linked
immunosorbent assay
(ELISA)-like, pin, or chip-based assays.
~ o The probes described above may also be used to monitor the progress of
conditions, disorders,
or diseases associated with abnormal levels of sptm expression, or to evaluate
the efficacy of a
particular therapeutic treatment. The candidate probe may be identified from
the sptm that are specific
to a given human tissue and have not been observed in GenBank or other genome
databases. Such a
probe may be used in animal studies, preclinical tests, clinical trials, or in
monitoring the treatment of
15 an individual patient. In a typical process, standard expression is
established by methods well known in
the art for use as a basis of comparison, samples from patients affected by
the disorder or disease are
combined with the probe to evaluate any deviation from the standard profile,
and a therapeutic agent is
administered and effects are monitored to generate a treatment profile.
Efficacy is evaluated by
determining whether the expression progresses toward or returns to the
standard normal pattern.
2 o Treatment profiles may be generated over a period of several days or
several months. Statistical
methods well known to those skilled in the art may be use to determine the
significance of such
therapeutic agents.
The polynucleotides are also useful for identifying individuals from minute
biological samples,
for example, by matching the RFLP pattern of a sample's DNA to that of an
individual's DNA. The
2 5 polynucleotides of the present invention can also be used to determine the
actual base-by-base DNA
sequence of selected portions of an individual's genome. These sequences can
be used to prepare PCR
primers for amplifying and isolating such selected DNA, which can then be
sequenced. Using this
technique, an individual can be identified through a unique set of DNA
sequences. Once a unique ID
database is established for an individual, positive identification of that
individual can be made from
3 o extremely small tissue samples.
In a particular aspect, oligonucleotide primers derived from the sptm of the
invention may be
used to detect single nucleotide polymorphisms (SNPs). SNPs are substitutions,
insertions and
deletions that are a frequent cause of inherited or acquired genetic disease
in humans. Methods of SNP
detection include, but are not limited to, single-stranded conformation
polymorphism (SSCP) and
3 5 fluorescent SSCP (fSSCP) methods. In SSCP, oligonucleotide primers derived
from sptm are used to
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amplify DNA using the polymerase chain reaction (PCR). The DNA may be derived,
for example,
from diseased or normal tissue, biopsy samples, bodily fluids, and the like.
SNPs in the DNA cause
differences in the secondary and tertiary structures of PCR products in single-
stranded form, and these
differences are detectable using gel electrophoresis in non-denaturing gels.
In fSCCP, the
s oligonucleotide primers are fluorescently labeled, which allows detection of
the amplimers in high-
throughput equipment such as DNA sequencing machines. Additionally, sequence
database analysis
methods, termed in silico SNP (isSNP), are capable of identifying
polymorphisms by comparing the
sequences of individual overlapping DNA fragments which assemble into a common
consensus
sequence. These computer-based methods filter out sequence variations due to
laboratory preparation
s o of DNA and sequencing errors using statistical models and automated
analyses of DNA sequence
chromatograms. In the alternative, SNPs may be detected and characterized by
mass spectrometry
using, for example, the high throughput MASSARRAY system (Sequenom, Inc., San
Diego CA).
DNA-based identification techniques are critical in forensic technology. DNA
sequences taken
from very small biological samples such as tissues, e.g., hair or skin, or
body fluids, e.g., blood, saliva,
15 semen, etc., can be amplified using, e.g., PCR, to identify individuals.
(See, e.g., Erlich, H. (1992)
PCR Technolo~y, Freeman and Co., New York, NY). Similarly, polynucleotides of
the present
invention can be used as polymorphic markers.
There is also a need for reagents capable of identifying the source of a
particular tissue.
Appropriate reagents can comprise, fox example, DNA probes or primers prepared
from the sequences
2 0 of the present invention that are specific for particular tissues. Panels
of such reagents can identify
tissue by species and/or by organ type. In a similar fashion, these reagents
can be used to screen tissue
cultures for contamination.
The polynucleotides of the present invention can also be used as molecular
weight markers on
nucleic acid gels or Southern blots, as diagnostic probes for the presence of
a specific mRNA in a
2 s particular cell type, in the creation of subtracted cDNA libraries which
aid in the discovery of novel
polynucleotides, in selection and synthesis of oligomers for attachment to an
array or other support, and
as an antigen to elicit an immune response.
Disease Model Systems Using s~tm
The polynucleotides encoding SPTM or their mammalian homologs may be "knocked
out" in
3 o an animal model system using homologous recombination in embryonic stem
(ES) cells. Such
techniques are well known in the art and are useful for the generation of
animal models of human
disease. (See, e.g., U.S. Patent Number 5,175,383 and U.S. Patent Number
5,767,337.) For example,
mouse ES cells, such as the mouse 12,9/SvJ cell line, are derived from the
early mouse embryo and
grown in culture. The ES cells are transformed with a vector containing the
gene of interest disrupted
35 by a marker gene, e.g., the neomycin phosphotransferase gene (neo;
Capecchi, M.R. (1989) Science
31
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244:1288-1292). The vector integrates into the corresponding region of the
host genome by
homologous recombination. Alternatively, homologous recombination takes place
using the Cre-loxP
system to knockout a gene of interest in a tissue- or developmental stage-
specific manner (March, J.D.
(1996) Clin. Invest. 97:1999-2002; Wagner, K.U. et al. (1997) Nucleic Acids
Res. 25:4323-4330).
s Transformed ES cells are identified and microinjected into mouse cell
blastocysts such as those from
the C57BL/6 mouse strain. The blastocysts are surgically transferred to
pseudopregnant dams, and the
resulting chimeric progeny are genotyped and bred to produce heterozygous or
homozygous strains.
Transgenic animals thus generated may be tested with potential therapeutic or
toxic agents.
The polynucleotides encoding SPTM may also be manipulated in vitro in ES cells
derived from
s o human blastocysts. Human ES cells have the potential to differentiate into
at least eight separate cell
lineages including endoderm, mesoderm, and ectodermal cell types. These cell
lineages differentiate
into, for example, neural cells, hematopoietic lineages, and cardiomyocytes
(Thomson, J.A. et al. (1998)
Science 282:1145-1147).
The polynucleotides encoding SPTM of the invention can also be used to create
"knockin"
15 humanized animals (pigs) or transgenic animals (mice or rats) to model
human disease. With knockin
technology, a region of sptm is injected into animal ES cells, and the
injected sequence integrates into
the animal cell genome. Transformed cells are injected into blastulae, and the
blastulae are implanted
as described above. Transgenic progeny or inbred lines are studied and treated
with potential
pharmaceutical agents to obtain information on treatment of a human disease.
Alternatively, a mammal
2 o inbred to overexpress sptm, resulting, e.g., in the secretion of SPTM in
its milk, may also serve as a
convenient source of that protein (Janne, J. et al. (1998) Biotechnol. Annu.
Rev. 4:55-74).
Screening Assays
SPTM encoded by polynucleotides of the present invention may be used to screen
for molecules
2 s that bind to or are bound by the encoded polypeptides. The binding of the
polypeptide and the molecule
may activate (agonist), increase, inhibit (antagonist), or decrease activity
of the polypeptide or the
bound molecule. Examples of such molecules include antibodies,
oligonucleotides, proteins (e.g.,
receptors), or small molecules.
Preferably, the molecule is closely related to the natural ligand of the
polypeptide, e.g., a ligand
3 0 or fragment thereof, a natural substrate, or a structural or functional
mimetic. (See, Coligan et al.,
(1991) Current Protocols in Immunology 1(2): Chapter 5.) Similarly, the
molecule can be closely
related to the natural receptor to which the polypeptide binds, or to at least
a fragment of the receptor,
e.g., the active site. In either case, the molecule can be rationally designed
using known techniques.
Preferably, the screening for these molecules involves producing appropriate
cells which express the
3 5 polypeptide, either as a secreted protein or on the cell membrane.
Preferred cells include cells from
32
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mammals, yeast, Drosophila, or E. coli. Cells expressing the polypeptide or
cell membrane fractions
which contain the expressed polypeptide are then contacted with a test
compound and binding,
stimulation, or inhibition of activity of either the polypeptide or the
molecule is analyzed.
An assay may simply test binding of a candidate compound to the polypeptide,
wherein binding
s is detected by a fluorophore, radioisotope, enzyme conjugate, or other
detectable label. Alternatively,
the assay may assess binding in the presence of a labeled competitor.
Additionally, the assay can be carried out using cell-free preparations,
polypeptide/molecule
affixed to a solid support, chemical libraries, or natural product mixtures.
The assay may also simply
comprise the steps of mixing a candidate compound with a solution containing a
polypeptide, measuring
2 o polypeptide/molecule activity or binding, and comparing the
polypeptide/molecule activity or binding to
a standard.
Preferably, an ELISA assay using, e.g., a monoclonal or polyclonal antibody,
can measure
polypeptide level in a sample. The antibody can measure polypeptide level by
either binding, directly or
indirectly, to the polypeptide or by competing with the polypeptide for a
substrate.
15 All of the above assays can be used in a diagnostic or prognostic context.
The molecules
discovered using these assays can be used to treat disease or to bring about a
particular result in a
patient (e.g., blood vessel growth) by activating or inhibiting the
polypeptide/molecule. Moreover, the
assays can discover agents which may inhibit or enhance the production of the
polypeptide from
suitably maiupulated cells or tissues.
Transcript Imaging and Toxicological Testing
Another embodiment relates to the use of sptm to develop a transcript image of
a tissue or cell
type. A transcript image represents the global pattern of gene expression by a
particular tissue or cell
type. Global gene expression patterns are analyzed by quantifying the number
of expressed genes and
2 5 their relative abundance under given conditions and at a given time. (See
Seilhamer et al.,
"Comparative Gene Transcript Analysis," U.S. Patent Number 5,840,484,
expressly incorporated by
reference herein.) Thus a transcript image may be generated by hybridizing the
polynucleotides of the
present invention or their complements to the totality of transcripts or
reverse transcripts of a particular
tissue or cell type. In one embodiment, the hybridization takes place in high-
throughput format,
3 o wherein the polynucleotides of the present invention or their complements
comprise a subset of a
plurality of elements on a microarray. The resultant transcript image would
provide a profile of gene
activity pertaining to cell signaling.
Transcript images which profile sptm expression may be generated using
transcripts isolated
from tissues, cell lines, biopsies, or other biological samples. The
transcript image may thus reflect
33
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sptm expression in vivo, as in the case of a tissue or biopsy sample, or in
vitro, as in the case of a cell
line.
Transcript images which profile sptm expression may also be used in
conjunction with in vitro
model systems and preclinical evaluation of pharmaceuticals, as well as
toxicological testing of
s industrial and naturally-occurring environmental compounds. All compounds
induce characteristic
gene expression patterns, frequently termed molecular fingerprints or toxicant
signatures, which are
indicative of mechanisms of action and toxicity (Nuwaysir, E. F. et al. (1999)
Mol. Carcinog. 24:153-
159; Steiner, S. and Anderson, N. L. (2000) Toxicol. Lett. 112-213:467-71,
expressly incorporated by
reference herein). If a test compound has a signature similar to that of a
compound with known
s o toxicity, it is likely to share those toxic properties. These fingerprints
or signatures are most useful and
refined when they contain expression information from a large number of genes
and gene families.
Ideally, a genome-wide measurement of expression provides the highest quality
signature. Even genes
whose expression is not altered by any tested compounds are important as well,
as the levels of
expression of these genes are used to normalize the rest of the expression
data. The normalization
15 procedure is useful for comparison of expression data after treatment with
different compounds. While
the assignment of gene function to elements of a toxicant signature aids in
interpretation of toxicity
mechanisms, knowledge of gene function is not necessary for the statistical
matching of signatures
which leads to prediction of toxicity. (See, for example, Press Release 00-02
from the National
Institute of Environmental Health Sciences, released February 29, 2000,
available at
2o http://www.niehs.nih.gov/oc/news/toxchip.htm.) Therefore, it is important
and desirable in
toxicological screening using toxicant signatures to include all expressed
gene sequences.
In one embodiment, the toxicity of a test compound is assessed by treating a
biological sample
containing nucleic acids with the test compound. Nucleic acids that are
expressed in the treated
biological sample are hybridized with one or more probes specific to the
polynucleotides of the
2 s present invention, so that transcript levels corresponding to the
polynucleotides of the present
invention may be quantified. The transcript levels in the treated biological
sample are compared with
levels in an untreated biological sample. Differences in the transcript levels
between the two samples
are indicative of a toxic response caused by the test compound in the treated
sample.
Another particular embodiment relates to the use of SPTM encoded by
polynucleotides of the
3 o present invention to analyze the proteome of a tissue or cell type. The
term proteome refers to the
global pattern of protein expression in a particular tissue or cell type. Each
protein component of a
proteome can be subjected individually to further analysis. Proteome
expression patterns, or profiles,
are analyzed by quantifying the number of expressed proteins and their
relative abundance under given
conditions and at a given time. A profile of a cell's proteome may thus be
generated by separating and
3 s analyzing the polypeptides of a particular tissue or cell type. In one
embodiment, the separation is
34
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WO 01/62918 PCT/USO1/03465
achieved using two-dimensional gel electrophoresis, in which proteins from a
sample are separated by
isoelectric focusing in the first dimension, and then according to molecular
weight by sodium dodecyl
sulfate slab geI electrophoresis in the second dimension (Steiner and
Anderson, supra). The proteins are
visualized in the gel as discrete and uniquely positioned spots, typically by
staining the gel with an
s agent such as Coomassie Blue or silver or fluorescent stains. The optical
density of each protein spot is
generally proportional to the level of the protein in the sample. The optical
densities of equivalently
positioned protein spots from different samples, for example, from biological
samples either treated or
untreated with a test compound or therapeutic agent, are compared to identify
any changes in protein
spot density related to the treatment. The proteins in the spots are partially
sequenced using, for
s o example, standard methods employing chemical or enzymatic cleavage
followed by mass spectrometry.
The identity of the protein in a spot may be determined by comparing its
partial sequence, preferably of
at least 5 contiguous amino acid residues, to the polypeptide sequences of the
present invention. In
some cases, further sequence data may be obtained for definitive protein
identification.
A proteomic profile may also be generated using antibodies specific for SPTM
to quantify the
~ s levels of SPTM expression. In one embodiment, the antibodies are used as
elements on a microarray,
and protein expression levels are quantified by exposing the microarray to the
sample and detecting the
levels of protein bound to each array element (Lueking, A. et al. (1999) Anal.
Biochem. 270:103-11;
Mendoze, L. G. et al. ( 1999) Biotechniques 27:778-88). Detection may be
performed by a variety of
methods known in the art, for example, by reacting the proteins in the sample
with a thiol- or amino-
2 o reactive fluorescent compound and detecting the amount of fluorescence
bound at each array element.
Toxicant signatures at the proteome level are also useful for toxicological
screening, and should
be analyzed in parallel with toxicant signatures at the transcript level.
There is a poor correlation
between transcript and protein abundances for some proteins in some tissues
(Anderson, N. L. and
Seilhamer, J. (1997) Electrophoresis 18:533-537), so proteome toxicant
signatures may be useful in the
z s analysis of compounds which do not significantly affect the transcript
image, but which alter the
proteomic profile. In addition, the analysis of transcripts in body fluids is
difficult, due to rapid
degradation of mRNA, so proteomic profiling may be more reliable and
informative in such cases.
In another embodiment, the toxicity of a test compound is assessed by treating
a biological
sample containing proteins with the test compound. Proteins that are expressed
in the treated biological
3 o sample are separated so that the amount of each protein can be quantified.
The amount of each protein
is compared to the amount of the corresponding protein in an untreated
biological sample. A difference
in the amount of protein between the two samples is indicative of a toxic
response to the test compound
in the treated sample. Individual proteins are identified by sequencing the
amino acid residues of the
individual proteins and comparing these partial sequences to the SPTM encoded
by polynucleotides of
3 5 the present invention.
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
In another embodiment, the toxicity of a test compound is assessed by treating
a biological
sample containing proteins with the test compound. Proteins from the
biological sample are incubated
with antibodies specific to the SPTM encoded by polynucleotides of the present
invention. The amount
of protein recognized by the antibodies is quantified. The amount of protein
in the treated biological
s sample is compared with the amount in an untreated biological sample. A
difference in the amount of
protein between the two samples is indicative of a toxic response to the test
compound in the treated
sample.
Transcript images may be used to profile sptm expression in distinct tissue
types. This process
can be used to determine cell signaling activity in a particular tissue type
relative to this activity in a
~. o different tissue type. Transcript images may be used to generate a
profile of sptm expression
characteristic of diseased tissue. Transcript images of tissues before and
after treatment may be used
for diagnostic purposes, to monitor the progression of disease, and to monitor
the efficacy of drug
treatments for diseases which affect cell signaling activity.
Transcript images of cell lines can be used to assess cell signaling activity
and/or to identify
1 s cell lines that lack or misregulate this activity. Such Bell lines may
then be treated with pharmaceutical
agents, and a transcript image following treatment may indicate the efficacy
of these agents in restoring
desired levels of this activity. A similar approach may be used to assess the
toxicity of pharmaceutical
agents as reflected by undesirable changes in cell signaling activity.
Candidate pharmaceutical agents
may be evaluated by comparing their associated transcript images with those of
pharmaceutical agents
2 0 of known effectiveness.
Antisense Molecules
The polynucleotides of the present invention are useful in antisense
technology. Antisense
technology or therapy relies on the modulation of expression of a target
protein through the specific
2 s binding of an antisense sequence to a target sequence encoding the target
protein or directing its
expression. (See, e.g., Agrawal, S., ed. (1996) Antisense Therapeutics, Humana
Press Inc., Totawa
NJ; Alama, A. et al. (1997) Pharmacol. Res. 36(3):171-178; Crooke, S.T. (1997)
Adv. Pharmacol.
40:1-49; Sharma, H.W. and R. Narayanan (1995) Bioessays 17(12):1055-1063; and
Lavrosky, Y, et
al. (1997) Biochem. Mol. Med. 62(1):11-22.) An antisense sequence is a
polynucleotide sequence
3 o capable of specifically hybridizing to at least a portion of the target
sequence. Antisense sequences
bind to cellular mRNA and/or genomic DNA, affecting translation and/or
transcription. Antisense
sequences can be DNA, RNA, or nucleic acid mimics and analogs. (See, e.g.,
Rossi, J.J. et al. (1991)
Antisense Res. Dev. 1(3):285-288; Lee, R. et al. (1998) Biochemistry 37(3):900-
1010; Pardridge,
W.M. et al. (1995) Proc. Natl. Acad. Sci. USA 92(12):5592-5596; and Nielsen,
P. E. and Haaima, G.
3 5 (1997) Chem. Soc. Rev. 96:73-78.) Typically, the binding which results in
modulation of expression
36
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
occurs through hybridization or binding of complementary base pairs. Antisense
sequences can also
bind to DNA duplexes through specific interactions in the major groove of the
double helix.
The polynucleotides of the present invention and fragments thereof can be used
as antisense
sequences to modify the expression of the polypeptide encoded by sptm. The
antisense sequences can
s be produced ex vivo, such as by using any of the ABI nucleic acid
synthesizer series (Applied
Biosystems) or other automated systems known in the art. Antisense sequences
can also be produced
biologically, such as by transforming an appropriate host cell with an
expression vector containing the
sequence of interest. (See, e.g., Agrawal, supra.)
In therapeutic use, any gene delivery system suitable for introduction of the
antisense sequences
~ o into appropriate target cells can be used. Antisense sequences can be
delivered intracellularly in the
form of an expression plasmid which, upon transcription, produces a sequence
complementary to at
least a portion of the cellular sequence encoding the target protein. (See,
e.g., Slater, J.E., et al. (1998)
J. Allergy Clin. Immunol. 102(3):469-475; and Scanlon, K.J., et al. (1995)
9(13):1288-1296.)
Antisense sequences can also be introduced intracellularly through the use of
viral vectors, such as
s5 retrovirus and adeno-associated virus vectors. (See, e.g., Miller, A.D.
(1990) Blood 76:271; Ausubel,
F.M. et al. (1995) Current Protocols in Molecular Biolo~y, John Wiley & Sons,
New York NY; Uckert,
W. and W. Walther (1994) Pharmacol. Ther. 63(3):323-347.) Other gene delivery
mechanisms include
liposome-derived systems, artificial viral envelopes, and other systems known
in the art. (See, e.g.,
Rossi, J.J. (1995) Br. Med. Bull. 51(1):217-225; Boado, R.J. et al: (1998) J.
Pharm. Sci.' 87(11):1308-
20 1315; and Morris, M.C. et al, (1997) Nucleic Acids Res. 25(14):2730-2736.)
Expression
In order to express a biologically active SPTM, the nucleotide sequences
encoding SPTM or
fragments thereof may be inserted into an appropriate expression vector, i.e.,
a vector which contains
25 the necessary elements for transcriptional and translational.control of the
inserted coding sequence in a
suitable host. Methods which are well known to those skilled in the art may be
used to construct
expression vectors containing sequences encoding SPTM and appropriate
transcriptional and
txanslational control elements. These methods include in vitro recombinant DNA
techniques, synthetic
techniques, and in vivo genetic recombination. (See, e.g., Sambrook, su ra,
Chapters 4, 8, 16, and 17;
3 o and Ausubel, supra, Chapters 9, 10, 13, and 16.)
A variety of expression vector/host systems may be utilized to contain and
express sequences
encoding SPTM. These include, but are not limited to, microorganisms such as
bacteria transformed
with recombinant bacteriophage, plasmid, or cosmid DNA expression vectors;
yeast transformed with
yeast expression vectors; insect cell systems infected with viral expression
vectors (e.g., baculovirus);
3 s plant cell systems transformed with viral expression vectors (e.g.,
cauliflower mosaic virus, CaMV, or
37
CA 02418496 2003-02-04
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tobacco mosaic virus, TMV) or with bacterial expression vectors (e.g., Ti or
pBR322 plasmids); or
animal (mammalian) cell systems. (See, e.g., Sambrook, supra; Ausubel, 1995,
su ra, Van Heeke, G.
and S.M. Schuster (1989) J. Biol. Chem. 264:5503-5509; Bitter, G.A. et al.
(1987) Methods Enzymol.
153:516-544; Scorer, C.A. et al. (1994) Bio/Technology 12:181-184; Engelhard,
E.K. et al. (1994)
s Proc. Natl. Acad. Sci. USA 91:3224-3227; Sandig, V. et al. (1996) Hum. Gene
Ther. 7:1937-1945;
Takamatsu, N. (1987) EMBO J. 6:307-311; Coruzzi, G. et al. (1984) EMBO J.
3:1671-1680; Brogue,
R. et al. (1984) Science 224:838-843; Winter, J. et al. (1991) Results Probl.
Cell Differ. 17:85-105;
The McGraw Hill Yearbook of Science and Technolo~y (1992) McGraw Hill, New
York NY, pp.
191-196; Logan, J. and T. Shenk (1984) Proc. Natl. Acad. Sci. USA 81:3655-
3659; and Harrington,
1 o J.J. et al. (1997) Nat. Genet. 15:345-355.) Expression vectors derived
from retroviruses, adenoviruses,
or herpes or vaccinia viruses, or from various bacterial plasmids, may be used
fox delivery of nucleotide
sequences to the targeted organ, tissue, or cell population. (See, e.g., Di
Nicola, M. et al. (1998)
Cancer Gen. Ther. 5(6):350-356; Yu, M. et al., (1993) Proc. Natl. Acad. Sci.
USA 90(13):6340-6344;
Buller, R,M. et a1. (1985) Nature 317(6040):813-815; McGregor, D.P. et al.
(1994) Mol. Immunol.
s5 31(3):219-226; and Verma, LM. and N. Somia (1997) Nature 389:239-242.) The
invention is not
limited by the host cell employed.
For long term production of recombinant proteins in mammalian systems, stable
expression of
SPTM in cell lines is preferred. For example, sequences encoding SPTM can be
transformed into cell
lines using expression vectors which may contain viral origins of replication
and/or endogenous
2 o expression elements and a selectable marker gene on the same or on a
separate vector. Any number of
selection systems may be used to recover transformed cell lines. (See, e.g.,
Wigler, M. et al. (1977)
Cell 11:223-232; Lowy, I. et al. (1980) CeII 22:817-823.; Wigler, M. et al.
(1980) Proc. Natl. Acad.
Sci. USA 77:3567-3570; Colbere-Garapin, F. et al. (1981) J. Mol. Biol. 150:1-
14; Hartman, S.C. and
R.C.Mulligan (1988) Proc. Natl. Acad. Sci. USA 85:8047-8051; Rhodes, C.A.
(1995) Methods Mol.
2 s Biol, 55:121-131.)
Therapeutic Uses of sptm
The polynucleotides encoding SPTM of the invention may be used for somatic or
germline gene
therapy. Gene therapy may be performed to (i) correct a genetic deficiency
(e.g., in the cases of severe
3 o combined immunodeficiency (SCID)-X1 disease characterized by X-linked
inheritance (Cavazzana-
Calvo, M. et al. (2000) Science 288:669-672), severe combined immunodeficiency
syndrome associated
with an inherited adenosine deaminase (ADA) deficiency (Blaese, R.M, et al.
(1995) Science 270:475-
480; Bordignon, C. et al. (1995) Science 270:470-475), cystic fibrosis
(Zabner, J. et al. (1993) Cell
75:207-216; Crystal, R.G. et al. (1995) Hum. Gene Therapy 6:643-666; Crystal,
R.G. et al. (1995)
3 5 Hum. Gene Therapy 6:667-703), thalassemias, familial hypercholesterolemia,
and hemophilia resulting
38
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from Factor VIII or Factor IX deficiencies (Crystal, R.G. (1995) Science
270:404-410; Verma, LM.
and Somia, N. (1997) Nature 389:239-242)), (ii) express a conditionally lethal
gene product (e.g., in
the case of cancers which result from unregulated cell proliferation), or
(iii) express a protein which
affords protection against intracellular parasites (e.g., against human
retroviruses, such as human
s immunodeficiency virus (HIV) (Baltimore, D. (1988) Nature 335:395-396;
Poeschla, E. et al. (1996)
Proc. Natl. Acad. Sci. USA. 93:11395-11399), hepatitis B or C virus (HBV,
HCV); fungal parasites,
such as Candida albicans and Paracoccidioides brasiliensis; and protozoan
parasites such as
Plasmodium falciparum and Trypanosoma cruzi). In the case where a genetic
deficiency in sptm
expression or regulation causes disease, the expression of sptm from an
appropriate population of
~ o transduced cells may alleviate the clinical manifestations caused by the
genetic deficiency.
In a further embodiment of the invention, diseases or disorders caused by
deficiencies in sptm
are treated by constructing mammalian expression vectors comprising sptm and
introducing these
vectors by mechanical means into sptm-deficient cells. Mechanical transfer
technologies for use with
cells in vivo or ex vitro include (i) direct DNA microinjection into
individual cells, (ii) ballistic gold
15 particle delivery, (iii) liposome-mediated transfection, (iv) receptor-
mediated gene transfer, and (v) the
use of DNA transposons (Morgan, R.A. and Anderson, W.F. (1993) Annu. Rev.
Biochem. 62:191-217;
Ivics, Z. (1997) Cell 91:501-510; Boulay, J-L, and Recipon, H. (1998) Curr.
Opin. Biotechnol. 9:445-
450).
Expression vectors that may be effective for the expression of sptm include,
but are not limited
2o to, the PCDNA 3.1, EPITAG, PRCCMV2, PREP, PVAX vectors (Invitxogen,
Carlsbad CA),
PCMV-SCRIPT, PCMV-TAG, PEGSH/PERV (Stratagene, La Jolla CA), and PTET-OFF,
PTET-ON, PTRE2, PTRE2-LUC, PTK-HYG (Clontech, Palo Alto CA). The sptm of the
invention
may be expressed using (i) a constitutively active promoter, (e.g., from
cytomegalovirus (CMV), Rous
sarcoma virus (RSV), SV40 virus, thymidine kinase (TK), ox (3-actin genes),
(ii) an inducible promoter
2s (e.g., the tetracycline-regulated promoter (Gossen, M. and Bujard, H.
(1992) Proc. Natl. Acad. Sci.
U.S.A. 89:5547-5551; Gossen, M. et al., (1995) Science 268:1766-1769; Rossi,
F.M.V. and Blau,
H.M. (1998) Curr. Opin. Biotechnol, 9:451-456), commercially available in the
T-REX plasmid
(Invitrogen); the ecdysone-inducible promoter (available in the plasmids
PVGRXR and PIND;
Invitxogen); the FK506/rapamycin inducible promoter; or the RU486lmifepristone
inducible promoter
3 0 (Rossi, F.M.V. and Blau, H.M. supra), or (iii) a tissue-specific promoter
or the native promoter of the
endogenous gene encoding SPTM from a normal individual.
Commercially available liposome transformation kits (e.g., the PERFECT LIPID
TRANSFECTION KIT, available from Invitrogen) allow one with ordinary skill in
the art to deliver
polynucleotides to target cells in culture and require minimal effort to
optimize experimental
3 5 parameters. In the alternative, transformation is performed using the
calcium phosphate method
39
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
(Graham, F.L. and Eb, A.J. (1973) Virology 52:456-467), or by electroporation
(Neumann, E. et al.
(1982) EMBO J. 1:841-845). The introduction of DNA to primary cells requires
modification of these
standardized mammalian transfection protocols.
In another embodiment of the invention, diseases or disorders caused by
genetic defects with
s respect to sptm expression are treated by constructing a retrovirus vector
consisting of (i) sptm under
the control of an independent promoter or the retrovirus long terminal repeat
(LTR) promoter, (ii)
appropriate RNA packaging signals, and (iii) a Rev-responsive element (RRE)
along with additional
retrovirus cis-acting RNA sequences and coding sequences required for
efficient vector propagation.
Retrovirus vectors (e.g., PFB and PFBNEO) are commercially available
(Stratagene) and are based on
s o published data (Riviere, I. et al. (1995) Proc. Natl. Acad. Sci. U.S.A.
92:6733-6737), incorporated by
reference herein. The vector is propagated in an appropriate vector producing
cell line (VPCL) that
expresses an envelope gene with a tropism for receptors on the target cells or
a promiscuous envelope
protein such as VSVg (Armentano, D. et al. (1987) J. Virol. 61:1647-1650;
Bender, M.A. et al. (1987)
J. Virol. 61:1639-1646; Adam, M.A. and Miller, A.D. (1988) J. Virol. 62:3802-
3806; Dull, T. et al.
15 (1998) J. Virol. 72:8463-8471; Zufferey, R, et al. (1998) J. Virol. 72:9873-
9880). U.S. Patent Number
5,910,434 to Rigg ("Method for obtaining retrovirus packaging cell lines
producing hightransducing
efficiency retroviral supernatant") discloses a method for obtaining
retrovirus packaging cell lines and
is hereby incorporated by reference. Propagation of retrovirus vectors,
transduction of a population of
cells (e.g., CD4+ T-cells), and the return of transduced cells to a patient
are procedures well known to
2 o persons skilled in the art of gene therapy and have been well documented
(Ranga, U. et al. (1997) J.
Virol. 71:7020-7029; Bauer, G. et al. (1997) Blood 89:2259-2267; Bonyhadi,
M.L. (1997) J. Virol.
71:4707-4716; Ranga, U. et al. (1998) Proc. Natl. Acad. Sci. U.S.A. 95:1201-
1206; Su, L. (1997)
Blood 89:2283-2290).
In the alternative, an adenovirus-based gene therapy delivery system is used
to deliver sptm to
2 s cells which have one or more genetic abnormalities with respect to the
expression of sptm. The
construction and packaging of adenovirus-based vectors are well known to those
with ordinary skill in
the art. Replication defective adenovirus vectors have proven to be versatile
for importing genes
encoding immunoregulatory proteins into intact islets in the pancreas (Csete,
M.E. et al. (1995)
Transplantation 27:263-268). Potentially useful adenoviral vectors are
described in U.S. Patent
3 o Number 5,707,618 to Armentano ("Adenovirus vectors for gene therapy"),
hereby incorporated by
reference. For adenoviral vectors, see also Antinozzi, P.A. et al. (1999)
Annu. Rev. Nutr. 19:511-544
and Verma, LM. and Somia, N. (1997) Nature 18:389:239-242, both incorporated
by reference herein.
In another alternative, a herpes-based, gene therapy delivery system is used
to deliver sptm to
target cells which have one or more genetic abnormalities with respect to the
expression of sptm. The
3 s use of herpes simplex virus (HSV)-based vectors may be especially valuable
for introducing sptm to
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
cells of the central nervous system, for which HSV has a tropism. The
construction and packaging of
herpes-based vectors are well known to those with ordinary skill in the art. A
replication-competent
herpes simplex virus (HSV) type 1-based vector has been used to deliver a
reporter gene to the eyes of
primates (Liu, X. et al. (1999) Exp. Eye Res.169:385-395). The construction of
a HSV-1 virus vector
s has also been disclosed in detail in U.S. Patent Number 5,804,413 to DeLuca
("Herpes simplex virus
strains for gene transfer"), which is hereby incorporated by reference. U.S.
Patent Number 5,804,413
teaches the use of recombinant HSV d92 which consists of a genome containing
at least one exogenous
gene to be transferred to a cell under the contxol of the appropriate promoter
for purposes including
human gene therapy. Also taught by this patent are the construction and use of
recombinant HSV
to strains deleted for ICP4, ICP27 and ICP22. For HSV vectors, see also Goins,
W. F. et a1. 1999 J.
Virol. 73:519-532 and Xu, H. et al., (1994) Dev. Biol. 163:152-161, hereby
incorporated by reference.
The manipulation of cloned herpesvirus sequences, the generation of
recombinant virus following the
transfection of multiple plasmids containing different segments of the large
herpesvirus genomes, the
growth and propagation of herpesvirus, and the infection of cells with
herpesvirus are techniques well
15 known to those of ordinary skill in the art.
In another alternative, an alphavirus (positive, single-stranded RNA virus)
vector is used to
deliver sptm to target cells. The biology of the prototypic alphavirus,
Semliki Forest Virus (SFV), has
been studied extensively and gene transfer vectors have been based on the SFV
genome (Garoff, H. and
Li, K-J. (1998) Curr. Opin. Biotech. 9:464-469). During alphavirus RNA
replication, a subgenomic
z o RNA is generated that normally encodes the viral capsid proteins. This
subgenomic RNA replicates to
higher levels than the full-length genomic RNA, resulting in the
overproduction of capsid proteins
relative to the viral proteins with enzymatic activity (e.g., protease and
polymerase). Similarly,
inserting sptm into the alphavirus genome in place of the capsid-coding region
results in the production
of a large number of sptm RNAs and the synthesis of high levels of SPTM in
vector transduced cells.
2 s While alphavirus infection is typically associated with cell lysis within
a few days, the ability to
establish a persistent infection in hamster normal kidney cells (BHK-21) with
a variant of Sindbis virus
(SIN) indicates that the lytic replication of alphaviruses can be altered to
suit the needs of the gene
therapy application (Dryga, S.A. et al. (1997) Virology 228:74-83). The wide
host range of
alphaviruses will allow the introduction of sptm into a variety of cell types.
The specific transduction
3 0 of a subset of cells in a population may require the sorting of cells
prior to transduction. The methods
of manipulating infectious cDNA clones of alphaviruses, performing alphavirus
cDNA and RNA
transfections, and performing alphavirus infections, are well known to those
with ordinary skill in the
art.
3 5 Antibodies
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Anti-SPTM antibodies may be used to analyze protein expression levels. Such
antibodies
include, but are not limited to, polyclonal, monoclonal, chimeric, single
chain, and Fab fragments. For
descriptions of and protocols of antibody technologies, see, e.g., Pound J.D.
(1998) Immunochemical
Protocols, Humana Press, Totowa, NJ.
s The amino acid sequence encoded by the sptm of the Sequence Listing may be
analyzed by
appropriate software (e.g., LASERGENE NAVIGATOR software, DNASTAR) to
determine regions
of high immunogenicity. The optimal sequences for immunization are selected
from the C-terminus, the
N-terminus, and those intervening, hydrophilic regions of the polypeptide
which are likely to be exposed
to the external environment when the polypeptide is in its natural
conformation. Analysis used to select
1 o appropriate epitopes is also described by Ausubel (1997, suQra, Chapter
11.7). Peptides used for
antibody induction do not need to have biological activity; however, they must
be antigenic. Peptides
used to induce specific antibodies may have an amino acid sequence consisting
of at least five amino
acids, preferably at least 10 amino acids, and most preferably at least 15
amino acids. A peptide which
mimics an antigenic fragment of the natural polypeptide may be fused with
another protein such as
15 keyhole limpet hemocyanin (KLH; Sigma, St. Louis MO) for antibody
production. A peptide
encompassing an antigenic region may be expressed from an sptm, synthesized as
described above, or
purified from human cells.
Procedures well known in the art may be used for the production of antibodies.
Various hosts
including mice, goats, and rabbits, may be immunized by injection with a
peptide. Depending on the
2 o host species, various adjuvants may be used to increase immunological
response.
In one procedure, peptides about 15 residues in length may be synthesized
using an ABI 431 A
peptide synthesizer (Applied Biosystems) using fmoc-chemistry and coupled to
KLH (Sigma) by
reaction with M-maleimidobenzoyl-N-hydroxysuccinimide ester (Ausubel, 1995,
suQra). Rabbits are
immunized with the peptide-KLH complex in complete Freund's adjuvant. The
resulting antisera are
2 5 tested for antipeptide activity by binding the peptide to plastic,
blocking with 1 % bovine serum albumin
(BSA), reacting with rabbit antisera, washing, and reacting with
radioiodinated goat anti-rabbit IgG.
Antisera with antipeptide activity are tested for anti-SPTM activity using
protocols well known in the
art, including ELISA, radioimmunoassay (RIA), and immunoblotting.
Tn another procedure, isolated and purified peptide may be used to immunize
mice (about 100
3 0 ~ g of peptide) or rabbits (about 1 mg of peptide). Subsequently, the
peptide is radioiodinated and used
to screen the immunized animals' B-lymphocytes for production of antipeptide
antibodies. Positive
cells are then used to produce hybridomas using standard techniques. About 20
mg of peptide is
sufficient for labeling and screening several thousand clones. Hybridomas of
interest are detected by
screening with radioiodinated peptide to identify those fusions producing
peptide-specific monoclonal
3 s antibody. In a typical protocol, wells of a mufti-well plate (FAST, Becton-
Dickinson, Palo Alto, CA)
42
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are coated with affinity-purified, specific rabbit-anti-mouse (or suitable
anti-species IgG) antibodies at
m~ml. The coated wells are blocked with 1 % BSA and washed and exposed to
supernatants from
hybridomas. After incubation, the wells are exposed to radiolabeled peptide at
1 mg/ml.
Clones producing antibodies bind a quantity of labeled peptide that is
detectable above
s background. Such clones are expanded and subjected to 2 cycles of cloning.
Cloned hybridomas are
injected into pristane-treated mice to produce ascites, and monoclonal
antibody is purified from the
ascitic fluid by affinity chromatography on protein A (Amersham Pharmacia
Biotech). Several
procedures for the production of monoclonal antibodies, including in vitro
production, are described in
Pound su ra). Monoclonal antibodies with antipeptide activity are tested for
anti-SPTM activity using
s o protocols well known in the art, including ELISA, RIA, and immunoblotting.
Antibody fragments containing specific binding sites for an epitope may also
be generated. For
example, such fragments include, but are not limited to, the F(ab~2 fragments
produced by pepsin
digestion of the antibody molecule, and the Fab fragments generated by
reducing the disulfide bridges of
the F(ab~2 fragments. Alternatively, construction of Fab expression libraries
in filamentous
~. s bacteriophage allows rapid and easy identification of monoclonal
fragments with desired specificity
(Pound, supra, Chaps. 45-47). Antibodies generated against polypeptide encoded
by sptm can be used
to purify and characterize full-length SPTM protein and its activity, binding
partners, etc.
Assays Using Antibodies
2 o Anti-SPTM antibodies may be used in assays to quantify the amount of SPTM
found in a
particular human cell. Such assays include methods utilizing the antibody and
a label to detect
expression level under normal or disease conditions. The peptides and
antibodies of the invention may
be used with or without modification or labeled by joining them, either
covalently or noncovalently,
with a reporter molecule.
2 s Protocols for detecting and measuring protein expression using either
polyclonal or monoclonal
antibodies are well known in the art. Examples include ELISA, RIA, and
fluorescent activated cell
sorting (FACS). Such immunoassays typically involve the formation of complexes
between the SPTM
and its specific antibody and the measurement of such complexes. These and
other assays are described
in Pound su ra).
3 o Without further elaboration, it is believed that one skilled in the art
can, using the preceding
description, utilize the present invention to its fullest extent. The
following preferred specific
embodiments are, therefore, to be construed as merely illustrative, and not
limitative of the remainder of
the disclosure in any way whatsoever.
The disclosures of all patents, applications, and publications mentioned above
and below,
35 including U.S. Sex. No. 60/205,287, U.S. Ser. No. 60/205,324, U.S. Ser. No.
60/205,286, U.S. Ser.
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No. 60/205,323, U.S. Ser. No. 60/185,215, U.S. Ser. No. 60/185,216, and U.S.
Ser. No. 60/205,232,
are hereby expressly incorporated by reference.
EXAMPLES
s I. Construction of cDNA Libraries
RNA was purchased from CLONTECH Laboratories, Inc. (Palo Alto CA) or isolated
from
various tissues. Some tissues were homogenized and lysed in guanidinium
isothiocyanate, while others
were homogenized and lysed in phenol or in a suitable mixture of denaturants,
such as TRIZOL (Life
Technologies), a monophasic solution of phenol and guanidine isothiocyanate.
The resulting lysates
1 o were centrifuged over CsCl cushions or extracted with chloroform. RNA was
precipitated with either
isopropanol or sodium acetate and ethanol, or by other routine methods.
Phenol extraction and precipitation of RNA were repeated as necessary to
increase RNA
purity. In most cases, RNA was treated with DNase. For most libraries,
poly(A+) RNA was isolated
using oligo d(T)-coupled paramagnetic particles (Promega Corporation
(Promega), Madison WI),
15 OLIGOTEX latex particles (QIAGEN, Inc. (QIAGEN), Valencia CA), or an
OLIGOTEX mRNA
purification kit (QIAGEN). Alternatively, RNA was isolated directly from
tissue lysates using other
RNA isolation kits, e.g., the POLY(A)PURE mRNA purification kit (Ambion, Inc.,
Austin TX).
In some cases, Stratagene was provided with RNA and constructed the
corresponding cDNA
libraries. Otherwise, cDNA was synthesized and cDNA libraries were constructed
with the UNIZAP
2 o vector system (Stratagene Cloning Systems, Inc. (Stratagene), La Jolla CA)
or SUPERSCRIPT
plasmid system (Life Technologies), using the recommended procedures or
similar methods known in
the art. (See, e.g., Ausubel, 1997, su ra, Chapters 5.1 through 6.6.) Reverse
transcription was
initiated using oligo d(T) or random primers. Synthetic oligonucleotide
adapters were ligated to double
stranded cDNA, and the cDNA was digested with the appropriate restriction
enzyme or enzymes. For
2 s most libraries, the cDNA was size-selected (300-1000 bp) using SEPHACRYL S
1000, SEPHAROSE
CL2B, or SEPHAROSE CL4B column chromatography (Amersham Pharmacia Biotech) or
preparative agarose gel electrophoresis. cDNAs were ligated into compatible
restriction enzyme sites of
the polylinker of a suitable plasmid, e.g., PBLUESCRIPT plasmid (Stratagene),
PSPORT1 plasmid
(Life Technologies), PCDNA2.1 plasmid (Invitrogen, Carlsbad CA), PBK-CMV
plasmid (Stratagene),
3 0 or pINCY (Incyte Genomics, Palo Alto CA), or derivatives thereof.
Recombinant plasmids were
transformed into competent E, coli cells including XL1-Blue, XLl-BlueMRF, or
SOLR from
Stratagene or DHSa, DH10B, or ElectroMAX DH10B from Life Technologies.
II. Isolation of cDNA Clones
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Plasmids were recovered from host cells by in vivo excision using the UNIZAP
vector system
(Stratagene) or by cell lysis. Plasmids were purified using at least one of
the following: the Magic or
WIZARD Minipreps DNA purification system (Promega); the AGTC Miniprep
purification kit (Edge
BioSystems, Gaithersburg MD); and the QIAWELL 8, QIAWELL 8 Plus, and QIAWELL 8
Ultra
s plasmid purification systems or the R.E.A.L. PREP 96 plasmid purification
kit (QIAGEN). Following
precipitation, plasmids were resuspended in 0.1 ml of distilled water and
stored, with or without
lyophilization, at 4°C.
Alternatively, plasmid DNA was amplified from host cell lysates using direct
link PCR in a
high-throughput format. (Rao, V.B. (1994) Anal. Biochem. 216:1-14.) Host cell
lysis and thermal
~ o cycling steps were carried out in a single reaction mixture. Samples were
processed and stored in 384-
well plates, and the concentration of amplified plasmid DNA was quantified
fluorometrically using
PICOGREEN dye (Molecular Probes, Inc. (Molecular Probes), Eugene OR) and a
FLUOROSKAN II
fluorescence scanner (Labsystems Oy, Helsinki, Finland).
15 III. Sequencing and Analysis
cDNA sequencing reactions were processed using standard methods or high-
throughput
instrumentation such as the ABI CATALYST 800 thermal cycler (Applied
Biosystems) or the PTC-
200 thermal cycler (MJ Research) in conjunction with the HYDRA microdispenser
(Robbins Scientific
Corp., Sunnyvale CA) or the MICROLAB 2200 liquid transfer system (Hamilton).
cDNA sequencing
2 o reactions were prepared using reagents provided by Amersham Pharmacia
Biotech or supplied in ABI
sequencing kits such as the ABI PRISM BIGDYE Terminator cycle sequencing ready
reaction kit
(Applied Biosystems). Electrophoretic separation of cDNA sequencing reactions
and detection of
labeled polynucleotides were carried out using the MEGABACE 1000 DNA
sequencing system
(Molecular Dynamics); the ABI PRISM 373 or 377 sequencing system (Applied
Biosystems) in
2 s conjunction with standard ABI protocols and base calling software; or
other sequence analysis systems
known in the art. Reading frames within the cDNA sequences were identified
using standard methods
(reviewed in Ausubel, 1997, su ra, Chapter 7.7). Some of the cDNA sequences
were selected for
extension using the techniques disclosed in Example VIII.
3 o IV. Assembly and Analysis of Sequences
Component sequences from chromatograms were subject to PHRED analysis and
assigned a
quality score. The sequences having at least a required quality score were
subject to various pre-
processing editing pathways to eliminate, e.g., low quality 3' ends, vector
and linker sequences, polyA
tails, Alu repeats, mitochondrial and ribosomal sequences, bacterial
contamination sequences, and
3 s sequences smaller than 50 base pairs. In particular, low-information
sequences and repetitive elements
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WO 01/62918 PCT/USO1/03465
(e.g., dinucleotide repeats, Alu repeats, etc.) were replaced by "n's", or
masked, to prevent spurious
matches.
Processed sequences were then subject to assembly procedures in which the
sequences were
assigned to gene bins (bins). Each sequence could only belong to one bin.
Sequences in each gene bin
s were assembled to produce consensus sequences (templates). Subsequent new
sequences were added to
existing bins using BLASTn (v.1.4 Washl~ and CROSSMATCH. Candidate pairs were
identified as
all BLAST hits having a quality score greater than or equal to 150. Alignments
of at least 82% local
identity were accepted into the bin. The component sequences from each bin
were assembled using a
version of PHRAP. Bins with several overlapping component sequences were
assembled using DEEP
1 o PHRAP. The orientation (sense or antisense) of each assembled template was
determined based on the
number and orientation of its component sequences. Template sequences as
disclosed in the sequence
listing correspond to sense strand sequences (the "forward" reading frames),
to the best determination.
The complementary (antisense) strands are inherently disclosed herein. The
component sequences
which were used to assemble each template consensus sequence are listed in
Table 2 along with their
15 positions along the template nucleotide sequences.
Bins were compared against each other and those having local similarity of at
least 82% were
combined and reassembled. Reassembled bins having templates of insufficient
overlap (less than 95 %
local identity) were re-split. Assembled templates were also subject to
analysis by STITCHERlEXON
MAPPER algorithms which analyze the probabilities of the presence of splice
variants, alternatively
2 o spliced exons, splice junctions, differential expression of alternative
spliced genes across tissue types or
disease states, etc. These resulting bins were subject to several rounds of
the above assembly
procedures.
Once gene bins were generated based upon sequence alignments, bins were clone
joined based
upon clone information. If the 5' sequence of one clone was present in one bin
and the 3' sequence from
2 s the same clone was present in a different bin, it was likely that the two
bins actually belonged together
in a single bin. The resulting combined bins underwent assembly procedures to
regenerate the
consensus sequences.
The final assembled templates were subsequently annotated using the following
procedure.
Template sequences were analyzed using BLASTn (v2.0, NCBI) versus gbpri
(GenBank version 120).
3 0 "Hits" were defined as an exact match having from 95 % local identity over
200 base pairs through
100% local identity over 100 base pairs, or a homolog match having an E-value,
i.e. a probability
score, of s 1 x 10-g. The hits were subject to frameshift FASTx versus GENPEPT
(GenBank version
120). (See Table 4). In this analysis, a homolog match was defined as having
an E-value of s 1 x 10-8.
The assembly method used above was described in "System and Methods for
Analyzing Biomolecular
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Sequences," U.S.S.N. 09/276,534, filed March 25, 1999, and the LIFESEQ Gold
user manual (Incyte)
both incorporated by reference herein.
Following assembly, template sequences were subjected to motif, BLAST, and
functional
analyses, and categorized in protein hierarchies using methods described in,
e.g., "Database System
Employing Protein Function Hierarchies for Viewing Biomolecular Sequence
Data," U.S.S.N.
08/812,290, filed March 6, 1997; "Relational Database for Storing Biomolecule
Information,"
U.S.S.N. 081947,845, filed October 9, 1997; "Project-Based Full-Length
Biomolecular Sequence
Database," U.S.S.N. 08/811,758, filed March 6, 1997; and "Relational Database
and System for
Storing Information Relating to Biomolecular Sequences," U.S.S.N. 09/034,807,
filed March 4, 1998,
s o all of which are incorporated by reference herein.
The template sequences were further analyzed by translating each template in
all three forward
reading frames and searching each translation against the Pfam database of
hidden Markov model-
based protein families and domains using the HMMER software package (available
to the public from
Washington University School of Medicine, St. Louis MO). (See also World Wide
Web site
http://pfam.wustl.edu/ for detailed descriptions of Pfam protein domains and
families.)
Additionally, the template sequences were translated in alI three forward
reading frames, and
each translation was searched against hidden Markov models for signal peptides
using the HMMER
software package. Construction of hidden Markov models and their usage in
sequence analysis has
been described. (See, for example, Eddy, S.R. (1996) Curr. Opin. Str. Biol.
6:361-365.) Only those
2 o signal peptide hits with a cutoff score of 11 bits or greater are
reported. A cutoff score of 11 bits or
greater corresponds to at least about 91-94% true-positives in signal peptide
prediction. Template
sequences were also translated in all three forward reading frames, and each
translation was searched
against TMAP, a program that uses weight matrices to delineate transmembrane
segments on protein
sequences and determine orientation, with respect to the cell cytosol
(Persson, B, and Argos, P. (1994)
2 5 J. Mol. Biol. 237:182-192, and Persson, B. and Argos, P. (1996) Protein
Sci. 5:363-371.) Regions of
templates which, when translated, contain similarity to signal peptide or
transmembrane consensus
sequences are reported in Table 1.
Template sequences are further analyzed using the bioinformatics tools listed
in Table 4, or
using sequence analysis software known in the art such as MACDNASIS PRO
software (Hitachi
3 o Software Engineering, South San Francisco CA) and LASERGENE software
(DNASTAR). Template
sequences may be further queried against public databases such as the GenBank
rodent, mammalian,
vertebrate, prokaryote, and eukaryote databases.
V. Analysis of Polynucleotide Expression
47
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Northern analysis is a laboratory technique used to detect the presence of a
transcript of a gene
and involves the hybridization of a labeled nucleotide sequence to ~a membrane
on which RNAs from a
particular cell type or tissue have been bound. (See, e.g., Sambrook, supra,
ch. 7; Ausubel, 1995,
supra, ch. 4 and 16.)
. Analogous computer techniques applying BLAST were used to search for
identical or related
molecules in cDNA databases such as GenBank or LIFESEQ (Incyte Genomics). This
analysis is
much faster than multiple membrane-based hybridizations. In addition, the
sensitivity, of the computer
search can be modified to determine whether any particular match is
categorized as exact or similar.
The basis of the search is the product score, which is defined as:
BLAST Score x Percent Identity
5 x minimum {length(Seq. 1), length(Seq. 2)}
The product score takes into account both the degree of similarity between two
sequences and the length
1 s of the sequence match. The product score is a normalized value between 0
and 100, and is calculated
as follows: the BLAST score is multiplied by the percent nucleotide identity
and the product is divided
by (5 times the length of the shorter of the two sequences). The BLAST score
is calculated by
assigning a score of +5 for every base that matches in a high-scoring segment
pair (HSP), and -4 for
every mismatch. Two sequences may share more than one HSP (separated by gaps).
If there is more
2 o than one HSP, then the pair with the highest BLAST score is used to
calculate the product score. The
product score represents a balance between fractional overlap and quality in a
BLAST alignment. For
example, a product score of 100 is produced only for 100% identity over the
entire length of the shorter
of the two sequences being compared. A product score of 70 is produced either
by 100% identity and
70% overlap at one end, or by 88% identity and 100% overlap at the other. A
product score of 50 is
2 s produced either by 100% identity and 50% overlap at one end, or 79%
identity and 100% overlap.
Alternatively, polynucleotide sequences encoding SPTM are analyzed with
respect to the tissue
sources from which they were derived. Polynucleotide sequences encoding SPTM
were assembled, at
least in part, with overlapping Incyte cDNA sequences. Each cDNA sequence is
derived from a cDNA
library constructed from a human tissue. Each human tissue is classified into
one of the following
3 0 organ/tissue categories: cardiovascular system; connective tissue;
digestive system; embryonic
structures; endocrine system; exocrine glands; genitalia, female; genitalia,
male; germ cells; heroic and
immune system; liver; musculoskeletal system; nervous system; pancreas;
respiratory system; sense
organs; skin; stomatognathic system; unclassified/mixed; or urinary tract. The
number of libraries in
each category for each polynucleotide sequence encoding SPTM is counted and
divided by the total
3 s number of libraries across all categories for each polynucleotide sequence
encoding SPTM. Similarly,
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each human tissue is classified into one of the following disease/condition
categories: cancer, cell line,
developmental, inflammation, neurological, trauma, cardiovascular, pooled, and
other, and the number
of libraries in each category for each polynucleotide sequence encoding SPTM
is counted and divided
by the total number of libraries across all categories for each polynucleotide
sequence encoding SPTM.
s The resulting percentages reflect the tissue-specific and disease-specific
expression of cDNA encoding
SPTM. Percentage values of tissue-specific expression are reported in Table 3.
cDNA sequences and
cDNA library/tissue information are found in the LIFESEQ GOLD database (Incyte
Genomics, Palo
Alto CA).
VI. Tissue Distribution Profiling
s o A tissue distribution profile is determined for each template by compiling
the cDNA library
tissue classifications of its component cDNA sequences. Each component
sequence, is derived from a
cDNA library constructed from a human tissue. Each human tissue is classified
into one of the
following categories: cardiovascular system; connective tissue; digestive
system; embryonic structures;
endocrine system; exocrine glands; genitalia, female; genitalia, male; germ
cells; heroic and immune
is system; liver; musculoskeletal system; nervous system; pancreas;
respiratory system; sense organs;
skin; stomatognathic system; unclassified/mixed; or urinary tract. Template
sequences, component
sequences, and cDNA library/tissue information are found in the LIFESEQ GOLD
database (Incyte
Genomics, Palo Alto CA).
Table 3 shows the tissue distribution profile for the templates of the
invention. For each
2 o template, the three most frequently observed tissue categories are shown
in column 2, along with the
percentage of component sequences belonging to each category. Only tissue
categories with
- percentage values of >_ 10% are shown. A tissue distribution of "widely
distributed" in column 2
indicates percentage values of <10% in all tissue categories.
2 s VII. Transcript Image Analysis
Transcript images are generated as described in Seilhamer et al., "Comparative
Gene
Transcript Analysis," U.S. Patent Number 5,840,484, incorporated herein by
reference.
VTII. Extension of Polynucleotide Sequences and Isolation of a Full-length
cDNA
3 o Oligonucleotide primers designed using an sptm of the Sequence Listing are
used to extend the
nucleic acid sequence. One primer is synthesized to initiate 5' extension of
the template, and the other
primer, to initiate 3' extemion of the template. The initial primers may be
designed using OLIGO 4.06
software (National Biosciences, Inc. (National Biosciences), Plymouth MN), or
another appropriate
program, to be about 22 to 30 nucleotides in length, to have a GC content of
about 50% or more, and to
3 s anneal to the target sequence at temperatures of about 68 °C to
about 72°C. Any stretch of nucleotides
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which would result in hairpin structures and primer-primer dimerizations are
avoided. Selected human
cDNA libraries are used to extend the sequence. If more than one extension is
necessary or desired,
additional or nested sets of primers are designed.
High fidelity amplification is obtained by PCR using methods well known in the
art. PCR is
performed in 96-well plates using the PTC-200 thermal cycler (MJ Research).
The reaction mix
contains DNA template, 200 nmol of each primer, reaction buffer containing
Mg2+, (NH4)ZS O4, and 13-
mercaptoethanol, Taq DNA polymerase (Amersham Pharmacia Biotech), ELONGASE
enzyme (Life
Technologies), and Pfu DNA polymerase (Stratagene), with the following
parameters for pximer pair
PCI A and PCI B: Step 1: 94°C, 3 min; Step 2: 94°C, 15 sec; Step
3: 60°C, 1 min; Step 4: 68 °C, 2
1o min; Step 5: Steps 2, 3, and 4 repeated 20 times; Step 6: 68°C, 5
min; Step 7: storage at 4°C. In the
alternative, the parameters for primer pair T7 and SK+ are as follows: Step 1:
94 °C, 3 min; Step 2:
94°C, IS sec; Step 3: 57°C, I min; Step 4: 68°C, 2 min;
Step S: Steps 2, 3, and 4 repeated 20 times;
Step 6: 68 ° C, 5 min; Step 7: storage at 4 ° C.
The concentration of DNA in each well is determined by dispensing 100 ~1
PICOGREEN
quantitation reagent (0.25% (v/v); Molecular Probes) dissolved in 1X Tris-EDTA
(TE) and 0.5 ~1 of
undiluted PCR product into each well of an opaque fluorimeter plate (Corning
Incorporated (Corning),
Corning NY), allowing the DNA to bind to the reagent. The plate is scanned in
a FLUOROSKAN II
(Labsystems Oy) to measure the fluorescence of the sample and to quantify the
concentration of DNA.
A 5 p1 to 10 p1 aliquot of the reaction mixture is analyzed by electrophoresis
on a 1 % agarose mini-gel
2 o to determine which reactions are successful in extending the sequence.
The extended nucleotides are desalted and concentrated, transferred to 384-
well plates,
digested with CviJI cholera virus endonuclease (Molecular Biology Research,
Madison WI), and
sonicated or sheared prior to religation into pUC 18 vector (Amersham
Pharmacia Biotech). For
shotgun sequencing, the digested nucleotides are separated on low
concentration (0.6 to 0.8%) agarose
2 5 gels, fragments are excised, and agar digested with AGAR ACE (Promega).
Extended clones are
relegated using T4 ligase (New England Biolabs, Inc., Beverly MA) into pUC 18
vector (Amersham
Pharmacia Biotech), treated with Pfu DNA polymerase (Stratagene) to fill-in
restriction site overhangs,
and transfected into competent E. coli cells. Transformed cells are selected
on antibiotic-containing
media, individual colonies are picked and cultured overnight at 37 ° C
in 384-well plates in LB/2x
3 o carbenicillin liquid media.
The cells are lysed, and DNA is amplified by PCR using Taq DNA polymerase
(Amersham
Phaxmacia Biotech) and Pfu DNA polymerase (Stratagene) with the following
parameters: Step 1:
94 ° C, 3 min; Step 2: 94 ° C, 15 sec; Step 3 : 60 ° C, 1
min; Step 4: 72 ° C, 2 min; Step 5 : steps 2, 3, and 4
repeated 29 times; Step 6: 72°C, 5 min; Step 7: stoxage at 4°C.
DNA is quantified by PICOGREEN
3 5 reagent (Molecular Probes) as described above. Samples with low DNA
recoveries are reamplified
CA 02418496 2003-02-04
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using the same conditions as described above. Samples are diluted with 20%
dimethysulfoxide (1:2,
v/v), and sequenced using DYENAMIC energy transfer sequencing primers and the
DYENAMIC
DIRECT kit (Amersham Pharmacia Biotech) or the ABI PRISM BIGDYE Terminator
cycle
sequencing ready reaction kit (Applied Biosystems).
In like manner, the sptm is used to obtain regulatory sequences (promoters,
introns, and
enhancers) using the procedure above, oligonucleotides designed for such
extension, and an appropriate
genomic library.
IX. Labeling of Probes and Southern Hybridization Analyses
1 o Hybridization probes derived from the sptm of the Sequence Listing are
employed for
screening cDNAs, mRNAs, or genomic DNA. The labeling of probe nucleotides
between 100 and
1000 nucleotides in length is specifically described, but essentially the same
procedure may be used
with larger cDNA fragments. Probe sequences are labeled at room temperature
for 30 minutes using a
T4 polynucleotide kinase, Ysap-ATP, and O.SX One-Phor-Atl Plus (Amersham
Pharmacia Biotech)
1 s buffer and purified using a ProbeQuant G-SO Microcolumn (Amersham
Pharmacia Biotech). The
probe mixture is diluted to 10' dpm/~~ml hybridization buffer and used in a
typical membrane-based
hybridization analysis.
The DNA is digested with a restriction endonuclease such as Eco RV and is
electrophor esed
through a 0.7% agarose gel. The DNA fragments are transferred from the agarose
to nylon membrane
2 0 (NYTRAN Plus Schleicher & Schuell, Inc., Keene NH) using procedures
specified by the
manufacturer of the membrane. Prehybridization is carried out for three or
more hours at 68 ° C, and
hybridization is carried out overnight at 68 °C. To remove non-specific
signals, blots are sequentially
washed at room temperature under increasingly stringent conditions, up to 0.
lx saline sodium citrate
(SSC) and 0.5% sodium dodecyl sulfate. After the blots are placed in a
PHOSPHORIMAGER cassette
2 5 (Molecular Dynamics) or are exposed to autoradiography film, hybridization
patterns of standard and
experimental lanes are compared. Essentially the same procedure is employed
when screening RNA.
X. Chromosome Mapping of sptm
The cDNA sequences which were used to assemble SEQ ID NO:1-79 are compared
with
3 o sequences from the Incyte LIFESEQ database and public domain databases
using BLAST and other
implementations of the Smith-Waterman algorithm. Sequences from these
databases that match SEQ
ID NO:1-79 are assembled into clusters of contiguous and overlapping sequences
using assembly
algorithms such as PHRAP (Table 4). Radiation hybrid and genetic mapping data
available from
public resources such as the Stanford Human Genome Center (SHGC), Whitehead
Institute for Genome
3 5 Research (WIGR), and Genethon are used to determine if any of the
clustered sequences have been
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previously mapped. Inclusion of a mapped sequence in a cluster will result in
the assignment of all
sequences of that cluster, including its particular SEQ ID NO:, to that map
location. The genetic map
locations of SEQ ID NO:l-79 are described as ranges, or intervals, of human
chromosomes. The map
position of an interval, in centiMorgans, is measured relative to the terminus
of the chromosome's p-
arm. (The centiMorgan (cM) is a unit of measurement based on recombination
frequencies between
chromosomal markers. On average, 1 cM is roughly equivalent to 1 megabase (Mb)
of DNA in
humans, although this can vary widely due to hot and cold spots of
recombination.) The cM distances
are based on genetic markers mapped by Genethon which provide boundaries for
radiation hybrid
markers whose sequences were included in each of the clusters.
XI. Microarray Analysis
Probe Preparation from Tissue or Cell Samples
Total RNA is isolated from tissue samples using the guanidinium thiocyanate
method and
polyA+ RNA is purified using the oligo (dT) cellulose method. Each polyA+ RNA
sample is reverse
transcribed using MMLV reverse-transcriptase, 0.05 pgl~l oligo-dT primer
(2lmer), 1X first strand
buffer, 0.03 units/~1 RNase inhibitor, 500 ~M dATP, 500 ~M dGTP, 500 ~M dTTP,
40 ~M dCTP,
40 ~M dCTP-Cy3 (BDS) or dCTP-Cy5 (Amersham Pharmacia Biotech). The reverse
transcription
reaction is performed in a 25 ml volume containing 200 ng polyA+ RNA with
GEMBRIGHT kits
(Incyte). Specific control polyA+ RNAs are synthesized by in vitro
transcription from non-coding yeast
2 o genomic DNA (W. Lei, unpublished). As quantitative controls, the control
mRNAs at 0.002 ng, 0.02
ng, 0.2 ng, and 2 ng are diluted into reverse transcription reaction at ratios
of 1:100,000, 1:10,000,
1:1000, 1:100 (w/w) to sample mRNA respectively. The control mRNAs are diluted
into reverse
transcription reaction at ratios of 1:3, 3:1, 1:10, 10:1, 1:25, 25:1 (w/w) to
sample mRNA differential
expression patterns. After incubation at 37° C for 2 hr, each reaction
sample (one with Cy3 and another
2 s with Cy5 labeling) is treated with 2.5 ml of O.SM sodium hydroxide and
incubated for 20 minutes at
85° C to the stop the reaction and degrade the RNA. Probes are purified
using two successive
CHROMA SPIN 30 gel filtration spin columns (CLONTECH Laboratories, Inc.
(CLONTECH), Palo
Alto CA) and after combining, both reaction samples are ethanol precipitated
using 1 ml of glycogen (1
mg/ml), 60 ml sodium acetate, and 300 ml of 100% ethanol. The probe is then
dried to completion
30 ~ using a SpeedVAC (Savant Instruments Inc., Holbrook NY) and resuspended
in 14 ~1 SX SSC/0.2%
SDS.
Microarray Preparation
Sequences of the present invention are used to generate array elements. Each
array element is
3 s amplified from bacterial cells containing vectors with cloned cDNA
inserts. PCR amplification uses
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primers complementary to the vector sequences flanking the cDNA insert. Array
elements are
amplified in thirty cycles of PCR from an initial quantity of 1-2 ng to a
final quantity greater than 5 fig.
Amplified array elements are then purified using SEPHACRYL-400 (Amersham
Pharmacia Biotech).
Purified array elements are immobilized on polymer-coated glass slides. Glass
microscope
s slides (Corning) are cleaned by ultrasound in 0.1 % SDS and acetone, with
extensive distilled water
washes between and after treatments. Glass slides are etched in 4%
hydrofluoric acid (VWR Scientific
Products Corporation (VWR), West Chester, PA), washed extensively in distilled
water, and coated
with 0.05 % aminopropyl silane (Sigma) in 95 % ethanol. Coated slides are
cured in a 110°C oven.
Array elements are applied to the coated glass substrate using a procedure
described in US
to Patent No. 5,807,522, incorporated herein by reference. 1 ~I of the array
element DNA, at an average
concentration of 100 ng/~1, is loaded into the open capillary printing element
by a high-speed robotic
apparatus. The apparatus then deposits about 5 n1 of array element sample per
slide.
Microarrays are UV-crosslinked using a STRATALINI~ER UV-crosslinker
(Stratagene).
Microarrays are washed at room temperature once in 0.2% SDS and three times in
distilled water.
15 Non-specific binding sites are blocked by incubation of microarrays in 0.2%
casein in phosphate
buffered saline (PBS) (Tropix, Inc., Bedford, MA) for 30 minutes at 60°
C followed by washes in 0.2%
SDS and distilled water as before.
Hybridization
2 o Hybridization reactions contain 9 ~ 1 of probe mixture consisting of 0.2 ~
g each of Cy3 and
Cy5 labeled cDNA synthesis products in SX SSC, 0.2% SDS hybridization buffer.
The probe mixture
is heated to 65° C for 5 minutes and is aliquoted onto the microarray
surface and covered with an 1.8
cm2 coverslip. The arrays are transferred to a waterproof chamber having a
cavity just slightly larger
than a microscope slide. The chamber is kept at 100% humidity internally by
the addition of 140 ~1 of
2 s Sx SSC in a corner of the chamber. The chamber containing the arrays is
incubated for about 6.5
hours at 60° C. The arrays are washed for 10 min at 45° C in a
first wash buffer (1X SSC, 0.1 % SDS),
three times for 10 minutes each at 45° C in a second wash buffer (0.1X
SSC), and dried.
Detection
3 o Reporter-labeled hybridization complexes are detected with a microscope
equipped with an
Innova 70 mixed gas 10 W laser (Coherent, Inc., Santa Clara CA) capable of
generating spectral lines
at 488 nm for excitation of Cy3 and at 632 nm for excitation of CyS. The
excitation laser light is
focused on the array using a 20X microscope objective (Nikon, Inc., Melville
NY). The slide
containing the array is placed on a computer-controlled X-Y stage on the
microscope and raster-
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WO 01/62918 PCT/USO1/03465
scanned past the objective. The 1.8 cm x 1.8 cm array used in the present
example is scanned with a
resolution of 20 micrometers.
In two separate scans, a mixed gas multiline laser excites the two
fluorophores sequentially.
Emitted light is split, based on wavelength, into two photomultiplier tube
detectors (PMT 81477,
s Hamamatsu Photonics Systems, Bridgewater NJ) corresponding to the two
fluorophores. Appropriate
filters positioned between the array and the photomultiplier tubes are used to
filter the signals. The
emission maxima of the fluorophores used are 565 nm for Cy3 and 650 nm for
CyS. Each array is
typically scanned twice, one scan per fluorophore using the appropriate
filters at the laser source,
although the apparatus is capable of recording the spectra from both
fluorophores simultaneously.
1 o The sensitivity of the scans is typically calibrated using the signal
intensity generated by a
cDNA control species added to the probe mix at a known concentration. A
specific location on the
array contains a complementary DNA sequence, allowing the intensity of the
signal at that location to
be correlated with a weight ratio of hybridizing species of 1:100,000. When
two probes from different
sources (e.g., representing test and control cells), each labeled with a
different fluorophore, are
15 hybridized to a single array for the purpose of identifying genes that are
differentially expressed, the
calibration is done by labeling samples of the calibrating cDNA with the two
fluorophores and adding
identical amounts of each to the hybridization mixture.
The output of the photomultiplier tube is digitized using a 12-bit RTI-835H
analog-to-digital
(A/D) conversion board (Analog Devices, Inc., Norwood, MA) installed in an IBM-
compatible PC
2 o computer. The digitized data are displayed as an image where the signal
intensity is mapped using a
linear 20-color transformation to a pseudocolor scale ranging from blue (low
signal) to red (high
signal). The data is also analyzed quantitatively. Where two different
fluorophores are excited and
measured simultaneously, the data are first corrected for optical crosstalk
(due to overlapping emission
spectra) between the fluorophores using each fluorophore's emission spectrum.
2 s A grid is superimposed over the fluorescence signal image such that the
signal from each spot
is centered in each element of the grid. The fluorescence signal within each
element is then integrated to
obtain a numerical value corresponding to the average intensity of the signal.
The software used for
signal analysis is the GEMTOOLS gene expression analysis program (Incyte).
3 o XII. Complementary Nucleic Acids
Sequences complementary to the sptm are used to detect, decrease, or inhibit
expression of the
naturally occurring nucleotide. The use of oligonucleotides comprising from
about 15 to 30 base pairs
is typical in the art. However, smaller or larger sequence fragments can also
be used. Appropriate
oligonucleotides are designed from the sptm using OLIGO 4.06 software
(National Biosciences) or
3 s other appropriate programs and are synthesized using methods standard in
the art or ordered from a
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WO 01/62918 PCT/USO1/03465
commercial supplier. To inhibit transcription, a complementary oligonucleotide
is designed from the
most unique 5' sequence and used to prevent transcription factor binding to
the promoter sequence. To
inhibit translation, a complementary oligonucleotide is designed to prevent
ribosomal binding and
processing of the transcript.
XIII. Expression of SPTM
Expression and purification of SPTM is accomplished using bacterial or vinzs-
based
expression systems. For expression of SPTM in bacteria, cDNA is subcloned into
an appropriate
vector containing an antibiotic resistance gene and an inducible promoter that
directs high levels of
1 o cDNA transcription. Examples of such promoters include, but are not
limited to, the trp-lac (tic)
hybrid promoter and the TS or T7 bacteriophage promoter in conjunction with
the lac operator
regulatory element. Recombinant vectors are transformed into suitable
bacterial hosts, e.g.,
BL21 (DE3). Antibiotic resistant bacteria express SPTM upon induction with
isopropyl beta-D-
thiogalactopyranoside (IPTG). Expression of SPTM in eukaryotic cells is
achieved by infecting insect
s s or mammalian cell lines with recombinant Autog-raphica californica nuclear
polyhedrosis virus
(AcMNPV), commonly known as baculovirus. The nonessential polyhedrin gene of
baculovirus is
replaced with cDNA encoding SPTM by either homologous recombination or
bacterial-mediated
transposition involving transfer plasmid intermediates. Viral infectivity is
maintained and the strong
polyhedrin promoter drives high levels of cDNA transcription. Recombinant
baculovirus is used to
z o infect Spodoptera fru~iperda (Sf9) insect cells in most cases, or human
hepatocytes, in some cases.
Infection of the latter requires additional genetic modifications to
baculovirus. (See e.g., Engelhard,
supra; and Sandig, supra.)
In most expression systems, SPTM is synthesized as a fusion protein with,
e.g., glutathione S-
transferase (GST) or a peptide epitope tag, such as FLAG or 6-His, permitting
rapid, single-step,
2 s affinity-based purification of recombinant fusion protein from crude cell
lysates. GST, a 26-kilodalton
enzyme from Schistosoma iaponicum, enables the purification of fusion proteins
on immobilized
glutathione under conditions that maintain protein activity and antigenicity
(Amersham Pharmacia
Biotech). Following purification, the GST moiety can be proteolytically
cleaved from SPTM at
specifically engineered sites. FLAG, an 8-amino acid peptide, enables
immunoaffinity purification
3 o using commercially available monoclonal and polyclonal anti-FLAG
antibodies (Eastman Kodak
Company, Rochester N~. 6-His, a stretch of six consecutive histidine residues,
enables purification on
metal-chelate resins (QIAGEN). Methods for protein expression and purification
are discussed in
Ausubel (1995, supra, Chapters 10 and 16). Purified SPTM obtained by these
methods can be used
directly in the following activity assay.
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XIV. Demonstration of SPTM Activity
An assay for SPTM activity measures the expression of SPTM on the cell
surface. cDNA
encoding SPTM is subcloned into an appropriate mammalian expression vector
suitable for high levels
of cDNA expression. The resulting construct is transfected into a nonhuman
cell line such as NIH3T3.
s Cell surface proteins are labeled with biotin using methods known in the
art. Immunoprecipitations are
performed using SPTM-specific antibodies, and immunoprecipitated samples are
analyzed using SDS-
PAGE and immunoblotting techniques. The ratio of labeled immunoprecipitant to
unlabeled
immunoprecipitant is proportional to the amount of SPTM expressed on the cell
surface.
Alternatively, an assay for SPTM activity measures the amount of SPTM in
secretory,
1 o membrane-bound organelles. Transfected cells as described above are
harvested and lysed. The lysate
is fractionated using methods known to those of skill in the art, for example,
sucrose gradient
ultracentrifugation. Such methods allow the isolation of subcellular
components such as the Golgi
apparatus, ER, small membrane-bound vesicles, and other secretory organelles.
Immunoprecipitations
from fractionated and total cell lysates are performed using SPTM-specific
antibodies, and
1 s immunoprecipitated samples are analyzed using SDS-PAGE arid immunoblotting
techniques. The
concentration of SPTM in secretory organelles relative to SPTM in total cell
lysate is proportional to
the amount of SPTM in txansit through the secretory pathway.
XV. Functional Assays
2 o SPTM function is assessed by expressing sptm at physiologically elevated
levels in mammalian
cell culture systems. cDNA is subcloned into a mammalian expression vector
containing a strong
promoter that drives high levels of cDNA expression. Vectors of choice include
pCMV SPORT (Life
Technologies) and pCR3.1 (Invitrogen Corporation, Carlsbad CA), both of which
contain the
cytomegalovirus promoter. 5-10 ~ g of recombinant vector are transiently
transfected into a human cell
2 s line, preferably of endothelial or hematopoietic origin, using either
liposome formulations or
electroporation. 1-2 ~g of an additional plasmid containing sequences encoding
a marker protein are
co-transfected.
Expression of a marker protein provides a means to distinguish transfected
cells from
nontransfected cells and is a reliable predictor of cDNA expression from the
recombinant vector.
a o Marker proteins of choice include, e.g., Green Fluorescent Protein (GFP;
CLONTECH), CD64, or a
CD64-GFP fusion protein. Flow cytometry (FCM), an automated laser optics-based
technique, is used
to identify transfected cells expressing GFP or CD64-GFP and to evaluate the
apoptotic state of the
cells and other cellular properties.
FCM detects and quantiFies the uptake of fluorescent molecules that diagnose
events preceding
3 s or coincident with cell death. These events include changes in nuclear DNA
content as measured by
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staining of DNA with propidium iodide; changes in cell size and granularity as
measured by forward
light scatter and 90 degree side light scatter; down-regulation of DNA
synthesis as measured by
decrease in bromodeoxyuridine uptake; alterations in expression of cell
surface and intracellular
proteins as measured by reactivity with specific antibodies; and alterations
in plasma membrane
s composition as measured by the binding of fluorescein-conjugated Annexin V
protein to the cell
surface. Methods in flow cytometry axe discussed in Ormerod, M. G. (1994) Flow
Cytometry, Oxford,
New York NY.
The influence of SPTM on gene expression can be assessed using highly purified
populations
of cells transfected with sequences encoding SPTM and either CD64 or CD64-GFP.
CD64 and CD64-
~. o GFP are expressed on the surface of txansfected cells and bind to
conserved regions of human
immunoglobulin G (IgG). Transfected cells are efficiently separated from
nontransfected cells using
magnetic beads coated with either human IgG or antibody against CD64 (DYNAL,
Inc., Lake Success
NY). mRNA can be purified from the cells using methods well known by those of
skill in the art.
Expression of mRNA encoding SPTM and other genes of interest can be analyzed
by northern analysis
z s or microarray techniques.
XVI. Production of Antibodies
SPTM substantially purified using polyacrylamide gel electrophoresis (PAGE;
see, e.g.,
Harrington, M.G. (1990) Methods Enzymol. 182:488-495), or other purification
techniques, is used to
immunize rabbits and to produce antibodies using standard protocols.
2 o Alternatively, the SPTM amino acid sequence is analyzed using LASERGENE
software
(DNASTAR) to determine regions of high immunogenicity, and a corresponding
peptide is synthesized
and used to raise antibodies by means known to those of skill in the art.
Methods for selection of
appropriate epitopes, such as those near the C-terminus or in hydrophilic
regions are well described in
the art. (See, e.g., Ausubel, 1995, supra, Chapter 11.)
2 s Typically, peptides 15 residues in length axe synthesized using an ABI
431A peptide
synthesizer (Applied Biosystems) using fmoc-chemistry and coupled to KLH
(Sigma) by reaction with
N-maleimidobenzoyl-N-hydroxysuccinimide ester (MBS) to increase
immunogenicity. (See, e.g.,
Ausubel, supra.) Rabbits axe immunized with the peptide-I~LH complex in
complete Freund's
adjuvant. Resulting antisera are tested for antipeptide activity by, for
example, binding the peptide to
3 o plastic, blocking with 1 % BSA, reacting with rabbit antisera, washing,
and reacting with radio-
iodinated goat anti-rabbit IgG. Antisera with antipeptide activity are tested
for anti-SPTM activity
using protocols well known in the art, including ELISA, RIA, and
immunoblotting.
XVII. Purification of Naturally Occurring SPTM Using Specific Antibodies
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Naturally occurring or recombinant SPTM is substantially purified by
immunoaffinity
chromatography using antibodies specific for SPTM. An immunoaffinity column is
constructed by
covalently coupling anti-SPTM antibody to an activated chromatographic resin,
such as
CNBr-activated SEPHAROSE (Amersham Pharmacia Biotech). After the coupling, the
resin is
blocked and washed according to the manufacturer's instructions.
Media containing SPTM are passed over the immunoaffinity column, and the
column is washed
under conditions that allow the preferential absorbance of SPTM (e.g., high
ionic strength buffers in the
presence of detergent). The column is eluted under conditions that disrupt
antibody/SPTM binding
(e.g., a buffer of pH 2 to pH 3, or a high concentration of a chaotrope, such
as urea or thiocyanate ion),
s o and SPTM is collected.
XVIII. Identification of Molecules Which Interact with SPTM
SPTM, or biologically active fragments thereof, are labeled with lzsl Bolton-
Hunter reagent.
(See, e.g., Bolton, A.E, and W.M. Hunter (1973) Biochem. J. 133:529-539.)
Candidate molecules
previously arrayed in the wells of a multi-well plate are incubated with the
labeled SPTM, washed, and
any wells with labeled SPTM complex are assayed. Data obtained using different
concentrations of
SPTM are used to calculate values for the number, affinity, and association of
SPTM with the
candidate molecules.
Alternatively, molecules interacting with SPTM are analyzed using the yeast
two-hybrid system
2 o as described in Fields, S. and O. Song (1989) Nature 340:245-246, or using
commercially available
kits based on the two-hybrid system, such as the MATCHMAKER system (CLONTECH).
SPTM may also be used in the PATHCALLING process (CuraGen Corp., New Haven CT)
which employs the yeast two-hybrid system in a high-throughput manner to
determine all interactions
between the proteins encoded by two large libraries of genes (Nandabalan, K.
et al. (2000) U.S. Patent
No.6,057,101).
All publications and patents mentioned in the above specification are herein
incorporated by
reference. Various modifications and variations of the described method and
system of the invention
will be apparent to those skilled in the art without departing from the scope
and spirit of the invention.
3 o Although the invention has been described in connection with specific
preferred embodiments, it should
be understood that the invention as claimed should riot be unduly limited to
such specific embodiments.
Indeed, various modifications of the above-described modes for carrying out
the invention which are
obvious to those skilled in the field of molecular biology or related fields
are intended to be within the
scope of the following claims.
58
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Table 1
SEQ
ID Template - Domain
N0:ID StartStop Frame Type Topology
1 LG:223939.1:2000FEB18202 288 forward2 TM N in
2 LG:397140.1:2000FEB18508 588 forward1 TM
2 LG:397140.1:2000FEB18236 319 forward2 TM N out
2 LG:397140.1:2000FEB18377 463 forward2 TM N out
2 LG:397240.1:2000FEB18288 374 forward3 TM
2 LG:397140.1:2000FEB18480 566 forward3 TM
3 LG:1094205.1:2000FEB18826 912 forward1 TM N in
3 LG:1094205.1:2000FEB18867 953 forward3 TM N out
4 LG:482361.5:2000FEB18215 201 forward1 TM N out
4 LG:481361.5:2000FEB18295 354 forward1 TM N out
4 LG:481361.5:2000FEB18373 459 forward1 TM N out
4 LG:481361.5:2000FEB18101 187 forward2 TM N out
4 LG:482361.5:2000FEB18369 443 forward3 TM N out
LG:981170.1:2000FEB1810 78 forward1 TM N out
5 LG:981170.1:2000FEB18598 648 forward1 TM N out
5 LG:981170.1:2000FEB18790 876 forward1 TM N out
5 LG:982170.1:2000FEB181057 2143 forward1 TM N out
5 LG:981170.1:2000FEB181372 1458 forward1 TM N out
5 LG:981170.1:2000FEB181678 1764 forward1 TM N out
5 LG:981170.1:2000FEB181885 1959 forward1 TM N out
5 LG:981170.1:2000FEB1811 82 forward2 TM N out
5 LG:981170.1:2000FEB18731 817 forward2 TM N out
5 LG:981170.1:2000FEB181025 1105 forward2 TM N out
5 LG:981170.1:2000FEB181364 1450 forward2 TM N out
5 LG:981170.1:2000FEB181643 1696 forward2 TM N out
5 LG:981170.1:2000FEB181895 1954 forward2 TM N out
5 LG:981170.1:2000FEB1824 110 forward3 TM N out
5 LG:981170.2:2000FEB18843 899 forward3 TM N out
5 LG:981170.1:2000FEB281068 1136 forward3 TM N out
5 LG:981170.1:2000FEB181599 1655 forward3 TM N out
5 LG:981170.1:2000FEB181707 1793 forward3 TM N out
5 LG:981170.1:2000FEB181875 1961 forward3 TM N out
6 LI:197623.1:2000FEB01140 226 forward2 TM N out
6 LI:197613.1:2000FEB01269 355 forward2 TM N out
7 LI:902682.1:2000FEB01225 311 forward3 TM N out
8 LI:212029.1:2000FEB012087 2149 forward2 TM N out
8 LI:212029.1:2000FEB012162 2224 forward2 TM N out
9 LI:249170.1:2000FEB01208 282 forward2 TM N in
LI:813218.1:2000FEB01466 552 forward1 TM N out
10 LI:813218.1:2000FEB01137 202 forward2 TM N out
10 LI:823218.1:2000FEB01356 436 forward2 TM N out
10 LI:813218.1:2000FEB01452 520 forward2 TM N out
11 LI:902522.3:2000FEB0199 158 forward3 TM N out
22 LI:474304.1:2000FEB0164 147 forward1 TM N in
12 LI:474304.1:2000FEB01217 285 forward1 TM N in
12 LI:474304.1:2000FEB01298 372 forward1 TM N in
22 LI:474304.1:2000FEB0126 88 forward2 TM N out
12 LI:474304.1:2000FEB01110 172 forward2 TM N out
12 LI:474304.2:2000FEB01200 271 forward2 TM N out
12 LI:474304.1:2000FEB01332 418 forward2 TM N out
12 LI:474304.1:2000FEB01890 952 forward2 TM N out
12 LI:474304.1:2000FEB0172 158 forward3 TM N out
12 LI:474304.2:2000FEB01273 332 forward3 TM N out
12 LI:474304.1:2000FEB01330 383 forward3 TM N out
12 LI:474304.1:2000FEB01606 674 forward3 TM N out
13 LI:027320.1:2000FEB01544 603 forward2 TM N out
13 L2:027320.1:2000FEB01694 768 forward1 TM N out
59
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Table
1
(cont.)
13 LI:027320.1:2000FEB011102 1182 forward1 TM N out
13 LI:027320.1:2000FEB011280 1236 forward1 TM N out
13 LI:027320.1:2000FEB01545 604 forward2 TM
13 LI:027320.1:2000FEB01851 913 forward2 TM
l3 LI:027320.1:2000FEB01932 994 forward2 TM
13 LI:027320.1:2000FEB021013 1075 forward2 TM
13 LI:027320.1:2000FEB011172 1228 forward2 TM
13 LI:027320.1:2000FEB01579 665 forward3 TM N in
13 LI:027320.1:2000FEB01720 806 forward3 TM N in
13 LI:027320.1:2000FEB01828 908 forward3 TM N in
13 LI:027320.1:2000FEB011020 1103 forward3 TM N in
13 LI:027320.1:2000FEB011116 1202 forward3 TM N in
14 LI:228319.1:2000FEB0176 162 forward1 TM N out
14 LI:228319.1:2000FEB01119 187 forward2 TM N in
14 LI:228319.1:2000FEB01506 592 forward2 TM N in
14 LI:228319.1:2000FEB0163 149 forward3 TM N in
14 LI:228319.1:2000FEB01369 455 forward3 TM N in
14 LI:228319.1:2000FEB01708 770 forward3 TM N in
14 LI:228319.1:2000FEB01786 848 forward3 TM N in
15 LG:197267.2:2000MAY1911 88 forward2 TM N in
15 LG:197267.2:2000MAY19200 271 forward2 TM N in
16 LG:403332.1:2000MAY19352 417 forward1 TM N in
16 LG:403332.1:2000MAY19490 552 forward1 TM N in
16 LG:403332.1:2000MAY19562 624 forward1 TM N in
16 LG:403332.1:2000MAY19721 783 forward1 TM N in
16 LG:403332.1:2000MAY19796 858 forward1 TM N in
16 LG:403332.1:2000MAY19871 948 forward1 TM N in
16 LG:403332.1:2000MAY191012 1098 forward1 TM N in
16 LG:403332.1:2000MAY191138 1188 forward1 TM N in
16 LG:403332.1:2000MAY191192 1278 forward1 TM N in
16 LG:403332.1:2000MAY191453 1530 forward1 TM N in
16 LG:403332.1:2000MAY19365 427 forward2 TM N in
16 LG:403332~.1:2000MAY19521 607 forward2 TM N in
16 LG:403332.1:2000MAY19644 727 forward2 TM N in
16 LG:403332.1:2000MAY19800 886 forward2 TM N in
16 LG:403332.1:2000MAY19911 973 forward2 TM N in
16 LG:403332.1:2000MAY19986 1048 forward2 TM N in
16 LG:403332.1:2000MAY191211 1297 forward2 TM N in
16 LG:403332.1:2000MAY191445 1504 forward2 TM N in
16 LG:403332.1:2000MAY19375 462 forward3 TM
16 LG:403332.1:2000MAY19495 557 forward3 TM
16 LG:403332.1:2000MAY19594 656 forward3 TM
16 LG:403332.1:2000MAY19681 767 forward3 TM
16 LG:403332.1:2000MAY19990 1052 forward3 TM
16 LG:403332.1:2000MAY191077 1139 forward3 TM
16 LG:403332.1:2000MAY191203 1274 forward3 TM
16 LG:403332.1:2000MAY191332 1385 forward3 TM
17 LG:983076.3:2000MAY19479 565 forward2 TM N in
17 LG:983076.3:2000MAY19704 790 forward2 TM N in
17 LG:983076.3:2000MAY19114 200 forward3 TM N out
17 LG:983076.3:2000MAY19261 317 forward3 TM N out
17 LG:983076.3:2000MAY19501 587 forward3 TM N out
17 LG:983076.3:2000MAY19738 794 forward3 TM N out
18 LG:216612.3:2000MAY19120 206 forward3 TM N in
18 LG:216612.3:2000MAY19234 284 forward3 TM N in
18 LG:216612.3:2000MAY19327 413 forward3 TM N in
18 LG:216612.3:2000MAY19444 530 forward3 TM N in
18 LG:216612.3:2000MAY29810 887 forward3 TM N in
19 LG:322465.1:2000MAY19239 319 forward2 TM N out
19 LG:322465.1:2000MAY19276 329 forward3 TM N out
60
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Table
1
(cont.)
20 LG:093477.1:2000MAY1925 111 forward1 TM N out
20 LG;093477.1:2000MAY1911 85 forward2 TM N out
20 LG:093477.1:2000MAY19242 295 forward2 TM N out
20 LG:093477.1:2000MAY1924 110 forward3 TM N in
20 LG:093477.1:2000MAY19657 719 forward3 TM N in
22 LG:222880.1:2000MAY19211 297 forward1 TM
21 LG:222880.1:2000MAY191663 1749 forward1 TM
21 LG:222880.1:2000MAY191801 1863 forward1 TM
21 LG:222880.1:2000MAY191906 1968 forward1 TM
21 LG:222880.1:2000MAY192269 2316 forward1 TM
21 LG:222880.1:2000MAY19425 487 forward2 TM N in
21 LG:222880.1:2000MAY19506 568 forward2 TM N in
21 LG:222880.1:2000MAY19611 691 forward2 TM N in
21 LG:222880.2:2000MAY19698 784 forward2 TM N in
21 LG:222880.1:2000MAY19875 961 forward2 TM N in
21 LG:222880.1:2000MAY191016 1078 forward2 TM N in
21 LG:222880.1:2000MAY191106 1168 forward2 TM N in
21 LG:222880.1;2000MAY191544 1630 forward2 TM N in
21 LG:222880.1:2000MAY191691 1774 forward2 TM N in
21 LG:222880.1:2000MAY191940 2026 forward2 TM N in
21 LG:222880.1:2000MAY192315 2395 forward2 TM N in
21 LG:222880.1:2000MAY191710 1784 forward3 TM N out
21 LG:222880.1:2000MAY191809 1895 forward3 TM N out
21 LG:222880.1:2000MAY191926 2009 forward3 TM N out
21 LG:222880.1:2000MAY192064 2129 forward3 TM N out
22 LG:898320.3:2000MAY19151 237 forward1 TM N out
22 LG:898320.3:2000MAY19478 534 forward1 TM N out
22 LG:898320.3:2000MAY19736 822 forward1 TM N out
22 LG:898320.3:2000MAY191528 1599 forward1 TM N out
22 LG:898320.3:2000MAY191663 1710 forward1 TM N out
22 LG:898320.3:2000MAY292017 2088 forward1 TM N out
22 LG:898320.3:2000MAY192131 2184 forward1 TM N out
22 LG:898320.3:2000MAY19719 796 forward2 TM N in
~
22 LG:898320.3:2000MAY191334 1420 forward2 TM N in
22 LG:898320.3:2000MAY191598 1681 forward2 TM N in
22 LG:898320.3:2000MAY191733 1819 forward2 TM N in
22 LG:898320.3:2000MAY191919 1984 forward2 TM N in
22 LG:898320.3:2000MAY192078 2140 forward2 TM N in
22 LG:898320.3:2000MAY192159 2245 forward2 TM N in
22 LG:898320.3:2000MAY1990 176 forward3 TM N out
22 LG:898320.3:2000MAY19411 485 forward3 TM N out
22 LG:898320.3:2000MAY19501 578 forward3 TM N out
22 LG:898320.3:2000MAY19600 686 forward3 TM N out
22 LG:898320.3:2000MAY19783 854 forward3 TM N out
22 LG:898320.3:2000MAY19912 989 forward3 TM N out
22 LG:898320.3:2000MAY191023 1097 forward3 TM N out
22 LG:898320.3:2000MAY191164 1226 forward3 TM N out
22 LG:898320.3:2000MAY191236 1298 forward3 TM N out
22 LG:898320.3:2000MAY191335 1421 forward3 TM N out
2? LG:898320.3:2000MAY192016 2093 forward3 TM N out
22 LG:898320.3:2000MAY192151 2237 forward3 TM N out
23 LG:1327047.1:2000MAY19466 552 forward2 TM N out
23 LG:1327047,2:2000MAY19137 202 forward2 TM N out
23 LG:1327047.1:2000MAY19356 436 forward2 TM N out
23 LG:1327047.1:2000MAY19452 520 forward2 TM N out
23 LG:1327047.1:2000MAY191131 1217 forward3 TM
24 LG:235157.21:2000MAY1911 91 forward2 TM N out
24 LG:235157.21:2000MAY19161 247 forward2 TM N out
24 LG:235157.21:2000MAY19467 529 forward2 TM N out
24 LG:235157.21:2000MAY19551 613 forward2 TM N out
61
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Table
1
(cons.)
24 LG:235157.21:2000MAY19686 760 forward2 TM N out
24 LG:235157.21:2000MAY19785 862 forward2 TM N out
25 LG:085713.1:2000MAY1997 183 forward1 TM N out
25 LG:085723.1:2000MAY191489 1575 forward1 TM N out
25 LG:085713.1:2000MAY191786 1854 forward1 TM N out
25 LG:085713.1:2000MAY192275 2361 forward1 TM N out
25 LG:085713.1:2000MAY192407 2493 forward1 TM N out
25 LG:085713.1:2000MAY19134 211 forward2 TM N in
25 LG:085713.1:2000MAY191481 1528 forward2 TM N in
25 LG:085713.1:2000MAY192099 2164 forward2 TM N in
25 LG:085713.1;2000MAY192387 2449 forward2 TM N in
25 LG:085713.1;2000MAY192474 2536 forward2 TM N in
25 LG:085713.1:2000MAY1972 158 forward3 TM N out
25 LG:085713.1:2000MAY191488 1574 forward3 TM N out
25 LG:085713.1:2000MAY192037 2108 forward3 TM N out
25 LG:085713.1:2000MAY192184 2270 forward3 TM N out
25 LG:085713.1:2000MAY192346 2432 forward3 TM N out
26 LG:482421.1:2000MAY19385 456 forward1 TM N out
26 LG:482421.1:2000MAY19715 777 forward1 TM N out
26 LG:482421.1:2000MAY19841 909 forward1 TM N out
26 LG:482421.1:2000MAY19970 1056 forward1 TM N out
26 LG:482421.1:2000MAY191222 1284 forward1 TM N out
26 LG:482421.1:2000MAY191423 1491 forward1 TM N out
26 LG:482421.1:2000MAY192185 2271 forward1 TM N out
26 LG:482421.1:2000MAY192518 2604 forward1 TM N out
26 LG:482421.1:2000MAY192674 2760 forward1 TM N out
26 LG:482421.1:2000MAY1911 64 forward2 TM N out
26 LG:482421.1:2000MAY19260 346 forward2 TM N out
26 LG:482421.1:2000MAY19416 502 forward2 TM N out
26 LG:482421.1:2000MAY19506 586 forward2 TM N out
26 LG:482421.1:2000MAY19857 943 forward2 TM N out
26 LG:482421.1:2000MAY19965 1021 forward2 TM N out
26 LG:482421.1:2000MAY191934 1987 forward2 TM N out
26 LG:482421.1:2000MAY192120 2206 forward2 TM N out
26 LG:482421.1:2000MAY192549 2635 forward2 TM N out
26 LG:482421.1:2000MAY192693 2773 forward2 TM N out
26 LG:482421.1:2000MAY1912 65 forward3 TM N out
26 LG:482421.1:2000MAY19258 332 forward3 TM N out
26 LG:482421.1:2000MAY19603 689 forward3 TM N out
26 LG:482421.1:2000MAY19690 773 forward3 TM N out
26 LG:482421.1:2000MAY19822 905 forward3 TM N out
26 LG:482421.1:2000MAY19972 1028 forward3 TM N out
26 LG:482421.1:2000MAY191074 1130 forward3 TM N out
26 LG:482421.1:2000MAY192403 2489 forward3 TM N out
26 LG:482421.1:2000MAY192550 2636 forward3 TM N out
26 LG:482421.1:2000MAY192673 2753 forward3 TM N out
27 LG:330944.4:2000MAY19389 475 forward2 TM N out
28 LI:223060.1:2000MAY01433 519 forward1 TM N in
28 LI;223060.1:2000MAY011267 1353 forward1 TM N in
;?8LI:223060.1:2000MAY011639 1704 forward1 TM N in
28 LI:223060.1:2000MAY011759 1842 forward1 TM N in
28 LI:223060.1:2000MAY01260 334 forward2 TM N out
28 LI:223060.1:2000MAY01938 1003 forward2 TM N out
28 LI:223060.1:2000MAY011553 1639 forward2 TM N out
28 LI:223060.1:2000MAY011428 1514 forward3 TM N out
29 LI:213087.1:2000MAY01732 818 forward3 TM N in
30 LI:405330.1:2000MAY01103 165 forward1 TM
30 LI:405330.1:2000MAY01406 492 forward1 TM
30 LI:405330.1:2000MAY011276 1362 forward1 TM
30 LI:405330.1:2000MAY011396 1449 forward1 TM
62
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Table
1
(coat.)
30 LI:405330.1:2000MAY011615 1674 forward1 TM
30 LI:405330.1:2000MAY011864 1917 forward1 TM
30 LI:405330.1:2000MAY011966 2016 forward1 TM
30 LI:405330.1:2000MAY012017 2097 forward1 TM
30 LI:405330.1:2000MAY012257 2319 forward1 TM
30 LI:405330.1:2000MAY012329 2397 forwardl TM
30 LI:405330.1:ZOOOMAY012416 2478 forward1 TM
30 LI:405330.1:2000MAY01485 550 forward2 TM N out
30 LI:405330.1:2000MAY01671 757 forward2 TM N out
30 LI:405330.1:2000MAY011283 1357 forward2 TM N out
30 LI:405330.1:2000MAY012511 1579 forward2 TM N out
30 LI:405330.1:2000MAY011877 1933 forward2 TM N out
30 LI:405330.1:2000MAY012339 2395 forward2 TM N out
30 LI:405330.1:2000MAY012411 2473 forward2 TM N out
30 LI;405330.1:2000MAY01249 320 forward3 TM N in
30 LI:405330.1:2000MAY01678 764 forward3 TM N in
30 LI;405330.1:2000MAY01990 1070 forward3 TM N in
30 LI:405330.2:2000MAY011650 1721 forward3 TM N in
30 LI:405330.1:2000MAY012265 2351 forward3 TM N in
30 LI:405330.1:2000MAY012433 2513 forward3 TM N in
31 LI:350243.2:2000MAY013799 3852 forward1 TM
31 LI:350243.2:2000MAY014453 4533 forward1 TM
31 LI:350243.2:2000MAY015392 5460 forward1 TM
31 LI:350243.2:2000MAY015944 6030 forward1 TM
31 LI:350243.2:2000MAY016256 6333 forward1 TM
31 LI:350243.2:2000MAY017003 7071 forward1 TM
31 LI:350243,2:2000MAY017333 7398 forward1 TM
31 LI:350243.2:2000MAY017552 7626 forward1 TM
31 LI:350243.2:2000MAY017780 7845 forward1 TM
31 LI:350243.2:2000MAY017867 7923 forward1 TM
31 LI:350243.2:2000MAY017954 8025 forward1 TM
31 LI:350243.2:2000MAY018407 8490 forward1 TM
31 LI:350243.2:2000MAY014361 4447 forward2 TM N out
31 LI:350243.2:2000MAY014724 4807 forward2 TM N out
31 LI:350243.2:2000MAY015402 5488 forward2 TM N out
31 LI:350243.2:2000MAY015618 5668 forward2 TM N out
31 LT:350243.2:2000MAY015687 5767 forward2 TM N out
31 LI:350243.2:2000MAY016263 6334 forward2 TM N out
31 LI:350243.2:2000MAY016488 6574 forward2 TM N out
31 LI:350243.2:2000MAY017610 7696 forward2 TM N out
32 LI:350243.2;2000MAY027814 7900 forward2 TM N out
31 LI:350243.2:2000MAY017991 8047 forward2 TM N out
31 LI:350243.2:2000MAY018501 8587 forward2 TM N out
31 LI:350243.2:2000MAY018699 8785 forward2 TM N out
31 LI:350243.2:2000MAY013975 4052 forward3 TM N in
31 LI:350243.2:2000MAY015037 5108 forward3 TM N in
31 LI:350243.2:2000MAY016090 6155 forward3 TM N in
31 LI:350243.2:2000MAY016276 6338 forward3 TM N in
31 LI:350243.2:2000MAY016357 6419 forward3 TM N in
31 LI:350243.2:2000MAY016492 6557 forward3 TM N in
31 LI:350243.2:2000MAY017005 7055 forward3 TM N in
31 LI:350243.2:2000MAY017185 7271 forward3 TM N in
31 LI:350243.2:2000MAY017365 7439 forward3 TM N in
31 LI:350243.2:2000MAY017650 7727 forward3 TM N in
31 LI:350243.2:2000MAY017818 7868 forward3 TM N in
31 LI:350243.2:2000MAY017881 7949 forward3 TM N in
31 LI:350243.2:2000MAY018445 8507 forward3 TM N in
31 LI:350243.2:2000MAY018526 8585 forward3 TM N in
32 LI:445188.1:2000MAY0110 63 forward1 TM N in
32 LI:445188.1:2000MAY01169 240 forward1 TM N in
63
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Table
1
(cont.)
32 LI:445188,1:2000MAY01337 408 forward1 TM N in
32 LI:445188.1:2000MAY01406 471 forward1 TM N in
32 LI:445188,1:2000MAY01796 861 forward1 TM N in
32 LI:445188.1:2000MAY01967 1041 forward1 TM N in
32 LI:445188.1:2000MAY011135 1209 forward1 TM N in
32 LI:445188.1:2000MAY011228 1314 forward1 TM N in
32 LI:445188.1:2000MAY011396 1473 forward1 TM N in
32 LI:445188.1:2000MAY01131 217 forward2 TM N in
32 LI:445188.1:2000MAY01335 421 forward2 TM N in
32 LI:445188.1:2000MAY01980 1042 forward2 TM N in
32 LI:445188.1:2000MAY011136 1189 forward2 TM N in
32 LI:445188.1:2000MAY011445 1522 forward2 TM N in
32 LI:445188.1:2000MAY0112 59 forward3 TM N out
32 LI:445188.1:2000MAY01135 221 forward3 TM N out
32 LI:445188.1:2000MAY01258 344 forward3 TM N out
32 LI:445188.1:2000MAY01351 431 forward3 TM N out
32 LI:445188.1:2000MAY01573 650 forward3 TM N out
32 LI:445188.1:2000MAY01819 893 forward3 TM N out
32 LI:445188.1:2000MAY011008 1094 forward3 TM N out
32 LI:445188.1:2000MAY011149 1235 forward3 TM N out
32 LI:445188.1:2000MAY011695 1763 forward3 TM N out
33 LI:244378.1:2000MAY0128 114 forward1 TM N out
33 LI:244378.1:2000MAY01403 462 forward1 TM N out
33 LI:244378.1:2000MAY01466 549 forward1 TM N out
33 LI:244378.1:2000MAY011972 2058 forward1 TM N out
33 LI:244378.1:2000MAY0111 76 forward2 TM N in
33 LI:244378.1:2000MAY01401 487 forward2 TM N in
33 LI:244378.1:2000MAY01533 619 forward2 TM N in
33 LI:244378.1:2000MAY011313 1369 forward2 TM N in
33 LI:244378.1:2000MAY011985 2035 forward2 TM N in
33 LI:244378.1:2000MAY0124 86 forward3 TM N out
33 LI:244378.1:2000MAY01108 170 forward3 TM N out
33 LI:244378.1:2000MAY011980 2045 forward3 TM N out
34 LI:236574.15:2000MAY011 81 forward1 TM N out
34 LI:236574.15:2000MAY0197 183 forward1 TM N out
34 LI:236574.15:2000MAY0195 166 forward2 TM N out
34 LI:236574.15:2000MAY01239 325 forward2 TM N out
34 LI:236574.15:2000MAY0193 155 forward3 TM N in
35 LI:010100.20:2000MAY0143 96 forward1 TM N in
35 LI:010100.20:2000MAY01169 255 forward1 TM N in
35 LI:010100.20:2000MAY01328 399 forward1 TM N in
35 LI:010100.20:2000MAY01658 720 forward1 TM N in
35 LI:010100.20:2000MAY01742 804 forward1 TM N in
35 LI:010100.20:2000MAY01910 996 forward1 TM N in
35 LI:020100.20:2000MAY011117 1203 forward1 TM N in
35 LI:010100.20:2000MAY011240 1317 forward1 TM N in
35 LI:010100.20:2000MAY011528 1611 forward1 TM N in
35 LI:010100.20:2000MAY011822 1908 forward1 TM N in
35 LI:010100.20:2000MAY012206 2280 forward1 TM N in
35 LI:010100.20:2000MAY012671 2754 forward1 TM N in
35 LI:010100.20:2000MAY012899 2973 forward2 TM N in
35 LI:010100.20:2000MAY013037 3123 forward1 TM N in
35 LI:010100.20:2000MAY013349 3435 forward1 TM N in
35 LI:010100.20:2000MAY0126 109 forward2 TM N in
35 LI:010100.20:2000MAY01146 232 forward2 TM N in
35 LI:010100.20:2000MAY01530 592 forward2 TM N in
35 LI:010100.20:2000MAY01743 796 forward2 TM N in
35 LI:010100.20:2000MAY01953 1039 forward2 TM N in
35 LI:010100.20:2000MAY011154 1207 forward2 TM N in
35 LI:010100.20:2000MAY011274 1360 forward2 TM N in
64
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
Table
1
(cont.)
35 LI:010100.20:2000MAY011364 1435 forward2 TM N in
35 LI:010100.20:2000MAY011544 1630 forward2 TM N in
35 LI:010100.20:2000MAY011748 1822 forward2 TM N in
35 LI:010100.20:2000MAY011922 2008 forward2 TM N in
35 LI:010100.20:2000MAY012354 2440 forward2 TM N in
35 LI:010100.20:2000MAY012663 2731 forward2 TM N in
35 LI:010100.20:2000MAY012732 2818 forward2 TM N in
35 LI:010100.20:2000MAY013287 3373 forward2 TM N in
35 LI:010100.20:2000MAY013386 3472 forward2 TM N in
35 LI:010100.20:2000MAY01141 227 forward3 TM
35 LT:010100.20:2000MAY01375 452 forward3 TM
35 LI:010100.20:2000MAY01768 824 forward3 TM
35 LT:010100.20:2000MAY01969 1049 forward3 TM
35 LI:010100.20:2000MAY011146 1214 forward3 TM
35 LT:010100.20:2000MAY011281 1367 forward3 TM
35 LI:010100.20:2000MAY011590 1652 forward3 TM
35 LI:010100.20:2000MAY011704 1766 forward3 TM
35 LI:010100.20:2000MAY011908 1976 forward3 TM
35 LI:010100.20:2000MAY012208 2294 forward3 TM
35 LI:010100.20:2000MAY012700 2762 forward3 TM
35 LI:010100.20:2000MAY012781 2843 forward3 TM
35 LI:010100.20:2000MAY012862 2924 forward3 TM
35 LI:010100.20:2000MAY012946 3020 forward3 TM
35 LI:010100.20:2000MAY013051 3131 forward3 TM
35 LI:010100.20:2000MAY013135 3206 forward3 TM
35 LI:010100.20:2000MAY013324 3389 forward3 TM
36 LI:037940.6:2000MAY01163 249 forward1 TM N in
36 LI:037940.6:2000MAY0114 100 forward2 TM
36 LI:037940.6:2000MAY01161 247 forward2 TM
36 LI:037940.6:2000MAY01365 451 forward2 TM
36 LI:037940.6:2000MAY0112 92 forward3 TM N out
36 LT:037940.6:2000MAY01387 473 forward3 TM N out
37 LI:228550.3:2000MAY011537 1602 forward1 TM N in
37 LI:228550.3:2000MAY011603 1680 forward1 TM N in
37 LI:228550.3:2000MAY011846 1899 forward1 TM N in
37 LI:228550.3:2000MAY014165 4239 forward1 TM N in
37 LI:228550.3:2000MAY014549 4629 forward1 TM N in
37 LI:228550.3:2000MAY014651 4737 forward1 TM N in
37 LI:228550.3:2000MAY015371 5430 forward1 TM N in
37 LI:228550.3:2000MAY017300 7362 forward1 TM N in
37 LI:228550.3:2000MAY017408 7470 forward1 TM N in
37 LI:228550.3:2000MAY017582 7659 forward1 TM N in
37 LI:228550.3:2000MAY011622 1678 forward2 TM N in
37 LI:228550.3:2000MAY011718 1804 forward2 TM N in
37 LI:228550.3:2000MAY011841 1927 forward2 TM N in
37 LI:228550.3:2000MAY011976 2038 forward2 TM N in
37 LI:228550.3:2000MAY012066 2128 forward2 TM N in
37 LI:228550.3:2000MAY012150 2236 forward2 TM N in
37 LI:228550.3:2000MAY012546 2608 forward2 TM N in
37 LI:228550.3:2000MAY013746 3829 forward2 TM N in
37 LI:228550.3:2000MAY014457 4543 forward2 TM N in
37 LI:228550.3:2000MAY014724 4810 forward2 TM N in
37 L2:228550.3:2000MAY017229 7303 forward2 TM N in
37 LI:228550.3:2000MAY017637 7723 forward2 TM N in
37 LI:228550.3:2000MAY013978 4031 forward3 TM N in
37 LI:228550.3:2000MAY014362 4424 forward3 TM N in
37 LI:228550.3:2000MAY014440 4502 forward3 TM N in
37 LI:228550.3:2000MAY014575 4637 forward3 TM N in
37 LI:228550.3:2000MAY014671 4733 forwaxd3 TM N in
37 LI:228550.3:2000MAY015070 5135 forward3 TM N in
65
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
Table
1
(cont.)
37 LI:228550.3:2000MAY016963 7049 forward3 TM N in
37 LI:228550.3:2000MAY027308 7361 forward3 TM N in
37 LI:228550.3:2000MAY017482 7535 forward3 TM N in
37 LI:228550.3:2000MAY017617 7703 forward3 TM N in
38 LI:027320.1:2000MAY01637 723 forward1 TM N in
38 LI:027320.1:2000MAY01796 882 forward1 TM N in
38 LI:027320.2:2000MAY01970 1050 forward2 TM N in
38 LI:027320.1:2000MAY011081 1167 forward1 TM N in
38 LI:027320.1:2000MAY01692 778 forward2 TM N in
38 LI:027320.1:2000MAY01857 928 forward2 TM N in
38 LI:027320.1:2000MAY01932 1012 forward2 TM N in
38 LI:027320.1:2000MAY011079 1165 forward2 TM N in
38 LI:027320.1:2000MAY011220 1306 forward2 TM N in
38 LI:027320.1:2000MAY011032 1118 forward3 TM N out
38 LI:027320.1:2000MAY011128 1190 forward3 TM N out
38 LI:027320.1:2000MAY011242 1292 forward3 TM N out
39 LI:321475.1:2000MAY01610 681 forward1 TM N out
39 LI;321475.1:2000MAY011081 1167 forward1 TM N out
39 LI:321475.1:2000MAY011207 1284 forward1 TM N out
39 LI;321475.1:2000MAY01125 187 forward2 TM N out
39 LI:321475.1:2000MAY01200 262 forward2 TM N out
39 LI:321475.2:2000MAY01356 442 forward2 TM N out
39 LI:321475.1:2000MAY01641 727 forward2 TM N out
39 LI:321475.1:2000MAY01791 877 forward2 TM N out
39 LI:321475.1:2000MAY01920 982 forward2 TM N out
39 LI:321475.1:2000MAY011013 1075 forward2 TM N out
39 LI:321475.1:2000MAY011124 1186 forward2 TM N out
39 LI:321475.1:2000MAY011202 1264 forward2 TM N out
39 LI:321475.1:2000MAY011409 1495 forward2 TM N out
39 LI:321475.1:2000MAY01822 908 forward3 TM N in
39 LI:321475.1:2000MAY011125 1208 forward3 TM N in
40 LI:899552.5:2000MAY01286 351 forward1 TM N in
40 LI:899552.5:2000MAY01970 1056 forward1 TM N in
40 LI:899552.5:2000MAY011114 1176 forward1 TM N in
40 LI:899552.5:2000MAY011900 1947 forward1 TM N in
40 LI:899552.5:2000MAY011079 1165 forward2 TM N in
40 LI:899552.5:2000MAY011691 1765 forward2 TM N in
40 LI:899552.5:2000MAY01834 896 forward3 TM N in
40 LI:899552.5:2000MAY01915 977 forward3 TM N in
40 LI:899552.5:2000MAY01996 1058 forward3 TM N in
41 LI:1071848.1:2000MAY01961 1020 forward1 TM N out
41 LI:1071848.1:2000MAYOl1117 1194 forward1 TM N out
41 LI:1071848.1:2000MAY011058 1144 forward2 TM N out
41 LI:1071848.1:2000MAY01996 1067 forward3 TM N in
41 LI:1071848.1:2000MAY011080 1142 forward3 TM N in
41 LI:1071848.1:2000MAY011155 1217 forward3 TM N in
42 LI:1072337.2:2000MAY0149 135 forward1 TM N out
42 LI:1072337.2:2000MAY01463 525 forward1 TM N out
42 LI:1072337.2:2000MAY01652 726 forward1 TM N out
42 LI:1072337.2:2000MAY012344 2397 forward1 TM N out
42 LI:1072337.2:2000MAY012518 2589 forward1 TM N out
42 LT:1072337.2:2000MAY012614 2667 forward1 TM N out
42 LI:1072337.2:2000MAY012923 3000 forward1 TM N out
42 LI:1072337.2:2000MAY013181 3252 forward1 TM N out
42 LI:1072337.2:2000MAY013577 3657 forward1 TM N out
42 LI:1072337.2:2000MAY014264 4344 forward1 TM N out
42 LI:1072337.2:2000MAY0177 136 forward2 TM N out
42 LI:1072337.2:2000MAY01230 316 forward2 TM N out
42 LI:1072337.2:2000MAY011997 2047 forward2 TM N out
42 LI:1072337.2:2000MAY012057 2125 forward2 TM N out
66
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
Table
1
(cont.)
42 LI:2072337.2:2000MAY0126092686 forward2 TM N out
42 LI:1072337.2:2000MAY0128612914 forward2 TM N out
42 LI:1072337.2:2000MAY0132423328 forward2 TM N out
42 LI:1072337.2:2000MAY0134403496 forward2 TM N out
42 LI:1072337.2:2000MAY0135873673 forward2 TM N out
42 LI:1072337.2:2000MAY0143914468 forward2 TM N out
42 LI:1072337.2:2000MAY0123822435 forward3 TM N in
42 LI:1072337.2:2000MAY0125292594 forward3 TM N in
42 LI:1072337.2:2000MAY0128772948 forward3 TM N in
42 LI:1072337.2:2000MAY0129943065 forward3 TM N in
42 LI:1072337.2:2000MAY0136183695 forward3 TM N in
42 LI:1072337.2:2000MAY0143864460 forward3 TM N in
43 LI:251489.5:2000MAY01 31 127 forward1 TM N out
43 LI:251489.5:2000MAY01 44 130 forward2 TM N out
44 LI:902018.107:2000MAY01595 681 forward1 TM N out
44 LI:902018.107:2000MAY0114291515 forward1 TM N out
44 LI:902018.107:2000MAY0120982184 forward1 TM N out
44 LI:902018.107:2000MAY0123412409 forward1 TM N out
44 LI:902018.107:2000MAY0128332895 forward1 TM N out
44 LI:902018.107:2000MAY0129262988 forward1 TM N out
44 LI:902018.107:2000MAY0136163666 forward1 TM N out
44 LI:902018.107:2000MAY0137663837 forward1 TM N out
44 LI:902018.107:2000MAY0139373990 forward1 TM N out
44 LI:902018.107:2000MAY0126752761 forward2 TM N in
44 LI:902018.107:2000MAY0136113697 forward2 TM N in
44 LI:902018.107:2000MAY0140434117 forward2 TM N in
44 LI:902018.107:2000MAY0141514237 forward2 TM N in
44 LI:902018.107:2000MAY0130573143 forward3 TM N in
44 LI:902018.107:2000MAY0135553638 forward3 TM N in
44 LI:902018.107:2000MAY0136813734 forward3 TM N in
44 LI:902018.107:2000MAY0139153977 forward3 TM N in
44 LI:902018.107:2000MAY0140024064 forward3 TM N in
44 LI:902018,207:2000MAY0140804160 forward3 TM N in
44 LI:902018.107:2000MAY0142704226 forward3 TM N in
45 LI:220495.1:2000MAY01 91 150 forward1 TM N out
45 LI:220495.1:2000MAY01 205 291 forward1 TM N out
45 LI:220495.1:2000MAY01 499 579 forward1 TM N out
45 LI:220495.1:2000MAY01 637 699 forward1 TM N out
45 LI:220495.1:2000MAY01 718 780 forward1 TM N out
45 LI:220495.1:2000MAY01 853 936 forward1 TM N out
45 LI:220495.1:2000MAY01 994 1080 forward1 TM N out
45 LI:220495.1:2000MAY01 15131590 forward1 TM N out
45 LI:220495.1:2000MAY01 15911671 forward1 TM N out
45 LI:220495.1:2000MAY01 17021788 forward1 TM N out
45 LI:220495.1:2000MAY01 19392022 forward1 TM N out
45 LI:220495.1:2000MAY01 23442430 forward1 TM N out
45 LI:220495.1:2000MAY01 25422592 forward1 TM N out
45 LI:220495.1:2000MAY01 779 832 forward2 TM N in
45 LI:220495.1:2000MAY01 851 916 forward2 TM N in
45 LI:220495.1:2000MAY01 14181504 forward2 TM N in
45 LI;220495.1:2000MAY01 15891642 forward2 TM N in
45 LI:220495.1:2000MAY01 16821768 forward2 TM N in
45 LI:220495.1:2000MAY01 18231885 forward2 TM N in
45 LI:220495.1:2000MAY01 18981960 forward2 TM N in
45 LI:220495.1:2000MAY01 28942974 forward2 TM N in
45 LI:220495.1:2000MAY01 486 536 forward3 TM N in
45 LI:220495.1:2000MAY01 618 677 forward3 TM N in
45 LI:220495.1:2000MAY01 960 1034 forward3 TM N in
45 LT:220495.1:2000MAY01 16921751 forward3 TM N in
45 LI:220495.1:2000MAY01 18121895 forward3 TM N in
67
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
Table
1
(cont.)
45 LI:220495.1:2000MAY011932 1991 forward3 TM N in
45 LI:220495.1:2000MAY012307 2366 forward3 TM N in
45 LI:220495.1:2000MAY012391 2462 forward3 TM N in
45 LI:220495.1:2000MAY012835 2921 forward3 TM N in
45 LI:220495.1:2000MAY012970 3056 forward3 TM N in
46 LI:399478.1:2000MAY01823 885 forward1 TM N in
46 LI:399478.1:2000MAY01982 1059 forward1 TM N in
46 LI:399478.1:20DOMAY011087 2173 forward1 TM N in
46 LI:399478.1:2000MAY011330 1416 forward1 TM N in
46 LI:399478.1:2000MAY011639 1716 forward1 TM N in
46 LI:399478.1:2000MAY011756 1836 forward1 TM N in
46 LI:399478.1:2000MAY011849 1899 forward1 TM N in
46 LI:399478.1:2000MAY012497 2574 forward1 TM N in
46 LI:399478.1:2000MAY012726 2772 forward1 TM N in
46 LI:399478.1:2000MAY01107 178 forward2 TM N out
46 LT:399478.1:2000MAY011025 1087 forward2 TM N out
46 LI:399478.1:2000MAY011103 1165 forward2 TM N out
46 LI:399478.1:2000MAY011640 1702 forward2 TM N out
46 LI:399478.1:2000MAY011718 1780 forward2 TM N out
46 LI:399478.1:2000MAY012D63 2149 forward2 TM N out
46 LI:399478.1:2000MAY01519 605 forward3 TM N in
46 LI:399478.1:2000MAYOl834 914 forward3 TM N in
46 LI:399478.1:2000MAY011014 1076 forward3 TM N in
46 LI:399478.1:2000MAY011101 1263 forward3 TM N in
46 LI:399478.1;2000MAY011386 1439 forward3 TM N in
46 LI:399478.1:2000MAY011509 1595 forward3 TM N in
46 LI:399478.1;2000MAY011659 1745 forward3 TM N in
46 LI:399478.1:2000MAY011803 1886 forward3 TM N in
46 LI:399478.1:2000MAY012583 2669 forward3 TM N in
47 LI:229648.2:2000MAY01556 606 forward1 TM
47 LI:229648.2:2000MAY011009 1095 forward1 TM
47 LI:229648.2:2000MAY011324 1410 forward1 TM
47 LI:229648.2:2000MAY011633 1719 forward1 TM
47 LI:229648.2:2000MAY011840 1914 forward1 TM
47 LI:229648.2:2000MAY01776 832 forward2 TM N in
47 LI:229648.2:2000MAY01983 1069 forward2 TM N in
47 LI:229648.2:2000MAY011610 1663 forward2 TM N in
47 LI:229648.2:2000MAY011862 1921 forward2 TM N in
47 LI:229648.2:2000MAY01726 812 forward3 TM N in
47 LI:229648.2:2000MAY011002 1088 forward3 TM N in
47 LI:229648.2:2DOOMAY011533 1589 forward3 TM N in
47 LI:229648.2:2000MAY011641 1727 forward3 TM N in
47 LI:229648.2:2000MAY011809 1895 forward3 TM N in
48 LI:025643.2:2000MAY011526 1591 forward2 TM
48 LI:025643.2:2000MAY011542 1598 forward3 TM N out
49 LI:233942.1:2000MAY01184 270 forward1 TM N out
49 LI:233942.1:2000MAY01541 627 forward1 TM N out
49 LI:233942.1:2000MAY01671 745 forward2 TM N out
49 LI:233942.1:2000MAY011352 1438 forward2 TM N out
49 LI:233942.1:2000MAY011715 1768 forward2 TM N out
49 LI:233942.1:2000MAY012021 2104 forward2 TM N out
49 LI:233942.1:2000MAY01138 221 forward3 TM N in
49 LI:233942.1:2000MAY01558 614 forward3 TM N in
49 LI:233942.1:2000MAY01684 758 forward3 TM N in
49 LI:233942.1:2000MAY011179 1256 forward3 TM N in
49 LI:233942.1:2000MAY021986 2057 forward3 TM N in
50 LI:089158.1:2000MAY012443 2526 forward1 TM N out
50 LI:089158.1:2000MAY012602 2652 forward1 TM N out
50 LI:089158.1:2000MAY013772 3858 forward1 TM N out
50 LI:089158.1:20OOMAY011052 1120 forward2 TM N in
68
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
Table
1
(cont.)
50 LI:089158.1:2000MAY011523 1597 forward2 TM N in
50 LI:089158.1:2000MAY011643 1729 forward2 TM N in
50 LI:089158.1:2000MAY012396 2476 forward2 TM N in
50 LI:089158.1:2000MAY013335 3421 forward2 TM N in
50 LI:089158.1:2000MAY011020 1100 forward3 TM N in
50 LI:089158.1:2000MAY011497 1583 forward3 TM N in
50 LI:089158.1:2000MAY012722 1790 forward3 TM N in
50 LI:089158.1:2000MAY013069 3146 forward3 TM N in
51 LI:101046.1:2000MAY01292 378 forward1 TM N out
51 LT:101046.1:2000MAY01811 897 forward1 TM N out
51 LT:101046.1:2000MAY011261 1308 forward1 TM N out
51 LI:101046.1:2000MAY01368 451 forward2 TM N in
51 LI:101046.1:2000MAY01827 913 forward2 TM N in
51 LI:101046.1:2000MAY012102 2188 forward2 TM N in
51 LI:101046.1:2000MAY01711 785 forward3 TM N out
51 LI:101046.1:2000MAY01873 932 forward3 TM N out
51 LI:101046.1:2000MAY011002 1079 forward3 TM N out
52 LI:368676.2:2000MAY012077 2163 forward1 TM
52 LI:368676.2:2000MAY013079 3165 forward1 TM
52 LI:368676.2:2000MAY012984 3058 forward2 TM N in
52 LI:368676.2:2000MAY012937 3023 forward3 TM
53 LI:238713.1:2000MAY01844 930 forward1 TM
53 LI:238713.2:2000MAY01120 184 forward2 TM N out
53 LI:238713.1:2000MAY01194 256 forward2 TM N out
53 LI:238713.1:2000MAY01728 814 forward2 TM N out
53 LI:238713.1:2000MAY01297 383 forward3 TM N out
53 LI:238713.1:2000MAY01423 485 forward3 TM N out
53 LI:238713.1:2000MAY01570 656 forward3 TM N out
53 LI:238713.1:2000MAY01696 782 forward3 TM N out
53 LI:238713.1:2000MAY012101 1154 forward3 TM N out
53 LI:238713.1:2000MAY011635 1721 forward3 TM N out
54 LI:720928.1:2000MAY01208 264 forward1 TM N out
54 LI:720928.1:2000MAY01637 693 forward1 TM N out
55 LI:221874.1:2000MAY01877 954 forward1 TM N out
55 LI:221874.1:2000MAY012086 2172 forward1 TM N out
55 LI:221874.1:2000MAY011187 1258 forward2 TM N out
55 LI:221874.1:2000MAY012171 2230 forward2 TM N out
55 LI:221874.1:2000MAY01348 434 forward3 TM N in
55 LI:221874.1:2000MAY011116 1190 forward3 TM N in
56 LI:1143545.3:2000MAY01458 523 forward2 TM
56 LI:1143545.3:2000MAY012144 2230 forward2 TM
57 LI:1143605.1:2000MAY01349 435 forward1 TM N in
57 LI:1143605.1:2000MAY01445 528 forward1 TM N in
57 L2:1143605.1:2000MAY01544 624 forward1 TM N in
57 LI:1243605.1:2000MAY01775 861 forward1 TM N in
57 LI:1143605.1:2000MAY011202 1188 forward1 TM N in
57 LI:1143605.1:2000MAY011240 1302 forward1 TM N in
57 LI:1143605.1:2000MAY011378 1464 forward1 TM N in
57 LI:1143605.1:2000MAY011726 1800 forward1 TM N in
57 LI:1143605.1:2000MAY011828 1890 forward1 TM N in
57 LI:1143605.1:2000MAY011918 1980 forward1 TM N in
57 LI:1143605.1:2000MAY0117 82 forward2 TM N out
57 LI:2143605.1:2000MAY01368 445 forward2 TM N out
57 LI:1143605.1:2000MAY01632 718 forward2 TM N out
57 LI:1143605.1:2000MAY01899 958 forward2 TM N out
57 LI:1143605.1:2000MAY011043 1102 forward2 TM N out
57 LI:1143605.1:2000MAY011157 1243 forward2 TM N out
57 LI:1143605.1:2000MAY011607 1681 forward2 TM N out
57 LI:1143605.1:2000MAY011766 1849 forward2 TM N out
57 LI:1143605.1:2000MAY011859 1927 forward2 TM N out
69
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
Table
1
(cont.)
57 LI:1143605.1:2000MAY011940 1999 forward2 TM N out
57 LI:1143605,1:2000MAY01351 437 forward3 TM N out
57 LI:1143605.2:2000MAY01513 584 forward3 TM N out
57 LI:1143605.1:2000MAY01735 821 forward3 TM N out
57 LI:1143605.1:2000MAY011326 1412 forward3 TM N out
57 LI:1143605.1:2000MAY011446 1526 forward3 TM N out
57 LI:1143605.1:2000MAY011605 1688 forward3 TM N out
57 LI:1143605.1:2000MAY011806 1868 forward3 TM N out
57 LI:1143605.1:2000MAY011893 1955 forward3 TM N out
58 LI:474069.7:2000MAY01706 783 forward1 TM
58 LI:474069.7:2000MAY011366 1428 forward1 TM
58 LI:474069.7:2000MAY011738 1824 forward1 TM
58 LI:474069.7:2000MAY01698 748 forward2 TM N in
58 LI:474069.7:2000MAY01965 1051 forward2 TM N in
58 LI:474069.7:2000MAY011241 1300 forward2 TM N in
58 LI:474069.7:2000MAY011487 1537 forward2 TM N in
58 LI:474069.7:2000MAY012030 2107 forward2 TM N in
58 LI:474069.7:2000MAY0127 92 forward3 TM N in
58 LI:474069.7:2000MAY01699 785 forward3 TM N in
58 LI:474069.7:2000MAY01936 1001 forward3 TM N in
58 LI:474069.7:2000MAY011929 2003 forward3 TM N in
59 L2:245193.3:2000MAY011195 1275 forward1 TM N in
59 LI:245193.3:2000MAY011579 1656 forward1 TM N in
59 LI:245193.3:2000MAY011789 1860 forward1 TM N in
59 LI:245193.3:2000MAY012029 2091 forward1 TM N in
59 LI:245193.3:2000MAY011562 1621 forward2 TM N in
59 LI:245193.3:2000MAY011880 1957 forward2 TM N in
59 LI:245193.3:2000MAY012156 2206 forward2 TM N in
59 LI:245193.3:2000MAY012513 2575 forward2 TM N in
59 LI:245193.3:2000MAY012591 2653 forward2 TM N in
59 LI:245193.3:2000MAY012669 2731 forward2 TM N in
59 LI:245193.3:2000MAY011548 1634 forward3 TM N in
59 LI:245193.3:2000MAY011659 1745 forward3 TM N in
59 LI:245193.3:2000MAY012154 2231 forward3 TM N in
59 LI:245193.3:2000MAY012364 2450 forward3 TM N in
59 LI:245193.3:2000MAY012571 2618 forward3 TM N in
59 LI:245193.3:2000MAY012649 2735 forward3 TM N in
60 LI:403872.1:2000MAY01562 624 forward1 TM
60 LI:403872.1:2000MAY01730 780 forward1 TM
60 LI:403872.1:2000MAY011498 1575 forward1 TM
60 LI:403872.1:2000MAY011648 1722 forward1 TM
60 LI:403872.1:2000MAY012359 2433 forward1 TM
60 LI:403872.1:2000MAY01371 454 forward2 TM N in
60 LI:403872.1:2000MAY01731 781 forward2 TM N in
60 LI:403872.1:2000MAY01956 1012 forward2 TM N in
60 LI:403872.1:2000MAY011106 1192 forward2 TM N in
60 LI:403872.1:2000MAY011541 1600 forward2 TM N in
60 LI:403872.1:2000MAY011661 1747 forward2 TM N in
60 LI:403872.1:2000MAY011994 2050 forward2 TM N in
60 LI:403872.1:2000MAY012261 2332 forward2 TM N in
60 LI:403872.1:2000MAY012357 2443 forward2 TM N in
60 LI:403872.1:2000MAY01543 629 forward3 TM N out
60 LI:403872.1:2000MAY01708 782 forward3 TM N out
60 LI:403872.1:2000MAY011530 1601 forward3 TM N out
60 LI:403872.1:2000MAY011656 1715 forward3 TM N out
60 LI:403872.1:2000MAY011983 2069 forward3 TM N out
60 LI:403872.1:2000MAY012145 2225 forward3 TM N out
60 LI:403872.1:2000MAY012226 2309 forward3 TM N out
60 LI:403872.1:2000MAY012349 2426 forward3 TM N out
61 LI:1086294.1:2000MAY01748 834 forward1 TM N out
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
Table
1
(cont.)
61 LI:1086294.1:2000MAY012278 2352 forward1 TM N out
61 LI:1086294.1:2000MAY012306 2356 forward2 TM N out
62 LI:337514.3:2000MAY011906 1992 forward1 TM N in
62 LT:337514.3:2000MAY011512 1598 forward3 TM N out
63 LI:230711.1:2000MAY01898 978 forward1 TM N out
63 LI:230711.1:2000MAY011327 1389 forward1 TM N out
63 LI:230711.1:2000MAY012059 2145 forward1 TM N out
63 LI:230711.1:2000MAY01134 220 forward2 TM N out
63 LI:230711.1:2000MAY011517 1591 forward2 TM N out
63 LI:230711.1:2000MAY011631 1708 forward2 TM N out
63 LI:230711.1:2000MAY012033 2119 forward2 TM N out
63 LI:230711.1:2000MAY01214 188 forward3 TM N in
63 LI:230711.1:2000MAY01570 620 forward3 TM N in
63 LI:230711.1:2000MAY01648 716 forward3 TM N in
63 LI:230711.1:2000MAY011101 1160 forward3 TM N in
64 LI:040338.2:2000MAY01794 880 forward2 TM N in
64 LI:040338.2:2000MAY01162 233 forward3 TM N out
64 LI:040338.2:2000MAY01708 791 forward3 TM N out
65 LI:399174.2:2000MAY01622 693 forward1 TM
65 LI:399174.2:2000MAY01958 1008 forward1 TM
65 LI:399174.2:2000MAY011027 1080 forward1 TM
65 LI:399174.2:2000MAY011303 1377 forward1 TM
65 LI:399174.2:2000MAY01965 1018 forward2 TM N in
65 LI:399174.2:2000MAY01126 200 forward3 TM N out
66 LI:197275.5:2000MAY01211 285 forward1 TM N out
66 LI:197275.5:2000MAY01761 811 forward2 TM N out
66 LI:197275.5:2000MAY01210 281 forward3 TM N out
66 LI:197275.5:2000MAY01537 623 forward3 TM N out
67 LI:336872.1:2000MAY01175 231 forward1 TM N out
67 LI:336872.1:2000MAY011099 1185 forward1 TM N out
67 LI:336872.1:2000MAY011450 1536 forward1 TM N out
67 LI:336872.1:2000MAY01182 247 forward2 TM N in
67 LI:336872.1:2000MAY011001 1072 forward2 TM N in
67 LI:336872.1:2000MAY011169 1246 forward2 TM N in
67 LI:336872.1:2000MAY011373 1447 forward2 TM N in
67 LI:336872.1:2000MAY01171 224 forward3 TM N out
67 LT:336872.1:2000MAY011089 1175 forward3 TM N out
67 LI:336872.1:2000MAY011302 1364 forward3 TM N out
68 LI:1092901.1:2000MAY01272 258 forward1 TM N out
68 LI:1092901.1:2000MAY01299 379 forward2 TM N out
68 LI:1092901.1:2000MAY01425 511 forward2 TM N out
69 LI:022387.5:2000MAY011195 1281 forward1 TM N out
69 LI:022387.5:2000MAY01710 796 forward2 TM N out
69 LI:022387.5:2000MAY011214 1276 forward2 TM N out
69 LI:022387.5:2000MAY01675 743 forward3 TM N out
69 LI:022387.5:2000MAY011092 1175 forward3 TM N out
69 LI:022387.5:2000MAY011215 1301 forward3 TM N out
70 LI:1188334.1:2000MAY01208 294 forward1 TM N out
70 LI:1188334.1:2000MAY01370 456 forward1 TM N out
70 LI:1188334.1:2000MAY0111 82 forward2 TM N out
70 LI:1188334.1:2000MAY01131 190 forward2 TM N out
70 LI:1188334.1:2000MAY0112 80 forward3 TM N in
70 LI:2188334.1;2000MAY01123 194 forward3 TM N in
71 LI:1188664.1:2000MAY01274 348 forward1 TM N in
71 LI:1188664.1:2000MAY01607 657 forward1 TM N in
71 LI:1188664.1:2000MAY01254 304 forward2 TM N in
71 LI:1188664.1:2000MAY01494 580 forward2 TM N in
72 LI:247388.1:2000MAY011126 1212 forward1 TM N out
72 LI:247388.1:2000MAY01134 220 forward2 TM N in
72 LI:247388.1:2000MAY01389 448 forward2 TM N in
71
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WO 01/62918 PCT/USO1/03465
Table
1
(cont.)
72 LI:247388.1:2000MAY01968 1033 forward2 TM N in
72 LI:247388.1:2000MAY01741 812 forward3 TM N in
72 LI:247388.1:2000MAY011200 1277 forward3 TM N in
73 LI:816339.4:2000MAY01466 534 forward1 TM N in
73 LI:816339.4:2000MAY01562 648 forward1 TM N in
73 LI:816339.4:2000MAY01937 1017 forward1 TM N in
73 LI:816339.4:2000MAY011162 1248 forward1 TM N in
73 LI:816339.4:2000MAY011306 1368 forward1 TM N in
73 LI:816339.4:2000MAY011390 1452 forward1 TM N in
73 LI;816339.4:2000MAY01407 487 forward2 TM N out
73 LI:816339.4:2000MAY01575 652 forward2 TM N out
73 LI:816339.4:2000MAY01698 784 forward2 TM N out
73 LI:816339.4:2000MAY01950 1012 forward2 TM N out
73 LI:816339.4:2000MAY011043 1105 forward2 TM N out
73 LI:816339.4:2000MAY011136 1198 forward2 TM N out
73 LI:816339.4:2000MAY011244 1306 forward2 TM N out
73 LI:816339.4:2000MAY011334 1396 forward2 TM N out
73 LI:816339.4:2000MAY011424 1486 forward2 TM N out
73 LI:816339.4:2000MAY01468 554 forward3 TM N out
73 LI:816339.4:2000MAY01591 644 forward3 TM N out
73 LI:816339.4:2000MAY01933 1010 forward3 TM N out
73 LI:826339.4:2000MAY011182 2244 forward3 TM N out
73 LI:816339.4:2000MAY011257 1319 forward3 TM N out
74 LI:1188967.1:2000MAY0114 67 forward2 TM N out
74 LI:1188967.1:2000MAY01272 325 forward2 TM N out
75 LI:236230.3:2000MAY021081 1149 forward1 TM N in
75 LI:236230.3:2000MAY011195 1281 forward1 TM N in
75 LI:236230.3:2000MAY011330 2416 forward1 TM N in
75 LI:236230.3:2000MAY01182 253 forward2 TM N out
75 LI:236230.3:2000MAY011016 1102 forward2 TM N out
75 LI:236230.3:2000MAY011154 1240 forward2 TM N out
75 LI:236230.3:2000MAY011346 1432 forward2 TM N out
75 LI:236230.3:2000MAY0163 149 forward3 TM N out
75 LI:236230.3:2000MAY01396 449 forward3 TM N out
75 LI:236230.3:2000MAY01567 644 forward3 TM N out
75 LI:236230.3:2000MAY011107 1181 forward3 TM N out
75 LI:236230.3:2000MAY011320 1382 forward3 TM N out
75 LT:236230.3:2000MAY011410 1472 forward3 TM N out
76 LI:246728.3:2000MAY011633 1695 forward1 TM N out
76 LI:246728.3:2000MAY011783 1854 forward1 TM N out
76 LI:246728.3:2000MAY012492 2566 forward2 TM N out
76 LI:246728.3:2000MAY01792 854 forward3 TM N in
76 LI:246728.3:2000MAY012325 2375 forward3 TM N in
77 LT:1190057.1:2000MAY01646 696 forward1 TM N in
77 LI:1190057.1:2000MAY011195 1263 forward1 TM N in
77 LI:1190057.1:2000MAY011591 1668 forward1 TM N in
77 LI:1190057.1:2000MAY012104 2169 forward1 TM N in
77 LI:1190057.1:2000MAY012233 2295 forward1 TM N in
77 L2:1190057.1:2000MAY012320 2382 forward1 TM N in
77 LI:1190057.1:2000MAY012623 2703 forward1 TM N in
77 LI:1190057.1:2000MAY013124 3207 forward1 TM N in
77 LI:1190057.1:2000MAY011217 1270 forward2 TM N out
77 LI:1190057.1:2000MAY011595 1681 forward2 TM N out
77 LI:1190057.1:2000MAY012267 2353 forward2 TM N out
77 LI:1190057.1:2000MAY012420 2491 forward2 TM N out
77 LI:1190057.1:2000MAY012624 2698 forward2 TM N out
77 LI:1190057.1:2000MAY012720 2785 forward2 TM N out
77 LI:1190057.1:2000MAY013014 3067 forward2 TM N out
77 LT:1190057.1:2000MAY013116 3202 forward2 TM N out
77 LI:1190057.1:2000MZ~Y011905 1991 forward3 TM N in
72
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
Table
1
(cont.)
77 LI:1190057.1:2000MAY012217 2297 forward3 TM N in
77 L2:1190057.1:2000MAY012601 2657 forward3 TM N in
77 LI:1190057.1:2000MAY013072 3143 forward3 TM N in
78 L2:221836.3:2000MAY01775 846 forward1 TM N out
78 LI:221836.3:2000MAY012050 2106 forward1 TM N out
78 LI:221836.3:2000MAY012197 2265 forward1 TM N out
78 LI:221836.3:2000MAY012539 2613 forward1 TM N out
78 LI:221836.3:2000MAY012216 2302 forward2 TM
78 LI:221836.3:2000MAY012582 2668 forward2 TM
78 LI:221836.3:2000MAY011899 1976 forward3 TM N out
78 LI:221836.3:2000MAY012034 2120 forward3 TM N out
78 LI:221836.3:2000MAY012199 2261 forward3 TM N out
78 LI:221836.3:2000MAY012283 2345 forward3 TM N out
78 LI:221836.3:2000MAY012490 2564 forward3 TM N out
79 LI:334047.3:2000MAY01115 201 forward1 TM N out
79 LI:334047.3:2000MAY0156 142 forward2 TM N in
79 LI:334047.3:2000MAY01497 577 forward2 TM N in
73
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
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74
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
M L~ L~
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CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
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76
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
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77
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CA 02418496 2003-02-04
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79
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WO 01/62918 PCT/USO1/03465
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CA 02418496 2003-02-04
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M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
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M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M
86
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
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CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
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CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
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N
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v-I CO N 00 dl N O O 00 00 00 00 00 00 00 M ~ ~ L~ a0 O M L~ N O 00 N l~ O ~
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LC1 LCl M r-I L~
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10 ~l7 M C~ Ill
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M M M N M M M M M M M M M M M M M M M M M M M M N l0 01 ~O l0 dl
O O O O O O O O O O O O O O O O O O O O O O O O L~ d~ l0 l~ L~ L~ ~ O~ 01
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I~ O O O O O O
r1 r-I r1 c-i r1 c-I c-1 r1 r1 r1 w-I v-I r1 r1 v-I r1 v-I r1 u-I c-1 r-I w-I
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i r1 c-I r1 r-I r1 c--I
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l0 c---1 l0 01 l0 f11 l0 O M 01 N M l~ l0 N N 00 t17 l0 00 r1 l0 v-I l0 N P.i'
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LC7 L(1 L(1 U1 LC7 ~O l0 l0 l0 l0 l0 l0 ~O L~ L~ l~ L~ l~ L~
M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M
92
CA 02418496 2003-02-04
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01 01 ~ O c-I L~ ~ lf7 c-I lD O M N N M O t11 Ln l0 N O L~ L~ N 'di l~ O d~ M
M d~ N di ~0 N c-1 ~O di
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O O N c-I N Ll'1 O L~ OJ 1W
00 l0 dl OD 00 O 00 L~ r1 v--I OO N 01 01 01 O1 ~ 01 v-1 O Q1 M M M 01 d~ N d~
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M N M M 117 L~ L~ t ~ ~
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~ d~ dl d~ dl d~ dl dW N G~ dl di dl di d~ d~ d~ dl d~ d~ dl d1 ~tl d~ dl di
dl d~ di dl dl d~ dl dl d~ ~ dl V~
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c~ y-1 y-I c-1 ,'7 r5 ,~ t~ ~-I ,~ ,~ r1 ~ ~J ~ ~I ~ ~ ~ ~ ~ ~ v~' ~
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01 N N l0 CO M 01 OJ 10 l0 l0 01 CO O O O1 O Lf7 lD l0 O l0 l0 l0 l~ l0 CO l0
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N M dl M d~ O d1 dl
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l0 l~ 01 Lfl 00 O O a1 L
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M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M
93
CA 02418496 2003-02-04
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M 01 O OD M ~ N L(1 M l0 N M ~O 00 01 L~ L~ dl l0 O v-1 u-I O 00 ~1 l0 ~ t1'1
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l0 t17 L(1 LY1 l>7 l0 N l0 lD 01 l~ 01
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l0 l0 CO N 01 r1 r-I 01 ~0 M
N N N dl dl L L~ 00 01 O r1 dl its L t m ~ ~ it1 l0 C L L L c0 00 O1 r-I N N
dl C L~ r1 ~-i i--W-I N
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M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M
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M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M
97
CA 02418496 2003-02-04
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98
CA 02418496 2003-02-04
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l0 CO d~ l0
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00 l0 01 c-I O N dl dl r1 O dl
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l0 M ~--I M 01 6l d~ dl L~ d~
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00 01 l0 O 61 00 l~ c-I M d1 M
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dl G~ dr dl dl dl ~H dl di dl C~ dl
99
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N o0 M Lf7 In lD N l0 M l0 00 ~ L~ lO N c0 O C~ 01 N o0 Ln Lf1 00 41 c-i r--1
t11 N LCW -1 r-1 N o0 L~ M d~ ~H
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l0 01 N L~ 01 l0 10 l0 L(1 Ln
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dl d~ dl d~ dl d~ dl dl dl dl dl d~ dl di ~N d~ dl d~ d~ dl d~ ~H d~ d~ di di
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100
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01 dl LC1 O 'dl 01 LC7 01 O r-I N dl c-i r1 O tt7 tf1 M Ol LC1 L~ O u-I O c-I
N d~
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101
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N L~ lW -I d~ M N O L~ LC7 00 d~ dW -I 10 Lf1 00 L~ 01 O 00 01 O O L('1 O 01
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LC7 l0 M M O O dl ~N dl M N O dl 01 M
O O O O O N Q1 O Lf7 IJ) 11) II) O O O dl O O dl O O O O O N CO 00 h h 00 117
Ln M h 00 M O l0
h h h h h N N h N N N N h h h N h h II7 h h h h h h N N VI dl M dl dl h Ll7 N
N M dl
CO ~ ~ CO 00 ~ ~ 00 ~ ~ 00 00 ~ 00 00 00 00 00 CO ~ OD 00 00 00 Ol 6l 01 Ol Ol
01 Ol Ol 01 61 01 Ol 01 01
dl dl dl dl dl dl GI dl dl dl dl dl dl dl dl dt dl dl dl dl dl dl ~ dl dl dl
dl dl dl d~ dl dl dl dl dl dl dl dl
01 l0 N M LCl d~ 00 ~ 00 01 h N N dl Lf7 M M h rl c-I o0 01 N ~ L17
dl ~ 01 O1 O h CO 00 r1 t17 r1 O l0 lfl 01 N N N O M O1 l0 rl dl II) h l0 O r1
l(1 01 e0 h dl 00 ~ h dl
M dl M v-I M N c-1 c-I c-I N M M O N N u--I M LC7 l0 l0 N N M N M Lfl 01 Lll
CO O M dl Ol CW -I 01 Ol O
v-I c-1 r1 u-1 c-1 r1 v-I w-I c-1 r-I v-I u-1 r1 v-I r1 c-I r1 r1 u-I c-I c-I
c-I w-I N c--I L(1 LC7 l0 OW -I 10 N h h c-I 00 CO 61
lIl l0 l0 dl 01 LC1 l0 01 dl c-I O Lf1 01 h dl 01 h O 01 M dl M N M ~ h 10 O
lO ~ O O L(l
dl N M dl dl L(1 Lf7 Lf1 00 h N M M Ill O N dl l0 l0 00 00 01 O O lD h CO rl
dW -I N M dl dl h
h ~ 00 CO CO 00 L(7 L(1 L(7 LI7 l0 1D l0 l0 h h 01 01 07 O1 61 01 c-i c-I r1
L(1 N M M M dl N N dl dl d1 dl dl
cW -I w1 v-1 v-I r1 c-i r1 r1 ~ c-I w-i r1 u-I v-W -I c-1 c-~ r1 r1 u-I r1 w-I
r1 v-I w-I s-I
N ~ N c-I N L~fl 0~1 h c~-1 ~ N 1.(l W-~1 O~0 x ~ N t~ x N x x W x x x x ~ ~ ~
x Ill 01 M O c~-I c~~'1
O h ~N dl 00 lO l0 ~-I 01 N M 111 M Lf7 dl O dl l0 dl L(1-1 LC7 N 01 01 N M c-
I h 01 dl N l0 N N N ~
L(1 Ill c-1 c-I dl dl N dl Ol dl ~O M dl ~ h ~ M h 00 M h O tI1 M M N ~ L(1 l0
dl Il7 Il1 Lfl M N Ol L~ Ol
r1 O1 O O O 01 01 01 O a1 CO N dW -I O h M O c-I 00 N M N M M v-I DO M Ol N M
Ol Ol M O O O h
h l0 h h h l0 10 l0 h ~O l0 h l0 h h M 10 h h 10 10 h 10 O O dl r-I h l0 Lf1
~O O ~O O h h h
II) LI) t11 Lfl L(l Lf7 L(1 117 LI1 Lf1 Lf7 Lt1 In Ill L(1 O Ill t11 111 l0 Lh
If1 r1 L('1 Ill t>7 N M LC1 LC7 L(1 l0 LC7 h Ln In Ill LC7
O O O O O O O O O O O O O O O O O O O 00 O ~-i tf7 dl dl ~ O N O O O d~ O dl O
O O O
h h h h h h h h h h h L~ h h h h h h h l0 h l0 Ll7 N N lfl h N h h h M h t31 h
h h h
dl dl dl dl dl dl dl dl dl dl dl VI d~ dl dl dl dl dl dW H dl dl dl dW N dl dl
<H dW N dl dl ~N dl dl dl dl dl
104
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d~ L~ dl 01 01 LC7 O N M 61 l(7 O Lf1 00 N In M In N O L(1 O r1 00 dl M L~ L(7
LC1 N O lIl
O M M r1 'dl O l0 N 00 M h Ill Lf7 dl ~ N ~ N dl dl O dW I M CO L~ N O N v-I
01 N u'7 00 ~ C~ M N
l0 L~ 00 L~ LP'1 l0 L~ CO CO O O1 N N M N M N L!1 C~ l0 L~ ~D r1 I~ dl L~ l0 N
CO M c-1 N dl lD l0 ~ l0 N
N N N N N N N N N M N M M M M M M M M M M M dl tl7 l0 a1 O O l0 v-1 c-1 v-I ~-
1 w1 u-I c-I rl N
L dl l0 L L~ N dl Ct' O O 00 l0 M CO 01 Lt1 M O1 O l0 dl Lt1 a0 01 lfl O M ~
CO dl
M L~ LC1 LI1 CO u-I O OJ dl M 00 dl OO ~ dl L~ l0 L~ 00 CO r1 L~ r1 M l0 l0 M
M r-f M N L~ 01 v-I dl dl O
O O r1 ri c-~ N N N M dl lf1 l0 1fl l0 l~ L~ 01 r-I r1 v-I N M ~ 111 L('1 II)
O O L~ L~ O O N M M M L~
N N N N N N N N N N N N N N N N N M M M M M M r-I M dl Lf1 l0 l0 L~ t~ c-I ~-I
ml ~-I c-I w-I ~-I
r1 w-1 r-( v-I v-I w( r-I w-I ~-I w-! r-I w-I w-I
o~o~oc~~tx~NO~oxc~~t~~~m~G~~ox~x WxxulxxxxWxxxxx f-~1- xh
M dl L(1 N c-1 L~ Ol O N r1 lfl 01 O l0 N O N Lf1 00 M L~ M dl L~ M <-I 01 O O
M L~ M c-I c-I M Lf1 II7 M
c-I CO L~ dl c-I h v-I ~O N L~ M LCl OO 61 N O N M ~O dl dl dl lO N N N C~ d1
O1 lf7 CO l0 01 M O M M lIl
c-I c-I M N O N M 01 N Ol M dl c-I O M M M N N ~ M ~ dl dl N l0 N O O r-i l0 N
~H 01 lD ~ CO v-I
O O O O dl O O 01 c-I 01 O O O O N O N ~ h O1 dl d1 L~ a0 c-I l0 dl CO ~ l0 LW
-I N L l~ L~ l~ ~D
00 a0 c0 CO Lf1 00 00 L~ c-I L~ 00 00 ~ CO l0 c0 l0 ~ l0 rl 00 i-1 N N O1 61 ~
117 II1 t17 l0 O L~ r1 r1 L L~ LI1
O O O O CO O O O M O O O O O dl O dl N O r-I 01 c-I v-1 N O 61 L~ M 00 L~ 01
r1 01 M M ~ CO l~
L~ L~ L~ L~ l0 l~ h l~ l0 L~ L~ l~ L~ L~ M L~ M ~7 L~ to 10 L(1 X37 L~ L~ Lf7
M N N l0 111 h L11 ~7 X31 lI1 L(1 l0
O O O O O O O O O O O O O O O O O O O O O O O r-I u-1 r-I u-I r1 w-I rI c-I v-
I c-I r1 r1 v--i r1 c-1
II7 LC7 Ll7 N L.(7 L(1 L(7 1-c1 Lf1 t17 LC1 L11 tI7 LP7 If7 Lf7 L11 L(7 Il'7
II) 1.f7 L17 tI7 LCt if7 IIS if1 t17 II7 Ifl t17 tf7 tn Lc'7 tI7 tfS t!'1 t17
dl 01 Ll1 M O M O N L~ L~ M LC7 00 N v-I L~ l~ r1 L(1 00 If7 Ol N t!1 l0 dl N
Ol 00
N ~ O M N O M l~ L~ 01 01 Ll1 O r-I u-I N L~ O1 lO ~D v-I r1 rl M N d~ lD M L~
LO \O h dW -I L(1 M M M
M N 'dl L~ f~ a1 L~ N In dl 01 r1 M M If7 Lf7 d~ M L71 dl !~ l0 l0 II) CO Ol
01 O 01 M M M In II) M M l0 l0
N N c-I M 111 dl M l~ L~ C~ l0 v-I r-I r1 v-i ri c-i r1 w-I r1 c-I r-I c-I u-1
r-I v-I r1 N r1 N N N N N N N N N
OO O ~ M N L~ r1 l0 Ll1 L~ l0 In L~ Lf1 dl O M LP1 l0 l0 M
dl 01 M In L~ f11 01 07 dl O !n CD 07 N h ~ M M dl OJ O O c-I w-I dl ~ l0 L~
Ll1 l0 O~ 01 M O
p r1 ~-1 M r1 O1 O lD O Lf1 Lf1 N M M l17 L~ O O u-I c-I w1 r1 r1 dl dl L(1 lO
\O L L~ CO ~ CO a0 61 O
N N c-I w-I h Lc1 v-1 c-I N M dl LC7 l0 L~ CO 00 rb CO w-1 c-I v-I u-I u-I r1
v--I v-1 c-I u-1 v-I c-1 r1 c-1 r1 r1 r1 r1 u-I N
N
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r ~
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L~ N N N N v-I N N ~0 r1 d~ M ~ 01 O N r1 L(7 M r1 00 Ol L~ dW -1 M ~0 r1 L~ N
W -1 l~ N ~ Ol OO M
r-1 l0 dl d~ S1I ~ dl O L~ 01 O In M O M dl N 01 GI M dl O dl M r1 M 01 dl N
111 dl O N r1 N dl 01 M
N dl CO 00 r1 dl 00 M 01 01 O 01 O O O O O L~ O O O O O l0 O O 01 O l0 O O O O
O O O 01 O
r1 c-I M M ~ r1 M 10 111 v-I O ~ CO 00 00 CO CO O ~ 00 00 00 CO lf7 00 00 L~
CO rI CO O 00 CO ~ CO 00 L~
M Lf1 l0 l0 01 'dl lD L~ M lD 01 01 O O O O O M O O O O O O O O O O M O O O O
O O O O O
r-I ~--I N N l0 b1 N l0 L~ L71 tf1 l0 L~ L~ C~ t~ L l0 L~ L~ L L~ L~ C~ L~ L
t~ L b1 l~ L L~ l~ L~ l~ L~ L~ C
01 01 O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O
dl ~N U7 Lf7 l!> 111 LC7 Ln tf1 L(1 Ln Ln L(1 L!7 U1 U1 U1 Il1 L(1 111 LC1 111
L(1 Ln U7 LI> 111 Ln U1 L(7 L<7 Il1 L(7 lf1 L(7 U1 U7 Il1
M ~-I r1 L~ L~ N r-I 01 r1 Q1 L~ l0 L~ Lf7 01 01 dl 01 M Ol N O l0 ~-1 O N Q1
~-1 N O 01 61 01 M Ol 01 N N
dl L~ M l0 10 L~ M l0 L~ l0 N l0 lQ M l0 l0 L~ l0 L~ 10 L~ l0 L~ l~ l0 M l0 L~
L~ N l0 N l0 L~ l0 l0 LC7 L~
N N 01 N N N N N N N r1 N N N N N N N N N N N N N N N N N N N N N N N N N M N
N N ~-I N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N
01 Lf7 lD L~ dl dl t11 N iI1 01 M M M L~ 00 d1 O 00 O M ~ 00 01 61 01 O O r1
dl c-I O M L~ O 00 L~ 01 N
Lf1 L~ L~ O 61 01 01 O c-1 N M M dl LI1 00 t~ c-I r1 N N N N N N N M ~ dl dl
10 h O O r-I M L~ 00 N
L~ l~ L~ L~ L~ L L~ ~ CO 00 O CO ~ 00 00 ~ 01 01 01 01 01 01 O1 01 01 01 01 01
01 01 01 O1 O O O O O u-I
r1 v-i c-I r1 ~-I v-I v-I v-I r1 c-I u-I w-I c-1 r1 r1 r1 r1 u-I c-I w-I r1 w-
I w-I r1 u-i r1 c-I r1 v-I c-I w-I u-I N N N N N N
H t~ x ~-1 dl u1 H N M dl x fx dl x f~, ~--W o ~ N ao 00 00 0o M ~ H dl In ,-I
~ M H N omo M r-1 n
l~ N l0 117 to c-I Lf1 M 00 L(1 LI1 L(1 dl 00 l~ II7 M r1 N O l~ L~ O OD O dl
O1 c-I L~ x dl LC7 tIl v-I dl O x N
M d1 O M 01 dl O dl O1 r1 01 01 O u1 N 1-C7 L~ O O l0 N d~ l0 L~ L(1 O N dl N
L(1 II7 Ol dl M lD d~ N L~
M dl d~ M N O II7 L~ O v-I ~O l0 N r1 l0 LC7 00 O v-I O O 01 M Ol N 01 lD Lfl
O l11 l0 l0 61 M N l0 r1 lfl
r1 ~ ~ 00 t-I Ol dl dl M lO v-I ~-I M M dl r-1 O Lf1 N M M a0 L~ O O1 u-i t11
61 M M Ol r1 c-I lO N N O lf1
M ~ l0 v-I Ctt Lfl L~ l0 M N 00 a0 01 dl ri Ctl c-I Lf1 01 M lO c-I O c-I M L~
~O O l0 l0 CO 00 N dl L~ M N L~
~ dl M dl M L(7 01 M M dl L~ L~ M N to M M rl M dl II7 N dl dl dl 01 c-I M tIl
C'ft M L~ N l0 c-I 117 lIl M
dl b1 N b7 YSl b7 r-1 b1 b7 ~7 r1 v-I ~7 dW -I b7 b1 b1 b7 b7 l71 X51 X31 b7
X51 r1 b7 X31 b7 117 b7 v-I b1 ~7 b177 ~ b7
O1 Ol Ol 01 Ol 01 01 01 01 61 O1 Ol O1 Ol Ol 01 O1 01 O1 61 41 Ol Ol O1 al Ol
O1 Ol 01 O1 01 Ol Ol O1 O1 01 O1 Ol
dl VI dl dl G~ dl dl dl dl dl dl dl ~H dl dl ~ dl dl dl dl dl dl dl dl dl dW N
dl dl dl dl dl dl dl dl dl dl dl
CA 02418496 2003-02-04
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L~ M CO dl 01 LC7 o LO
II7 l0 L~ dl O tf7 M Q1 LW -I c-( c-I w-I O M ~ N (~ LW -I O L~ M LW H L~ C~
01 lD c-i l0 01 OJ M LCt L~ M Ln
l0 01 O l0 L~ O 10 O r1 N O O O N ~O c-I l0 ~ dl L~ O ~ M Lf1 00 LCl L~ Lf7 01
O dl 00 00 L~ N M d~ Cn
c-I c-1 N v-I l0 Lfl 1W --I L(l c-i M M M LC7 ~O L~ l0 L~ L~ l~ 00 10 M l0 l0
L~ l0 L~ Ol c-I lD CO 00 00 r1 01 d~ Ill
N LC1 L~ ~ N LCW -I dl Lf~ Vl L(1 O N l0 L~ r1 c-1 CO L~ ~N O O dl ~ Lc1 l0
l.Cl --I Lf1 M c-I N L('1 O
dl dl dl dl dl L~ O 01 N O M M l0 L~ ~ ~ O M M M L~ CO 01 01 O r-I c-I v-I N
dl Il7 tf7 lO ~ ~O OD
r1 v-I c-I u-1 L~ CO r1 10 w1 L~ c-1 u--I r1 v-I r1 c--I N N N N N M M M dl dl
Ll1 Ll7 Lfl Il) LC7 tIl Il1 111 l0 l0 r1 c-I
u-I ,5 c-I 'J c-I y-1 ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ vh ~ ~ ~ ~ r1
,'7=', r1 ,"L', Lf7 rx' N ~i O N M L~ Lf1 CO LW -I 01 00 ',7.,' M C~ dl c-I ~I
'~i CO c-1 II1 l0 ~ l0 00 O lD O u-I ~,Ci M 01
dl dl 00 N u-1 N 01 dl L11 00 O 01 L(1 L~ 01 N 10 CO c-I O ~O 1.(1 c--I w-i 01
N a0 L~ N c-i 01 N r1 01 l0 M N M
OD M L~ dl I~ 00 M CO CO 00 00 O l0 L~ N 00 00 L~ 01 00 01 h N N N l~ 01 ~O 01
dl O L(1 M N 01 l~ L~ 01
L~ Lf1 01 L~ CO N 01 ~ N ~N L~ ~ L~ N N N N OO N N dl O M M O N ~ L~ 01 111 01
00 CO ~ N l0 N N
N In 01 !11 L~ In 1D dl In II) In N dl 1I7 1.11 In u1 1J) IJ1 Lll 111 In !~ f~
111 LO dl dl dl LIl dl dl CH II) LO ! 11) i1)
N N O1 N O N 01 N N N N N N N N N N l~ N N N N O1 01 N N N N N N N N N N N O1
N N
M O L~ O O O dl O O O O O O O O O O L(1 O O O O O O O O O O O O O O O O O O O
O
r1 L~ l17 L~ <' L~ l0 L~ L~ t~ L~ L~ L~ I~ L~ L~ L~ l0 L~ I~ C~ C' Ln U1 L~ L~
L~ L~ L~ L~ L~ l~ <' L~ L~ LCl L~ l~
N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N
Lf7 In Ln Ll7 111 111 lf7 L11 111 LC1 lfl U1 Ln 11'1 Ln 111 Ln lf1 LC1 Ul V7
U'7 lf1 111 II1 Ln 1.17 L(1 LY7 Lf7 lP 111 N l11 l1'1 Lf1 lfl 11'7
M dl N lC1 t1W -i L~ CN M Ill dl to C~ Lll r1 v-I O CO Q1 O Ln O1 O ~ t~ O I~
N c-I l0 u-,' O~ l0 M O OJ 01 l0
r1 N O ri v-I O O1 l0 l0 r1 01 01 L!'1 01 O dl M O N M ~ 01 a0 Ol dl OW -I M
Ol O1 CO O1 c-I N dl Ol L~ dl
M N N N N M N N v-i N N N t~ N M l0 l0 lO C~ ~O M lO Lf1 111 l0 lO dl L~ lO dl
dl M I t11 L~ lIl ~ Ill
M N N N N N M M M N M M N M M N N N N N N N N c-I r1 c-I u-I r1 r1 c-I v-I v-1
r-I r1 r1 u-I c--I v-I
M M Ill O lp M CO lO r1 Lf7 O N N N CO N N N N N N M c-I L~ 01 r1 O d~ L~ L~ O
N 01 M c--1 L~ 00 dl
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O1 r1 dl L~ O L~ L~ O O M dl Lfl Lfl l~ 01
p ~ 01 01 O O r1 00 !p 01 r1 01 01 rl 01 O c-I r1 r1 v--I r1 c-I r1 M O c-I v-
I v-1 N N N M M M M M M M M
U N v-I ~-i N N N N N N N N N N N M N N N N N N N N r1 ~-I w1 v-I r1 r1 c-I w1
r-I v--I v-i r1 r1 ~-I r1
N
c-1 r1 c-I rl -i r1 r1 -I w-1 v-I ri c-1 v-I r1 r1 r1 v-I w-I r-1 -I c-I w-I c-
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Lf1 i.n Lf7 M O N rl l0 rI Ol
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L!'1 ~O l0 M L~ OO 00 N u-I lO l11
dW -I C~ dl 01 lD v-I LCl O O N w1 v-I M Ill O L~ M l0 N O M N to dl dl a0 dl
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01 N LC1 Lf1 Cn 01 L~ dl tf1 Lf7 O1 O1 01 01 M c-1 01 01 01 (31 ~-I 61 dl Lll
111 111 h Lf1 00 ~0 01 01 LC1 IIl Lf7 l0 111 dl
l0 M N c--I N ~ M ~O L~ N l0 l0 10 lD Ill -I l0 \O l0 lD c-I lO Ill N N N Ln N
dl VI ~O Ol N N N lIl N N
O N O M O O L M r1 O O O O O dl L O O O O L O ~ O O O O O M M r-I L O O O 00.
O O
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N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N
LI1 Ln Ln Lfl l!1 Il1 Lll 111 LP7 L(1 Ln Lf1 LC1 l11 to u1 U7 u1 u1 lfl LCl Ul
111 Ln 111 Lll l11 LCl Ln L(7 Lfl tf7 L(1 to U1 tll LO U1
l0 CO r-I M M v-I 01 W H M M l0 LCl O l0 lf7 d1 L~ N 01 l0 r1 c-I N N lIl dl
LIl t11 Lf7 II)
OO L~ O Lf1 In 10 Lf7 dl O r1 dl M l0 LC7 N l0 OJ M O l0 M dl O L~ O v-I w-I
Lll O II) O L~ c-I ~H v-I 01 01 dl
N O c-i M M lIl Lf7 L~ CO lIl O L11 c-1 01 l0 l0 ~ L~ 01 01 c-I L~ r1 Ol N O1
c--1 N O N N N N N O N N N
N N N N N M N N c-I M Lf1 M ml N N N N N N N M N M N M N M M M M M M N M M M M
M
M M M N l0 d1 ~ 01 N L~ N N Ill dl CO O~ N l0 O c--I r1 Q1 dl 01 L~ l~ 01 l0
r1 L~
N N N r1 N O c-I N dl Ill CO 01 O L~ CO O u-I Lfl LCl 00 O O r1 M l~ M OO Ol O
v-I M
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L~ L~ L~ Ol L~ L~ CO DO QO
v-I c-I r-I c-I c-I c-I c-I W -I c-I u-I dl L~ N N N N N N N N N N N N N N N N
N N N w-I N N N N N
c-1 wi w-I c--1 r1 w-I v-I c-r W -I v-I c-I c-I c-I c-I r1 u-I c--I w1 w-I c-i
v-i c-1
f1-I x x H H W x x rI M u1 x N oo x r-I o1 ~ M o0 0o M x o u1 ~ u1 f=, x .-I N
dl own O ~o N ~-I
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00 01 01 N 01 ~ N Ill l0 Ill
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01 CO 111 dl Ol dl l0 L~ l~
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r1 dl M Lf1 Lf7 l0 LC7 dl l0 N
l0 l0 l0 L~ l0 dl dW -I dl dl t11 M LIl 61 dl 01 01 01 01 01 01 O v-I 01 01 01
01 L~ l~ 01 M 01 L17 01 Ol 01 01 01
O O O L~ O M 00 M N N N c-I N l0 M l0 l0 l0 l0 lf) l0 L~ L~ W l0 l0 CO M M l0
O1 l0 N l0 l0 l0 l0 l0
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O O O O
c--I c-I r1 L(1 c-I u--I c-1 dl L~ L~ l~ M l~ L~ M l~ L~ L~ L~ L~ l~ L~ l0 L~
L~ L~ ~1 M M L~ ~l l~ L~ l~ L~ C~ l~ C~
c-I ~-I ~-I r-1 ~-I N N N N N N N N N N N N N N N N N N N N N N N N N N N N N
N N N N
111 LC1 !!1 t17 U7 L(1 LI'1 tt> LI> u1 LI7 L(1 I11 In Lf1 lIl L~ LI'1 U1 LIl
LCl lIl l11 l1'1 Lll l11 11'7 Lf1 II1 L(1 Lf1 lf1 Lh lf1 LC7 LIl 1.(1 Lfl
106
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O ao ~ M o1 c-I d~ dl In dW-I d~
M M c-I h O [~ N r1 LC7 N 61 N r1 Lf1 O r-I [~ O 00 N M Lf1 M L(1 Lf1 c-1 M M
CO 01 CO O M l0 lO <N lIl 01
L~ di N 00 ~ LW -I N 10 M M '<H ~ N L~ Lf1 00 l0 CO 10 00 d~ d~ l.(1 Lf1 M 00
r1 l0 O l~ d~ N l~ LC1 CO O ~
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di d~ M M d~ N 111 tIl t11 d~ N M r-I Ill
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L~ l~ Lf7 l0 N dl M M c-I O II1 tI1 O 00 N dl N 00 i11 111 d~ O1 d~ L~ c-1 00
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111 01 00 Ill M dl L~ ~ L~ L~ c-i CO L~ r1 01 L~ 01 O 01 v-I ll1 N N M r1 O r1
L~ 00 N LW -I CO ~ M dl CO 01
L~ l0 M M O 01 O 01 c-I r1 c-1 LW -I 01 00 w-I 00 N O N 00 Ol Ol u-I N O N M
01 O O O O l0 01 01 d~ L~
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a
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N N N N N N ~-I r1 N O N N CO N 01 N O1 dl N N N N N di N O N OD N 01 l0 N c-I
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01 01 N
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l0 Lf1 O o0 r-I L11 c-I O h L~ ~ 01 ~ L~ L~ 01 L~ d~ O1 l~ O dl N O1 v-I dl O1
N r1 L r1 O N N l0 C~ N d~
M d~ O M 'dl 01 ~H L(1 Lf1 O r1 N L(1 r1 c-I O M <-I w-I O M L(1 M M LC7 LCl
dl O N N N dl O N M O O 01
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N N N N N N N dl dl N N N N N N M N O1 O1 N Ll7 N r1 N N N N ~-I N N N N N N
dl t11 N N
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107
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
c-I M L~ O CO M N d~ L~ C~ M 00 M Lf1 61 l0 l0 IPW -I 01 In 01 00 M 10 L~ l0 h
01 OO lW -1 01 v-I N d~ 01 L~
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CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
t-I c-I ~ N dl M L~ Ol Lf7 c-I L(W -1 M ~ O L~ G~ r1 M O O rl
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109
CA 02418496 2003-02-04
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110
CA 02418496 2003-02-04
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112
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113
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118
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119
CA 02418496 2003-02-04
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12a
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
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SEQ
Table 3
ID NO: Tissue Distribution
1 Unclassified/Mixed - 71%, Endocrine System - 16%
2 Embryonic Structures - 82%, Nervous System - 18%
3 Germ Cells - 62%, Connective Tissue - 17%, Unclassified/Mixed -
16
4 Endocrine System - 71%, Nervous System - 29%
Nervous System - 76%, Endocrine System - 18%
6 Endocrine System - 63%, Liver - 23%
7 Endocrine System - 29%, Hemic and Immune System - 24%, Exocrine
Glands - 19%
8 Endocrine System - 42%, Germ Cells - 19%
9 Endocrine System - 66%, Sense Organs - 21%, Nervous System - 11%
Germ Cells - 30%, Sense Organs - 24%, Nervous System - 17%
11 Nervous System - 100%
12 Embryonic Structures - 18%, Pancreas - 17%, Hemic and Immune
System - 17% '
13 Exocrine Glands - 42%, Cardiovascular System - 21%, Respiratory
System - 16%
14 Nervous System - 86%
Unclassified/Mixed - 17%, Sense Organs - 12%
16 Unclassified/Mixed - 28%, Embryonic Structures - 20%, Liver - 16%
17 Endocrine System - 100%
18 Digestive System - 57%, Hemic and Immune System - 29%, Nervous
System - 14%
19 Unclassified/Mixed - 90%
Exocrine Glands - 50%, Respiratory System - 38%, Nervous System -
13
21 Unclassified/Mixed - 20%, Connective Tissue - 10%
22 Sense Organs - 17%
23 Female Genitalia - 32%, Hemic and Immune System - 24%, Endocrine
System - 20%
24 Sense Organs - 15%, Embryonic Structures - 13%
Sense Organs - 43%, Unclassified/Mixed - 11%
26 Unclassified/Mixed - 16%, Embryonic Structures - 13%, Germ Cells -
13%
27 Respiratory'System - 43%, Nervous System - 21%, Female Genitalia -
21
28 Liver - 33%, Germ Cells - 12%
29 Endocrine System - 31%, Germ Cells - 25%, Liver - 12%
Exocrine Glands - 29%, Germ Cells - 28%
31 Exocrine Glands - 18%, Cardiovascular System - 10%
32 Sense Organs - 23%, Embryonic Structures - 15%, Endocrine System -
33 Sense Organs - 17%, Endocrine System - 11%, Skin - 10%
34 Musculoskeletal System - 86%
35 Connective Tissue - 16%, Embryonic Structures - 14%, Digestive
System - 11%
36 Pancreas - 40%, Female Genitalia - 20%, Cardiovascular System -
16
37 Respiratory System - 12%, Urinary Tract - 12%
38 Embryonic Structures - 53%, Digestive System - 17%, Nervous System
- 12%
39 Digestive System - 40%, Nervous System - 32%, Nervous System - 28%
40 Exocrine Glands - 47%, Sense Organs - 21%
41 Connective Tissue - 60%, Unclassified/Mixed - 22%
42 Hemic and Immune System - 15%
43 Sense Organs - 21%, Female Genitalia - 13%
44 Hemic and Immune System - 18%, Female Genitalia - 17%
45 Embryonic Structures - 32%, Female Genitalia - 17%
46 Male Genitalia - 49%, Skin - 32%
47 Nervous System - 42%, Nervous System - 40%, Endocrine System - 14%
48 Digestive System - 41%, Nervous System - 15%, Liver - 14%
49 Exocrine Glands - 34%, Unclassified/Mixed - 22%
50 Nervous System - 57%, Unclassified/Mixed - 11%
51 Nervous System - 52%, Digestive System - 25%, Connective Tissue -
52 Digestive System - 24%, Germ Cells - 22%, Exocrine Glands - 11%
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Table 3 (cont.)
53 Endocrine System - 32%, Digestive System - 19%
54 Embryonic Structures - 58%, Nervous System - 37%
55 Female Genitalia - 18%, Nervous System - 18%, Embryonic Structures
- 18%
56 Connective Tissue - 29%, Germ Cells - 22%, Liver - 13%
57 Musculoskeletal System - 15%, Embryonic Structures - 11%
58 Stomatognathic System - 27%, Urinary Tract - 11%
59 Sense Organs - 25%, Endocrine System - 16%
60 Exocrine Glands - 33%, Urinary Tract - 27%, Nervous System - 14%
61 Endocrine System - 16%, Musculoskeletal System - 13%
62 Exocrine Glands - 27%, Skin - 15%, Female Genitalia - 15%
63 Female Genitalia - 36%, Urinary Tract - 22%, Digestive System -
22
64 Germ Cells - 16%, Endocrine System - 11%, Liver - 11%
65 Pancreas - 24%, Unclassif~ed/Mixed - 21%, Male Genitalia - 17%
66 Endocrine System - 43%, Embryonic Structures - 14%,
Unclassified/Mixed - 12%
67 Embryonic Structures - 42%, Male Genitalia - 19%, Female Genitalia
- 19%
68 Male Genitalia - 67%, Nervous System - 33%
69 Urinary Tract - 50%, Endocrine System - 18%
70 Respiratory System - 100%
71 Skin - 43%, Nervous System - 19%, Nervous System - 19%
72 Cardiovascular System - 35%, Nervous System - 27%, Male Genitalia
- 19%
73 Female Genitalia - 12%, Germ Cells - 11%
74 Male Genitalia - 28%
75 Embryonic Structures - 30%, Urinary Tract - 22%, Respiratory
System - 16%
76 Musculoskeletal System - 16%, Respiratory System - 12%
77 Nervous System - 35%, Male Genitalia - 31%, Germ Cells - 11%
78 Stomatognathic System - 19%, Liver - 12%, Exocrine Glands - 11%
79 Respiratory System - 38%, Female Genitalia - 38%, Male Genitalia -
2 5, %
125
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127
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
<110> INCYTE GENOMICS, INC.
PANZER, Scott R.
SPIRO, Peter A.
BANVILLE, Steven C.
SHAH, Purvi
CHALUP, Michael S.
CHANG, Simon C.
CHEN, Alice
D'SA, Steven A.
AMSHEY, Stefan
DAHL, Christopher R.
DAM, Tam C.
DANIELS, Susan E.
DUFOUR, Gerard E.
FLORES, Vincent
FONG, Willy T.
GREENAWALT, Lila B.
HILLMAN, Jennifer L.
JONES, Anissa L.
LIU, Tommy F.
ROSEBERRY, Ann M.
ROSEN, Bruce H.
RUSSO, Frank D.
STOCKDREHER, Theresa K.
DAFFO, Abel
WRIGHT, Rachel J.
YAP, Pierre E..
YU, Jlmmy Y.
BRADLEY, Diana L.
BRATCHER, Shawn R.
CHEN, Wensheng
COHEN, Howard J.
HODGSON, David M.
LINCOLN, Stephen E.
<120> SECRETORY MOLECULES
<130> PT-1134 PCT
<140> To Be Assigned
<141> Herewith
<150> 60/185,215; 60/185,216; 60/205,232; 60/205,323; 60/205,287;
60/205,324; 60/205,286
<151> 2000-02-24; 2000-02-24; 2000-05-16; 2000-05-17; 2000-05-17;
2000-05-17; 2000-05-17
<160> 159
<170> PERL Program
<210> 1
<211> 608
<212> DNA
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LG:223939.1:2000FEB18
<400> 1
gtgaaataat ggaattagtc ctggtgaaat accagggcaa aaactggaat ggacatttcc 60
gcatacgtga tacactacca gaattctttc ctgtgtgttt ttcttctgac tccacagaag 120
tgacgacagt cgacctgtca gtccacgtca ggagaattgg cagccggatg gtgctgtctg 180
tctttagtcc ctattggtta atcaacaaga ctacccgggt tctccagtat cgttcagaag 240
atattcatgt gaaacatcca gctgatttca gggatattat tttattttct ttcaagaaga 300
agaacatttt tactaaaaat aaggtacaat taaaaatttc aaccagtgcc tggtccagta 360
gtttctcatt ggatacagtg ggaagttatg ggtgtgtgaa gtgtcctgcc aacaatatgg 420
1/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
agtacctggt tggtgttagc atcaaaatga gcagtttcaa cctttcacga atagttaccc 480
tgactccctt ttgtaccatt gcaaacaagt catcattaga actagaagtt ggcgagattg 540
catctgatgg ctcaatgcca actaataaat ggaactatat tgcttcttca gagtgccttc 600
cattttgg 608
<210> 2
<211> 755
<212> DNA
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LG:397140.1:2000FEB18
<400> 2
tatggaaatg cactttatat ttatttgcac acatcaagaa tacttttgga aaccaggatt 60
tagaaaaata aaagatattt ctttcctggg gacaaagtga cctgcaaatg attggcttct 120
gtacaatgtt gcaatccctt aatgtcagac tcttaggaaa atgggtggga catctgtgtg 180
tttgtgttgg agtgaatgtg cccataaccc tgtgctccca taagtctgtg tgcccgtgat 240
catatgcata tgggtgaatg tttgtgtgcc catgatttta tgcatatagg tgaatatttg 300
tgtgcccatg agcatatgca tatgggtgaa tgtttgtgtg cccatgagta tatgcatacg 360
ggtgaatgtt tgtgtgccca tgagtatatg catatgggta tatgtttgtg tgcccgtgat 420
tatatgcata tgggtgaatg tttgtgtgcc cgtgattata tgcatgtggg tgaatgttca 480
tgaacaaaca ggtacactcg gagtagaaaa caaatgaagc aaaagtttag catcctctca 540
tgtgtgtcaa cattgtagtt ttacatgtac tttcttctaa tctattaaac ataagtatgg 600
ctccattttt ttagtattac cagaagccct cccaatacgg caatattacc ttctgtgtaa 660
tccacttgcc gacagcatgt tttctgttga aatgggacat caagaatttt gaatccaagg,720
ccatatgctg catgctcatg atttacaatg gtttg 755
<210> 3
<211> 1078
<212> DNA
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LG:1094205.1:2000FEB18
<400> 3
ctcccaagat ggcggctcct ccgggcgagt acttcagcgt tgggagccag gtgtcgtgcc 60
ggacgtgcca ggagcagcgg ctgcagggcg aggtggtagc ctttgactac caatccaaaa 120
tgctggcttt aaaatgtccc tcttccagtg gaaagcccaa ccatgcagac atcttgctca 180
taaacttaca gtatgtttca gaagtggaaa taattaatga ccgaacagaa acccctcctc 240
ccctagcttc actcaatgtt agtaagcttg ccagcaaagc acggacagag aaggaggaga 300
agctgagcca ggcctatgca atcagtgctg gtgtctctct agagggccag cagctcttcc 360
agaccattca caagaccatt aaagactgta aatggcaaga aaaaaacatc gtagtcatgg 420
aagaagttgt tattacaccc ccatatcaag tggaaaactg taaaggcaaa gaggggagtg 480
cactgagcca tgtacgcaaa atagttgaaa aacattttag agacgtggaa agccaaaaga 540
tactgcaacg ttcacaagcc cagcaaccac agaaggaggc tgccctgtca tcctgagtcc 600
gtacacatgg aggactcttc cagcatccag ccaaggaggc gctggtggtg gcttcagcgg 660
aggcaggccg ggggagggaa gggatcctat atgtcctgtt ggctcttaac aaagggtcag 720
catttccaac tcttagactt gaacaaacaa aacacccaac aaaaaagaac aagagaataa 780
tttaaaagtt gaatcattac ttgactaaca gacttcggtc caccatgtcc ttttcacagc 840
cctcttctgg aacagtcacc ttggtaattt tattttggaa aattattttc ccactctgcc 900
ctttacttct gactttcctt tcctagattg ttcctgccat tctgtgttta taagtggcta 960
cacttgcctt ctgaatgatt gaaagaaact tttacatctt ttcttccaaa ataaaagtaa 1020
caagctgact gtgattctta aattgagacc agagcagcaa acgtctcact ttaaattt 1078
<210> 4
<211> 533
<212> DNA
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LG:481361.5:2000FEB18
2/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
<400> 4
gttcttttcc ccttttctcc agagataaat gtgttgatct taaacatttg cttctgtgag 60
aagctccagc acctgtgtgt cactgtcatc gagatcagta ggctgtttga tggtgatgaa 120
gatggtggcc tccttactca gaatgctttt ttctcatttc ctagtgggat tttagtgtgc 180
actgatgtga tggcccgggg aattgatatt cctgaagtca actgggtttt gcagtatgac 240
cctcccagca atgcaaggta tggtacgagg ctgccaccca ctctctgttg aggaatttag 300
ccaccacatg tgaaaattac aattactttc ttcaaagtca gcatatattc ctaatacatg 360
cttccacgca taggaaaatg cctataaacc cccaagtgtt gatgattact cctgaggtta 420
ttggtcattt tcattttatt ctttgtattt ttcattgttt cccagatttt ccactgggga 480
ctatgtccca cctgtatgat cagagagaaa gatacaagtt atacttaaga gta 533
<210> 5
<211> 2149
<212> DNA
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LG:981170.1:2000FEB18
<400> 5
aatttttgac tttctccttt gtaattaatc tctatctggg tttctctctt tctctgtgcc 60
atttggtttc cttaattagt tccctgtgcc agcccatagt cagagccata attggctctg 120
gggaagatcc aagttatttt ctgagtaaga tattaggctt ccatatgatc cagagatgca 180
aagaaatccc tagagagtgt aggagttgtc taaatccatg tgtcagatgt agccaacgaa 240
ttatgtcaga agcagagaga aaaggcctga aaagcagctc tctcccactc ctcaggccct 300
tgtctccaac cttacatgag gctttttgaa catctcctcc tggcccagct ggggtgagag 360
caagtcctcg aaggcactgc ctttgagcct tgctcagccc atctgaacta tcccaactct 420
agaattgact gctttcgaat tgtgtgacct tgggaatgtt atctggcttc aaccacaatg 480
ccctaccccc agctcctctc ccaaatgatc ctagatacag ggctgcttcc ccccgaccct 540
accccacctc gggacacagg ctcatggcct catggcactt caccaccaga agtggtgctc 600
agagttccta tttccacatc taacccccta attcctggga aagtctgagg cctggtcccc 660
ccagtgcttt ccctggctgg cctctccaca ttttcatctg atggtggagt gagatcagga 720
aaaataggac aggagctttg ccttggggga gaagagagtt aagtgtggaa aggggtgagt 780
tataggaggt taagcagtcc aagatttctc tctctgtgta ggaggccatt tcctgatgtg 840
aggggtctga acccaattat gatgggacag ggttgggcat tgacttccca tctcttctct 900
ctgtttttct cccactatct gtagcccaaa actcttatgg aggactttga tctttagtat 960
aggctattgg tcagggccat aggaactaac cccgatcctc actccaccag gatctaccac 1020
atcccctaca cacaaacaca tgctgtgggg agggagtttt cccctgggtc aagttgagga 1080
tccttagatc accttgtgct cctgtggact ggtgtgtgcg tgtgtgtgtg tgtgtgtgtg 1140
tgtgtgtgtg tgtgtgtgtg tatgtgggga aacttagctt tcagagaatg tctatgggct 1200
ctcattttct ctctcacaca aaaatactcg ggacttctcc aagtccctga ggagcctgac 1260
cactgaagct gatcatgaga tgactgtatg ctgacacacc cccttcaggg gcctggcctt 1320
gacttagggc tgcactgtat cctcagcaac ggccttgcag gagccccttt tggactgctt 1380
tccctattca gCCCagagtt ggggtggtgg gagaagaggg gttggagtga atccatctct 1440
attcaaattc cagctgggat tactctagga gtcttcctgg cttgttttgg gctcaaactt 1500
agctacattg tttattggct cccaaagtcg ggattgaaga gtgaaaagat gcaggcaatg 1560
aatccttctg cacactcctc cccaaccttt ccagcgcttt tctacttagg aggccagtgg 1620
aagggaggag aggccatgcc ctagcccaca ggggacaagg ttcattgttc ttccaggctt 1680
ggttcactct gcttttgatt cagaagctct ttccctaccc agcaagacta cactttcttg 1740
ccttctttct attttttctt tttgtgcgta taaatggtat gttgtgatat attctcagtg 1800
cttgtgccca ccttggaact ctgttcttgc tcttcattcc gcatgtgata ctctggtcca 1860
agatcttggc caggtgcctt ctgctcaaat atcgtctcag aggtgcttcc cttgaaaact 1920
cggtgctgtt tccatagtta ctctatttga tcactctaag tttggttgtc ttcatagcac 1980
ttgtcaccct ctggaactat tctattcatt tatttacttg tttaatgctt ggctcttttc 2040
ccctcctaac gtaaactcca tgattgccaa cacctgttta cttactacag ttccccctcc 2100
ccccacattc ctgacactag taagaaccaa taaacacttg ttgacggaa 2149
<210> 6
<211> 669
<212> DNA
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:197613.1:2000FEB01
3/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
<400> 6
tgcatcctct gggcacgctc cacttgccgc ttccacccgg aaagcccccc aggctgagtg 60
cggcatgatc tccatcaccg aatggcagaa gattggtgtg gggatcaccg gtttcggcat 120
cttcttcatc ctctttggaa cactcctgta ctttgattcc gtgctcctgg cctttggaaa 180
cctgctgttc ctgacgggcc tgtccctcat cattggcctg aggaagacct tttggttctt 240
cttccaacgg cacaaactca agggaaccag cttcctcctg gggggtgtgg ttatcgtgct 300
cctacgctgg cccctcctcg gcatgttcct ggaaacctac ggattcttca gcctctttaa 360
ctgttccgga gacttcaagg cactagctcg atggtctgaa aaacagagat gagctccttg 420
aacttggatc attggttgag ggggctagag ggagaatggg aaccaccccc tcagtcccct 480
gcactgactc actccccgac atatccggac ctccccaagt ccagaaggaa ggaatggagc 540
tgagcaactg acgtcaaatc cccaagtcga ctcaagaggc tgccaggaag cagagatgca 600
gaccccaagg agactgggct ggggctggta tcacaccctc acacgcacaa cttggggtct 660
669
cgagtctag
<210> 7
<211> 463
<212> DNA
<213> Homo sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:902682.1:2000FEB01
<400> 7
taagtaatga ggagccaaat gctaatcacc aaagcaatgg ggaaaatgtc tccagggcat 60
gtcagagacc ttcacagcag cctctcccat cataggcctg gagacctagg acagaaaaat 120
ggtttcctag gctgctgcta ttctgtgcag tgtcagaaca tgttcgcctg tgtcccagtg 180
acttcagctt cagctgtggg ctgaaagagg ccaaggcaca gctcagaccc ttgcttctaa 240
gggtgtaaac cctaagcctt gcagtttccc acatggtgtt tggcctgttg gtgcatagaa 300
gtcaaaaatc gaggtttgag aacctccacc tagatttcgg aggatgtatg gaaatgcctg 360
gatatccagg cagaattttg ctggagaggc agagccctaa cagagaacct ctgctaaggc 420
agtgcagaag ggaaatgttg,ggtcagaact cccaggcaga gtc 463
<210> 8
<211> 2271
<212> DNA
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:212029.1:2000FEB01
<220>
<221> unsure
<222> 54, 1164, 2259
<223> a, t, c, g, or other
<400> 8
ctaccctgct cctcagcctg tgagaacaga tgtggccgtc ctgcggtacc agcnaccccc 60
tgagtatggg gtaacgagcc gcccatgcca acttccgttc ccatcaacca tgcagcagca 120
cagccccatg tcctcccaga cctcttccgc cagcgggcca ctgcactctg tctccctgcc 180
gcttccactc ccgatggccc tgggtgctcc acagcccccg cctgccgcct cccccagcca 240
gcagcttggt ccagatgcct ttgcgattgt ggagcgagcc cagcaaatgg tggagatatt 300
aacagaggag aaccgggtgc ttcaccagga acttcagggt tactacgaca atgccgacaa 360
gctccacaag tttgaaaaag aacttcagag aatttcggaa gcctatgaaa gtctggtcaa 420
gtctaccacc aagcgagaat cgctggacaa ggccatgaga aacaaattgg aaggcgagat 480
tagaagactt catgatttca acagagacct ccgagatcga ctagagactg ctaacaggca 540
actatccagc agggaatacg aagggcatga agacaaagct gcagaggggc attatgcttc 600
ccagaacaaa gaattcttga aggaaaagga gaaattagaa atggagttag cagcagtgcg 660
gactgcaagt gaggaccatc ggagacacat cgagatcctg gaccaggctt tgagcaacgc 720
ccaggccagg gtcatcaagc tggaagagga gttacgagag aagcaagcat atgttgagaa 780
agttgagaag ctgcagcagg ccctgaccca gctgcagtct gcatgtgaga agcgagaaca 840
gatggagcgg agactgcgga cttggctgga gagagagctg gatgcactga gaacccagca 900
gaaacatgga aatggccagc cagccaacat gccggaatac aatgccccag ccctcctgga 960
acttgtgcgg gagaaggagg agcggatcct ggccctggag gccgacatga caaagtggga 1020
gcagaagtac ctggaggaga gcaccatccg acactttgcc atgaatgccg cagccactgc 1080
agcagctgag agggacacca cgatcatcaa ccactcacgg aatggcagct acggagagag 1140
4/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
ctcgctggag gcccacatct ggcnagagga ggaggaggtg gtgcaggcca acagaaggtg 1200
tcaggacatg gaatacacta ttaaaaatct ccatgccaaa atcatagaga aagatgctat 1260
gattaaggtc ctgcagcagc gatctcgtaa agatgccggg aagacagact cctccagcct 1320
acgtcctgcc cgctccgttc catccatagc agcagctact gggacacact ctcgccagac 1380
ctctcttacc agcagccagc tggctgagga aaagaaggaa gagaagacct ggaaggggag 1440
cataggattg ctgctgggga aggagcacca tgagcatgcc tctgccccac tgctgctacc 1500
cccacccacc tcagcactgt cctccatagc ctccactacg gcagccagca gtgcccacgc 1560
caagacaggc agcaaggaca gcagcacaca gactgacaag agtgccgagc tcttctggcc 1620
cagcatggcc tcccttccca gccgcggccg gctgagcacg acccctgctc acagccccgt 1680
cctgaaacac ccagcggcca aagggaccgc agagaaactg gagaactctc ctggccatgg 1740
gaagtcgcct gaccacagag gccgggtcag cagcttgctg cacaagcccg agttccctga 1800
tggagagatg atggaagtcc tcatctaact gccatccctg tggaatttca gtacagaaca 1860
ctgacaaaca aggaaagcgg cagagaaaga agaaagacct agaaggttgt agatgggaaa 1920
tcaggaatga tttgaactga taaagatttc agactcataa gaacacattt tataaatgtt 1980
aaacacaaaa actacatgac tgaagataga agagaatgcg atggatttta ttacacatgg 2040
tggaagagag aagaggcgtg taggtttgca aacaaagtta agaaatagga aactgaattt 2100
ttcattgtac agaaaatgta tctcttgggg agggcctgtg tacccccatt ctctgattat 2160
aaacagataa acccaaatgt ggatcatcct tggaataccc ccattcgcct tgcctcttag 2220
catgtttgat ttaagagaag cctccaggaa atcttgagng cctgtgttgg c 2271
<210> 9
<211> 1240
<212> DNA
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:249170.1:2000FEB01
<400> 9
tccgcctgtg ctggacactc cctttctcct gcagccatgg atgccgctct gctcctgaac 60
gtggaagggg tcaagaaaac cattctgcac gggggcacgg gcgagctccc aaacttcatc 120
accggatccc gagtgatctt tcatttccgc accatgaaat gtgatgagga gcggacagtc 180
attgacgaca gtcggcaggt gggccagccc atgcacatca tcatcggaaa catgttcaag 240
ctcgaggtct gggagatcct gcttacctcc atgcgggtgc acgaggtggc cgagttctgg 300
tgccacacca tccacacggg ggtctacccc atcctgtccc ggagcctgag gcagatggcc 360
cagggcaagg accccacaga gtggcacgtg cacacgtgcg ggctggccaa catgttcgcc 420
taccacacgc tgggctacga ggacctggac gagctgcaga aggagcctca gcctctggtc 480
tttgtgatcg agctgctgca ggttgatgcc ccgagtgatt accagaggga gacctggaac 540
ctgagcaatc atgagaagat gaaggcggtg cccgtcctcc acggagaggg aaatcggctc 600
ttcaagctgg gccgctacga ggaggcctct tccaagtacc aggaggccat catctgccta 660
aggaacctgc agaccaagga gaagccgtgg gaggtgcagt ggctgaagct ggagaagatg 720
atcaatactc tgatcctcaa ctactgccag tgcctgctga agaaggagga gtactatgag 780
gtgctggagc acaccagtga tattctccgg caccacccag gcatcgtgaa ggcctactac 840
gtgcgtgccc gggctcacgc agaggtgtgg aatgaggccg aggccaaggc ggacctccag 900
aaagtgctgg agctggagcc gtccatgcag aaggcggtgc gcagggagct gaggctgctg 960
gagaaccgca tggcggagaa gcaggaggag gagcggctgc gctgccggaa catgctgagc 1020
cagggtgcca cgcagcctcc cgcagagcca cccacagagc cacccgcaca gtcatccaca 1080
gagccacctg cagagccacc cacagcacca tctgcagagc tgtccgcagg gccccctgca 1140
gagccagcca cagagccacc cccgtcccca gggcactcgc tgcagcactg agccccctga 1200
ggcccacagc cacccaggca gggcagcaag tggcctggtc 1240
<210> 10
<211> 1564
<212> DNA
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:813218.1:2000FEB01
<220>
<221> unsure
<222> 307, 317-318, 335, 918, 921, 943, 1011
<223> a, t, c, g, or other
<400> 10
5/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
aggcaaggga catggactct tctcatagga tgcacagtca agtcacgtga caggaataca 60
taatgttaat acatttgagg aataatccta acacatcaag ttaaagtaag ctgcttttga 120
tccccctttt gaaaaggatg ccagtttagt tgttacatac caagtgccag aggctgagtt 180
tttttttttc ctggtgaaga tattgcattc gttgaaaaca aaaccacact gagttaccat 240
ttcatgttca ctaggatgac tgcagtcaaa aagatggaaa attgcaagtg ctgttgagga 300
tgtgaancaa ttggaanntt catgcactac tggtnggaaa gtgaaatggt gcagtcactt 360
tgggaaagtt tggcagttct tcaaatggtt aaacgtagag ctactatatg gcctagcaat 420
tccccttaca ggcatatgcc caagataatt gaaaatatat gttcagggct accctctttg 480
ggtcccctcc ctttgtatgg gagctctgtt ttcactctat taagtcttgc ttctgcactc 540
ttctggtcca tgtttgttaa ggctcgagct gagcttttgc tcgccgtcca ccactgctgt 600
ttgccaccgt cgcagacccg ctgctgactc ccatccctct gaatctggca gggtgtccgc 660
tgtgctcctg atccagtgag gcgcccattg ccgctcctga tcaggctaaa ggcttgccat 720
tgttcctgca cagctaggtg cctgggttcg tcctaattga gctgaacact agtcactggg 780
ttccatggtt ctcttctgtg acccacagct tctaatagag ctgtaacact caccgcatgg 840
cccaaggttc cattccttgg aatccataag gccaagaacc ccaggtcaga gaacacgagg 900
cttgccacca tcttggangc nacccaccac catcttggaa gtngctcgcc accatcttgg 960
gagctctgtg agcaaggacc cctggtaaca ctttggtgac cacgaagtga ncctccaagg 1020
tgaattgaaa ctgtaaaact acaaatggtt catcaaatgg agccccagat gcagtccatg 1080
actaagatcc accgtagacc cccggaccgg tctcccagcc catgctctgg tgttaatgac 1140
atcgaaggca cccctcccaa ggaaatctca gctgcacaac ccctcctatg ccccagttca 1200
gcaggaagca gttagagcag tcatcggcca acctccccaa tagcacttgg gttttcctgt 1260
tgagagtggg gactgagagg actagctgga tttcctaggc cgactaagaa tccctaagcc 1320
tagctgggaa ggtaactaca tccatcttta aacatggggc ttgcaactta gctcacaccc 1380
aaccaatcag agagctcact aaaatgctaa ttaggcaaaa acaggaggta aagaaatagc 1440
caatcatcta ttgcctgaga gcacagcggg agggacaagg atcaggatat aaatccaggc 1500
attccagcca gcaatggcaa ccccctttgg gtcgcctcct tgtatgggag ctctataagt 1560
actc 1564
<210> 11
<211> 284
<212> DNA
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:902522.3:2000FEB01
<400> 11
gtggtctgag tttgtggctg catttttatc tctggtggct ctgctacggc ggcgcagaaa 60
tgaggcagaa gcggaaaggg tgaaaaccaa gacagctgcc aaatatggcc tttctgccca 120
gccccgcctg gtggatatca ttgctgccgt ccctcctcag tatcgcaagg tcttgatgcc 180
caagttaaag gcgaaaccca tcagaactgc tagtgggatt gctgtcgtgg ctgtgatgtg 240
caaaccccac agatgtccac acatcagttt tacaggaaat atat 284
<210> 12
<211> 1209
<212> DNA
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:474304.1:2000FEB01
<400> 12
attttaggta ctttgtttat ggatctgttg aatctgagga gaagtgattg ctttgagtta 60
gctagtttta aattcatgac actttcccaa cataattagg tatttgaacc taagtgtgtg 120
ctagtgtatt gtatattttt cattaattac tttattgaaa gttgctttgg gaatcaattc 180
acttcaatat attttactgt tctcagtgaa gaatgtgact aataagtatt tggactttca 240
aaaagtgata cagtctttgt gatagttttt tacctttaca ttaatgagtt ggaaaataac 300
tttgttcaaa ggaatagaaa tgcatatttt gcttaaatat taacaatatg tttttaattc 360
agtgtgtctc agtaaactat gttttggatt gctgtgtttt tacctcatgt ttattttttc 420
tgtctacctg gtaatttgag aaccctcgct tgcaacatat caccatatta ttcgcctgtt 480
tgatcaacct ggagaccctt taaagagatc atccttcatc atttatgata taatgaatga 540
attaatggga aagagatttt ctccaaagga cccggatgat gataagtttt ttcagtcagc 600
catgagcata tgctcatctc tcagagatct agaacttgcc taccaagtac atggcctttt 660
aaaaaccgga gacaactgga aattcattgg acctgatcaa catcgtaatc tctattattc 720
caagttcttc gatttgattt gtctaatgga acaaattgat gttaccttga agtggtatga 780
61104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
ggacctgata ccttcagcct actttcccca ctcccaaaca atgatacatc ttctccaagc 840
attggatgtg gccaatcggc tagaagtgat tcctaaaatt tggaaaggtc agttttactt 900
tttatgtgtc cgggtgcatc tcacctcaat atcctctact ttgataatga atgtgctaac 960
attactgtta gggatgaaaa cttccatttt gactgaacca aatgtgttag ttgagatgta 1020
cttcaaggtc atgtgctcat gttgcatgtt ggctatcagg agaaaatttt gttgaaaatg 1080
acttaagtca gtcccttcgt gacataggaa tgagctgagt tttgtgcacc tgttgcagga 1140
tatgacccaa agaaaataaa tgctaatggc gtggcaaacc ctaaatctga ataaaggtct 1200
ttgacccgg 1209
<210> 13
<211> 1358
<212> DNA
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:027320.1:2000FEB01
<220>
<221> unsure
<222> 95, 1349
<223> a, t, c, g, or other
<400> 13
actccgacgg cggctcggac gccgacttcg gaggtgggtc cggggagccc gactcggacc 60
gcggaggtga gcgggagctg aggctgagga gaggngagct tggggggcgc ctgctgccaa 120
gggcagcgga ggaggaaatg gcaggtccta atcaactctg cattcgccgc tggactacca 180
agcatgtagc tgtgtggctg aaggatgaag gcttttttga atatgtggac attttatgca 240
ataagcaccg acttgatgga atcacattgc taacattgac tgaatatgat ctccggtctc 300
ctcctctgga aatcaaagtc ttaggggaca ttaaaaggtt aatgctctca gtccgaaaat 360
tgcagaaaat acatattgat gttttagaag agatgggcta caacagtgac agtcccatgg 420
gttccatgac ccctttcatc agtgctcttc agagtacaga ctggctctgt aatggggagc 480
tttcccatga ctgtgacgga cccataactg acttgaattc tgatcagtac cagtacatga 540
atggtaaaaa caaacattct gttcgaagat tggacccaga atactggaag actatactga 600
gttgtatata tgtttttata gtatttggat ttacatcttt cattatggtt atagtccatg 660
agcgagtgcc tgacatgcag acctatccac cactcccaga tatattctta gacagcgttc 720
ctagaatccc atgggccttt gccatgacgg aagtatgtgg catgattctg tgctatattt 780
ggctcctggt tcttcttctt cacaagcaca gatatatggc agtgtatggg agaaattaca 840
tcgagccttt gccatttgga gtggctttgg tatgaccctg actggcgttc acacatgtgg 900
agattacatg tttagtggcc acacagtcgt cctaactatg ctgaatttct ttgtcaccga 960
atatacacca agaagctgga atttcttgca cactttatcc tgggttctca acctctttgg 1020
aatcttcttc atcttggctg cccatgaaca ttattctatt gatgtgttta ttgcttttta 1080
tataacaaca agactctttt tgtactacca tactctggcc aataccagag catatcagca 1140
gagtaggaga gcaaggattt ggtttcccat gttctctttt tttgaatgca atgttaatgg 1200
cacagtacct aatgaatatt gttggccatt ttcaaaacca gcaataatga aaagactaat 1260
tggatgaata ctatctttct aatgaatttg tgattaaata tatcatagtt gttgaaaatg 1320
agtaactttg cgttctcccc ctaggttcnt cttaaagc 1358
<210> 14
<211> 1035
<212> DNA
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:228319.1:2000FEB01
<400> 14
caaagctggt ttcaagccac tttcctagtc tttgttgaat ggtaaatgtt ccttcaagag 60
ttgcaggaag agcatgcctt gcttgcgcca tggggtgggg ctgcaccatc ttgcttgctg 120
cgtgtgcttg tattgttcat catacacaat tcatggtttc ttttcaggaa tttttgaagt 180
cgcttgtcca ttctatgaag gtcagtttgg ttaaaattaa agcattttaa ctgagtactt 240
acaaactgta gtagacccag ataggctgaa agcaaaagta ggatggaggg cttggcttcg 300
gtgaggacca agcctcttct gtcagccact cctgtgcgac tgtcaggccc agggatccac 360
tcagggaagg tacctgtgtc aacctcaata ttaactgtta tcaaagcttc ctgtctcttt 420
tattttagcc agaagcaata cttttaatgg attccttcca cgtccaaatg gatcatgtgt 480
acccctcctg ggcaaccacc ggaagactct gggtattgtg tgcgttgtcc gctcagtgac 540
71104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
gaggatcttc ataatttcct tcctgcaaaa aggacattag ttttcagtgt ttccaacaat 600
tatccagcaa taccatctaa acaccatttc tgtaatctag gagcaagctg aagaggaaaa 660
gaagcccaag gatagcacaa ccccttttga gtcacggtta tcccaatcca gaaaattttc 720
ctggacagaa tacctggaag ctactcaaac caatgcagtt cctgccaaag tttttaaaat 780
gaggttgcct catggttttc tgccaaatat gaaacttgaa gttgtggata aacggaaccc 840
caggttaatt cgtgttgcta cgattgtaga tgttgatgac caaagagtaa aggttcattt 900
tgatggttgg gaccataagt atgactactg ggtggaggca gacagccctg atatccaccc 960
gatcggattg tgtgatgtca cagggcatcc actggaagtg ccaaagcgaa cgaaatgacc 1020
tgaagatcct tccag 1035
<210> 15
<211> 912
<212> DNA
<213> Homo sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LG:197267.2:2000MAY19
<220>
<221> unsure
<222> 24
<223> a, t, c, g, or other
<400> 15
cgtgctgcag ccgccgctgc tgcngctcct gctggcgctg ctgctggcgg cgctgccgtg 60
cggtgccgaa gaggcctcgc cgctgcgccc cgcgcaggtc acgttgtcgc cgccgccggc 120
cgtgacgaac gggagccagc cgggcgcgcc acacaacagc acgcacacgc gtccgccggg 180
ggcgtcgggc tcggcgctga cgcgctcctt ctacgtgatc ctgggcttct gcggcctgac 240
cgcgctctac ttcctgatcc gggcgtttag gttgaagaag cctcagcgga ggcgatacgg 300
cctcctcgcc aacactgagg accccacgga gatggcctcg ctggacagcg acgaggagac 360
ggtctttgag tcccggaatc tgagatgatg ctgagccagg gaggcggccc ttccagcagc 420
catgagggaa ggacaggaga tggggcccac cccagtgccc agcaaccccc tgctccaccg 480
ctcattcccc tgctggcccc ggggctggtc tcacccagtg cccagcaacc ccctgctcca 540
ccgctcattc ccctgctggc cccggggctg gtctcaccca gtgccaaccc gagagctcct 600
tttggaacct gcacagcccg ccgacctgtt gccacctgca cccaccgctg gaccatgcag 660
cctcgcctcc tggatgctgt cccagcctgg ccgagggtcc caggtgaaga ctggagggac 720
cccaacagcc accgcccagg acgctgaggc tcccttgcct gactgtgact tgtgcctctc 780
tcctgccccc gtggggacat ggcagcccag agccaaggct gggtgggcag gtgacccaag 840
gaacctttct gggaacacct tctcgccggg ctgggaacaa taaatgcagc catgtctctg 900
cagctggtgc tg 912
<210> 16
<211> 1615
<212> DNA
<213> Homo sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LG:403332.1:2000MAY19
<220>
<221> unsure
<222> 99, 1070
<223> a, t, c, g, or other
<400> 16
cgggctgttc ctgtaaggcg gggagacaat gagtaaactc tccttccgag cgcgggcgct 60
ggacgccgcc aagccgctgc ctatctaccg cggcaaggnc atgcctgatc tcaacgactg 120
cgtctccatc aaccgggccg tgccccagat gcccaccggg atggagaagg aggaggaatc 180
ggaacatcat ttacagcgag caatttcagc acagcaagtg tttagagaaa aaaaagagag 240
tatggtcatt cctgttcctg aggcagagag caacgtcaac-tattacaatc gcttgtacaa 300
aggagagttt aaacagccaa aacagttcat tcatattcag cgcatttggg gacactacca 360
accggagacc acgttaaagt ttttgcttgt ttgttttgtt catttgtttt tggaccacag 420
tattagcttt aatttaggct gcagatctgc tcaaggttca gttctcagga agattttttg 480
cttctccttt ctacctaagg gcaagttgag aaatacaaaa ttctttgctt tccctttctg 540
catggctaat ttatttcttt aatcttacac tgagggcata gccctttggt aatgtatctt 600
8!104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
tattcagtag cattctatac taatattaac acacaagcat aaagcttttt tctttcttat 660
ggtatatata gtaatgttgt gtctttaatt gatggcagtt tagatttgat agaattcaat 720
aatagtcata ttctctagta tgaatattag gttctttgta atttgttccc gctttctcct 780
ttaacgtcat ttatttttgc tcttcccttc actctgtgta ccatagggac tacgaaaatt 840
accctcattc accttctttc atatttaaca tttccttgga tgtgctattg aagtcttctt 900
tcccttccta tagctcatta aagacttaac tcccttatga aagccacctt gacttttctc 960
actctacctg tcttctttgc ttatcgtagt atcttttaca tacttctgtt agaggactca 1020
ccatacttta ttgcaattat ttgtaaccat tctttctctc cttttagacn gtgagctcct 1080
tgagggcagg aactatatat tttattttct tttgtgtttt cagagtaaag tgcttggttt 1140
atagatgctc aataaatgat gtgtttgtcg actgaattgt tttaaaatgg ctttaaaaag 1200
tcttttggtg gtacagccat tttccacaga tttcttttct ctgaaatagt ctagagaaac 1260
acacatgcga aaattattta tgtatatttt tttctcctgt gttctttgac tttgagtcct 1320
attagctttt tgaatttgcc tttaccttct atcagtcagg aaggagataa ctattcataa 1380
tagaaatttt aaggatctct cttaagccaa agtatcaatt attttgtatt ttgataatat 1440
tgcagttagg caggaagacc atttgtaaaa accattctag gaaaccaaga actaaaaatc 1500
gggtgtaact catgtgggtc aggcccatcg aatacaataa acattattct tgtgttggtt 1560
tttttcattt cattttattc tattattgta aaaaacaata aaaataatag aaatt 1615
<210> 17
<211> 880
<212> DNA
<213> Homo sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LG:983076.3:2000MAY19
<400> 17
aatggaactt aatgtctatt cctcttttct cttttctgtg ttaccaaagg gatctagagc 60
cttatgggta ctacttagaa aatgagcact catacatata caatatctgg aaataccttg 120
aaagtaatca cgaatactcc ttctgtttca cttccatact gctgaattgc ctcttcatct 180
tctgtcacca taacaattgg catcctgtcc tggcagtgat gatagtacca aacagctgcg 240
ttgtatatgc tcctggtctg ccacttctcc atggactctc ctctttcccg tggcagatag 300
cagcattgct ggaattcatt agcaaagaga atgcaatcat gacgcgcatc cttcagcagg 360
tttcgcagtt tgttatactg tctgtgacac ggaggagaaa aataactcta acaaagcagg 420
tactcatcca ctgctatctc ttgctaagga tcaaaaaagg atggggtatt ttagagccaa 480
agattgatta ctttaaacct gaagaacatg tatttatatt ggtctcagtg tgctcagtcc 540
tatcgggctg ctattgtttc tcgattttgc ctgctagaag gtgcttgggc agggcctagt 600
taattagttt gcagatcaat taaactcctt ccctctcctt tccccttcag agacttccag 660
ccattttatt atgtaattat accaccttgc cctgcctagc cccttcttca aagcctgagt 720
gcacggaggc aagcagagag tttagcactt tatttttgga cctcactttg ttctataaat 780
gtcattaagc attaatacat ttgacttttt gctggcagcc ctagacaaga acatgtaagg 840
taaataagtt tggggattta tctgtgaatt taatttatgc 880
<210> 18
<211> 1049
<212> DNA
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LG:216612.3:2000MAY19
<400> 18
cgggtaccgg gcctcacgga tccgcgccgc gccccccacc tgtgtgctgc gcgcggggtg 60
ggctgcgctc ccctgggcgg cgccgggcgc ccggggctgg tggcgagatg ggccgctact 120
ctggcaagac gtgccggctg ctcttcatgc tggtgctcac cgtcgccttc ttcgtggcgg 180
agctggtctc cggctacctg ggcaactcca tcgcgctgct ctccgactcc ttcaacatgc 240
tctccgacct gatctcgctg tgcgtgggcc tgagcgccgg ctacatcgcc cggcgcccca 300
cccggggctt cagcgccacc tacggctacg cccgcgccga ggtggtgggc gcgctgagca 360
acgcggtctt cctcaccgcg ctctgcttca ccatcttcgt ggaggccgtg ctgcgcctgg 420
cccggcccga gcgcatcgat gaccccgagc tggtgctcat cgtcggcgtc ctggggctgt 480
tggtcaacgt ggtggggctg ctcatcttcc aggactgcgc cgcctggttc gcgtgctgcc 540
tccggggacg cagtcgccgc ctgcagcagc ggcagcagct gtcggagggc tgtgtccccg 600
gcgctttcgg ggggcctcag ggcgcggagg acccgcggcg cgcggcggac ccgacagccc 660
caggctcgga ctcggccgta accctccggg ggacctcggt ggaaaggaag cgggagaagg 720
gggcgaccgt gttcgcaaac gtagcaggtg attccttcaa cacccagaat gagccagaag 780
9/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
acatgatgaa aaaagagaaa aagtctgaag ctctgaatat cagaggtgta cttttgcatg 840
tgatgggaga tgccctgggg tccgtggttg tggtcatcat cattttgtca tctgccttcc 900
cgcttatcaa ggagaccgct gccattctgc tacagatggt cccaaaagga gtcaacatgg 960
aagagctgat gagtaaactc tctgctgtgc ctggaattag cagtgtacat gaagtgcaca 1020
tctgggaact tgtaagtgga aagattatt 1049
<210> 19
<211> 958
<212> DNA
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LG:322465.1:2000MAY19
<400> 19
acttccagaa tgtcacactg cttttgcaca ctctcaaata ggcatctgct tgtgtgggag 60
ctgtgattcc ctctcccctc cccactgtcc tctagtattg tttaaaaatg acggaagaaa 120
caatagctag ctccacagaa gtcatcctca caagccagat gtcaagtgag ggctggcaac 180
gttggggcaa aattaaaagt gatggagggg gaaacagtgg tgtgcccctt gggtggatag 240
aaggtttcat taatgtctgt gatggaatca tgaaccacaa cagtgaggca tttccgcctc 300
tggccttttt ttggtttttg ttttttttag aatcaggatc tcaaaaaaaa taaaaataaa 360
gaaaacaaat taaagttcat cagtcatgaa gcctccattc caggccctag ctccaggatg 420
acaattctag acacatcctg ggccagaagg gaatctgctg ccctgaaggg aaggtcccag 480
tcctagcagc atacatcacc tgataactga agagcccttg ggccctgaat aaccagcaga 540
gagccaggcg cggtggatca cacctgtaat cccagcactt tgggaggcca aggcaggtag 600
atcacttgag tccaggagtt caggaccagc ctagccaata tggtgaaact ccctctctac 660
taaaaataca aaaattagcc aggcgtggtg gcacacacct gttaatccca gttacttggg 720
aggctgaggc atgagaatca cttgaacctg ggaggcggag gcggcagtaa gccaagatca 780
cgccccttca ctccagcctg ggcaacaaag tgagactctg tctcaaaaaa ataaatttaa 840
aaattaaaaa ataatcagca gtgacaccca ggtacccaag tactacattg gagagcttgg 900
tgattataaa agaccttatc ttttataatg ccagaagcaa gtcaatctta tttcaaac 958
<210> 20
<211> 830
<212> DNA
<213> Homo sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LG:093477.1:2000MAY19
<400> 20
ggagcctggt ttgttagatg ttactttaga aataataaca gcactttatt gctgttatta 60
ttgagtgctt actatatact aggtgcatta ttcatcataa tcattaacaa tgaatttttt 120
ttttgagatg gagtctctct ctgttgcccg ggctgagtgc agtgccgtga tcttgactca 180
ctgcaacctc cacctcttgg gttcaagcaa ttctcctgcc tcagcctcct gagtagctag 240
gactacaggt gcacaccacc acgcctggct aagttttgta tttttagtag agatgggggg 300
atttcaccat gttggccaga ctggtcttga actcctgacc tcaagtgatc cacctgcctc 360
ggcttcccaa agtgctggga ttataggagt gagccacccc acccagccaa caacgaatat 420
taatgcagta cttatgatgt accaaactca taagcacact tacctcacca ggtcttagaa 480
gaacactccc tctggagcca tcacgtacgc gtgaggacat tgaggccctg agcttagata 540
acttgttcaa aatggccctg ctgataagct acatggacga agtcagcggt tttgggcatg 600
tctttccacc agcttctgga agaacagcac acaggccgtt cccctctccc ccattttaaa 660
gtggcaggag aaggtggaat gaagaaaata aacagggctg ttcctggctc tgtgtggtca 720
gagggtgata ctggttcagg gtccagctta tcagtgctgc actgatattc acagagcatt 780
cggctccgga ggctttgcac tgtttgtaat gcattgtcaa aacttggtgt 830
<210> 21
<211> 2591
<212> DNA
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LG:222880.1:2000MAY19
10!104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
<400> 21
cgtcgcccaa ggtcgcgggc cgcttgggga gtcagcagcg cgccaggccc cttcgggccc 60
cacacgcatt aggtgccttc tagaagggta cggagtgaac gcgggcggcg gcgggaccga 120
ggcagcgccc agtttgtaac cgccgcgccg cccgtgcccg cgcgcgccac accccagcgc 180
gcttccggcc gggccacgtg accgcgcgtg cacgtgttcc ggcctctccg cttcgccgct 240
ccgaacctcc tcctggtcgt cccggcattc gtccacgcgg agccggcttg ggcggggccc 300
gggaggcggc ggccggagaa gccgcggaga cgcgagcgcc gagcgtcgcg agggagcagg 360
cccgggcagg caagcggcgg cctccgccat gaaccccagg ggcctgttcc aggacttcaa 420
ccccagtaag tttctcatct acacctgcct gctgctcttc tcggtgctgc tgcccctccg 480
cctggacggc atcatccaat ggagctactg ggccgtcttt gcccccatat ggctgtggaa 540
gcttctagtc gtcgcaggcg cctccgtggg cgcgggcgtt tgggcccgca accctcgcta 600
ccgcaccgag ggagaggcct gtgtggagtt caaagccttg ctgatcgctg tgggcatcca 660
cctgctgctg ctcatgttcg aagtcctggt ctgcgacagg gtggagaggg gcacccactt 720
ctggctgctg gtcttcatgc ctctcttctt cgtgtccccc gtgtccgtgg ctgcctgcgt 780
ctggggcttt cgacacgata ggtcgctgga gctggagatc ctgtgctcgg tcaacatcct 840
gcagttcatc ttcatcgccc taaagctgga caggattatt c'actggccgt ggctggtggt 900
gtttgtgccc ctgtggatcc tcatgtcgtt cctttgcctg gtcgtcctct attacatcgt 960
ctggtccctc ctgttcctgc ggtccctgga tgtggttgcc gagcagcgga gaacacacgt 1020
gaccatggct atcagttgga taacgattgt cgtgcctctg ctcacttttg aggtcctgct~1080
ggttcacaga ttggatggcc acaatacatt ctcctacgtc tccatatttg tccccctttg 1140
gctttcctta ctaactttaa tggccacaac atttaggcga aaggggggca atcattggtg 1200
gtttggcatt cgcagagact tctgtcagtt tctgcttgaa attttcccat ttttaagaga 1260
atatgggaac atttcatatg atctccatca cgaagatagt gaagatgctg aagaaacatc 1320
agttccagaa gctccgaaaa ttgctccaat atttggaaag aaggccagag tagttataac 1380
ccagagccct gggaaatacg ttcccccccc tcccaagtta aatattgata tgccagatta 1440
aactcctaga gaggacccag gcacacacag actccacttg gccttcgcct cttgttcatt 1500
catcccaaac ctggaaatgg aaacaggctt caaacactcg tctcacgccg tgtttgagat 1560
caccgcctca tcagtatgca tcatagatgg aggtggtttc agtatgtggg tgtgtgtgat 1620
gtgtacctgg gtaagagact tgctttccag gttcgcactt tcaggtgtag ctgggggcag 1680
taagtcgaat tgttttagta ggtcctcaaa aggaataacc acacagctgt ttgtttaaat 1740
gctactgtac ctatcaaaac tattgtttaa aaagtatttt tatacactgc taatctaaaa 1800
ttgtatttca gattgtgcct gtcataacaa tagcaaatgt aaaaagttct ctttcccacc 1860
acttgtttat aaacctcata gttgatattt ttagtgttcc tactgttaaa atactctctc 1920
cttgggcttt gctgatactg gtctttaata ttctgatagg tgaatttttc taatggaatg 1980
aacccatgca tatatagtat ttatatgaat attttagcag tgtaatatgt tgaattctag 2040
ttctctgcat taccattatt acgttaaagt attttttaaa gcttaggtgt gaagatatgt 2100
gtctattgca gatgtccttg aaaactgcat aaaacagtat gtgcctggtg tggatcttac 2160
caaagtacta ggcatgaatg tagggactgc aaatcccatg ggtcttaata tttaggtgtt 2220
agtaaccaag gtctctggta gtacccgtta gtagaggaag aggccactgc ccttgggaac 2280
ttgtgacagg ctctagtgtg gtaccaggcc ataaagtgac actgttattt agcaacttga 2340
atttttccac acaggtagta actgtgtgga aataagcaac aagtggtttg tccatttcta 2400
agaatcttaa actattagtt ggctgtagtg tgaagcatta cttgtcattg gaaagatgga 2460
gagagtggcc ttaaccggaa gtggtcagta gaagcaggtg tcattttaag ggccaaactt 2520
taatctgtca gcaataggga aacaactgtt caaattatct ttgtagataa gaacagtgtt 2580
tcttttttct t 2591
<210> 22
<211> 2482
<212> DNA
<213> Homo sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LG:898320.3:2000MAY19
<220>
<221> unsure
<222> 2464
<223> a, t, c, g, or other
<400> 22
ccctctcttt cgctgtttga gagtctctcg gctcaaggac cgggaggtaa gaggtttggg 60
actgccccgg caactccagg gtgtctggtc cacgacctat cctaggcgcc atgggtgtga 120
taggtataca gctggttgtt accatggtga tggccagtgt catgcagaag attatacctc 180
actattctct tgctcgatgg ctactctgta atggcagttt gaggtggtat caacatccta 240
cagaagaaga attaagaatt cttgcaggga aacaacaaaa agggaaaacc aaaaaagata 300
ggaaatataa tggtcacatt gaaagtaagc cattaaccat tccaaaggat attgaccttc 360
11/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
atctagaaac aaagtcagtt acagaagtgg atactttagc attgcattac tttccagaat 420
accagtggct ggtggatttc acagtggctg ctacagttgt gtatctagta actgaagtct 480
actacaattt tatgaagcct acacaggaaa tgaatatcag cttagtctgg tgcctacttg 540
ttttgtcttt tgcaatcaaa gttctatttt cattaactac acactatttt aaagtagaag 600
atggtggtga aagatctgtt tgtgtcacct ttggattttt tttctttgtc aaagcaatgg 660
cagtgttgat tgtaacagaa aattatctgg aatttggact tgaaacaggg tttacaaatt 720
tttcagacag tgcgatgcag tttcttgaaa agcaaggttt agaatctcag agtcctgttt 780
caaaacttac tttcaaattt ttcctggcta ttttctgttc attcattggg gcttttttga 840
catttcctgg attacgactg gctcaaatgc atctggatgc cctgaatttg gcaacagaaa 900
aaattacaca aactttactt catatcaact tcttggcacc tttatttatg gttttgctct 960
gggtaaaacc aatcaccaaa gactacatta tgaacccacc actgggcaaa gaaagtatcc 1020
ctttaatgac agaagccaca ttcgatactc tgcgactctg gttaataatc ctgctgtgtg 1080
ctttgcggtt ggccatgatg cgtagtcacc tgcaagctta tttaaattta gcccaaaaat 1140
gtgtggatca gatgaagaaa gaagcggggc gaataagcac ggttgagcta cagaaaatgg 1200
taatcattcc tggggtattt atccagaatc tatctctacc ttaccagtgg ataatagtct 1260
actgtccaat tctgtttact ctgaattacc atcagctgaa gggaaaatga aggtaactgt 1320
tacacaaata acagtggcac tgagcagctt aaaaaatatt tttactcctc ttctttttcg 1380
aggacttctg tcttttctga cctggtggat tgctgcttgc ctcttttcta caagcctttt 1440
tgggcttttc tatcaccagt atctgactgt ggcatgaatc tcagttaaca aaaaagcata 1500
tccaaatcac cctttaaatt aaaatatctg tgcccttaaa gggctgatga aaaccagaag 1560
aaagcaaata caatgggaaa aaaaaaacat atcagaatgt cttgtattaa atgtttcctc 1620
tgtattctca gggtgaatta atgtagtaat atttaaaatt acaaaataga ttgttaactg 1680
ttacactgtg gcattggaat tttaactctt tgtatttact ggtatgagag ggctatctac 1740
aagggtaata tttctgatta ccctggttta cagaaacctc cagcagtctt tgaaacatct 1800
cacatgactc tagttattga ttgcttttaa tggttttatg gtactgttga tagtcatagt 1860
ggctgcctat agaacaatct tcaaactgag ccatgcttta ggggagggaa aggggctaaa 1920
gtctcttctg ttggtaattt attagttact cttgaaacaa taaaatccaa cagaaaggaa 1980
gagatagcta ctgtatatta cagtaaagaa agctgcatag ttattttaaa tttaatggag 2040
atgaatatgg ttaaaatata taactactgc tgcttgagaa tagcaagagt attgttttaa 2100
aacatattcc acccaacttg agagttcttt taaaatgatt ggccatatga acatttgtaa 2160
tcttgccatt aggtttggac ctgccatatt ttgttttatt ctgtgatcct aactagttcc 2220
ttttaatagg ctaaaatatt tatcaatact gatcagactt taaagaaatt actttgtaaa 2280
cctgctgact acctgtatgt attgtatata tattatatat taaatatata atatattgag 2340
attataaaag atgaaaatat tgaatcctta taatatttta agttgcagaa tgtatgttaa 2400
aaagtgactt gaatgagatg tatttgtatc tagaaatttt atttcttttt ggaatgagat 2460
taanatacat tttgaaagtt ca 2482
<210> 23
<211> 1334
<212> DNA
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LG:1327047.1:2000MAY19
<220>
<221> unsure
<222> 307, 317-318, 335
<223> a, t, c, g, or other
<400> 23
aggcaaggga catggactct tctcatagga tgcacagtca agtcacgtga caggaataca 60
taatgttaat acatttgagg aataatccta acacatcaag ttaaagtaag ctgcttttga 120
tccccctttt gaaaaggatg ccagtttagt tgttacatac caagtgccag aggctgagtt 180
tttttttttc ctggtgaaga tattgcattc gttgaaaaca aaaccacact gagttaccat 240
ttcatgttca ctaggatgac tgcagtcaaa aagatggaaa attgcaagtg ctgttgagga 300
tgtgaancaa ttggaanntt catgcactac tggtnggaaa gtgaaatggt gcagtcactt 360
tgggaaagtt tggcagttct tcaaatggtt aaacgtagag ctactatatg gcctagcaat 420
tccccttaca ggcatatgcc caagataatt gaaaatatat gttcagggct accctctttg 480
ggtcccctcc ctttgtatgg gagctctgtt ttcactctat taagtcttgc ttctgcactc 540
ttctggtcca tgtttgttaa ggctcgagct gagcttttgc tcgccgtcca ccactgctgt 600
ttgccaccgt cacagacccg ctgctgactc ccatccctct gaatctggca gggtgtccgc 660
tgtgctcctg atccagtgag gcgcccattg ccgctcctga tcaggctaaa ggcttgccat 720
tgttcctgca cggctaagtg cctgggttcg tcctaattga gctgaacact agtcactggg 780
ttccacggtt ctcttccgtg acccatgact tctaatagag ctgtaacact caccgcatgg 840
cccaagattc cattccttgg aatccgtgag gccaagaacc ccaggtcaga gaacacgagg 900
12/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
cttgccaccg tcttggaagc agcctgccac tatcgggagc tctgggagta aggaccccca 960
gtaacatttg gtgaccacga agggatctcc aaagcaatgg gaaacgttcc ccccaaggca 1020
gaaacgcccc tgagatgtat tctggagaat tgggaccaac tggactctca catgctaaga 1080
aataaacgac ttatattctt ctgcagtacc acctggccac gatatcctct tcaaggggga 1140
gaaacctggc ctcctgaggg aagtataaat tataacacta gcttacagct acacctcttt 1200
tgtagaaaag aaggcataag gagtgaagtg ccatatgtac aaactttctt ttcattaaga 1260
gacaactcgc aattatgtaa aaagtgtgat ttatgtccta caggaagccc tagagtctac 1320
ctccctaccc tggt 1334
<210> 24
<211> 937
<212> DNA
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LG:235157.21:2000MAY19
<400> 24
ttccacgccc gagggcatcg cgctggccta cggcagcctc ctgctcatgg cgctgctgcc 60
catcttcttc ggcgccctgc gctccgtacg ctgcgcccgc ggcaagaatg cttcagacat 120
gcctgaaaca atcaccagcc gggatgccgc ccgcttcccc atcatcgcca gctgcacact 180
cttggggctc tacctctttt tcaaaatatt ctcccaggag tacatcaacc tcctgctgtc 240
catgtatttc ttcgtgctgg gaatcctggc cctgtcccac accatcagcc ccttcatgaa 300
taagtttttt ccagccagct ttccaaatcg acagtaccag ctgctcttca cacagggttc 360
tggggaaaac aaggaagaga tcatcaatta tgaatttgac accaaggacc tggtgtgcct 420
gggcctgagc agcatcgttg gcgtctggta cctgctgagg aagcactgga ttgccaacaa 480
cctttttggc ctggccttct cccttaatgg agtagagctc ctgcacctca acaatgtcag 540
cactggctgc atcctgctgg gcggactctt catctacgat gtcttctggg tatttggcac 600
caatgtgatg gtgacagtgg ccaagtcctt cgaggcacca ataaaattgg tgtttcccca 660
ggatctgctg gagaaaggcc tcgaagcaaa caactttgcc atgctgggac ttggagatgt 720
cgtcattcca gggatcttca ttgccttgct gctgcgcttt gacatcagct tgaagaagaa 780
tacccacacc tacttctaca ccagctttgc agcctacatc ttcggcctgg gccttaccat 840
cttcatcatg cacatcttca agcatgctca gctacgagtc ctcggcggaa atcctgcctc 900
ataccccgag gctcacccac ttccacacaa catacga 937
<210> 25
<211> 2811
<212> DNA
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: L,G:085713.1:2000MAY19
<220>
<221> unsure
<222> 2789, 2799, 2805, 2807
<223> a, t, c, g, or other
<400> 25
ctttgaccaa gtcatttgac ctctctgggc ccatctttat tggaaaatgt caagtagatg 60
gtctctaata aatttttgtc cagttctaac attatgtgat tctaaatgta tttatactga 120
ccttcttaac ttgaactctt tgttttttca gcatttagta tgagaaccta tgtttgccat 180
atttgtagta ttgcttttac atctttagat atgttccggt cccacatgca aggaagtgaa 240
catcaaatta aagaatccat tgttatcaat ctagtgaaga attcaaggaa gacacaagac 300
tcttaccaaa atgagtgtgc agattacatc aatgtgcaga aagccagagg actagaggcc 360
aagacttgtt tcagaaagat ggaagagagt tctttggaaa cccgtagata cagagaagtg 420
gtcgattcca gacccagaca tagaatgttt gaacaaagac tcccatttga gactttccgg 480
acatacgcag caccatacaa tatttcacaa gcaatggaaa agcagttacc tcattcaaag 540
aagacatatg actctttcca agatgaactt gaagattaca tcaaagtaca gaaagccaga 600
ggactagatc caaagacttg tttcagaaag atgagagaga actctgtgga tactcatggg 660
tacagagaaa tggttgattc tggacccaga tcaagaatgt gtgagcaaag attttcacat 720
gaggcttccc agacctacca acgaccatac catatttcac cagtggaaag ccagttacct 780
cagtggctac caacccattc aaagaggaca tatgattctt tccaagatga acttgaagat 840
tacataaaag tgcagaaagc cagaggacta gagccaaaaa cttgtttcag aaagatagga 900
gatagctctg tagaaacaca caggaacaga gaaatggttg atgtcagacc cagacataga 960
13/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
atgttggagc aaaagctccc atgtgagact ttccagacct attcaggacc atatagtatt 1020
tcacaagtag tggaaaacca gttacctcat tgcttaccag ctcatgatag caaacagaga 1080
ctagattcta ttagctactg tcaactcacc agagactgtt tcccagaaaa accagtaccc 1140
ttgagcctta atcagcaaga aaataactct ggctcataca gtgtagaatc tgaagtttac 1200
aagcacctct cttcagaaaa caatactgct gaccatcaag caggtcataa acggaaacat 1260
cagaagagaa aacgacacct agaagaaggc aaagaaaggc cagagaaaga gcagtccaag 1320
cataaaagga aaaagagtta tgaagataca gatttagaca aagacaagag catcagacaa 1380
aggaaaagag aggaggatag agtcaaggtc agttcaggaa agcttaagca tcgaaaaaag 1440
aaaaaaagcc atgatgtacc ctccgagaaa gaagaacgta agcacaggaa agagaaaaag 1500
aaatctgttg aagaaaggac agaagaggaa atgctttggg atgagtctat tcttggattt 1560
tgaatgttta gttttgttta cccaaggttg aattgaaaaa aaaaaacagt caatatggat 1620
ttagaaaaag gaacacctga tgaagaaaag gagaggtaga tacagtcagt gtcacttcag 1680
gacacttagg ttttttttgt ataaaaattt aaattgaatt aaaagaagga aaaaaaaagc 1740
ccaaacttaa cctctgagaa aagaacataa gaactcaagg agaacataag agaaaaggaa 1800
acctgttaca gaaaagacaa gaatctgtgt tttggaatga gtctattctt gggtattgaa 1860
cttttagttt tgtttgccca aggattaatt gaggaaatca gctaagaaaa tggactttag 1920
acaaaagcaa gaggatcaga tgaagaaaag gagaggtaga tacagtcagt gtcacttcag 1980
gaaagctatt taaaaaaact tgaaatttaa ttgaaagaag aaacaacaac aaaaaagcct 2040
aaacctagcc tctgaacaac actaacatga gaacacaaga acttaagaga aaaagaaacc 2100
tactcaagaa aagacagaag agacagtgat ttgggatgag tctactctag gattttcaac 2160
tttttagttt tgttccttca aagttgaagg aaaaaaagtt tggttttata aaattcatgt 2220
tattgtaatt tttctaggtg gatggctact ttaatctcta aaaaagccaa gtgaagtaaa 2280
agtattcagt atgccttttc ctcaagttac tttccttcat tttcttaaaa aagaaaaaaa 2340
attattaaat gtttctcaca tatctcacat ataatgtaat ttccctaaat gaagttgtct.2400
ctacttctgc tcatcaaatt gctgtgatag tgaattattt attcatggga gataatttat 2460
tttaaaggac agaattacca agcgttacaa aatcagttct ttccttggtt ttgtgttagt 2520
gttggtggta ttttattgtt gtttttctgt gtttatgtgt ctcagctttc tccaaggaat 2580
atgtatgaaa taacttaaac tgattttttc tttgttaaat ctaatttgca gtgtattttt 2640
gcattttcta gttctgaaag tggaaaatga aacagtctat aataaactta gatgatatat 2700
agttttaaaa cggtctcaaa aagtactgat ataaggtcag tctatattct ggaaatgttt 2760
atattaaagt gttttaattt ctaaaaaana aaaaaaaana gaaananaaa a 2811
<210> 26
<211> 2963
<212> DNA
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LG:482421.1:2000MAY19
<220>
<221> unsure
<222> 1741, 1900, 1932, 1972, 2006
<223> a, t, c, g, or other
<400> 26
gaggtgcctt gaaattgtaa atgtattttt tttcttttat tttaagctgg taaatacagg 60
gtaaaatctc tttagatctc aatcatgcct attagacaca caattttatt taaactattt 120
aacctgtcag atttaagaaa ataatttgga aaactcactt ttgtaacaaa ttgcaggtac 180
aaaaattact catttggaat agtcagaata cagatgctac tcacctgtga gcacagatat 240
attcatattt ctatgtcaga ccaaaatcct gcttaaacac acaaacattc ctaacaatgt 300
cataatgttt actctttctc ctggcttaat aaactatatt tctgatatta ttggaagatt 360
attgttagaa ttgaaggaga taatacaggt tgagcagccc ttatggaaaa tgcttgggac 420
caaccaatag tgtttcagat tttgattttt ttcaggttat ggaatatttg catacacata 480
aggagatacc ttggtgttgg gacccaactc taaacacaaa attcatttat gtttcctata 540
cacctttaca cagagcctaa aggtaattta tacaatattt taaataagtt tgtgcatgaa 600
aaaagtttgt gtacattgaa ccatcagaaa gcaaaggtgt cactatctca gcgacccaag 660
tggtggtgtc agcactcaaa aagttttgga ttttggggta tttcagattt tagatttttg 720
tatgaggaat gttcaacctg tatttgaaca agcattacca aatatcattg aatattaata 780
tcttttgcgt aaaaactgct attatcagca tcatagtttc tctaaaaaga aaacttgggg 840
atcatagccg atagagagac ttgctaaaat ataaatcagc ctctgcaaaa ctgtttacat 900
atttattggt ttacatattt tattggttta tttctatccc ctgttcactt tttctcttcc 960
acttccaatt atgaagagaa aatatttgtt cagggttgtc cccccgcccc ccgtcactgc 1020
ataatttctc ctcttacaag ctgcttttgg ctttcattaa taacagcttc cttttagaag 1080
gtctgataag gatatttaag gaagaagaga atgactctgt tattaaaggt ggcatggaga 1140
ctgtggaggg aatatttttt aaagcactac tcatatcctt taaactaaat tttgccaaag 1200
14/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
cccgagacaa cattaaggag aaattgtacc ttaagttagt aattccaaat ctatctgagt 1260
tgtataccca tcaaagacaa tacagttatt aacatagatg aaggtatgct ataggcatca 1320
ttcattatct ctatattgaa taggtgaaag ataactgtag tcaggtgaaa ggcattcatt 1380
atttttaagc tgaaaagggg atccttgaaa acactgaaaa cctctacaac aatcttcagg 1440
aagcctgcta tcttgggatt cactaataat aggccaagaa caaaggcaag catccattcc 1500
tcactccacc acttttctat ttcagtgggt gtcgttgcta cgatgaagac tttggaaatt 1560
tcctttctct tttaggacag ggtcaggatt taggactcat agcctgaaag ctcattacat 1620
actccttgta accatcagtc caaggttcag ttcactaaag tgcatgttct aaaacaagag 1680
ctatcctcat tccaaatttt aaaatatgta ctctggtcgg ttgcagtggc tcacgcctgt 1740
natcccagca ctttggcagg ccgagatggg cggatctttt gaggtcagga gtttgagacc 1800
agcctggcca acatggtgaa accccgtctc tactaaaaat acaaaaatta gccaggcatg 1860
gtggcatttg cctgtaatcc cagctactcg ggaggctgan gcaggagaat cacttgaacc 1920
tgggaggcag angttgcagt gagctgagat tacaccactg cactccagcc tnggtgacag 1980
agtgagatcc atctcaaaaa ctgaanataa aaataaaaat atgtattctc ctaactgaaa 2040
tatttactta atctggaaaa caatgtaact atttttaaag tggttacatc tattcttgct 2100
gaagaacaat aaacagaatt ttttgacgaa gcataaccaa atttcagaac agtctaatca 2160
atgccaagta tccaaggcaa actctaatac ccatccattg tgcaaaacca caagcacgca 2220
agtattaaat aagagcaagc tgtcctgagc ccatacctaa tgaatttgtg tcttaaatat 2280
tgtacattgt gtttgaggct tgtcaaaact gggattatgg caagaaaggt tgcctaactc 2340
atacctttct gcctcaaatt ccaggtgcta aaggctaatg gcattttaaa catcttacat 2400
ttttaaaaat ttatattgcc tctg'ccaaac aggcctaata gttaaaagca agttgagaca 2460
aaccaggcag attcagtgtg tggaacagga aggatgtgct ttaaaaaaag gtggaatccc 2520
tcaaaaaatt ctatagggag acagcagcct taatctacat aattcttcat ctcgccaatt 2580
cagccgcagc ctttaaagag ttagtgttaa tggctttctg gtttgaaaac aaaaatgcat 2640
ctatgtggtt gaaagtttgg gaggagattc accaatatct gaggagaaga tggagtgaag 2700
ggaattctta ctttttgctt tatacctttc tataatattt agattttttt ttactgtaag 2760
tatggatcaa attgcaaaat aaagaaaaat gccaacctta gaaaagacaa taaatgcaca 2820
aaagatataa acaggaacag caaatattta tattttttcc attttgctct ttttaaatct 2880
atgtttagaa ctttatatct tgggacttat gtatatatat accttttaaa taaaataaat 2940
tttctaaata aaaagttgaa aaa 2963
<210> 27
<211> 643
<212> DNA
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LG:330944.4:2000MAY19
<400> 27
tagcaggaat tgaacaacat taccaagctc aatgaacact tcagcaaatt tggaactatt 60
gttaatatcc aggttgcttt taagggtgac ccagaagcag ccctaatcca atatcttacc 120
aatgaggagg ccaggaaagc catttctagc acagaagcag ttctaaacaa ccgattcatt 180
cgagtcttgt ggcataggga aaataatgag caaccgacac tacagtcctc agcacagctg 240
ctcctgcaac aacagcaaac acttagtcac ctctcacagc agcaccatca cctgccacag 300
catctacatc agcagcaggt gctagtggcc cagtctgctc cttcaacagt gcacggaggt 360
atccagaaga tgatgagcaa accacagaca tcaggtgcat atgttcttaa caaagttcct 420
gttaaacatc gtcttggaca tgcaggtggt aaccagagtg atgcatcaca tttgttgaat 480
cagtctggtg gtgctggaga agattgccag atattttcaa ctccaggcca tccaaaaatg 540
atttacagct cctcaaactt aaagacacct tcaaagctct gttcagggtc taaatctcat 600
gatgttcaag aagtgcttaa aaaaaaaaaa caaagcggcc gcc 643
<210> 28
<211> 1966
<212> DNA
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:223060.1:2000MAY01
<220>
<221> unsure
<222> 39
<223> a, t, c, g, or other
151104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
<400> 28
gggacaaatg actttttctt gttgaggcaa atagcgaana ctctgcttaa tttccacgga 60
atttgtgcca gttttcaaag actacaattt gaagaggcat tatatgcaaa aacgtgctga 120
caaatttggt gtgtatgtgt tgtaaggaca aaatagcaga actgaaaaaa agtctgtctt 180
ttcaacaaaa aagatttttt agaaaagtta caactcggac tcaatcgtaa ggtaaaacct 240
agttatgtgg tagcaaattt aatagcaaaa aaatcaaaac catttactga tggtgagttt 300
attaagcaat gtctggaaga tgtggtagat attatttgcc ttgagaaact gatatttcta 360
aaatcagttt gtctcaccag actatagcca ggagaattgg agaaattggg aaatctattg 420
aaagacgttt ggagagtaaa actgctaatt taaaatttta tgctttggtg atggatgaag 480
gcactgacac tacagatacg gcacaacttg ctatttttat tagaggtatt gatgatgaat 540
ataatgtcac tgaccgaaat cgaaatgtca ccatgctatt aaaagacaca actaaatcaa 600
gagatttata tgaagcagtg aaaaatatgt taaagcaatt ttctttgtcc tttgtaaaca 660
tatgtgatat agctacagat gctgccctgg cgatggtagg taaaaagaga gggacttgta 720
caattaatag atgatgcagt tgccacacaa aactcacatt tgatgaagta ttattgcata 780
atacatcaag aaaatccatg tgcacaagct ttaaaagtag ataacgtcat gcaaattgtc 840
atcaaggctg taaatttcac aagggcccag gaattgaatc atcgctagtt tcaggaattc 900
cttaaaagta tggatgctga ctctagcaag tcattcactt tttagaagta agatggttaa 960
gtcaaggcaa aatgtaaaga ttttatgctt tgtgatgtga aatcaagctg tttatggtat 1020
caaacaaaat tggtgccaga acttgacaat gaaaactggg cttacagatt tagcattttt 1080
agtgggtttg acggcccatt taagtgagtt aaacctgtgt cttcaagttg aaaacccact 1140
ttaccaatac aatgtttcaa accataacag cattccatat gaaactgaaa ttatgggaag 1200
gctcaaatta aggcaaacaa ttttatgcat ttcgacatgt tggctaaaca tggtcctgtg 1260
aacagccaaa aatacgcagc cttgcttttc aatttgatac aggaatttga aaacaggtat 1320
ttcaagattt ctgaaaaaat catcaatatt ttggtatatt tgcaactcca ttttcagtcg 1380
acatatatat gttacctggc aattttgaaa tggaatgcct agagctgcaa tctgatgttc 1440
aacttataga aaaatttgat tttgcctctt tactggactt ttgtaagacc tgtcttccca 1500
atgacaaata tcccttgctt cacaatcaca ccttgttcat gtcattgctt ttggggagca 1560
cttacatttg tgagctacta ttttcaagga tgaagaacac gaagagtaaa attagaacca 1620
aaatatctga tgagcacctt gagaactcac tgagaattgc aactacttcc atcaagccag 1680
atactgatgg attacgtttc tcaaaaacaa tgtcaagtac cccactagtt ttatgttgtt 1740
ctcttttctt ttataataaa aaatatcaaa aaagtagtga agtttagcta gatatgtaca 1800
ttttctgtat cagtgattgc aaacttggaa cctgttcaat gattttgaaa gaccctctga 1860
atggggcagt gcataattag gattattatg caagggacat ttttgcttat ctgtggtggt 1920
agatatataa tgaaaactat acacagacca tttgtgtgtg tgtgtg 1966
<210> 29
<211> 897
<212> DNA
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:213087.1:2000MAY01
<220>
<221> unsure
<222> 592, 601
<223> a, t, c, g, or other
<400> 29
gtcgaggcgc agcgctgcca tggctggggg ccgtggggcc cccgggcgcg gccgggacga 60
gcctccggag agctacccgc aacgacagga ccacgagcta caggccctgg aggccatcta 120
cggcgcggac ttccaagacc tgcggccgga cgcttgcgga ccggtcaaag agccccctga 180
aatcaattta gttttgtacc ctcaaggcct aactggtgaa gaagtatatg taaaagtgga 240
tttgagggtt aaatgcccac ctacctatcc agatgtagtt cctgaaatag agttaaaaaa 300
tgccaaaggt ctatcaaatg aaagtgtcaa tttgttaaaa tctcgcctag aagaactggc 360
caagaaacac tgtggggagg tgatgatctt tgaactggct taccacgtgc agtcatttct 420
cagcgagcat aacaagcccc ctcccaagtc ttttcatgaa gaaatgctgg aaaggcgggc 480
tcaggaggag cagcagaggc tgttggaggc caagcggaaa gaagagcagg agcaacgtga 540
aatcctgcat gagattcaga gaaggaaaga agagataaaa gaagagaaaa anaggaaaga 600
natggctaag caggaacgtt tggaaattgc tagtttgtca aaccaagatc atacctctaa 660
gaaggaccca ggaggacaca gaacggctgc cattctacat ggaggctctc ctgactttgt 720
aggaaatggt aaacatcggg caaactcctc aggaaggtct aggcgagaac gtcagtattc 780
tgtatgtaat agtgaagatt ctcctggctc ttgtgaaatt ctgtatttca atatggggag 840
tcctgatcag ctcatggcgc ccaaagggaa atgtattggc agtgatgaac aacttgg 897
<210> 30
16/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
<211> 2792
<212 > DNA
<213> Homo sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:405330.1:2000MAY01
<400> 30
ctgtccttaa gatggtcacc atattcttat tcaggctgtt gtcattttcc ccagagatgg 60
tttgtttaac gaatgatagg ctctgtgcct ggggatgtta gcagactctg gggtttgtac 120
agtgatgcct tctccctggc ccagagctga atattcatct agaattaaag ttggatttga 180
tataacaaat ttctttctat acaggtttta cataagagag acagtaataa tgtcaaggat 240
agcctgtgtg ggcagaaatt ggtaatccgg cttttggatt gtcagctgta gagccaactc 300
tgattatcta gccattgatc atacaaattg atagaaacat tagtcagtaa ttttagcttc 360
ttgccaaatt gttcacaaca tctaaatgta atgtgatgtg atgaagataa gtagtacaaa 420
gagaccaaaa taatttggga gaattaggaa tgatgacaat tttttttaac aactttacct 480
ctaatagggt tacttggatg agccaactcc gcttccttcc catggatatg gaaagggact 540
ctgtgtatta ttcaggttta ttggcacgaa gatacttgtt ttaagttcct tgagaaccca 600
tgatggacag ttgacagaat gcttaaacct gtcaaaagat gagtgatttt gtgtgggaaa 660
agccttccca ggcgtctgta ccgaaaggat gcagcaaaca aggggctaat ccatgagcag 720
tgttctgtag gctctgtgac atctttggtt tataggattt tggagccttt tattgtccgg 780
gaactatttg aggggtttca ttataggcct tggttctctc caggggccag atgagtttat 840
tgtggaatct ttgaaaggac aaggcctctg tgaatgaatc agtcccaggg aagcatttgg 900
tggtggcggc agtggaggat tgcccggtga acctataaat cagcagtctc ttgggcagag 960
gagcaagccc ctcgaacatg atttcaaaca agcaggtcct cttctctcat ctcacgtcct 1020
tagtctctgt taatgaacat actggatgtg gagtttaata aattacctac tatcatctgg 1080
ccacttagat tattatcaca ccactgtgga ctgttcctgg ggggagaaga acagaccgat 1140
ttgaaagatt caagggagaa agattaagga tcaggattgc atgaaagaag aaaatccttc 1200
aatatttaaa atgtttctta caatacccac ggagcacttt tatggttcca gccgagcgtt 1260
cctgaaatga actgaccatt aacagcgcct ctttgatagg ttaccctgat gctgctaaag 1320
taaagcctta agtgtgtttt tgggacaacg tgctgcttat tccacctcag ccacatatgt 1380
gtttgtgttt aggatattgt aaatctttgc taagtagtgt tttccttggt gaatgaagtc 1440
attgttgtct tcaagtgtac catctgccta gcaaaaaatt gctacaaact ttctcttatg 1500
gcaatagtcc ttgggtactt ctaatatttt taggcaagag acaattttct gtactaggaa 1560
tcttccactg ccaggaaaac acagtgccag taagggttct acatacacac tgaccatctg 1620
cttaatagac atgtatttcc tttgagtagg acattagctt ttgattataa agctcaacta 1680
gtataagcaa aaatataaca tctagaagca cagttttagc caggatgttt aaaaattaca 1740
gttttgtgag acttaagggt ctttttaacc taggtaagtt tatatgacct aacttaattg 1800
tagccctatt cttggtacct tcccttttgg aaagtagagg ttgcggtaaa caagcgctag 1860
ggtattataa gagacttttc ctgaggcacc tgtttggaat ctggttttct cagcggcagc 1920
ttgacatgtg cacccttttg tattaaacac tgcaagggtg attgcagggg agcaggaaag 1980
ccatcctaaa ctcactactg agtacgattc agtatgttcc tgtggatgtc tgctgtgact 2040.
aatataaatt tcttgcagaa tcagctacac ttaattatgt tgctgataga caagcatcca 2100
cgcttcagct gggcactaag tgttttcatt gtaggatcag cagcaggtta aagactgaac 2160
ggttagtgaa gactaaatgt cttaagaggg tgcgatgtct aggttgggct tgtgacgttc 2220
ttagtggcct agcgcttctg gatggcacct tgagaagtga acttctagag aatctacatt 2280
taaaaggcga agcgtttaga aagcagagct agtctattct agttagctga tgcgaactaa 2340
aattctgtag tttcttaaga tggagccact gacgagatgt cacagtatag agcctgcagt 2400
ctcaactcat tgtgatccta atggtctggg tgattggatg gtttgagttg ttagggattt 2460
tgaagttttt cattttaatt gcatatcctg ggttggatgt tagaactaaa ggaaacccca 2520
ggaatattta cctgggtgtt acatttaata tttaatgtaa ctggtcctag caacatttaa 2580
gggggatttc tgaagcccaa ctccgggagg ctgtgggctg cacattttgc actgttttta 2640
tatacttgta ttcatatcct cttatcacct cagactcaga cacaaggcct tttacatgga 2700
aattttacaa attacttcca tttatgtaaa ataacgtcct gtgaccaagt tgtttaaatg 2760
gaaaataaag tgctttcttt aaggaaaaaa as 2792
<210> 31
<211> 9549
<212> DNA
<213> Homo sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:350243.2:2000MAY01
<220>
17/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
<221> unsure
<222> 878, 1210, 8010, 8017-8018, 8030, 8032
<223> a, t, c, g, or other
<400> 31
tgggcatgta ctgaccaatg tggcaggtct gagaacatag ctgaagctga aaataggaaa 60
gctgggggca aggaagagcc ttgaatcttg aggtgggacg ttgactctaa gatgttcttg 120
aaccagtggg agcctccgga gggaaaggag tggatgcaaa cccggttgag acatacgaca 180
gtggggatga atgggacatt ggagtaggga atctcatcat tgacctggta cgccgatctg 240
gaaaaggacc agcagaaact ggaaatgtca ggctcaaagg aggtggggat accggctccc 300
aatgctgtgg ccacactacc agacaacatc aagtttgtga ccccagtgcc aggtcctcaa 360
gggaaggaag gcaaatcaaa atccaaaagg agtaagagtg gcaaagacac.tagcaaatcc 420
actccaggga cttccctgtt cactccaagt gagggggcag ctagcaagaa agaggtgcag 480
gggcgctcag gagatggtgc caatgctgga ggcctggttg ctgctattgc tcccaagggc 540
tcagaagaag gcggctaagg catcccgcaa gtgtagccgg gttcccaaaa ggagaaggag 600
aacagctcat ctaagagcaa gaaggagaga agcgaagtga gctggtgtga cttgttccag 660
acaaatggat tcctggggtc ctccatgcca tgttcccatt gtggaaggac tggtgtgtgt 720
gtcagtatga tggaagtgca agggttgata caaggagctg tggcagccac ttgggagtat 780
agctattgag cctggggcag ctgctcaatc ctttgggaac tatcacggat cctagagtga 840
aggcgggaat gagtgtcgcc ttgctaacag aaagtcanat gtctgaatag gatggagtcc 900
ccttgtttcc acacccagca gtgctgccaa tacacctttt ggtgcccagt ggtcaacaat 960
gacatctcat ctccttgttg tagcagatca tggttcgtga ccccatcaga gtggggtgct 1020
caccactatg tgatgtggct ctggccacag agcctgagtg cttgggcccc tgtgaacctg 1080
gaactagcgt caaccttgaa ggcatcgtgt ggcaggaaac agaagatggg atgttggtgg 1140
taaatgtaac gtggagggaa caagacaata atgtaggtac acgtcctgtg acgtgcacac 1200
gacatgatgn tgggcacccc cgcaggttct gtgactcccc gaccagtgac ctggagaatg 1260
cgcaatggcc ggggtagagg caaacgcatg cgtcccaaca gtgatacacc tgtcaatgag 1320
acagccacag cctcgtgaca gcaaaggcac cgagtgacag cagctattca ctgggctagg 1380
agccaatagc aaaggccgtc ggggcagcca gaattcttca gagcaccgcc cacctagcca 1440
gcagcacttc tgaggatgta caaggccagc ccctcctcag ctaataagcg gatttacaaa 1500
cccctttcag acatggagct gaattctagc tcagaggact ccaaagggac caagcgtgtc 1560
cgtactaatt ccatgggctc agccactggc ccccttcctg ggacaaaggt agaacccact 1620
cttctggaca gaaactgccc ctccccccgt cctaattgaa ctgtccccac ccaaactgca 1680
acaagaagta caagcacatc aatggactta agtaccacca agctcatgcc catacagatg 1740
atgacagcaa gccgggaagc gggatgggga cagtgagtac ggagaggaac ctattctcca 1800
tgcagatctt gggagctgca acggtgcatc tgtctctaca aaaaggttcc ttgtcccctg 1860
cccgctcagc atacccccta agttcgactt gtagagcccc catagccctt cgtccttcaa 1920
gcaaatttca gcacaaaagg cctctgtaag aaaaagttga gtggggaagg ggacacagac 1980
cttgggggcc ttatcccaat gatggctctg atgatggacc ctcagtgatg gatgaaacaa 2040
gcaatgatgc ctttgattct ttagacagga agtgtatgga aaaagacaca atgtacaaac 2100
acctctagtt taaaaccgtg aaaagattcc attccaagag cctaaagtca gcccagtccc 2160
attgcccctg ccatcccccc acagcaaatc tacaccttcc agacagccac cttcactagc 2220
agcgagccca ggctcttcct caggcttgac cgccacagtg gcacaagcca tgccctacag 2280
tccccaactc aagcccattc agcccatagc ccactgttat gggagaacct ttcacagtca 2340
accctgcctt gactccagcc aaggacaaga aaaagaaaga caaataatag aaggaatctt 2400
caaaggaact tgtaagtcct ctgacccctg ggacaccctt gtcgagcaga tggtaagtca 2460
ttatagccca ttcagggaat cttcaggaaa tgggatgaaa atggaggggc tcctaaatgg 2520
ctcatcagac ccccaccaaa gccgactggc tagcatcaag gctgaagccg acaagatcta 2580
cagtttcacg gacaatgccc ccagcccttc cattggaggc agtagccgcc ttgaaaacac 2640
tacccctact cagcccctga ctcccttaca tgtggtgacc cagaatggag ctgaagccag 2700
ctcagtcaaa accaacagcc ctgcatactc tgacatctct gatgctgggg aggatgggga 2760
gggcaaggta gacagtgtca aatcaaagga cgccgaacag ttggttaaag aaggggctaa 2820
gaaaactctt tttccccctc agcctcagag caaagactca ccatattacc aaggctttga 2880
gagttactat tctccaagtt atgcacagtc cagccctggg gctctgaacc ccagcagcca 2940
ggcaggagtg gagagccagg ccctgaagac aaaaagggat gaggaacctg agagcataga 3000
agggaaagtg aagaacgata tctgtgaaga aaagaagccc gagctgagca gttccagtca 3060
gcagccctcg gtcatccagc agcgtcccaa tatgtacatg cagtccctgt actacaacca 3120
gtatgcctat gtacccccct atggctacag cgaccagagt taccacaccc accttctgag 3180
cactaacacg gcttaccggc agcagtacga agaacagcag aaacgccaga gcttagagca 3240
gcagcagcgg ggagtggaca agaaggcaga gatgggcctg aaggagcggg aggcagcact 3300
caaggaagag tggaagcaaa agccgtcaat tccaccaact ctcaccaagg cccccagcct 3360
gacagacctg gtgaaatcag gacctggcaa ggccaaggag ccaggggctg acccagccaa 3420
atcagtcatc attcccaagt tagatgactc ttcaaaactc ccgggccagg cccctgaagg 3480
ccttaaagtg aagctgagtg atgccagcca cctaagcaag gaggcctctg aggccaagac 3540
aggtgctgag tgtggtcgac aggcagagat ggatccaata ctctggtacc gacaggaggc 3600
agagccccgg atgtggacat atgtttatcc tgccaagtac tcagacatca agtcagagga 3660
tgagcggtgg aaggaggagc gggaccgcaa attgaaggag gaaaggagtc ggagtaagga 3720
18/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
ctctgtcccc aaggaagatg ggaaggaaag cacaagtagt gactgcaagc tgcccacgtc 3780
agaggagtct cgccttggga gcaaggagcc ccggccaagt gtccatgtgc ctgtgtcctc 3840
cccacttacc cagcaccagt cctacatccc ctacatgcac ggctattcct acagtcagtc 3900
ctacgacccc aaccacccca gctaccggag catgcctgct gtgatgatgc agaactaccc 3960
aggttcctac ctgccttcca gctactcttt ttccccatat ggcagcaagg tctcaggtgg 4020
tgaagatgct gacaaggcac gagccagccc cagtgtgact tgtaaatcca gctcagagtc 4080
caaagccctg gacatcttgc agcagcatgc cagtcactac aagagcaagt ctcccacgat 4140
aagtgataaa acttctcagg agagagatcg aggaggctgt ggggtggttg ggggtggtgg 4200
cagctgtagc agcgtcgggg gagcaagtgg gggtgaacgg agtgttgacc ggccccgcac 4260
ctctccttcc cagcgcctga tgtccacaca ccaccaccac caccacttgg ggtactcatt 4320
gctcccagca cagtacaact taccctatgc agcagggctt tcttctacag ccattgttgc 4380
cagccaacaa ggctcaactc cctcactcta cccacccccc aggaggtgag aatgacacca 4440
agtgcccgga taaagtcagc ttcacgggcc cggactggct tacccaagga ggtgctgaag 4500
gtgccgttta gacatcagtt aaatggtgtt gatcatcctg tttgccgttt ccaccatgac 4560
tgaaggcaga cccttggcta tctcacctcc accagacctc cggactacct gaccctacct 4620
cttcctcagg agctggagag ctggtactta gcaaaaatat ttattctctc agccacagtt 4680
atgactattg tggcctctgt ggagatgaag gcacgggaag caaccagggg aacatggcct 4740
cagcccagag aagccactgc tctgttcccc aagcccttgg tctgctgctg gagcagtacc 4800
agcccccccg cccaccaggg agggaccccc acccccaaga cactgggtaa ggtctgaaga 4860
cagcacagca gccatacccc tcaccatcat taccaccatc accagattct gcatctccct 4920
agtgctttgc accctgggaa ttggcagcat gtggaggaac tagaatctca ggaaagaaat 4980
tgggggttgt tttctacata attgtgaaaa caaggtcttc aaatgtggag acttctcccc 5040
atttacatga gcacatataa acgctcacaa cctagcctgg aaagggaaga ccaaggcatc 5100
tgccccaaca tggccttgag ctgcctgtga ggcagggggc aggggttcca acaccagcac 5160
agggctcccc agggacactg ggagcaagct ggtgctggag catgaatgac gtctgtgaag 5220
tagaacctgc gtccccacta agtcctgctg gcttcttatt ccccacactc cttgcccttt 5280
tcccttccct cctaacccct tggtgccttt gcccaggggg atccccacac tgggtcttgc 5340
ctcttctttt ccactgctgg gctcttaagc ctcagaccag ataaactagt attcccccca 5400
gcttggggag accttggagt ctgccaggtc accttagggc aaggcccaga aggcagcccc 5460
tgggagcacc cagcagttct tggagatgtc ctgtcatcta gccatctgat atcttcctca 5520
tttgaggcca cagatatata cagcccaatt cctctgtcta caagtacatg attttatata 5580
gctcagtcta taacctccat gtgggccaat ataagctgtg tttcttgggt aacacatatc 5640
cttgtttgag gggcccactg gccatgggag gttatttgtt ccttagaccc tggaataaca 5700
catccaagcc attacttatt agagtctcag aatgtactca gtggagctgt gctttgaggc 5760
agccaacatt tctctgctct ccttagaaat gcagtctccc aatggaagct ttatactctt 5820
tgtactggga aagtgaggat gatttggtag ctttattggg gtcatgtctt ccccaaggtg 5880
tggggagctt agcttacttg gcttttgagg tatcatccct ctgttctccc ctcctatctt 5940
tccatgaccc tctggattga gagagagaga taaagactga cagacaccag tgtaggctgg 6000
aaaagggagt gtgtgaccag agtgccaaaa gtgactagga gcaggaactt ggctccgact 6060
tcagtttgga aaactgggaa atacggggca cagctaagca caatgcccag tagtagttga 6120
tttccaagga ccctggaacc ctacacttga gaggcttagg gtcaccatct gctcaagagg 6180
atcccctctg atctacaggc cttttcccta ggtttctgcc tcctcgtttt tgttcaagtt 6240
gggttctgag tcctccccaa aaaccattgt tttagacctc ttggcagggg ccccaaaaca 6300
gcctccctca tacccatcat tccgtctgcc ttctgctgcc ctcatgggca gtgctctgag 6360
cagtgacctc cctttcctcc gtggaagtag ctagtgcaga caccgtcatc ccaccccacc 6420
tgagtcaccc caaccaagag gggtgacttg aatttcagcc tgattatgcc ctcctggggc 6480
tcctgtgagg tggagccaag gttcccttct tcttgttccc tgtattgttt ttaaatattg 6540
ttgtgtgttt tgtatctgtg gcactggcct gcagcatact ctgtatatat tgtaaaagga 6600
aaccgttagg agtaattttc ttttgcattg gggcaggcat ggccctgcat tcctgccctt 6660
tccactacat tctgtaacac agaggacgaa cttctgtatt aactggggca gccttgggtt 6720
ctccagaaga agaacaggtt tttcttttcc ttggtgaatt tttcttctta aacattttgg 6780
ctctttgatc ctcatatcca agttctcccc tgaagagtag gagctgctca gaagagcagg 6840
ttgaaagcca ccatgggcag atcctgatgc ctggccgggc ctagtcttcc ctctgaaata 6900
acatgaagca gcagctgtgg agattcttga caagtgctga gtgaaagatg ttgcttgcca 6960
cacctgctac atggtggatg gagataacat catggtgtgg agcttaccat gtggcatcca 7020
tgacctagtc agaggggatg agatgctcag caggggtcac tcacatgcgc tatcccaccc 7080
cacaaaatca taatgtgcat ggataaaatt tgctaccaag ggcacaagac caccagacca 7140
agcctgttta tgagccacac cactgcccag gccctcacag accattgctc acggggcttc 7200
ccatagagga gaagctaaag agggaggggg cctcatcccc agatagatca ggcaaggctt 7260
gggagagctg ctctttagga ttccacatca actacttcct cattttaagg tatggcagtt 7320
cccttcatcc ccttttcctg ccttgtacat gtacatgtat gaaatttcct tactcttacc 7380
gaactctctc cacacatcac aaggtcaaag aaccacacgc ttaggaaggg taagaggggc 7440
accctatgga aatgaaatgg gtgatttctt gagtctcttt tttccacgtt taaggggcca 7500
tggcaggact tagagttgcg agttaagact gcagagggct agagaattat ttcatacagg 7560
ctttgaggcc acccatgtca cttatccccg tataccctct caccatcccc ttgtctactc 7620
tgatgccccc aaagatgcaa ctgggccagt taagttgggc ccccataatt ctgggggcct 7680
ttgttgtttg ttttaattac ttgggcatcc ccaggaagct ttccaagtga tcttcctacc 7740
19/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
atgggccccc ctcctgggat caagcccctc cccaggccct gtccccagcc cctcctgccc 7800
cagcccaccc gcttgccgct tggtgctcag cccgcagcat tgggagcagg tcggctccac 7860
actggaggcc cgggctggag gggcagtgtt gctgttcata gattttgttc cattggcgtt 7920
gctctgttga atttaatttc aagtcttcct gattcttccc ttctgtaaaa gtgtacatta 7980
ccaagttcct tgttttttta tatatatatn tgggtgnnta tatatacaan cngtactctt 8040
tttgcctttg tacattcagg caagaagaga aaataaatct ttttaagaga caatcacaaa 8100
tctgtgaggg ctgctggtta tttctcctgg agtttgctgc tgagctgcct cttccttcct 8160
cccaattttc ctgttctccc tcagctctcc tgatcttcct ggccctgctc catatgcatc 8220
ctcagcttca ctttcccgtg gctgatggca agctgtggaa tccagtgtcc agactacctg 8280
ccttgtaacc cttttctgcc cagcattgtt ttctggcttg gccactggct tagcccagga 8340
gctttactct gtgcccctgg cctcccctct cttcaccttt agatttccat tcaccgaagt 8400
ggctttggac ccctgggtac tctgggacct gtttcctgga ggccctggct tgggacactc 8460
acctgagaaa actatgcagc tgggagctct ctgcctaaga gtttgcacta tttaaacctg 8520
cctgggagtt aggacggatg gttttaggaa tgaccggaaa aactacccct aaaactcccc 8580
cgacattcca gcctctagaa tgctctgatc cagagctcag tggatgattc ccagctggtg 8640
gactcctgtg gctaccccat caagacaaag ggctaggggt ttatgggtca agagtatttg 8700
atcagaattt taaagggtgg tatactctga aacacagccc aacctaaacc attgtttggc 8760
cgctttctct tttcctctac cttcctcatc cccacttttt tccctttctc tctacttcct 8820
cttcttaatt ggctttggaa ttgaaatata tttttaaatt atttgttgta tttattgaat 8880
aaagttttta atgtccctgt tcttaaaaaa aaaaaaaaaa aaaaaaaagt ttgggacact 8940
ggactcccgt gagctggaag gaacagattt aatatctagg ggctgggtat ccccacatta 9000
actcatttgg ggggtccagg gaccctgggc aatataagta ttctagctca gtgtcgtgga 9060
gatcatctac ccagtgctgg ggcttctgtg gacagtgcga ggacccacgt gaccctggag 9120
gagctggtcc aggtggactg aactcccggc atctttacaa gagcagagcg atgatcagca 9180
ttcctgccgc tgcttgctgg ggctcagcca tgggctgcac aggagccagt gtggcttcgt 9240
ggcccatgtg ggaacgcacc tgtctgttgg atgatgctgg gactccaaag gatttcacat 9300
actgcatctc cttcaacaag gatctgctga cctgctggga tccagcagga gaataagcat 9360
ggccccttgt cgaacttggg ggtgctgaat agcttggcga atgtcctctc acagcacctc 9420
aaaccaaaaa gacaccctga tgcagcgctt gcggcattgg gcttcagaat ggtgccacac 9480
acacccagcc cttctgggga tcactgacca acaggacacg gccaccatct gtgcaagtat 9540
gccaaaaca 9549
<210> 32
<211> 1818
<212> DNA
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:445188.1:2000MAY01
<400> 32
gtcagctatt ttctacatgc ttcatttgca gtgtaatatt ggattgtatg agactttggg 60
ttttgtgtta atacctacag aaaatgttga tattttctct tagcaggctg tcaaccaggt 120
taggttcagg tcataagttt ctacccacat tctttgaact gtagttgtca ttttagttta 180
tttttcaaaa acttttgcag tacctttttg gtctgtcttg tgtgtgcctt gcagtgaaca 240
gtctggattt ggacagtggt ctgtctgtta gttcagtttc tcaagccttt gtcacactaa 300
taggattgga tttatgtatg tccagcttgg gaattattac aggaattaaa aacaactttt 360
tagagtgctt tcctgagctc tctttctatt tgttccccct tctacttttt gcttccctgt 420
ggctgctgtt tctatcctcc agccagagag ctagtgttta ttttctccat tgtgttacac 480
acttgtgcag ctgcaaccac catatccagg gcccaatggt aggaggtaga gaagaaaagc 540
aaaagggatt ggcctcatcc tcttacaacg atagttccat tgaatagaga gaaaggtttt 600
cctgcctcag agtgttggct gcactaggct tttgttactg tagtctggcc ctgttaccat 660
gggattgctt gcatgtgggg atacaggaga attcagaaaa gaaaaaaaga tttgctattt 720
ctacattctc cctgagcatt aagacttccc ttgcccattc ctcaattcaa agctaaggct 780
tcttctggag ctgcctctgt gggcggttcg ggagatacca aaggagaaaa agtaccactg 840
ttgatatggt ggtatttcaa attctggtct accctatttc acatgccttg tttacttttc 900
agagctgaca gattgctgct ccatgcattc tgtccagttt cctaagagag acagcttgga 960
gtatgcttaa tccatcttac ctgggactga aacagctgct tattttgccg ttaaaaatta 1020
catgcagttt actgcgtggc tccgggtttg tttgtctgtt tttcctcctt taataggttt 1080
attcagaaaa catgtccact gcaattaggg aggtaggagt ttggagacag accagaacac 1140
ttctactgaa gaattactta attaaatgca gaaccaaaaa gagtagtgtt caggaaattc 1200
tttttccact atttttttta ttttggttaa tattaattag catgatgcat ccaaataaga 1260
aatatgaaga agtgcctaat atagaactca atcctatgga caagtttact ctttctaatc 1320
taattcttgg atatactcca gtgactaata ttacaagcag catcatgcag aaagtgtcta 1380
ctgatcatct acctgatgtc ataattactg aagaatatac aaatgaaaaa gaaatgttaa 1440
catccagtct ctctaagccg agcaactttg taggtgtggt tttcaaagac tccatgtcct 1500
20/ 104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
atgaacttcg tttttttcct gatatgattc cagtatcttc tatttatatg gattcaagag 1560
ctggctgttc aaaatcatgt gaggctgctc agtactggtc ctcaggtttc acagttttac 1620
aagcatccat agatgctgcc attatacagt tgaagaccaa tgtttctctt tggaaggagc 1680
tggagtcaac taaagctgtt attatgggag aaactgctgt tgtagaaata gatacctttc 1740
cccgaggagt aattttaata tacctagtta tagcattttc accttttgga tactttttgg 1800
caattcatat cgtagcag 1818
<210> 33
<211> 2198
<212> DNA
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:244378.1:2000MAY01
<400> 33
gagattttgg aatctggtga tactgttgtt tattacacta gcctattaca ttttctttct 60
ttataataac tgtttatgtg agtttcattg aaaatcgtgg ctctattgct ttattcatgg 120
tttccacaac tctttttgta acaccttaat tttctctctt aggtattttc ctgttaaata 180
agatatcaaa agcatcaatc acaagacaga gaaaacgtat taggaaaaac ttgtactagt 240
atattctaaa ctgaaatgga aaaactcatt attcatattt taataaataa aactcccaaa 300
tgatcttgct aaattatccc actatttaga agtagaaaat aagagaagag tgctttcaag 360
gaaatttgtc atattctccc ttctatctag aagttgacaa tgaattgcaa taaaactaag 420
acataactga atgctgaaaa ataccatgga ttaatgttat ggcttcttta tttttgtata 480
tccattccca caaaattgaa tttaagatta ttaatgaaaa ttctatatta agtaataatg 540
cttgtattag taatgggcaa agaagtcttt ctttgttaca agtaaccgtt agtaaaagat 600
gtactttgac atttctgaag gttaaacctt atatgtaaat attgtaattt aaatatgatt 660
ggacagctgt taagttttcg gggagggaag cagatgccag cgttctctgc tgaaaagaac 720
aagatggcgc ttgacggacc acagcagatg gagctggagg aggaaaaggc aggcagtgga 780
ctttgccagt attatcttgt cccaggattg gagaactcca gggtccactg gcatattaat 840
tgggtggggg gaaagccaca aggaacagtt ctgaactcca ggtgcatttg cagctgattt 900
tgaatgataa gacccaaaac ctctggaggc ggcaggtgca cgggaatgaa ctaaatgttt 960
aaagtgtgcc ttattacagg aggagctaca gctgctccca ggaattagga ctccctgtgt 1020
acagggaagt agtccaggcc atgggtaaga agaaagtgtt ggtcaaggtg catctcaagg 1080
acaagtttgt catagactgt ggacaaaaat atcagcatca gtgatgtgac acaccagttc 1140
cttggtggtt ctaagaaatg gaggtatact ttgtgcacaa ggatccttac cccacaaggt 1200
ggactccttg gtgtcactgg tgtattgtgt agagaaagtg tcccagtatc tcagtcttat 1260
agaaatgatt gggtagacct ggataaggca gaatcacaga agcatcaaca gaagtgatct 1320
gacctgcctg ctaagcatcc cgagctcttt caaagcactg gggcattgca cagccccaag 1380
tggaatgcgt gcttaggaag agactgttgg ccctgggctc tggctcatta ttaggggctg 1440
gggtccctta atccaggtct ctggcttttg aatgggtcca gaaattcatt ggggaatttc 1500
tgtgatggcc agagaaaatg ctcatctgtc atcttcatgg atgaaattga ctcttttggc 1560
tcctcagagc tggaggggga tgctggaggg aacagtgaag tgcagcagat gatgctttcg 1620
agggtggctt tgaggccacc aagagtatca cgcacggttt atcacgggtg cgaatacgag 1680
atgagatacc tcgtgactcc ggctgtgttt gtcgcccagg ggcaccattg acagaaaaat 1740
tgaattccca acctgcaatg agtaggcctg gctggtcact ttgaagattc attctacaga 1800
aatgaaccct gacccagggg gatcaacctg agaaaaattg ctgagcttat gccaggagca 1860
tcaggctgaa gtgaagggca tgtgcaccag aaaccggcat gtatgccctg agtagcgagt 1920
ccatgtcact cagaaggact ttgaggtagt ccaaagtcct atctcatgcc aaaggacagt 1980
gaggaaaaac atgtccatca agaaactatg gaattgaggg cacatccttt gtgtgtatca 2040
catacaataa aactcagtgg gacaagcaaa aaaaaaaaaa aaaaaagttt tggggaggga 2100
tgatctgcta gtgtataatc aataactttt aacatttagc ttgtatttag taacatttca 2160
ttgtgttttg aaaaaaagta aaaaatcttt tgaagcac 2198
<210> 34
<211> 431
<212> DNA
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:236574.15:2000MAY01
<400> 34
tataaatggc atttcttaat cttactgtat ttccatggaa taaaagtaat tcttatgcac 60
actgaagtta aaaaaaaata gcatttaaaa tttctgctca ggaaagtagt ataattttta 120
21/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
acataagtga gtttctcttt gtgttataat gtaatgaatt cttatacgca tatggagagg 180
aaaatgacat ttttctattt atggttttag ttcagccttt aagatacctt gatgaagacc 240
tggactattg aatggagcag aaattcacct ctctcactga ctattacagt tgcattttta 300
tggagttctt cttctcctag gattcctaag actgctgctg aatttataaa aattaagttt 360
gtgaatgtga ctacttagtg gtgtatatga gactttcaag ggaattaaat aaataactca 420
gaatgttatt g 431
<210> 35
<211> 3730
<212> DNA
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:010100.20:2000MAY01
<400> 35
ctgaggttat tttggagggg aaggggggct tctagatgta ccttttatgc tttattaaaa 60
agtatattac ctattaaagt ttgtttaaat ctatttgagt taaaaatttg agatgtaccg 120
tgttttctaa acactgtctc cagtggcttc aaaaacacag gtactgttgg aaggcattca 180
cttttgagtg gcctttgacc tcagttttaa tctgattaat tcagtcattt tataatcttg 240
ctcttggtga gtttaaacta gatttggcta aaatagaggt gggagtgttg gcccttcaaa 300
gacagtttga tgtgttcaaa attgtagtgc atttaaaagg gttagacttc tgtgatattt 360
gtccaacgtc aatcagtact cattgcattt ttttacttag gctcttgagt gtgagtggac 420
tactggtatc atatgcaact tctgaactaa gttttaagag aatatgaatc atcagttgaa 480
taaaaacctg aacagtggtg aatgcaactt tgagacatat ggaaaggcta gagttggcat 540
ccaggggaca caaatagttt gaagactctg gtagtagaat gatgcaagtt tccttaaaat 600
taggcaatat ataatattga tactacgaaa ttcagtactt ttccggtagg agggggtcag 660
gtctcattgc ctttgtccgt accccaaaaa tatgaaaagg tggtctacaa gtttggttgt 720
ggcattgtca cagcagttgg ccccatgtta catttcctct tgtggcacct ctgagaggtg 780
tgtcttcatt acctcttgac aagagtatat tttgattgac tgctctatgt gcttgttgat 840
cttttatagc atttaaatca aacggtatcg agatggattg cgttatgaaa ccataatggt 900
cccagatgac gctagtgatg ggacagtacg acttcgtgga ctaccatttg gttgcagcaa 960
agaggaaata gttcagttct ttcaaggtac ctctagtatt agtcaaagtt tagtagtatt 1020
gtaattttat atttgtattg ttttactgtt tttaatttgt aaaacccatt tgattttgga 1080
acttttaagt ttaactatga tagtcttggt taatgtatta aaataatatg ctccagttaa 1140
tattcaatac agaatgtgta gaatatgtaa aacctaatta atgtgcagta acatatttga 1200
gaattgtgat gaaatgaacc gtgaattagt atatggagca tatatttgat tttgtagccc 1260
ttttttcatg taatataggt gggcttttag agtgtgtaat tacacagtgt tgtttacact 1320
aggtcgcaaa gaaatttatt taatccagta atatttgaaa aaatctttca tttgtattat 1380
ggggtgatgg gaaactaagc ttttttgttt tgttttgttt tgttttgttt agacttgttt 1440
taaatatttg attcagatgg gaatgtttca gcctttaaca ctgttcccct tgatggggtt 1500
atttgtcctt gggttaaagg gttggaaatc gtgccaaatg ggataacatt gacgatggac 1560
taccagggga gaagcacagg ggaggccttc gtgcagtttg cttcaaagga gatagctaga 1620
aaatgctctg gggaagatat aaggaaagaa tagggcacag gtggcgatgg agagtttggg 1680
atggtgttaa atttttattt ttgggggttg tgggtcacta ttgcttaaat gggggggtag 1740
ccataacatt tttctggggt agtttaaaag aattgataat tatctaaatt taacttggaa 1800
actacagatt tgggtgggga attaatgcta atagttaaat gtcaaaatta gggattgttt 1860
cccattttct cctgtaggga tgttgttaga taaaatgctt ttagtataaa tcaccctatt 1920
tcccttttaa aacaccctat tatgtactta aaaggagaca aagctaaaaa tatactttta 1980
tgaattgttt ttccgtgact aaattccttt ggtaaaactt aaatagtcgg aattaagttt 2040
gtaggtttaa actgttgact tacggtgtat tttaggcaat ttaaatttgg ggttatgtat 2100
ctagatgata gaaaaactta ctgcattttg cccatgtatc taatttacac taatacattt 2160
atgctggaaa ccctgcacct taaaaacatt tttaaaatag gtatattgga gaccttcaga 2220
agtagcagga ggtcaaacca aaggatttta tgatccaccc aagaagattg ccggggacag 2280
cgacccgggg accattatga tagacccatt aggaggaaaa aggggggtta ttatgggagc 2340
tgggccgtgg aagtatgtat gacagaatgc gacgaaggag gtgattggat atgatggtgg 2400
ttatggaggt tttgatgact atggtgggta taataattaa cgggtatagt ggaattaatg 2460
gttttgatga cagaatgaga gatggaagag gtatgggagg acatggctat ggtggagctg 2520
gtgatgcaag ttccaggttt ccctggtggt catttcgtac atattagagg gttgcctttt 2580
cgtgcaactg aaaatgacat tgctaatttc ttctcaccac taaatccaat acgaagttca 2640
tattgatatt gggaagctga tggccagagc cacaggagaa gcagatgtta gagtttgtga 2700
cacatgaaga tgcagtagct gccatgtcta aagataaaaa taacatgcgt aagtggtgtc 2760
tttggcacac aatcttattt cctaaacgtg aatttataaa ataagaggct ctaagatctg 2820
taggtaacgc ttggcagttg ttggggattt aaaaccattt gacctctata atggctttct 2880
gtgggcttta tatatcgctt gtactagtaa ttaataagca tactttgttt aatattacct 2940
taattgatct tttttacaaa gcttgtattg atgaatttta tccatcattc ctttctcccc 3000
22/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
tgttactctt tctttttttc ttaaagaaca tcgatatatt gaactcttct tgaattctac 3060
tcctggaggc ggctctggca tgggaggttc tggaatggga ggcctacgga agagatggaa 3120
tgcggcatgt aaagttttta aaatatgtca gggttagctg cttatcgatg agtctcaatt 3180
ttttttcttt tttcttttta aagataatca gggaggctat ggatcagttg gaagaatggg 3240
aatggggaac aattacagtg gaggatatgg tactcctgat ggtttgggtg gttatggtaa 3300
gtatctctag ttcagtttgt gttagtccgc atatgtagtg caaactttaa agtgcaggta 3360
ttacttttat tattttatgc agatatctcc tgctgagtga ttcttaatat ctttttctta 3420
aggccgtggt ggtggaggca gtggaggtta ctatgggcaa ggcggcatga gtggaggtgg 3480
atggccgtgg gatgtactga aaaccaaaaa caccaacata caagtcttga caacagcatc 3540
tggtctacta gactttctta cagatttaat ttcttttgta ttttaagaac tttataatga 3600
ctgaaggaat gtgttttcaa aatattattt ggtaaagcaa cagattgtga tgggaaaatg 3660
ttttctgtag gtttatttgt tgcatacttt gacttaaaaa taaattttta tattcaaacc 3720
acaaaaaaaa 3730
<210> 36
<211> 790
<212> DNA
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:037940.6:2000MAY01
<400> 36
ggaagagtgt agaacagagt ttttctttct gagtgttctt tttaacttca gtgttagtgc 60
tagtagtaac cttatatgtc atctctccag aggtcttcat caaggattca catggcagtc 120
ctgatctgaa gggcatattt aaaatgtact tgtccagatt tcactgctaa agattatgat 180
tcagtaggtc taggatgggc ttcagccgtt tgggttgatt gtgatagcat acatgtcttt 240
agttgaggac tgctggtatt acctgcaatt ttgagataga gaaaagtgca ggaaaatctt 300
cctccaggat cactaaagct gagccctagc ttgttacctg tggaggcatt gagacatttg 360
ttcacagaaa gtacagtttg gatttttggt tttttttaga agaaagctca ttatttagaa 420
attttgcaat gttaactttt ctactaataa cacaatcatc ttcacttata tttttaggct 480
catgctgaag attcggttat ggaccatcat ttccggaagc cagcaaatga tataacgtct 540
cagctggaga tcaattttgg agacccttgg ccgcccagga cgtggcggca ggggaggacg 600
aggtggacgt gggcgtggtg ggcgcccaaa ccgtggcagc aggaccgaca agtcaagtgc 660
ttctgctcct gatgtggatg acccagaggc attcccagct ctggcttaac tggatgccat 720
aagacaaccc tggttccttt gtgaaccctt ctgttcaaag cttttgcatg cttaaggatt 780
ccaaacgact 790
<210> 37
<211> 8059
<212> DNA
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:228550.3:2000MAY01
<220>
<221> unsure
<222> 461, 5072
<223> a, t, c, g, or other
<400> 37
ggcagaggaa tctgttcctc aaggcattca cggacttcct ggccttcatg gtcctcttta 60
actacatcat ccctgtgtcc atgtacgtca cggtcgagat gcagaagttc ctcggctctt 120
acttcatcac ctgggacgaa gacatgtttg acgaggagac tggcgagggg cctctggtga 180
acacgtcgga cctcaatgaa gagctgggac aggtggagta catcttcaca gacaagaccg 240
gcaccctcac ggaaaacaac atggagttca aggagtgctg catcgaaggc catgtctacg 300
tgccccacgt catctgcaac gggcaggtcc tcccagagtc gtcaggaatc gacatgattg 360
actcgtcccc cagcgtcaac gggagggagc gcgaggagct gtttttccgg gccctctgtc 420
tctgccacac cgtccaggtg aaagacgatg acagcgttag nacggcccca ggaaatcgcc 480
ggacgggggg aaatcctgtg tgtacatctc atcctcgccc gacgaggtgg cgctggtcga 540
aggtgtccag agacttggct ttacctacct aaggctgaag gacaattaca tggagatatt 600
aaacagggag aaccacatcg aaaggtttga attgctggaa attttgagtt ttgactcagt 660
cagaaggaga atgagtgtaa ttgtaaaatc tgctacagga gaaatttatc tgttttgcaa 720
aggagcagat tcttcgatat tcccccgagt gatagaaggc aaagttgacc agatccgagc 780
23/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
cagagtggag cgtaacgcag tggaggggct ccgaactttg tgtgttgctt ataaaaggct 840
gatccaagaa gaatatgaag gcatttgtaa gctgctgcag gctgccaaag tggcccttca 900
agatcgagag aaaaagttag cagaagccct atgagcaaat agagaaagat cttactctgc 960
ttggtgctac agctgttgag gaccggctgc aggagaaagc tgcagacacc atcgaggccc 1020
tgcagaaggc cgggatcaaa atctggggtt tcaccgggag acaagatgga gacgcccgcg 1080
gccacatgct acgcctgcaa ggctcttccg caggaacacg cagctgctgg agctgaccac 1140
caagaggatc gaggagcaga gcctgcacga cgtcctgttc gagctgagca agacggtcct 1200
gcgccacagc gggagccttg accagagaca acctgtccgg actttcagca gatatgcagg 1260
actacggttt aattatcgac ggagctgeac tgtctctgat aatgaagcct cgagaagacg 1320
ggagttccgg caactacagg gagctcttcc tggaaatctg ccggagctgc agcgcggtgc 1380
tctgctgccg catggcgccc ttgcagaagg ctcagattgt taaattaatc aaattttcaa 1440
aagagcaccc aatcacgtta gcaattggcg atggtgcaaa tgatgtcagc atgattctgg 1500
aagcgcacgt gggcataggt gtcatcggca aggaaggccg ccaggctgcc aggaacagcg 1560
actatgcaat cccaaagttt aagcatttga agaagatgct gcttgttcac gggcatttgt 1620
tattacatta ggatcgtgct gaggctcgtg cagtacttgc ttctataaga acgtctgctt 1680
catcttccct cagtttttat accagttctt ctgtgggttt tcacaacaga ctttgtacga 1740
caccgcgtat ctgaccctct acaacatcag cttcacctcc ctccccatcc tcctgtacag 1800
cctcatggag cagcatgttg gcattgacgt gctcaagaga gacccgaccc tgtacaggga 1860
cgtcgccaag aatgccctgc tgcgctggcg cgtgttcatc tactggacgc tcctgggact 1920
gtttgacgca ctggtgttct tctttggtgc ttatttccgt gtttgaaaat acaactgtga 1980
caaggcaacg gcgcagcata tttggcaaac gtggacgttt ggaacgctgg tattcaccgt 2040
gatggtgttc acagttacac taaagcttgc attggacaca cactactgga cttggatcaa 2100
ccattttgtc atctgggggt cgctgctgtt ctacgttgtc ttttcacttc tctggggagg 2160
agtgatctgg ccgttcctca actaccagag gatgtactac gtgttcatcc agatgctgtc 2220
cagcgggccc gcctggctgg ccatcgtgct gctggtgacc atcagcctcc ttcccgacgt 2280
cctcaagaaa gtcctgtgcc ggcagctgtg gccaacagca acagagagag tccagactaa 2340
gagccagtgc ctttctgtcg agcagtcaac catctttatg ctttctcaga cttccagcag 2400
cctgagtttc tgatggaaca agagcccagg ctaccagagc acctgtccct cggccgcctg 2460
gtacagctcc cactctcagc aggtgacact cgcggcctgg aaggagaagg tgtccacgga 2520
gcccccaccc atcctcggcg gttcccatca ccactgcagt tccatcccaa gtcacagctg 2580
ccctaggtcc cgtgtgggaa tgctcgtgtg atggatggtc ctaagcctgt ggagactgtg 2640
cacgtgcctc ttcctggccc ccagcaggca aggagggggg tcacaggcct tgccctcgag 2700
catggcaccc tggccgcctg gacccagcac tgtggttgtt gagccacacc agtggcctct 2760
gggcattcgg ctcaacgcag gagggacatt ctgctggccc accctgcgcg ctgtcatgca 2820
gaggccattc ccccaggcct gtgtcttcac ccacctgccg tcattggcct ttgctgtcac 2880
tgggagagaa gagccgtcca gggacccatg gtggcccaca tgtggatgcc acatgctgct 2940
gtttcctgct tgcccggcca ccacccatgc cctccatagg gtgaggtgga gccatggtgg 3000
tgcgtccttt actcaacaac cctccaatcc ggatgctgtg ggaagggccg ggtcactcgg 3060
ataccatcat ccctgcggat gcaccgccgt accctgctca tctgggagtg gtttccctgc 3120
ggttacgtcc aagcccgcct gccctgtgtg ttggggctgg ctgagtttcg gtctccccat 3180
caccggccgc ctcgtggaga aggcagtgcc acgtgggagg acaaggccac gccggcagct 3240
tccagccctg ccgcagaagt gccaggatgt ccatcagcca ctcgccaggg cacggagccg 3300
tcagtccact gttacgggag aatgttgatt tcgcgggtgc gagggccggg agacagatac 3360
ttggctgtga tgagcagaca tcctctgtcc ccgtggaggg gtcaacacca aggtggtgtt 3420
cgtgcaccag aacctgtctc gggctgacgg gggtggcaca caggacacgg gtggatccca 3480
acaggcagca ccgcacctcc gcccgcctcc cgcactgcag ctccgcccgc cgggctctgc 3540
gtctccacgt cccctcgtcc catccccacg tcccctcatc ccgtcacctc gtccccacat 3600
ccccttgccc cgtcacctcg tcctcatgtc cccttgtcct gtcacctcgt ccccacgtcc 3660
cctcgtctca tccccacgtc ctctcgtccc cttgtcccgt ccccacatac cctcgtcccc 3720
atgtccccac gcaggggctc tccttcgtct taggatctgt tcagcgctgc tctgggtggg 3780
ttagcaaccc cagggctgct gtgataggaa gtccctgttg ttctccgtac tggcatttct 3840
atttctagaa ataatatttg acatagcctt aatggtcctt aaagaagaca tttcagtgtg 3900
agattcagac ttcagacgct gaaactgctg ccttttagga aagcaccacc aacgctggag 3960
gaggagccgg ccctcacgcc cgccccgcgc cacgctgtgg aacggggctc cggcaagtga 4020
aacccagagg gtgtttccga agtgtcttca ccattagtta tttttggaag ctcagatttc 4080
accaatttga ttgtataatc ttttacctat aaaatattta tttgaagtag agggtaaatc 4140
agcggtaaga acagtgaaca cagtggttgg gataaaataa ggtgacaaac atcaccccca 4200
aagatgaggg tagcgagcaa ctggcttgag cagacagaac gtgggaagac tccatetctg 4260
tcccgagggg ggcaggcgga gggggtcccc aggggccacc ctgcccttga ggtccttgtg 4320
ttggccgccc ttggtttggc agccctgtgc ccaacgcttg cccccgggca aacaagtggt 4380
gtgtgcgttt ttacagcccc tttttaggaa cccaaatatg ggcataaatg taacacctat 4440
agcgggggca gattctctgt atgtccagtt aacaaattat gggtaaggta tttgttgaga 4500
aatcttaaaa tggccttggc acggaagtat ttccatagct gttaatatct cttttatcca 4560
tttattgaac atactggtct aaattttaac aaataggttt ttaaacgctt tcatttttaa 4620
gtttatgaaa tttggggcac tttaacattt aaaattctgg tgagagtttt gactgaatgt 4680
tccaatctct gagtgtatac gcaaatttct acagattaga ttttatctct ctacacaccc 4740
ctcttctttt ctgggtattt ctggtggcag tgattagttg aacagcacat ttaaggcacg 4800
24/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
ataattgcta acaccttttc ctttaacaat ttggtggcaa tttcatctgc tttcctaatt 4860
gttttcattg ttaattgcca tccttcagcc ttaaaaatag aagattctca cgtgaaggtt 4920
tagtaagttg gggtcccagg ctttggccgg ttgttggaga ttgtccccca tggttacttt 4980
gtgaacacca ggttttaagc tgtgaaagtc actaaaactt ttacacactc ccaaaaggtc 5040
tttttaacaa attgctgtgg gaaattatta cnaatgaatg tgcctgatga tttggaacat 5100
agaccaaggc ggcactgaga taaaaaacag aacaggatgc agatagatcc ctcaggtgaa 5160
ctggacgttg ccagggtctt ccatgccaat gtttccacct cgcagtagtt agtatttact 5220
tgccattaaa ctaactttga agcaagtaat gtgcacactt tgagcacttt gttgagtttt 5280
gaaaaatctt atttgttgct gcaccagggt taataaataa ccaattttgt aattccagca 5340
tgttggtcca gagacaccgg tcactgattc acaccccagt ccctgccaca gaccggccac 5400
agaccgtctc agacacgcac agtgggcctg ctgccaatga ttcacacccc agttccctgc 5460
cacagaccgt ctcagacacg gcacagttgg gcctgtgggt agtgatacac ccacgagtcc 5520
ctgccacaga ccgtactcag acacgcaaca gtgggcactg cttgcattcg cgttgttacc 5580
ctgggctttt ggctccacgc gtcactccat agccactgtc caccatgggg gactatgcac 5640
cacaggaatc actcactata ttgtactatt gtacccacca caaagcgtgc aagctctcgt 5700
gcacactatg ccatgcacac aaacggtggt acaccaagtt gttgaagctc ctacacgcta 5760
tacacacgac acacgtgtac attgcaccaa gagcagtgtg tgacccctac agacattgca 5820
gaacgatgca gcggtgtttt acacattacc ccacagacca cgccccgtgt gacgatgctc 5880
ccctacacaa ttacattatt gcaccattat tcatggaacc agcggtaagg ttacctaaca 5940
cacgggacgc tggtgctaca gtgcagtgta ccacggtaaa agcacactgt acaacgctct 6000
ctacagggct tgcgtcctca cacactgtgt tatgccacag cagaagagca cgtatgagct 6060
tctactggca cacatgcaca cacatcacgc acatgtacat ttcactacac actgtgcagc 6120
ctcgcgtgca acacgggtgc actattttcc agtgtgtgta caacccaaac aaattgatgt 6180
tcccaagaac gtgtgtaaac ctacacggtt gcacactatc tgtacacatt gtgagctccc 6240
acacgttaca cacaggatgg cacatgggac acaccccaac acacgacaca cggactccct 6300
aacagcacca ctagacacac cacgatgtta caccaccaaa cgagctccca gacatgtaaa 6360
ccacacgtct cccaacaccc gtgagcttcc cacacatgta cacatgcaca tgtacgcacc 6420
accaacacta tggcggaagc tcctgcaggc gtgaatacac acatgcacac acatatacac 6480
acacggtgcc acaaacaagt gcacactgtc ctggtgtccc tggcaactgc atcctggcct 6540
ccttgctgag gggcccctgg tgagaggcct ctggatgggc atgggaagat gggctccctg 6600
gccccccagc ccatgcctcc ctgggatgaa gagtccccct cctggcagaa tgtctgggct 6660
ttgcagaagc aggccccggg agtgaagtcg cagcttcact tacaccaggc tgctctgtga 6720
gcaaggcttg gtgccctgga caaggccctt ccccctttag ggaggtccag ccttcgcaag 6780
ctgaaacctc ccctcggctc agccctatac ccgggcggcc acagaaggac tggccacacc 6840
cacgccgcac ctcaatccgt gcacgcgtcg gagcccccgc cagccttctg ccacgagcca 6900
gctgggaagg gccgcggctg cctaaagccc cagtcaaccc cagcctgtgt ctgagccaga 6960
cacaggcgaa ccagccaggc cacaccgttc tcgagggagg aggcccagat tcggccagcg 7020
tctccaacag gggtgaccat cccgctcggc ttgctgagcc gtttaaacca aatgtttaga 7080
ccaggctgtg gggactcccc tgagttgagc cttggccaag gggtccggtg ctgtcgccgg 7140
gaaacctccc agcccttgtt cttccaaacc cactcagctc aatgtgtttt gcactgaact 7200
agtactggat aatacaacca ctcttaattt~ aaatgttagt attaatttaa tttgacaaac 7260
tcagtgtcta acagctttga tatgcaggtc cttgcattcc ctacatttcc tttaggaagt 7320
tacccatttg taacttttaa aaacaggaaa aatatcaagt tggccaaaag ccaatctttt 7380
tgttttttta agctaaaggg tggggtgaac tgggaatgaa aacctttcct gatgtggtgg 7440
tctataagca gccttggatg ggatatggtt agaagtggtc atggaaagtg cgtggattct 7500
acttttggca gaaaaatcta aagatcaatt tatatagctt agatttttta ctttatcaag 7560
ggtatacaga aattttaata tgcatatatt ggtgtctgac ttaaaattat aatggtctgg 7620
gtcaccattt aaaatggtcg gttcattatg taattgtaat aaaagaaggt cttcaaaaat 7680
gtatttaagc atgaatgggt atccatagtt gtcatcatca taaatactgg agtttatttt 7740
taaaattatt aaacatagta ggtgcattaa tcataaatca gtctcccaca cagtaacatt 7800
taactgataa ttcattaatc agctttgaga aaattaacat tgttcaatta agaccaatct 7860
aacatttcag taaagtttat tttgtatgct tctgttttta actttttatt tctgtagata 7920
agactgactg gataatatta taattggact ttttcttctt agattatcta agcaggagac 7980
ctgaatctgc ttgcaataaa gaataaaagt ctgcttcagt ttctttataa agaaactcac 8040
acaaaaaaaa aaaaaaaga 8059
<210> 38
<211> 1423
<212> DNA
<213> Homo sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:027320.1:2000MAY01
<400> 38
gcggccggga cgatgcctgc gcgcagtcgc accgccccgc ctccactccg gctccccgcc 60
25!104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
ccgggctccg cccccgccgc ttgaggcgct tcactccggc gaggcgggga gggccccgga 120
ctccgacggc ggctcggacg ccgacttcgg aggtgggtcc ggggagcccg actcggaccg 180
cggaggtgag cgggagctga ggctgaggag aggggagctt ggggggcgcc tgttgccaag 240
ggcagcggag gaggaaatgg caggtcctaa tcaactctgc attcgccgct ggactaccaa 300
gcatgtagct gtgtggctga aggatgaagg cttttttgaa tatgtggaca ttttatgcaa 360
taagcaccga cttgatggaa tcacattgct aacattgact gaatatgatc tccggtctcc 420
tcctctggaa atcaaagtct taggggacat taaaaggtta atgctctcag tccgaaaatt 480
gcagaaaata catattgatg ttttggaaga gatgggctac aacagtgaca gtaccatggg 540
ttccatgacc cctttcatca gtgctcttca gagtacagac tggctctgta atggggagct 600
ttccccatga ctgtgacgga cccatagact gacttgaatt ctgatcagta ccagtacatg 660
aatggtaaaa acaaacattc tgttcgaaga ttggacccag aatactggaa gactatactg 720
agttgtatat aatgttttat aatatttggg atttacatct ttcattatgg ttatagtcca 780
tgagcgagtg cttgacatgc agacctatcc acgactccca gatatattct tagacagcgt 840
tcctagaatc ccatgggccc tttgccatga ccggaagtat gtggcatgat tctgtgctat 900
atttggctcc tggttcttct tcttcacaag cacagatata tgggcagtgt atgggagaaa 960
ttacatcgag cctttgccat ttggagtggc tttggtatga ccctgactgg cgttcacaca 1020
tgtggagatt acatgtttag tggccacaca gtcgtcctaa ctatgctgaa tttctttgtc 1080
accgaatata caccaagaag ctggaatttc ttgcacactt tatcctgggg ttctcaacct 1140
ctttggaatc ttctttatct tggctgcccc atgaacatta ttctattgat gtgtttattg 1200
ctttttatat aacaacaaga ctctttttgt actaccatac tctggccaat accagaagca 1260
tatcagcaga gtaggagagc aaggatttgg tttcccatgt tctctttttt tgaatgcaat 1320
gttaatggca cagtacctaa tgaatattgt tggccatttt caaaaccagc aataatgaaa 1380
agactaattg gatgaatact atctttctaa tgaatttgtg att 1423
<210> 39
<211> 1594
<212> DNA
<213> Homo sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:321475.1:2000MAY01
<220>
<221> unsure
<222> 280
<223> a, .t, c, g, or other
<400> 39
ctcactcatt tctaaggagg actttaagca aatgagtcca gggatcatcc agcagctcct 60
cagctgctcc tgccacttac ccaaggacca acaagcaaag ctgccaccta ccactctgga 120
gaaatacggc tacagcacgg tggctgtcac ccttctcaca ctgggctcca tgctggggac 180
agcgctggtc cttttccata gctgtgagga gaactacagg cttatcttac agctgtttgt 240
gggcttggcc gtcgggacac tgtctgggga cgctctgccn ccaccttatc cctcaggttc 300
ttgtgtttac ataagcagga agccccagaa tttgggcatt tccatgaaag caaaggtcaa 360
tatttggaaa ctgatgggat taattggagg catccatgga tttgttcttg atagaacaaa 420
tgttttattc ttcttgtatc accaaatgac aagcagggcc tgtcattggt taatgggcac 4'80
gtgggtcatt cccaccatct tgcactcaac tctgaattaa gtgaccaggc aggcagaggc 540
aaatctgctt caactatcca gttgaaaagc ccagaagatt cacaggcagc tgaaatgcct 600
ataggccagt atgacagcct ccagacagaa aatgtaaagc cattagcttt gttagcaatc 660
atgattctgg ttggggacag cctgtcataa ttttgcagat ggcctagcca taggagcagc 720
cttctcatca tgcatccgag tccaggagtg accactacga ttgctatctt gtgtcatgga 780
aatcccacat gaaatgggag actttgccgt gctcttaagc tctggacttt ctatgaagac 840
tgccatcctg atgaatttta taagctccct aactgccttc atgggattat acattggcct 900
ttccgtgtca gctgatccat gtgttcaaga ctggatcctt cacagtcact gctgggatgt 960
tctaatattt atcccttggt tgaaatgctt cctgaaatga ctcattgttc aaacacaacg 1020
accctggcat gatgtttctg cctgcaaaaa ctttggattg atcctaggtt ggctttctct 1080
cctgctcttg gctatatatg agcaaaaata ttaaaatata agtgaggatc ttcaacatct 1140
ttcaaaaatg catttatata gtcttacttt gtttctttca ttgcactcta taatgatttt 1200
taaattaaga attttttatc ttaggcaaag tgtgtctctt tcaattcatt aacttattaa 1260
ttttataatg ccggtttatt ttttggaaac atataaatat cagactgtcc ttaattgaaa 1320
ttttgtcttt ggtttccaac accatgatga agctcttgct tttttaaaaa gtagttagta 1380
aattctgcat gaagttttag taaactttaa aaaatagatt ttttccctaa ggaaagaatg 1440
gtcttggtag aaatttacaa gtgggacagg atgcctgtcg ggggtaaaat caactgcaac 1500
ctttttgatg gttaattttt ttccctgtgc aattataaaa ctataagcaa gtcaagtgcc 1560
aagccaatgt tataaagact agttttaaaa aaaa 1594
26/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
<210> 40
<211> 2138
<212> DNA
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:899552.5:2000MAY01
<400> 40
gtgaatatca agtctcccca accccacctg gaggggtttc atccagcaag agcttgcctt 60
ctgctcagca cactcctggg agtaacctat gagtgtcaca gctgcaactc cgaggtgcca 120
accaagccca gggctctggc ttcttctggg gtcaggccgc,tcttcagggt tcttcgcact 180
gcagtggtgg tgcaggtcac acccaaaggg atgagaagaa aaggaagtat gagcagcaag 240
gcacagggca gtcaagactc cagtcccccc ttctccccag ggacttccag agaagccaga 300
gggttcacac tctgtacctt cctgctcttg ctgaagtgcc ctgcagtctg tctgccagga 360
caaaagtttg gggctacaca ggctggccta acaatgccac aggtgctgat ttggagggcc 420
gagaggagtg atgcgggcac ttataaagag gagagaaagg aggagaggct caccctcacg 480
aggcttctga gaagggggtg aactgcagaa gtgcagaggg caggagagac ctcagcatct 540
acccagtatg aggagtgtat cagagctggg aaggtgattc cagagcaggg gaaaatgcaa 600
gctccactaa tacaaatgag gtgaggcaac cagtgcacag cgaggggttc cacaagaccc 660
aacaacctca caaatccaac agacgaccaa caatagctgg ggacatgctc aagacccaca 720
gagcaagtgc atgaagccag ggcaaggggc agcagtgagg acaaatctct ccatgagtac 780
tgtgggtctt agcctcaact cactaaaagg cctctagaga caataattaa aataaccagt 840
ggctcctcga ggaatggagg ctaatgagca aactgccaaa cttattctgg ctggaattgg 900
tggctgcttt ctatggaaca cacaagtctc aagaatggcc aatgaccact ctcactgggg 960
ggttgcagct ggcaactgga gggatgctca tatttaactg acttagaatt ggcttgtgtc 1020
tagcttggca tgatggtatt cccattgttt agtatttcaa tttcaacatc aaaataaagg 1080
ctggataagg gtgaatgagg aggtagctgc ctcacccaag acaagtcttc atttgaaagg 1140
gtggctaatt acattttcct taatttacaa attgtatttg acccactgtg tatttcttta 1200
aagttcgcac agagtttggg gtattcattt tcagaagaga aacgttattg gatctgcctt 1260
caccctaaat ccctaaatca gccagagttc ctggaaatga ccagggcagg ctgttgatca 1320
aagttcagag aaagtaagct caccttaatg tctccccagt tcctttgcca actcccctca 1380
tctactcccc agaggccagg gcccacctca tgcatctgca ggccacaccc catggtctat 1440
gccttcccat catcccctaa atataagctc actcagcctg tggacaaaag atctgaaaga 1500
cctatgtcca tggcagaatc aatggggact aatacctatt atgaaaataa agggctcctt 1560
ctcttccagg aatcagcact tggaacaggg gtcaacataa tatccatcaa ttggtcaacc 1620
aacaaaatga tttattgaga acccattgtg tgctcagcat ttaactcaaa gaatcaaaac 1680
acagacatca agtatgggtt tttagagaga catgggatat gtggtgaggg gttctcgtca 1740
aatcgtgtta ctgcaactac tgtatttcca agccttacct ttgggccctg aagcaatcta 1800
tctgtagctg ttcttgcact agctcctctt tcccccaccc ctgatccctt ggcctccaga 1860
ctgaatgttt gggctcaaca agacaaaatg tttggctcct aagtctcagc tggagacaga 1920
ttacattcaa ctgagcaaca gaatttgttc tatggggcag caataaaaat actagtttgt 1980
aataaccttt tatgttcttt aaagactcct tagagtgttt gttaaagaaa gataatttta 2040
acaacagtaa ataagataaa atatctctct tgacaagaaa gacctcttgc tgcaacttct 2100
taaccaagat acaaaatact tccttaaaaa gtccatgc 2138
<210> 41
<211> 1345
<212> DNA
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:1071848.1:2000MAY01
<400> 41
ggcgggaagg cgccggccgc taagaagccg aaagatgtcc aggtcgggcg cggcggctga 60
gaaggcggac tccagacagc gaccccagat gaaggtaaat gaatataaag aaaatcaaaa 120
catcgcttat gtgtctctga gaccagcaca gactacagtt ttaataaaaa cagctaaggt 180
ctatcttgcc cccttttcac tcagtaatta ccagctagac cagcttatgt gccccaaatc 240
cctatcagaa aagaattcta acaatgaagt ggcgtgtaag aagactaaaa taaagaaaac 300
ttgcagaagg attatacctc caaagatgaa aaacacatct tccaaggcag aatccacgct 360
gcaaaattca tcctcagctg ttcatactga aagtaacaag ctacaaccca agagaacggc 420
agatgcgatg aatctcagtg ttgatgtgga aagtagtcag gatggagaca gtgatgaaga 480
taccacacca tccctggatt tttcggggat tgtcacccta cggaaggaag agactgaaga 540
acatatcaga aaacgcagac ttttttgctt ctcttcagtt gtctgagtct gctgcaagac 600
27/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
tccgtgaaat gatagagaag agacagcctc ctaaatccaa aagaaagaag cctaagagag 660
aaaatgggat tggatgtaga aggtcaatgc gattactaaa agttgatcct tcgggagttt 720
cattaccagc agctccaaca ccgccgacat tagtagcaga tgaaactcct ttgttacctc 780
ctgggccttt agaaatgact tctgaaaatc aagaagacaa caatgaacga tttaaaggat 840
ttctgcacac atgggcagga atgagcaagc caagtagtaa gaacactgag aagggattat 900
ctagcattaa aagctaccaa agccaattta aatggcatgg tcattagtga agataccgtt 960
tacaaagttt accacaggcc caatattctc tatggctctc catccatcag aaactagaac 1020
tttggtagca gttgggccca aatttgggca agttggactt tgtgatttgg taagttatta 1080
aatttcttga atatattata gtttgactaa agcaaatagg ctggaagaga ataggctaga 1140
gccatgtgtt tataaatgtt gcgtgagact tacaattttg ggctttatga tgctttatga 1200
ttccaaattt tagaaatctg gaagaattta aatttgcttt atagaacttt aatattttta 1260
gcttgaatat cattaaccat ctggtcataa attaactgcc agaaaacttt gttacacttt 1320
gtgtgatctt ttcacatata cattt 1345
<210> 42
<211> 4707
<212> DNA
<213> Homo sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:1072337.2:2000MAY01
<220>
<221> unsure
<222> 994, 3721, 3729
<223> a, t, c, g, or other
<400> 42
ttttctatat gatcagaaga gcagctactg tgattcctgg gctaatgaag cctagacccc 60
agctggattg gaagcaaagg cctttccttc actgggaaag gtgctgctgc tacccatctc 120
attattctaa gagtgattga gaatagaggg gctgaaggga aacgaaagta ggagaatgtt 180
ggccagagct agtagagaaa gaacgtaata ttgagaaagc agacatcagt gctaggtgag 240
gtgctttctt tagagagctg tgtgtataga ctggggagga gtctgtctgg ggacaggaat 300
gctgattcct tttttttccc tgggcagaat cctaatgtac ctggctagct ggtggtgagt 360
aggggctttg gggccaactt ggtgggctcc ccaaggaaac ccctttgaaa ccaatggatg 420
cattcacggg ctcgggtctc aagaggaagt tcgatgatgt ggatgtgggc tcatcagttt 480
ccaactcaga tgatgagatc tccagcagtg atagtgctga cagctgcgac agcctcaatc 540
ctcctaccac tgccagcttc acacccacat ccatcctgaa gcggcagaag cagctgcgga 600
ggaagaatgt acgctttgac caggtgactg tatactactt tgcccggcgc caaggtttta 660
ccagtgtgcc cagccagggt ggtagctctc tgggcatggc ccagcggcat aactctgtac 720
ggagctatac actctgtgag tttgcccagg aacaggaggt gaaccatcga gagattctgc 780
gtgagcacct gaaggaagag agactccatg ccaagaaaat gaagctgacc aagaatggga 840
cagtggagtc ggtggaggct gatggcctga cgctggatga tgtgtcagat gaagatattg 900
atgtggaaaa tgtggaggtg gatgattact tcttcctgca gcctctgccc accaaacggc 960
gacgggccct gctgagggct tctggggtcc accngtattg atgctgaaga gaagcaagaa 1020
cttcgagcca tccgcctgtc acgggaagaa tgtggttgtg actgccgact gtattgtgac 1080
ccagaagcgt gtgcctgcag ccaggctggg gattaaatgc caggtcagtg gatcgcatgt 1140
cctttccatg tgggctgctt cccgggatgg ctgtgggaac atggcaggac gcattgaatt 1200
'taatccaatc cgggtccgga ctcattacct ccacaccatt atgaagctgg agctggagag 1260
caagcggcag gtgagccgcc cagcagcccc agatgaggag ccctccccga ctgccagttg 1320
cagcctgaca ggagcacagg gctctgagac ccaggacttc caggagttca ttgctgagaa 1380
tgagacagca gtgatgcacc tgcagagtgc agaggaactg gagcggctca aggcagaaga 1440
agattccagc ggctctagtg ccagcctgga ctcgagcatc gagagcctgg gtgtgtgcat 1500
cctagaggag cctctggctg tccccgaaga gctgtgccca ggccttacag cccccattct 1560
catccaggct cagctgcccc caggctcctc tgtcctgtgt tttaccgaga actcagacca 1620
cccaactgcc tcaacggtga acagcccatc ctacttgaac agtgggcccc tggtctatta 1680
tcaagtggag cagaggccag tcttgggagt gaaaggagag ccttggtacg gaagaaggct 1740
cagcctcttt cccaaaggag aaggatctga atgtcttctc tctccctgtt acctcactcg 1800
tgggcttgta gctccacaga cccagctgcc ctctgtaaat cagaggtggg gaaaacaccc 1860
accctagaag ctctattgcc cgaagattgt aagccctgag gagcctgaaa atgaagactt 1920
ccacccttcc tggtccccct caagcctccc cttccgcacg gacaatgaag agggctgtgg 1980
gatggtgagg gaggtcccac gcagaatgag gatcggcccc cctgaagatt cttccattag 2040
aactccctct ggcagtgtgg acaggcgcta gaggtcctgc ctcttaccca ttctctattt 2100
attcccttat tttatctaac accatttcaa aacaaaactg tagaagcagc tgcttgctcc 2160
cccagtgatt attttattgg ggtctttggg gaatgggtgg gaaaggattg tttgagtatt 2220
ttttaaaagg gaaacagtac caaggagacc agccctacct tgatctgggg atagtcttgg 2280
281104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
ggcaaagaaa gctgcgtagt gcgtgaacat taagctttct gggccacttt gaacaaagaa 2340
ctaggatctc acaggaaaag ctgggtaact caagcagcta ttctttctgt agggacccag 2400
aacacgagaa tttgaagagc atggcaaagc cctttctctc ccaagcccca ggcagagtac 2460
aagctcattt ttctcggtgg gttattctga tatcccattt tggtgtgtca taatacttca 2520
aactggaaag tcacctggtc gagtctaggg aggagggagt gggaagggtc tctgcttctg 2580
tacaaaatct ccaggattta caaaaatgta acctgccttc cttcaatccc atatttgggt 2640
aaataaagtt aatatttgac atgtttggtg ttctctgacc tgttccccac actggggata 2700
tcctggtctg taacttgaat tgtttcttcc acatgttctt aagtactaga gttaaacttg 2760
tctatgtgtc ttttttctct ccatcccttt tttccttcgg agaaagagct ggattgggct 2820
ggggatatgg tataacgagc ctgagccttt ctgtacgtgt ccgaccatta gcactgtcag 2880
gcagctttcg gctggggctc acccatccca taggaggcct atgtggagca ttaactgtgg 2940
ccaaaggagg cagcgggaac aggctgcttg ctatctggaa agatgacata tttgtgccat 3000
gcttgttttt tcacccaggt ttttccctct ttgtgagatc tgagctttag tggaatgtag 3060
aatgtggcaa tcttaaggtc accaatcagt ttttgttctt ttttcctgga tctaccctca 3120
tggtcgtttt caacatagcg ggttagagtt cttatactgt tccagttcaa ttccaagaat 3180
tgcaaatgtt tattggaccc ctccatcttg atgatatata aaaattggaa gccaaaccag 3240
ttcttaaatg ctacatgcaa ctcccagatt ccaaaggatt caagttctaa ttataacctt 3300
tgaagcgtat agaatggaac tcattcagtt tgattcagtt cttacctctg tcaggaggga 3360
atacagttcc tgttcatcct gtgttctaag atctccattg aacagcactg atttcctttc 3420
attaggcaaa gtgatctttg tctctgttct aaaatgggag ggcagtaggg gagcaaaacc 3480
tattcttctc aagcatccct ttacaccata ctttacttct gggtatgggt ttattaacca 3540
cacacacaca caaaagtgaa aaactgtgtt gggggggaga cactactcct actgtatctt 3600
cgctccataa agccttatct ggatgggata tataagggcc tgggtgtctt accagaaacc 3660
catcaccgta atgtcgccag ccagccattg tcacccgctg taaaggtctt cgtaaactcc 3720
ntggaagcnc ctgagaaagg gaatttgtaa atttaataca cataacattt tttagttcat 3780
tctgtggttt cctatttgtt ccagtttttg cttggtttta gtttggaggg gaacttaagt 3840
acacagatcc ttaatctctc cccatcccct agcctcacaa aacacagttg agagtctttt 3900
taagtacctg agctctcgaa ggttacccag aactggaact agactcccct accttagact 3960
gggtaccctc aaaacacagg actgaagctt aattggggaa tttggcttta tgggagaaaa 4020
ggaatctttt tcacaagttt gtgtcggaaa ggggagggtg aggtttgccc actgtctctg 4080
caggaaaggc tccggcttaa atctagggaa gtaggattcc agctgcacga tgagggaaca 4140
cattagcttt tgggatcaaa ccaggaatat gaatctgtta attatttaag gctcattgcc 4200
aacccacaag atatgtttct gaaaacctgt agtttcttaa tttaagtcca tccccttcat 4260
taacgctaca gttgtgactc acactgatcc caaaactttt aagtgctaaa tattaacatt 4320
tagcattaac tgtcttgtca agcgaaaggc ccttctctac aaccctagtc ccatcctcac 4380
cttctggtgc ctaccctgag ttggacagaa ttcctagcct catgggttgc ctagggaaag 4440
ctaggcctct gatcataaga agcaaatagc tttcagtccc agtctaggcc tagataaatg 4500
actcttatta ccacaaccct tattattttc caatttcctt tctcacatac tgtacacagg 4560
tagtattttc aatgtgaatc caaagcttgt ctggttctct gaaaataatt tttttcccct 4620
ttaggttctt tacattgtga taatgctgta tttaaagaga atatttaaat gtaatattaa 4680
agaaatattc aaaagaaaaa aaaaaaa 4707
<210> 43
<211> 1069
<212> DNA
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:251489.5:2000MAY01
<400> 43
gaattcttgg aaacttagtc agctgttact taagagttac gtattatcct atcattatgt 60
attaatatta attttttcat acacatgtcc atgcagaaca tattaggtat cttggtgtag 120
aaaacactaa tgttgaaatg aactaaattc caatctttta gtattctccc agtttagtat 180
cataaacttt tgtatctttt ccatgacctg cctttcatta gaggccttcg aggaagaggc 240
ccacctcctt catgggcctc tgagcctgaa cgcccatcca ttcttagtgc atcagaactg 300
aaggagcttg ataaatttga taacctagat gctgaagctg atgaaggttg ggcaaggtgc 360
taagatggaa gtagattata cagagcaact gaatttcagt gatgatgatg aacaaggaag 420
ttacaggcct taaagagaat aaccagtgag gatcaaggtt caaaagcctc tgaaaacaac 480
ggaaaacaaa aaagaaacag atgaagtttc caacactaaa tacatcttcc caaatacctg 540
cccaaaccat cagtagcaaa agttccctat gggaaaagga ccttcattta atcaggaacg 600
tggaacatct tcacatctgc caccacctac caaagttgct tgcacagcag catccacctc 660
cagatcgaca ggcagtacct gggaagacca ggcccctttc cctccaagca gcaaagtagc 720
tgatgaagat gaaatattgg aagcaaagac gaagacgaca atcagaaatt tctgcagcag 780
tagaatcgtg ctcgtaaacg gcgtgaagag gaagagcgaa gaatggaaga acaaagcgaa 840
ggcagcttgt gcggagaaac tgaaacgatt ggctgacgaa gcttggcatc ctggaaaaac 900
29/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
aaccatctcc agaggaaatc agggaaaggg agcgtagtat aaaagaacgg gagcgtgtag 960
aaagaacttg aaaaagaaca agaacaggag cgagagaagg agagggaaaa agacagagag 1020
tagacagcag gaaaaggaga aagagctgga gaaggagcag gaaaaacaa 1069
<210> 44
<211> 4375
<212> DNA
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:902018.107:2000MAY01
<220>
<221> unsure
<222> 179, 4314
<223> a, t, c, g, or other
<400> 44
cttccagttg tcttgaacag cctggcagtg tcagggccga gtgggggttt ctccccactg 60
tccggcaagc gtcggtcagc cgaacactgt gtgcctggtg gtgtgtgttc acatgtgtgc 120
gtgcgtgtgc ccggcagagc agcaaacagc tgcgcccgag agctgtggcg ctttccctnc 180
ctatggaagt tccttttatg cgttggagga aaaacatgtt ggcttttctc ttgacgtggg 240
agaaattgaa aagaagggga aggggaagaa aagaagggga agaagatcaa agaaggaaag 300
aagaagggga agaaaagaag gggaagaaga tcaaaaccca ccatgcccca ggctcagcag 360
ggagctgctg gatgagaaag agcctgaagt cttgcaggac tcactggata gatgttattc 420
gactccttca ggttatcttg aactgcctga cttaggccag ccctacagca gtgctgttta 480
ctcattggag gaacagtacc ttggcttggc tcttgacgtg gacagaatta aaaaggacca 540
agaagaggaa gaagaccaag gcccaccatg ccccaggctc agcagggagc tgctggaggt 600
agtagagcct gaagtcttgc aggactcact ggatagatgt tattcaactc cttccagttg 660
tcttgaacag cctgactcct gccagcccta tggaagttcc ttttatgcat tggaggaaaa 720
acatgttggc ttttctcttg acgtgggaga agatcaaaga aggaaagaag aaggggaaga 780
aaagaagggg aagaagatca aaacccacca tgccccaggg ctcagcaggg agctgctgga 840
tgagaaaggg cctgaagtct tgcaggactc actggataga tgttattcaa ctccttcagg 900
ttgtcttgaa ctgactgact catgccagcc ctacagaagt gccttttaca tattggagca 960
acagcgtgtt ggcttggctg ttgacatgga tgaaattgaa aagtaccaag aagtggaaga 1020
agaccaagac ccatcatgcc ccaggctcag cggggagctg ttggatgaga aagagcctga .1080
agtcttgcag gagtcactgg atagatgcta ttcaactcct tcaggttgtc ttgaactgac 1140
tgactcatgc cagccctaca gaagtgcctt ttacatattg gagcaacagc gtgttggctt 1200
ggctgttgac atggatgaaa ttgaaaagta ccaagaagtg gaagaagacc aagacccatc 1260
atgccccagg ctcagcaggg agctgctgga tgagaaagag cctgaagtct tgcaggactc 1320
actgggtaga tgttattcga ctccttcagg ttatcttgaa ctgcctgact taggccagcc 1380
ctacagcagt gctgtttact cattggagga acagtacctt ggcttggctc ttgacgtgga 1440
cagaattaaa aaggaccaag aagaggaaga agaccaaggc ccaccatgcc ccaggctcag 1500
cagggagctg ctggaggtag tagagcctga agtcttgcag gactcactgg atagatgtta 1560
ttcaactcct tccagttgtc ttgaacagcc tgactcctgc ,cagccctatg gaagttcctt 1620
ttatgcattg gaggaaaagc atgttggctt ttctcttgac gtgggagaaa ttgaaaagaa 1680
ggggaagggg aagaaaagaa ggggaagaag atcaaagaag gaaagaagaa ggggaagaaa 1740
agaaggggaa gaagatcaaa acccaccatg ccccaggctc agcagggagc tgctggatga 1800
gaaagggcct gaagtcttgc aggactcact ggatagatgt tattcaactc cttcaggttg 1860
tcttgaactg actgactcat gccagcccta cagaagtgcc ttttatgtat tggagcaaca 1920
gcgtgttggc ttggctgttg acatggatga aattgaaaag tacaaagaag tggaagaaga 1980
ccaagaccca tcatgcccca ggctcagcag ggagctgctg gatgagaaag agcctgaagt 2040
cttgcaggac tcactggata gatgttattc gactccttca ggttatcttg aactgcctga 2100
cttaggccag ccctacagca gtgctgttta ctcattggag gaacagtacc ttggcttggc 2160
tcttgacgtg gacagaatta aaaaggacca agaagaggaa gaagaccaag gcccaccatg 2220
ccccaggctc agcagggagc tgctggaggt agtagagcct gaagtcttgc aggactcact 2280
ggatagatgt tattcaactc cttccagttg tcttgaacag cctgactcct gccagccgta 2340
tggaagttcc ttttatgcat tggaggaaaa acatgttggc ttttctcttg acgtgggaga 2400
aattgaaaag aaggggaagg ggaagataag aaggggaaga agatcaaaga agaaaagaag 2460
aaggggaaga aaagaagggg aagaagatca aaacccacca tgccccaggc tcaacagcgt 2520
gctgatggaa gtggaagagc ctgaagtctt acaggactca ctggatagat gttattcgac 2580
tccatcaatg tactgtgaac tacgtgactc attccagcac tacagaagtg tgttttactc 2640
atttgaggaa cagcacatca gctttgccct tgacatggac aataggttct ttactttgac 2700
ggtgacaagt ctctatctgg tcttccagat gggagtcata ttcccacaat aagcagccct 2760
tactaagccg agaggtgtca ttcctgcagg caggacctat aggcgcctga agatttgaat 2820
gaaactatag ttccatttgg aagcccagac ataggatggg tcagtgggca tggctctatt 2880
30/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
cctattctca gagcatgcca gtggcaacct gtgctcagtc tgaagacaat ggacccacgt 2940
taggtgtgac acgttcacat aactgtgcag cacatgccgg gagtgatcag tcggacattt 3000
taatttgaac cacgtatctc tgggtagcta caaaattcct cagggatttc attttgcagg 3060
catgtctctg agcttctata cctgctcaag gtcagtgtca tctttgtgtt tagctcatcc 3120
aaaggtgtta ccctggtttc aatgaaccta acctcattct ttgtgtcttc agtgttggct 3180
tgttttagct gatccatctg taacacagga gggatccttg gctgaggatt gtatttcaga 3240
accaccaact gctcttgaca attgttaacc cgctaggctc ctttggttag agaagccaca 3300
gtccttcagc ctccaattgg tgtcagtact taggaagacc acagctagat ggacaaacag 3360
cattgggagg ccttagccct gctcctctca attccatcct gtagagaaca ggagtcagga 3420
gccgctggca ggagacagca tgtcacccag gactctgccg gtgcagaata tgagcaatgc 3480
catgttcttg cagaaaacgc ttaacctgag tttcatagga ggtaatcacc agacaactgc 3540
agaatgtaga acactgggca ggacaactga cctgtctcct tcacatagtc catatcacca 3600
caaatcacac aacaaaaagg agaagagata ttttcggttg aaaaaaagta aaaagataat 3660
gtagctgcat ttctttagtt attttgaacc ccaaatattt cctcatcttt ttgttgttgt 3720
catggatggt ggtgacatgg acttgtttat agaggacagg tcagctgtct ggctcaatga 3780
tctacattct gaagttgtct gaaaatgtct tcatgattaa attcagccta aacgttttgc 3840
cgggaacact gcagagacaa tgctgtgagt ttccaacctc agcccatctg cgggcagaga 3900
aggtctagtt tgtccatcac cattatgata tcaggactgg ttacttggtt aaggaggggt 3960
ctaggagatc tgtccctttt agagacacct tacttataat gaagtacttg ggaaagcagt 4020
tttcaagagt ataaatatcc tgtattctaa tgatcatcct ctaaacattt tatcatttat 4080
taatcctccc tgcctgtgtc tattattata ttcatatctc tacactgcaa attttgggtc 4140
tcaattttta ctgtgccttt gtttttacta gtgtctgctg ttgcaaaaag aagaaaacat 4200
tctctgcctg agttttaatt tttgtccaaa gttaatttta atctatacaa ttaaaacctt 4260
ttgcctatca ctctggactt ttggattgtt tttcacattc agtgttataa tatntgatta 4320
tgctgattgg ttttggtggg tactgatgcg aattaataaa aacatttcat ttcaa 4375
<210> 45
<211> 3220
<212> DNA
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:220495.1:2000MAY01
<220>
<221> unsure
<222> 703, 2052
<223> a, t, c, g, or other
<400> 45
acaggctcgg ggccagccgg gcgcgcatcc ccgggcgccc tgcgcggtgg agagcttggc 60
gggctgcggg tgccgcagga caggagtgga caaagcaaga tggcagggat cttagcctgg 120
ttctggattt agaggttttg gctcccgcac aatgtcacct gggcggacct gaagaacacg 180
gaggaggcca ccttcccgca ggctgaggac ctctatctcg cttttcccct ggccttctgt 240
atcttcatgg tgcggctcat cttcgagaga tttgtagcca aaccgtgcgc catagccctc 300
aacattcagg ccaatggacc acaaattgct ccgcccaatg ccattctgga aaaggtcttc 360
actgcaatta caaagcatcc tgatgaaaag agattggaag gcctctccaa gcaactggac 420
tgggatgttc gaagcattca gcgctggttt cgacaaagac gcaatcagga gaagccaagc 480
acgctgacga ggttctgtga gagcatgtgg agattttcat tttaccttta tgtatttacc 540
tacggagtca gattcctgaa aaagaccccc tggttgtgga atacgaggca ttgctggtac 600
aactacccct atcagccact cacaactgac cttcactact attacatcct ggagctgtcg 660
ttttatgggt cttggatgtt gttctcagtt cactggatat canaaagaat caggacttgt 720
ggcgattaat gttccctgca ccaccttgta tctattttct tgattacctt ttcatatgtc 780
aacaatatgg cccgagtagg aacgctggtc cttggtcttc atgattcagc tgatgctctt 840
ctggaggctg ccaaaatggc aaattatgcc aagtttcaga aaatgtgtga tctcctgttt 900
gttatgtttg ccgtggtttt tatcaccaca cgactgggta tatttcctct ctgggtgtta 960
aataccacat tatttgaaag ctgggagatc gttggacctt acccttcctg gtgggttttt 1020
aacctactgc tattgctagt acaagggttg aactgcttct ggtcttactt gattgtgaaa 1080
atagcttgca aagctgtttc aagaggcaag gctgggaagt ggaacccttt acatgtgtcc 1140
aaggatgatc gaagtgatat ttgagtctag ctcagatgag gaggagtcag aacctccggg 1200
aaagaatccc cacactgcga caaccaccaa tgggaccagt ggtaccaacg ggtatctcct 1260
gactggctcc tgctccatgg atgattaatt acttcaaaac ttacaagtcc caaggcaaag 1320
tgaactattt gttcctggaa gtatttaata agttgcaaat gccagttcct ttcataatat 1380
ctcagcacca gaaacaaaaa ttaagattat caaacgcatt ttgaatacgt gcactgccat 1440
gtgtcctgtc tgtgcactga agacgaatta ccattctctc tttgtaggca tgctgtatgt 1500
aatttgacac aagggaacag tatttgcatt tgtactggtc ttagaatatt atttattttt 1560
31/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
tttgtatttg taaatctgtg gacaaaagag ggtttcctca ctccttttac tcactggggc 1620
tcatgacagt gaaggagatg ctccatctgg cttctccccc tttctcttgc tgtagtccaa 1680
tgtgctatga gcatcagctt actttgtcac ttagagcaag caaaacccag tgcaagagtc 1740
tcgttcagct cttaaatagg gtttgctttc ttttagttac agtgcccatt ttgaaattgc 1800
ctatacagtc ttagtgacca tttaaaccgg acgaactagg tgtttaattt tcactcttca 1860
tgttcaatta gcagttcaaa ttaaagaaga tggttattgg agaacttttt tgaatggttt 1920
tgtattaaat tgctttgaaa tagatttcat ttcttgtgca cacagcccaa gatttcttca 1980
atgggtgtga gctagttgag ggttaacctt gtaggttgca gagtgtattt gtttgtttgt 2040
ttgtttttct cngtgatgag gtcagtgctc tgattttgaa ggaggatatt cactgaagct 2100
catagttata aacaaggaaa tcactgttaa gaatgggaat ttgtcctgtg ttctgggaat 2160
aacataaaga gagcaactga tttcagccca ggttttgcca ctaccctata attagtgcag 2220
tcttatgtta taaaagaaag aagttaacta tatttgggga caaaaaaata tttcaagagt 2280
tgataaagat tacctgtgca gtgcagagca ctttaatgca accagctttc aagaaaaagc 2340
cctatctagt acttgatgtt gatgttttta ttttgctgag caaaataaag ccaatgggag 2400
aaagactatt ttaccctttg cttttctcct taaacgtaat ccagatgact ttcctgttac 2460
taaacactga gcagcattac actacaatgc ttctttggtt tccaggaatt tttttcaaat 2520
ggggctgttt ctggaaaaat gaaaaattct attggacaat ggcaatatca acaatgagga 2580
aaattactga agaataagtt tccataagtc tcctacatag cagtgttatt tatgtacaga 2640
taagaaaacc atatgtcagc caaagcattt tatctcttct tctaactttt agtcacgagg 2700
caaaaggggt tataaaacct ttcattaatt caggaaggcc atcatttaga aggaacccca 2760
aaaaaaattg ccatattata aatgtgtgaa tcagggctgt gaaggacaaa acagggcagc 2820
acacatgcgt aacaagcgtt gcagaaacac cagagagtgc gtatcctgct cagaaccatt 2880
cacatttaat tcaattcttg gaaaaaatta aagctttttg cccacaattt gcaatctgtg 2940
ggttaatagt taaaagaatg ttcccaacca aaaaattctt accgtaatat tatatcttgg 3000
ccctacttat ttacaaaata atatgtttct gttatggtcc ttagtaataa ttgaagaggc 3060
ttagaaatac atctgcttgt ttattgagaa aacgatgcga ataattctgc ttttagagcc 3120
ttgttatttt atttcacaaa acaggcatat gtctaggagt gtaatatgtg gatggttgag 3180
tttgtaagaa caatcataaa aggacttgtt agtctccaga 3220
<210> 46
<211> 2961
<212> DNA
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:399478.1:2000MAY01
<400> 46 '
tgatcagtta ttgtgacctt gactcactca tttctgatga actttctggg gcccgatcaa 60
gcatctgcca tcactggttg ttgacagggg gctgatcagt ctattatggc ctcagctaaa 120
gtgactcagc tttcctctat ggttcttgta tccttcagta ggctagcttg agcttgtttt 180
catggccatg acgtggttcc aagagagata agaagcacac aagacctttg taaggatcag 240
tcccaccgct ggccacaatg gttcatgctt ataacttcac ctctttagga ggctgacgtg 300
tgagggtcac ttgaaaccag gaatttcaga ccagctgggc aacaaaggga gacctcatct 360
ctgatatttc cagtgtcaga gggacacagc caacgtgggg tcccttctag gctgacagcc 420
gctctccagc cactgccgcg agcccgtctg ctcccgccct gcccgtgcac tctccgcagc 480
cgccctccgc caagccccag cgcccgctcc catcgccgat gaccgcgggg aggaggatgg 540
agatgctctg tgccggcagg gtccctgcgc tgctgctctg cctgggtttc catcttctac 600
aggcagtcct cagtacaact gtgattccat catgtatccc aggagagtcc agtgataact 660
gcacagcttt agttcagaca gaagacaatc cacgtgtggc tcaagtgtca ataacaaagt 720
gtagctctga catgaatggc tattgtttgc atggacagtg catctatctg gtggacatga 780
gtcaaaacta ctgcaggtgt gaagtgggtt atactggtgt ccgatgtgaa cacttctttt 840
taaccgtcca ccaaccttta agcaaagagt atgtggcttt gaccgtgatt cttattattt 900
tgtttcttat cacagtcgtc ggttccacat attatttctg cagatggtac agaaatcgaa 960
aaagtaaaga accaaagaag gaatatgaga gagttacctc aggggatcca gagttgccgc 1020
aagtctgaat ggcgccatca aacttatggg cagggataac agtgtgcctg gttaatatta 1080
atattccatt ttattaataa tatttatgtt gggtcaagtg ttaggtcaat aacactgtat 1140
tttaatgtac ttgaaaaatg tttttatttt tgttttattt ttgacagact atttgctaat 1200
gtataatgtg cagaaaatat ttaatatcaa aagaaaattg atatttttat.acaagtaatt 1260
tcctgagcta aatgcttcat tgaaagcttc aaagtttata tgcctggtgc acagtgctta 1320
gaagtaagca attcccaggt catagctcaa gaattgttag caaatgacag atttctgtaa 1380
gcctatatat atagtcaaat cgatttagta agtatgtttt ttatgttcct caaatcagtg 1440
ataattggtt tgactgtacc atggtttgat atgtagttgg caccatggta tcatatatta 1500
aaacaataat gcaattagaa tttgggagaa gcaaatatag gtcctgtgtt aaacactaca 1560
catttgaaac aagctaaccc tggggagtct atggtctctt cactcaggtc tcagctataa 1620
ttctgttata tgaggggcag tggacagttc cctatgccaa ctcacgactc ctacaggtac 1680
32/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
tagtcactca tctaccagat tctgcctatg taaaatgaat tgaaaaacaa ttttctgtaa 1740
tcttttattt aagtagtggg catttcatag cttcacaatg ttcctttttt gtatattaca 1800
acatttatgt gaggtaatta ttgctcaaca gacaattaga aaaaagtcca cacttgaagc 1860
ctaaatttgt gctttttaag aatattttta gactatttct ttttataggg gctttgctga 1920
attctaacat taaatcacag cccaaaattt gatggactaa ttattatttt aaaatatatg 1980
aagacaataa ttctacatgt tgtcttaaga tggaaataca gttatttcat cttttattca 2040
aggaagtttt aactttaata cagctcagta aatggcttct tctagaatgt aaagttatgt 2100
atttaaagtt gtatcttgac acaggaaatg ggaaaaaact taaaaattaa tatggtgtat 2160
ttttccaaat gaaaaatctc aattgaaagc ttttaaaatg tagaaactta aacacacctt 2220
cctgtggagg ctgagatgaa aactagggct cattttcctg acatttgttt attttttgga 2280
agagacaaag atttcttctg cactctgagc ccataggtct cagagagtta ataggagtat 2340
ttttgggcta ttgcataagg agccactgct gccaccactt ttggatttta tgggaggctc 2400
cttcatcgaa tgctaaacct ttgagtagag tctccctgga tcacatacca ggtcagggag 2460
gatctgttct tcctctacgt ttatcctggc atgtgctagg gtaaacgaag gcataataag 2520
ccatggctga cctctggagc accaggtgcc aggacttgtc tccatgtgta tccatgcatt 2580
atataccctg gtgcaatcac acgactgtca tctaaagtcc tggccctggc ccttactatt 2640
aggaaaataa acagacaaaa acaagtaaat atatatggtc atatacatat tgtatatata 2700
ttcatataca aacatgtatg tatacatgac cttaatggat catagaattg cagtcatttg 2760
gtgctctgct aaccatttat ataaaactta aaaacaagag aaaagaaaaa tcaattagat 2820
ctaaacagtt atttctgttt cctatttaat acagctgaag tcaaaatatg taagaacaca 2880
ttttaaatac tctacttaca gttggccctc tgtggttagt tccacatctg tggattcaac 2940
caaccaagga cggaaaatgc t 2961
<210> 47
<211> 2099
<212> DNA
<213> Homo sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:229648.2:2000MAY01
<400> 47
ttggtttcct taattagttc cctgtgccag cccatagtca gagccattaa ttggctctgg 60
ggaagatcca agttattttc tgagtaagat attaggcttc catatgatcc agagatgcaa 120
agaaatccct agagagtgta ggagttgtct aaatccatgt gtcagatgta gccaacgaat 180
tatgtcagaa gcagagagaa aaggcctgaa aagcagctct ctcccactcc tcaggccctt 240
gtctccaacc ttacatgagg ctttttgaac atctcctcct ggcccagctg gggtgagagc 300
aagtcctcga aggcactgcc tttgagcctt gctcagccca ttctgaacta tcccaactct 360
agaattgact gctttcgaat tgtgtgacct tgggaatgtt atctggcttc aaccacaatg 420
ccctaccccc agctcctctc ccaaatgatc ctagatacag ggctgcttcc ccccgaccct 480
accccacctc gggacacagg ctcatggcct catggcactt caccaccaga agtggtgctc 540
agagttccta tttccacatc taacccccta attcctggga aagtctgagg cctggtcccc 600
ccagtgcttt ccctggctgg cctctccaca ttttcatctg atggtggagt gagatcagga 660
aaaataggac aggagctttg ccttggggga gaagagagtt aagtgtggaa aggggtgagt 720
tataggaggt taagcagtcc aagattttct ctccctgtgt aggaggccat ttcctgatgt 780
gaggggtctg aaacccaatt atgatgggac agggttgggc attgacttcc catctcttct 840
ctctgttttt ctcccactat ctgtagccca aaactcttat ggaggacttt gatctttagt 900
ataggctatt ggtcagggcc ataggaacta accccgatcc tcactccacc aggatctacc 960
acatccccta cacacaaaca catgctgtgg ggagggagtt tttccctggg gtcaaattga 1020
gggatccctt aggatcaact tgtgctcctg tggactggtg tgtgcgtgtg tgtgtgtgtg 1080
tgtgtgtgtg tgtgtgtgtg tgtgtgtatg tggggaaact tagctttcag agaatgtcta 1140
tgggctctca ttttctctct cacacaaaaa tactcgggac ttctccaagt ccctgaggag 1200
cctgaccact gaagctgatc atgagatgac tgtatgctga cacaccccct tcaggggcct 1260
ggccttgact tagggctgca ctgtatcctc agcaacggcc ttgcaggagc cccttttgga 1320
ctgctttccc tattcagccc agagttgggg tggtgggaga agaggggttg gagtgaatcc 1380
atctctattc aaattccagc tgggattact ctaggagtct tcctggcttg tatggggctc 1440
aaacttagct acattgttta ttggctccca aagtcgggat tgaagagtga aaagatgcag 1500
gcaatgaatc cttctgcaca ctcctcccca acctttccag cgcttttcta cttaggaggc 1560
cagtggaagg gaggagaggc catgccctag cccaccaggg gacaaggttc attgttcctt 1620
ccagggcttg gttcactctg cttttgattc agaagctctt tccctaccca gcaagactac 1680
actttcttgc cttctttcta ttttttcttt ttgtgcgtat aaatggtatg ttgtgatata 1740
ttctcagtgc ttgtgcccac cttggaactc tgttcttgct cttcattccg catgtgatac 1800
tctggtccaa gatcttggcc aggtgccttc tgctcaaata tcgtctcaga ggtgcttccc 1860
ttgaaaactc ggtgctgttt ccatagttac tctatttgat cactctaagt ttggttgtct 1920
tcatagcact tgtcaccctc tggaactatt ctattcattt atttacttgt ttaatgcttg 1980
gctcttttcc cctcctaacg taaactccat gattgccaac acctgtttac ttactacagt 2040
33/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
tccccctccc cccacattcc tgacactagt aagaaccaat aaaacacttg ttgacggaa 2099
<210> 48
<211> 1704
<212> DNA
<213> Homo sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:025643.2:2000MAY01
<400> 48
ggccagacat ggcggaagag gaggtggcca agttggagaa gcacttgatg cttctgcggc 60
aggagtatgt caagctgcag aagaagctgg cggagacaga gaagcgctgc gctctcttgg 120
ctgcgcaggc aaacaaggag agcagcagcg agtccttcat cagccgtctg ctggccatcg 180
tggcagacct ctacgagcag gagcagtaca gcgatctgaa gataaaggtt ggggacaggc 240
acatcagtgc tcacaagttt gtcctggcag cccgcagtga cagctgggag tctggctcaa 300
gcttgtgcct gtcccaccta aaagacgttg gacgctgtca gatgtggcaa ctcctgaggt 360
gacgatgaca aagtgttcgc tggaatctat acagatgagc tggagttcag agaggatgat 420
gtgttcctga ctgaactgat gaaactagca aatcggtttc agctacagct cctcagggag 480
agcatgtgag aagggtgttc atgtcctcta gttgaatgtc caggaacgtg gattccgcgt 540
tctaccagaa cgggcagcag gagcttgaat gccaacgcac acttgatgaa ctactggtgg 600
cagacaatta ttggcaacgt ccattggcga cagaccttga gcgaaggagg atttcaacgc 660
agcattgagc cgctccaagt ggttatacac aaatgatcaa atccaagacc agagtacccg 720
cgtacattaa agccatcaaa ggtggcgaga gaagacgtgg tcttcctgta atctgattga 780
aatggattcc cagctcccct ggaaagctga atgaagcgga tcataacgga gatctggcac 840
ttagaatctt agcccctctc acgacgactg gagaagtaaa ttgccaacca cgctggttag 900
tcaccaagct gatgtggaca tggtggacca agagtggctg gagccttgtt acaccaaggg 960
gattccaaag aaggagatct cttgtgctgc cactttccta cattaacgaa tggcggcctt 1020
gtgtcaacgc tgctacactg ggtgccccag gagacaccac ttgcaccttt gtgggccttt 1080
gtaccagttc cacaagaaac actcagctag atgtgatgcc tgagatggcc gcagattgca 1140
gaggcccttc tgcaggctgg gtgccaaccc ccaacatgca ggacagcaag gggaggactc 1200
ctgttacatg tgtgccatct atggccgcgg gatatgatat atgtgtctca gtcagctgct 1260
ccagtcgcaa acaactagat ttagaactca atagaccacg agggcaagca caggctactg 1320
tggcatggct agtgcagcat atcacaagtg tcttctgaac cagtctggga acccccttcg 1380
aagatgtccc cggtggtaaa ctgggacttc actttgagtg agaacacggt ttgcgagcca 1440
gaactccatc catgcgcggg cagtccacta catgactgca ccttgacacg gcgacaggta 1500
aagcacgtgc ctcccgaagg ggcgacgctg gggtcctgca ggcgccagga aatggcatgt 1560
aaatgccttc accccaaatt tagaaactga acggcatact atgaggataa ttatttggta 1620
cttaatttta tatacagtaa aagcctgggt tgtcattttt aaaaatcctg tgcttcaaac 1680
aattgagcag acatcaagtc cctg 1704
<210> 49
<211> 2276
<212> DNA
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:233942.1:2000MAY01
<220>
<221> unsure
<222> 1738, 1955, 1964, 1968-1969, 1976-1977
<223> a, t, c, g, or other
<400> 49
agagaataac aagtctggga ctgacgtagg aaaaacagta gtctgtttaa gttgagagga 60
ggaggatgtg gacgagagaa gggaggagag ggaagaactg aaatgtctcc tcacccaggg 120
tggttattgg gcccaacttg ggatggggtt gagtacgaag gttaaaaaac atatactttg 180
gtattatatt ggtcattgta atagcagttg taaaatatgg ggggaaaagg gatcatttgc 240
tttcctttca tggtgttaat gtgtgcctga atctatagcc gctaaaatgt aaggctgtcc 300
acctgactta tttaaatatt atcagagaat agaaagtaat cactttttaa gtgtacctat 360
gtgctgcccc ttaaaacatt catggcatct ggcaaataga cccttgtagg ctggcctggc 420
atattcagat gttgccgcat catcacagag aaggtccaat gaagatgtaa ccattgctgc 480
tcatgtgtct tctctaagca acaaggggag cgggatgtac gagagaagtt gctaatgata 540
ctgtacaaag gatggattaa ataatgaagt caatttcatt gatagaaaat gcaaatttta 600
34/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
agattctcag tgtatgaggt ctcagcctcg ggagcattta ttttttactt tcctgctaaa 660
aatccactgg ggaggtataa aattcactcc aaagaagttt gcctgggcca aaagcctcca 720
ggttccttct gagaacaaaa tactaatgat tttttttttt ttttggctgc ttgggagaga 780
ctttcagcat tctttcacga tatcccagat atgtcccttc agcacacaca ctcaactttc 840
tcatctggtt cgtttcatcc tcccgaaaga acggtgctct cccactctta ctctatttca 900
aagagctact ctgtctcaac cacagcagcc ctgccaagaa aaggcaagat gaaaggctag 960
agcatgtgct accttgagat ttcaagaagt gtcctacctc agctgaagat ggagaaacgg 1020
ggagtggaga ggggatcagc ccagggtacc atgtgatgac taatatgcca ctcattaagg 1080
gcttttacct cggctgtcca catccagtca tgcatttggg gccaggcatg cctgcgaaat 1140
gattgacatt cctgtaggtg ccccatagag gtgtggcatt gagaaattat gtctggaaaa 1200
tacagccagt gtagtgacca gctgagttac catatagcct gatgattccc cttctgtaac 1260
agaaggtgac aacaactttg tgaactttct atatctttat ctgatgcccc aagtggcatc 1320
ttctttatgt acatgcctta gttgagaata tgagactgct ctaatctttg tgaatgcctt 1380
cacacttcag ctgaggatgt caccttctct gtcactcccc atcctgcaac ctctggcctt 1440
tgctctgtct accccagcaa ttttcatagt gttatccagg tactgtgcta aaaggtcagc 1500
tcttctgtaa aatgccatgc ttcgcagctt caaaaagcaa aattctgtat ttcatggagg 1560
gagggaaggg tcattctctt ctaagaaaaa tagactggag caggcgaaat gcatgcatgc 1620
atgtgtttag agttgcttct cagagagaca taagagatga tagcaactat tacaatatga 1680
ctgaatgact gagtgaatga gttgaaggcc tagctcgggc tgataaagct tttgcctnta 1740
gtagaaggtt tatgtcaaca ccttcaggag ggaagccctt atttctgggt tgaactcccc 1800
ttcccatgat attatgctag ccattgccat cacttagttc ctggcgaagg cagaaaaaga 1860
aaccaaaaaa tcagcattgt cattgacaaa actggatgct gaagataaag taaaaattgt 1920
cttttccctt gtccccacat ttttggggat taaanccccc taangggnna aaaaannttt 1980
ggacatagga aatacagtac tatttctgaa gttgatagcc gatcttttaa gaagaccctg 2040
tctttagaat gaaactagca ggcaaacacc taaataatcg aaaattacca aagttcaacc 2100
acgaaacaag aaaacctaaa gatttttact tcctattctt attcctttcc ttattactgt 2160
gacacccctt gcattgctca gttgcttgtg tgtcaaaata acttgtggac gtctggaaat 2220
tatttgaaaa tgtattgtga aaaatgtaat aaaatgatga tatttttata caaaaa 2276
<210> 50
<211> 4111
<212> DNA
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:089158.1:2000MAY01
<220>
<221> unsure
<222> 2410, 2431, 2438, 2440, 2470
<223> a, t, c, g, or other
<400> 50
cactccagga gttccccatg gagttttcaa caagcagaga ataaaaataa atgtttgtga 60
ttgacaactt ttttccaaat gtttgaaact tcacatagaa aactgtaaag agatggccct 120
ccctcactgt atattaacat tttaagtaaa accctttgtc ccagtgttat acaagaaagt 180
tcaacaacaa aaggaaggaa aaaacaaagt gagaataagc ttcttggata ccatccctag 240
atgatgaagt gcagaaaact ggaaaaacct gacatcctgc atggagaccc aggaaataac 300
atggcatggc aaatcccagg gaagaaaact catgtgtaaa tcaaacagag ctcaaggaaa 360
agactgaaat ttcttctctt catgtttcaa aaagaattcc agaggtcaaa ggaacaggtg 420
caggtgcaaa tgtatataaa aataatgagc agcgctcatg acaaatcagg atagctacat 480
tcagtcatct ttcatgtatg tctaaactca ggccaagggg caataagtgt ccactgtgct 540
ttaaaaggtc tagaaataga aaaatcaacc cccaaatctt ttctaattcc acatggccat 600
ttgtcacgag atgactaaca atgtctgtgg ggtcaggttt aatacatttg cactgagctc 660
gtaccaggca gtccataaaa ctgttgtctt aaaatttctc cagtccccac atgtggctgt 720
tttagaggca tttccaaact taaaacccag cttctatagc tctccatacc tcttttacct 780
gcttagaaat gaatcccacc agacctccac gaatccaact ttgttaaatc atcccctatt 840
gctgatcaaa ctcactgctc cagcattcaa aaaacagaag gcataaaggt gaatacaaac 900
ataagaaagg agtttacatc gtggtcttgc agagctttcc atagtagtct cataaagtcc 960
tggtgaatcc cccagcccgc atatcttgtg cagagccaac ttgagtgtta tcaatcgcgt 1020
gtcaaacagt gataggagct tggtgtatgg gccgccgtcg ctctgggagg atggtggtgt 1080
aggaagtgaa cttgactctc ttcctctttg ggcccgaaga attcataggt tcatttttaa 1140
tttctttctc atagacatag ctcagagggt ctgagtagtt gactatgaaa agtcttctgg 1200
gaactgccat tcagaaggaa gttcctctcc tcgaactgca ggcccctgtc tatcatggtt 1260
gtgcactcct ctgatgggag tgtaatgtca acagggttct ccaaaaagtt ccacttcatt 1320
cccaagccag acccagtcgt gggaatgggg gatgttgccc tgctcactca cagcaaacct 1380
35!104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
tttgtgtctg tatttccagg caaacgccac gcagttgatc aagaagacca gaatggccag 1440
acagaagacg cagagcaagg catacatgcc aatctccaag tccgttagcc cccttgaggt 1500
cactgtgagg tcactaggat tattgggggt ccggtgactt cccttgagtg gggaagcttg 1560
taaaggcatc tggaccacca cttttgagta acttattctt cccttccatg ggagactggg 1620
gggttgtgct ttcgttggta ctttcctctt tggcaacagg tgtgccacgg tggaaccatt 1680
cctggactgc tctctcctgg tttccttcgc gctctatgga attactgagg tggtctttat 1740
attcccgatt tatgccctca atatcattgc tgcctccttg gtgctcatca ctacttggtt 1800
cgaatttgac cttgacattt cctttaccca cggcaagaac actcttcctc ttggtcttct 1860
ggacaaggtt cacttatcat catttctaac ttaatcaaag gcccttgtcc ttcaccctct 1920
gcaaccacaa ttggccattg tggactcaag gtttgcctgg acagacacca ccatttcatc 1980
caatgatgag acagtaacag aataatcctt aggatcgtaa atgtctaaag gtgtcaccga 2040
accatcactg aacaaaatcc aagaacttac tattgcttcc tgctgtgggg actgaagaac 2100
atccagggca gcagctgtgg agacgatggc ccttttgtct gctcggtgtg gctgcaggga 2160
gagagacatg ccagctacga gctgcactcc cagctccacg atggtgactc ggtcatccag 2220
gacaatcacc gtcttctcag ccaggatgga gtcagacaac ggcgagagga cctgcaccgt 2280
ggttattccc ggctcccgac cagccagggt cctgccgtcc tgtaactgag cgattttcgg 2340
ctcctccacc ttcatgaact cggtcacaaa gttccagtga tgtcaaactg ccagtcgggg 2400
cccagcattn gtaggtcagc tagccctaag nttccagngn ttgaaaacct tccgggggcc 2460
caagcaaaan cttgggtgag gacacgcact gtggcgtgct ggtactgcag ggatgcagcc 2520
tcagtccctt cttctcctca tcgtcctcgt tccatttcgc tttcccgggt aggccttctg 2580
ttggcagcaa ccgggatcct ccagcccttg atctggctca gctcggtgtc tgagatctca 2640
atctgcaggg ggagcctggg tgcccagaca gtgacctcga actgggaggt gaagtgctgg 2700
tgggtgaagt tcacaatcgt gtccactttg ctcttgcatt tccttcccag ttcacagaaa 2760
atggaatcac agttgttgga aaccttaatg acatcttcat cgcgcagact tgcattgcca 2820
cagactcatg acacatcgac cacagaacca tcctcgctgg acccccacga ctttgacagg 2880
aactgaaaca ggcctttcca gtgagaatgg cggtgttcaa aacctcggtg tccatggcaa 2940
gagggacgat gcccacgaag gttgtctggc tgacgaagat ctcggagacg accagctcac 3000
tcatggagtc ctcaatcggg tactccacct gccaggtaat ctgctgggcc ccagccaggt 3060
cactgctatt atcaattcca aagtccactt gcaagatctc atagaaggat ccatttaccc 3120
tgctctgcgt gtccgggcga tggcccatgc aggtgagggt ggccgacgtc tgagtgctgc 3180
cattatcaat ttcctcctgg actgcccatt ggtcctcact gctgactctc actgccgtta 3240
tcttcacacc tgctgccgcc ttaattctaa gagtgaactg gtctgccaca gagctactgg 3300
tcagagagac caaaaaggtg gccgtgtccc cttcccggac tagattcaga ggtaccgaga 3360
tgaccacatt ctcgtccaag ctcaccaggg accacttcag atcatccttg gttggttaga 3420
ccaccacact cccaatcctc tctcgggctg gaaacgcttg ctgggggctc tccaggcccg 3480
agtggatatt gttctcccac ttgccttcct cctccagagg acactggcca gccttgtcag 3540
ctgggtagag cgtgaagaag agctccattc gtggtgcccc cgaacagggc tgggatttcc 3600
ttctttggtt tccagttcca gccttaagtt gaaccattcg gccaccagtt ccagttcaag 3660
ccaacacaca gcccctgggc cccttgcagc cgacagctgg ctgccacttc cctggcctca 3720
gggaaagcaa acatcttgac acagggtaga tcttccgtaa ggtcactgtc atcccagccc 3780
atgccagtga cataaaacaa ggtctgcact ttgggtctgt tggagtagat ggagctgtca 3840
aggatgtggg atttcaattt ccagttgaag ggaaatttgt ccatgtttcc aaaggctgta 3900
gatgtcaaca ggagctcctg ggggattatc ttctccactg aaaatgggcc atagctggca 3960
ttgataatag ggggtgtcct ggctcggtag atgaagaatg gctccacccg ggcctgcaga 4020
ctggagttcc ttgtgaggtc ttggttggct tctttaagga aaaaggactc ctctgcattg 4080
gagatgtgca agttcgtggg gaggtaagca g 4111
<210> 51
<211> 2353
<212> DNA
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:101046.1:2000MAY01
<400> 51
gcagccagga agcacccaga actcttctgc cacagttgta gaattgtagg acccagtggg 60
caccaccttt gtctcctggg caagtccctt taccttccaa ggcctccttt ctcccaccct 120
gctccacttt tctcagcctc ctgaatgagg atggaggctt aatagacatg agaggatttt 180
gttttcagtt caatgacata gagttaagtg agctgtcagg gaagacgaga ggcatagctg 240
ctgtgagctc ctgagaccct gaaaatgctg gtttgcttca caggtgccat ctagaactta 300
acaggcactt tcggaaaaag ttggctgagg aggaacctgc tggggtatta gaagctgcca 360
ccagcgggtt ggtgattgat gttctttggg gccacggtga ggcatctttt tcattaaagt 420
ggggctttgt gtcctacaag tgctttgagt tcagagaaaa gatgaaccaa aaatgaagaa 480
aggaagtggc tcttgcttcc ccagcaaaga gttacttgcc ttctgaaaca caggccttgt 540
tgccacatag gaccagcccc tccagagtct cactcctcaa gttctgtgag acgctgcaga 600
36/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
ggacctggcc atggccttga tcttatctag accttgggaa cacccctcaa ccatcctcac 660
ctcacttcag cagaatggct gtctaggact ttaaaaatga atgttcacct ttatcgtgcc 720
ttacatcttg gaaaaagatg tttcataagt ttactcttct cagggtgaaa taggcctttt 780
tatttgtcct tcgcctgtct ttttcagatt tcaagggaga ttccttaatt cttacattcc 840
aggagtcagt gagacaatct atgcttcccc tccctgaccc tttttgtgtt tctcggtgtt 900
gatatttcac atgcttggtc cttctctttg aactttttag tgcttctggg tcatcatcct 960
gatctctctg tggcaatgcc ttcctccagc tcccacctct aaatcatctt ggcttcccac 1020
tgcctggcct tttctaaaag aaccccaatc ttcattgcct ttaaaacagc cagatttgag 1080
tcaatttcat attggtggcc agactgttta aacacaaatt ctctagctat ttacagggct 1140
cagagctgag gaggaagaaa ctcaagtccc caaataatga ctaatcacaa ttcattctca 1200
ccagcaagag ccatgaaatt ctaaggagct ggaatttggg atggcttcaa gtggccagta 1260
caattgaagc gtctggcaga caggcaaaga agcctacctt ctcccctccc cacggtggca 1320
tcaatggaat cactttcttg ggtccctcac ttaatatgaa tcatattcac ctggggcaac 1380
caacgcctga cagagttgta gtgcagaagg cacctctttg aagtgaaaac caggagatct 1440
tttatcactt ccccagccct gcaggctcag tcacatgtca aatagataat gaataaatgc 1500
atcgccaatg cactctattc atttattttt gacaagtgag ttggtgacag tgcccccttg 1560
catgctaata aaatatacag cagccacact tgtaaagtct ttgaaatacg aggcttcatg 1620
caagtactcc actattaaat ctttgcagga aaatggggta accagactgc tgggactctt 1680
gcaaaatgat tacgtttgaa gattagtgcc attctcctct acacaggcta tggtttcaga 1740
cagcaccatg gctttgataa agtggctccc agctcatagg aacttgataa ttaatgtcct 1800
ctgtgttgca tagagatcag gcatcaaaaa ctcggtggtg ctgagacgcc aacagaacag 1860
gattcttctg gtgtctggac cactgagggc tggttgtcaa ggagttatct tctcttggtc 1920
gcacctagtc cacgtgaggg agaggaaggc ttcacattgt ctttacttgg gcccttgaga 1980
ttctaggctt tagacaatct gaagctgtta gacctatcag ccaggcttct ctctgaccaa 2040
ggacaaccca aggggctcct tagaccagcc tcacctgtct ggatcaccat tctcctccag 2100
cttcaaaagt ccatccttcc tgcaaatctc atcaagactc gcggctctta aagataaccc 2160
tctccttcct gcagcacttc tatgcttgaa ggggaagggg ctggcacaca tcttctctgt 2220
gtggcctcct cctcctggcc acacggcctt tttcctggcc cctttcctta cactgttgac 2280
atgacaaggg atctgaaaag ggaataagtc caggttaaag cctcaaatgg cacagatcaa 2340
aacccactct ttc 2353
<210> 52
<211> 3301
<212> DNA
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:368676.2:2000MAY01
<220>
<221> unsure
<222> 2902
<223> a, t, c, g, or other
<400> 52
ccagggcgga cgcacgtgcg ccgggcttgc ggcgccctgg ggcccaccga ttccccaacc 60
gtcgttttcc ccaccgaggc cgaagcgtcc cggagtcatg gcccggccta aactgcgggg 120
tctctatcgc actgcctagg ggttctgctg cggggttgcg gggcgcctgc cgcgcggggc 180
agaagctttt gagattgctc tgccacgaga aagcaacatt acagttctca taaagctggg 240
gaccccagac tctagctggc aaaaccctgt taaccgggtc atttctaaaa gacatataac 300
catgttgtcc atcaagtctg cgagaaagaa tagtctttac ctttagctgc cagaagtcct 360
tgagagtcac tttgtcatag agatcccaga aaaaatattg aactgtatgt caggcccatg 420
tcccttttgg gggaggttca gcttcagccc tcgacatcgt tgttgcctac cctcaacaga 480
actttcatct gggatgtcaa agctcataag agcatcggtt tagagctgca gttttccatc 540
cctcgcatga ggcagatcgg tccggtgaag agctgcccag acggagtcac taactccatc 600
agcggccgaa tcgctgctac cgtggtcagg atcggaacct tctgcagcaa tggcactgtg 660
tcccggatcc aagatgcaag aaggagtgaa aatggcctta cacctcccat gggttccacc 720
ccagaaaatg tctccggctt cagcattgaa acccgctcat ctataaaacg tctgtgcatc 780
atcgagtctg tgtttgaggg tgaaggctca gcaaccctga atgtctgcca actacccacg 840
aaggctcccc tgaggatgag ctcatgacgt ggaagtttgc cgttcctgca cacctgcggg 900
ccagcgtctc cttcgtcaac ttcaccctct ccaacttaga gaggaaggag gagcgggttg 960
aatactacat cccagggctc caccacccaa ccccgaggtg ttcaagctgg aggacaagca 1020
gcctgggaac atggcgggga atttcaacct tctctctggc aaagctgtga ccaagatgcc 1080
ccaaagtcca gggatcctgc cggctgcagt tccaagtttt ggtccaacat ccacaaaatg 1140
cacagcaata aaatctacgt ggttgacttg agtcatgagc gagccatgtc actcagcatc 1200
gagccatggc ccgtcaaaca gagccgcaag tttgtccctg gctgtttcgt gtgtctagaa 1260
371104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
tctcggacct gcagtagcaa cctcaccctg acatctggct ccaaacacaa aatctccttc 1320
ctttgtgatg atctgacacg cctgtggatg aatgtggaaa aaaccataag ctgcacagac 1380
caccggtact gccaaaggaa atcctagctc actccagggt gcccgagtga catcctccac 1440
ctgcctgtgg agctgcatga cttctccctg gaagctgctg gatgcccagg gacaggcttc 1500
agcctggtgg ctggtgccag cccagaagct gcagcagcat acacacgaga agccctgcaa 1560
caccagcttc agctacctcg tggccagtgc catacccagc caggacctgt acttcgcctg 1620
cttctgcccg ggaggctcta tcaaagcaga tccaggtgaa gcaggaacat ctcgggtgac 1680
ccctcgcacc ctttgccccc agcttccata caagaggcct tccaggcagg gttgtgacgg 1740
gcgtccttta taccttattt caaaggagga aggccgtttt cacggtgacc cctgacacaa 1800
aaagcaaggg tctacctgag gacccccaac tgggaccggg gcctgccatc cctcacctct 1860
gtgtcctgga acatcagcgt gcccagagac caggtggcct gcctgacttt ctttaaggag 1920
cggagcggcg tggtctgcca gacagggcgc gcattcatga tcatccagga gcagcggacc 1980
cgggctgagg agatcttcag cctggacgag gatgtgctcc ccaagccaag cttccaccat 2040
cacagcttct gggtcaacat ctctaactgc agccccacga gcggcaagca gctagacctg 2100
ctcttctcgg tgacacttac cccaaggact gtggacttga ctgtcatcct catcgcagcg 2160
gtgggaggtg gagtcttact gctgtctgcc ctcgggctca ttcatttgct gtgtgaaaaa 2220
gaagaaaaag aagacaaaca agggccccgc tgtgggtatc tacaatggca acatcaatac 2280
tgagatgccg aggcagccaa aaaagtttca gaaagggcga aaggacaatg actcccatgt 2340
gtatgcagtc atcgaggaca ccacatggta taatgggcat ctgctacagg attccatgcg 2400
gctccttcct gcagaccaga ggtggacacc tacacggccg ttccagggca accatggggg 2460
tctgtcctcc cgtccccacc caccatatgc tccagggccc caacatgcaa aggttggcca 2520
catgaggagc cacctcctcg ctcccctcct gagtctgaga gtgaaccgta caccttctcc 2580
catcccaaca atggggatgt aagcaagcaa ggacacagac attcccttac tgaacactca 2640
ggagcccatg gagccagcag aataacttga tccattccag acgctttgct ggagtttcat 2700
aaagcagggc gctgagacac ccgtccgtgt tcctaaccag aaatcccaaa gaagaggaat 2760
tatacagaag gaacagcagg aggttttcct gtgacaccgc caacttcaca ttgctcagtg 2820
gactcattct aagggcaaga cattgaaaat gatgaattcc aatctggata cagtcatgac 2880
agctcatgtg ctcctcaaac tntaggcatg tgcaggttta gccaagccat gtaaatgaga 2940
ggagagaggc ctgagtcacc tagcataggg ttgcagcaag ccctggattc agagtgttaa 3000
acagaggctt gccctcttca ggacaacagt tccaagggca aggagcctac ctgaggtccc 3060
tagtctcact ggggtcccca ggatgaaaac gacaatgtgc ctttttatta ttatttattt 3120
ggtggtcctg tgttatttgg aggagatctg agtgtataac cacccagctc cggtcaccgg 3180
acttagtaat aactcatact aactggtttg gacgcatggg ttgtgacatt catactgacc 3240
gctagataaa cgtgtgcctg tcccccaggt ggtgggaata atttacaatc tgtccaccca 3300
g 3301
<210> 53
<211> 1834
<212> DNA
<213> Homo sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:238713.1:2000MAY01
<400> 53
agaaaccatt atatcccctt ggtaggcata aaaggggctg ctttgcccaa actgcctatg 60
aatttgcttc ctaaagcatg gggtgtgcct caggacctta ttaaaaagta cataaaactt 120
gaagaggatg gtggttgtgt tattggaggt gacagaagtt tgcaagataa atacttactt 180
aggcttgttg ctgctatgga agaagtcttt atggacaaac atggtatcca tcctagtttg 240
gttgctgatg tccatcagta tttctacaga aggactggag tgataggagt tcagcctgag 300
gaagtcacag cagctgctaa aaaaagcagt aatggataat cgccttcaca aatgtttgct 360
ctgtggtgcc ctttctgaac ttcatgttcc tccagagtgg ttggctcctg gagggaaatt 420
gtataacctg gcaaaaagta ctcatggaca gctgaggact gacaaaaatt acagctttcc 480
cttgaacaat ttggtttgct catatgattc agtgaaagat gttctggtac cagactatgg 540
aatgagtaaa ctaacagctt gtaattggtg ccatggcaca tctgtgcgaa aggtcagagg 600
agatgggtct attgtgtatt tggatggaga cagaactaat tctaggtcca ctggtggcaa 660
atgtggttgt ggattcaaac acttttggga tggtaaggag tatgacaatc taccagaagc 720
tttccctatt acttttagaa tggggtggaa gagtggtcta gagttaacag ttatattggt 780
tcctagtatg taagtgattc atctttgaat agtaatgttt acgatgttgc atatgaaact 840
tgttacctag catctttgcc aggtgaattt gggagtgaaa tcctagttca gaaagttgtc 900
ctacactata ttgcatcagt ctgcctcatt gtatcccgaa tgattatact cctgtaaata 960
tagatggtgc tcacgcccaa agagttggag atgttcaagg acaagaatca gagtctcagc 1020
tcccaactaa aattattctt actggacaga aaacaaaaac ttgtgcacaa ggaggagtta 1080
aacatgagta aaactgaaag aactattcaa cagaatatta cggaaccagg cttctgtaat 1140
gcagaaacgg aaaacagaga agttaaaaca agaacaaaaa gggcaaccca ggactgtttc 1200
tcccagtacc attcgtgatg gtccatcctc tgcacctgct acacctacca aggctcccta 1260
381104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
ttcaccgaca acttctaagg agaagaagat ccgaatcaca actaatgatg gacgacagtc 1320
catggttacc cttaagtctt caacaaactt ttttgaactt caggaaagta tagccagaga 1380
attcaacatt cctccatatt tacagtgtat tcgatacggg tttcctccta aagagttaat 1440
gccaccacag gcaggaatgg aaaaggaacc agttccttta cagcatggcg acagaattac 1500
aatagaaatt ctaaaaagta aagctgaagg tggtcagtct gctgcagcac actcagccca 1560
cactgtgaaa caagaagata ttgctgttac tggtaaactg tcatctaagg aacttcagga 1620
gcaagctgaa aaagaaatgt actccttgtg ccttttagca acattaatgg gagaagatgt 1680
atggtcttat gcaaagggac ttcctcacat gtttcagcag ggtggtgtat tctacagtat 1740
tatgaagaaa accatgggta tggctgatgg caagcattgt acttttccac atctgcctgg 1800
caaaaccttt gtctataatg cttctgaaga taga 1834
<210> 54
<211> 755
<212> DNA
<213> Homo sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:720928.1:2000MAY01
<400> 54
caaaccattg taaatcatga gcatgcagca tatggccttg gattcaaaat tcttgatgtc 60
ccatttcaac agaaaacatg ctgtcggcaa gtggattaca cagaaggtaa tattgccgta 120
ttgggagggc ttctggtaat actaaaaaaa tggagccata cttatgttta atagattaga 180
agaaagtaca tgtaaaacta caatgttgac acacatgaga ggatgctaaa cttttgcttc 240
atttgttttc tactccgagt gtacctgttt gttcatgaac attcacccac atgcatataa 300
tcacgggcac acaaacattc acccatatgc atataatcac gggcacacaa acatataccc 360
atatgcatat actcatgggc acacaaacat tcacccgtat gcatatactc atgggcacac 420
aaacattcac ccatatgcat atgctcatgg gcacacaaat attcacctat atgcataaaa 480
tcatgggcac acaaacattc acccatatgc atatgatcac gggcacacag acttatggga 540
gcacagggtt atgggcacat tcactccaac acaaacacac agatgtccca cccattttcc 600
taagagtctg acattaaggg attgcaacat tgtacagaag ccaatcattt gcaggtcact 660
ttgtccccag gaaagaaata tcttttattt ttctaaatcc tggtttccaa aagtattctt 720
gatgtgtgca aataaatata aagtgcattt ccata 755
<210> 55
<211> 2522
<212> DNA
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:221874.1:2000MAY01
<400> 55
cggcggagat gcctcgttgg ggctgggaaa ctcctgcaaa actcgagacc aggaagccag 60
cccgcacccc aacccccacc aaagccacct actcttcttc tgtgggaggc cagtccacat 120
ccgctctcac ccgatgagag atattcagct ggatccaaag tgactgatga agggaaggaa 180
atcatgtcaa gcgaagcctt tgaaaaagct gccctgagac ggtgtcccgc cgaaagaatg 240
ttggctcaat taagaaacat cagggagata aattcaaccc agtgtgtcta aaaatgacta 300
ccaaaacgga gtttgttttg tgcggttggg taccatgtcg ctgtctacgg agggggaaga 360
ggagactgtc actactcttg attattctca ttgcagcttt agaacaagtt ccggaaagag 420
atttttactt ttgaaaaaac tcttggagga actctattta gatgctaatc agattgaaga 480
gcttccaaag caacttttta actgtcagtc tttacacaaa ctgagtttgc cagacaatga 540
tttaacaacg ttaccagcat ccattgcaaa ccttattaat ctcaggggaa ctggatgtca 600
gcaagaatgg aatacaggag tttccagaaa actatcaaaa attgtaaagt gtttgacaat 660
tgtggaggcc agtgtaaacc ctatttccaa gctccctgat ggattttctc agctgttaaa 720
cctaacccag ttgtatctga atgatgcttt tcttgagttc ttgccagcaa attttggcag 780
attaactaaa ctccaaatat tagagcttag agaaaaccag ttaaaaatgt tgcctaaaac 840
tatgaataga ctgacccagc tggaaagatt ggatttggga agtaacgaat tcacaggaag 900
cgccctgaaa gtacgttgag caactaactc gattgactga gataattgga gagtatgcta 960
atagactgac ttttattcca gggtttattg gtagtttgaa acagctcaca tatttggatg 1020
tttctaaaaa taatattgaa atggttgaag aaggaatttc gacatgtgaa aaccttcaag 1080
acctcctagt atcaagcaat tcacttcagc agcttcgctg agactattgg ttcgttgaag 1140
aatataacaa cgcttaaaat agatgaaaac cagttaatgt atctgccaga ctctatagga 1200
gggttaatat cagtagaaga actggattgt agtttcaatg aagttgaagc tttgccttca 1260
tctattgggc agcttactaa cttaagaact tttgctgctg atcataatta cttacagcag 1320
39/ 104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
ttgcccccag agattggaag ctggaaaaaa aaaaactggg ctgtttctcc attccaatga 1380
acttgagaca cttccagagg aaatgggtga aaagccaaaa ttaaaagtca ttaatttaag 1440
tgataataga ttaaagaatt taccccttag ctttacaaag ctacagccat tgacagctaa 1500
gtggctctca gaaaatcaat cccaacccct gatacctctt ccaaaaggaa ctgattcaga 1560
gaccccgaaa atggggctta ccaaatacaa gttccctcaa cagccaagga ctgaggatgt 1620
taatttttaa tatcagataa tgaaagtttt aacccttcat tgtgggagga acagaggaaa 1680
cagcgggctc aagttgcatt tgaatgtgat gaagacaaag atgaaaggga ggcacctccc 1740
agggagggaa atttaaaaag atatccaaca ccatacccag atgagcttaa gaattatggt 1800
caaaactgtt caaaccattg tacatagatt aaaagatgaa gagaccaatg aagactcagg 1860
aagagatttg aaaccacatg aagatcaaca agatataaat aaagatgtgg gtgtgaagac 1920
ctcagaaagt actactacag taaaaagcaa agttgatgaa agagaaaaat atatgatagg 1980
aaactctgta cagaagatca gtgaacctga agctgagatt agtcctggga gtttaccagt 2040
gactgcaaat atgaaagcct ctgagaactt gaagcatatt gttaaccaat gatgatgttt 2100
ttgaggaatc tgaagaactt tcttctgatg aagagatgac aatggcggag atgcgaccac 2160
cattaattga aacctctatt aaccagccaa aagtcgtagc acttagtaat aacaaaaaag 2220
atgatacaaa ggaaacagat tctttatcag atgaagttac acacaatagc aatcagaata 2280
acagcaattg ttcttctcca tctcggatgt ctgattcagt ttctcttaaa tactgatagt 2340
agtcaagaca cctcactctg ctctccagtg aaacaaaact cgtattgatg ttaattccaa 2400
aatccggcaa ggagatgaaa attttaacag ccttttacaa aatggagata ttttaaacag 2460
ttcaacagag gaaaagttca aagctcatga taaaaaagat tttaacttac ctgaatatga 2520
tt 2522
<210> 56
<211> 2634
<212> DNA
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:1143545.3:2000MAY01
<220>
<221> unsure
<222> 1800
<223> a, t, c, g, or other
<400> 56
agcggagtgc caggctactc ctcccgcagt gtgggtggtt ccgaggctgg ctaccctgcg 60
gcggcgcggc tcgcagtcct tctcagcatg gaccgcactt gtgaggagag gcccgctgag 120
gatgggagct gcgaggaggt acccagactc catggaagcc ccaacccgga tccgggacac 180
tccggaagac atcgtgctgg aagctccggc tagtgggctg gcgttccatc cggcccgtgg 240
accttactgg ctgcagggga cgtggacggg gacgtgttcg tcttttccta c'tcttgccaa 300
gagggagaaa ccaaggagct ctggtcatca ggtcaccatc tcaaggcctt ccgagctgtg 360
ggctttctct gaagatgggc agaaactcat tactgtctcc aaggacaaag ccatccatgt 420
tctagatgtg ggagcagggc caactggaaa gacgtgtttt ccaaggctca tggtgccccc 480
atcaatagtc ttctgctggt ggatgagaat gttctggcca ctggggatga ccccaggtgg 540
tatccggtct ctgggaccag cggaaggagg gccccttaat ggatatgagg caacatgaag 600
agtacatcgc agacatggct ctggatccag ccaaaaagct gctgctgaca gccagcgggg 660
gaagggctgc acttgggcat cttcaacatt aaagaggcgt cggtttgagc tgctctcaga 720
acctcagtct gggtgacctg acctctgtca ctctcatgaa atggggggaa gaaggtaagc 780
ctgtggctcc agtgaaggta ccatctacct cttcaattgg aatggctttg gggccacaag 840
tgaccgcttt gcccttgaga gctgaatcta tccgactgca tggttccagt caccgagagt 900
ctgctgtgta ctggctccac tgatggagtc atcagggctc gtgaacatcc taccgaacca 960
gagtggtggg cagtgtgggc cagcacacct ggggagcctg tggaggagct ggccctctcc 1020
cactgtggcc gcttcctggc cagtagtggc catgaccagc gcctcaagtt ttgggacatg 1080
gcccagctgc gagcctgtgg tggtggatga ctaccgtcgg cgcaaaaaaa agggaggacc 1140
actgcgggct ctgagcagca agacttgggg gccccgatta cttctttcgc aagacttgag 1200
ggacgaggga gaagactcca tggctcagcg aagaaaagga ggagactggg gattaccggg 1260
gctctgaggg aatgaattga atcttgagac gggtcctcac cagccccagc cagaccacag 1320
gaggttgggc cccagactca ctgagtgcct gcagcagccg tacagacaca gcatccttgg 1380
ccacctcatg cccatcccgg ccatctaggg tcagcacaac ccagatgagg ccgctgaagg 1440
gcaccgggat ggccaggaat caccaccgtg gtaccagaag cggtgccagc cagcaggtcc 1500
tatgcccaaa cacttggtga ggaaacccca gggttggccc agtttcattc cgttggcaca 1560
gcaatctgca gggtagccct gagccctctt ggaaccctaa cgttgtctcc ttggccacaa 1620
gccacactgg gctggccgtc tggctgtggg gaccgcaagg aagggaccca ccaaagctgc 1680
tcggcagaag tctgctgcat tcaggtctgg cttgaggcca ctccacagcc acctgctctc 1740
cacagaggtt gtgactgccc tgtaaaggaa aaaatgcaaa gacaagggca ggtctaaaan 1800
40/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
ccctgggccc aagcctccag ggtggtgagc cctttggaaa gctacacagt cctgttaaat 1860
ttgtagcctg tgccatttcc tggtagtgtg atccatgggt aaagaaaaga caatgagagc 1920
cttcagccta cattatgttg caaaggtgag tagtaacagc aacgtgcgta cgcgttaaca 1980
gagtcttgcc tgtcggagat agtagctggt ttattgccag gctcttgtgc tgcctcagta 2040
agccatccat aatggcctaa tcctttactg gggaaaactt gcgtgtaagt ccagtcagtg 2100
tgctatacgt acacgtagca cccacttagt gttaccttaa cttgtcataa acagtctgag 2160
gaaacagatt cctatagtag taaaaaggct cagtttggat tccccttgag caaagtcaat 2220
ttctctaaca gtttctctca ttagcttgag ggtccctgtg ccctattttg cggtgtgggg 2280
gtgggggaag gttgagaatt aagtccagga ggtaatgctc gggaagtgtc acaaatttag 2340
gtaagcggtg gtggtagcac cattggaagt tttaaaaatc tgaggtgcaa atagtaaaag 2400
gttgcaaatt ctggcatgtt tgactctaag atcttgtaac tttaacagct atgctcagta 2460
taaagtgccg ggcagaacgc gtttggcccc aaccagcacc cccgccccag cctaccttcc 2520
accagggcct ttttggccat ggcagcggcc cggtgcgagc tgaatttgag cagagcgatc 2580
tgcccgggcg ccggtccggg gctgggcagc agccgcgcct cctgcaagcc ggga 2634
<210> 57
<211> 2196
<212> DNA
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:1143605.1:2000MAY01
<400> 57
gcataatgat caaatcaagg taatgttaaa tgcttgaggc gatgtatatc tccttatttt 60
tctaactgga cttaaattct aaagagacta tatataagtt aaaaatgaag aataaataag 120
agctcaatta aacgggaatt ttaaaagttc caataaattt gggataaaat gtaatgtaag 180
gtgtttcata tggagagcca tccctgcctt ttgatcactg tttccagaaa agcacagact 240
tgtgcacctc cctctgtgct ttcttatgtt ttgacagttg aacataccaa aacaggtgat 300
gagcaaactt gcaagcagtt tttactgata gtttttacat agcataatga agtataatgt 360
tatcaaccaa gaactgtaaa aaaaaaacac tgtgaggctt atgcctcttc cagacttgct 420
tttttgaact tttccataca ttttttgttt tagacctatt ccatctgggc tagcagttgt 480
aaaaacaaag cagagtgcaa tgaactccat ccgtctgttt ctgtggtaca gattttagcc 540
ttcatcctaa taagaaacat ccctggatat gcccgttcag tttacagttc attttttgct 600
tggtttggaa aaatttcatt agagctattt atttgccagt atcacatatg gctggcagcg 660
gacacaaggg gtatcttggt actgatacct gggaaaccct atgctcaaca tcattgtcag 720
cactttcata tttgtttgtg tggccacatg aaatttctca gatcactaat gatcttgcac 780
agattattat tcgctaaaga taactcatct ctcttgaaaa ggttggcatg tatagctgca 840
tttttttttt gtggactcct catcttatca tccattcaag ataaatcaaa acattaggtt 900
ccaaaaattc taaaaaacct aaactttttc caggctacct ttggtgtggc tccaaaaaaa 960
gaaaagcatc tatctggaga tataaatgtg tatgtaaata taaacgtttg tggcaagagg 1020
acagttctgt gacatctgtt gaacatatgt ggttgtaaat atgtgtaaat gtacatatcc 1080
caatatgaaa tactaagaca aacaaacaaa caaaaaacca gaatgcattg tataggattg 1140
catgtgaagt cttttctact gaatctatat ttccatttgt aagtgatttt aagttaacat 1200
atgaaggcag ggaaatgatt acctttccag taaaaagtat aggtaatttt aattaactta 1260
gtgacaccac caagtgtttt tgatataact aaaatttgtg gtaataaggc ttgtcttgca 1320
cctgtattca ttgtgggact tcctctttca ttggaaaatt tttttactca agaatgacgg 1380
cagtattgtt ttcttatatg tgcaatgaag tggaatgata aacagtatgc ctttaattta 1440
tatgtgttct tgttctgatg ttgtttcctg aaatgatttt tcttcctaac tgtggttttc 1500
gggtatgcaa gcctttaatc ttttgtacca ctttgtctca cagaatagtt ctgaggctcc 1560
atgacagggt tttgtcattg ttgatgttta ttgttgcttc gttttataaa aaagccaaaa 1620
ttttttttcc aatccaaacg ttcacctgtt tcctttcctc aagctatacc agttgtaata 1680
ccagttaccc tgtgggatcc atttaatatg ttatccccac taaataaatt tccatatatt 1740
atttcccaat atttgggaaa gcctctttat agcccatttg gggtatttcc tattacccac 1800
ctcctatttt aaatatttat cagtctaaac ttgtgcagtg tagtaaacat gcaagttgtt 1860
acgattgagc tgtattaccc ctaagtagaa tttctaagta aacctggtga atttggacca 1920
tagatgtttt tgctttttgt ttgatttttt tttacaagct aactgttaga ggtatacatt 1980
tatttatctg ttgtacagat atgattatga ttttaatgtt tgaaagattg cacttgtttg 2040
cttttactat atgtggggta aaatatattt tctgttcaca gtatatgaaa atatggagta 2100
atttaaacag taaataaaca ttctgtggat gcttattttt gtattggcaa agtatcaatt 2160
aaactatatg tgttcttttt caaaaaaaaa aaaaaa 2196
<210> 58
<211> 2250
<212> DNA
<213> Homo Sapiens
41/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
<220>
<221> misc_feature
<223> Incyte ID No: LI:474069.7:2000MAY01
<220>
<221> unsure
<222> 209, 1246, 1435
<223> a, t, c, g, or other
<400> 58
cccgcccgcc ggagactccc gcggcgggac ccgtcaaagc cccggggatg ccatggatcg 60
tcctcgttgg cggcttctgg acactgagcc actagagggc atcggtcccg gtaaggccgg 120
acggcaggct ccgggatacc gccacgctct ctatggcgcc cagaaagggg cggggtggcg 180
accgcagtcg ctttggctga ggctctgcng ggaagggaag gggggctttt acgtcatcaa 240
tctgcgccaa ctgactccca agtccctggc ttggagtggg aagtgaggtg tgggaagtag 300
gtcgctttct gatgaattca gtggcagtga attgagaccg gagggaatct ggcccctaga 360
ggctggtact tgggcccgaa acccccatct ccggcggaga gaccgtccga ggtaattgtc 420
tgccacgagt ggacattctg aaaacaggag attttagttc ctaaaaaatg ggaagaacct 480
acattgtaga agagactgtt ggccagtatc tttcaaacat aaatctccaa ggaaagggct 540
tttgtctctg gccttttaat aggcacagtg ttccgtcaca aaaggattat gtgatttctt 600
gccactagaa cggccaccca aagagggagc aaagtgagaa cctcaaacat cccaaaagct 660
aagtttggat aacttggatg aagaatgggc cacagaacat gcctgccagg tatccagaat 720
gctaccaggg ggacttttag ttcttgggag tatttattat tactacttta gaactggcaa 780
atgattttca aaatgccctg cgtagactaa tgtttgctgt ggaaaagtct ataaatagaa 840
agagattgtg gaatttcaca gaggaggaag tctcagaacg agtgacactt cacatttgtg 900
cttctacaaa aaaaatattt tgtcgaactt atgatatcca tgatccaaag agttcagcaa 960
gaccagcagg attggaagta tcaaagtgga ttatcatcct catggctttc tttagagtgt 1020
acagttcaca ttaatattca catcccactt tctgctactt ctgtcagcta tactctggag 1080
aaaaatacaa agaatggact tacacgctgg gccaaggaaa tagaaaatgg tgtttcattt 1140
cgcattaatg gacaagttaa agatgaaaga ttgtgaccta ttagaaggac agaaaaaaat 1200
cttctagagg aaatactcaa gcaactagtc attgttttgc atgtcnacga gtgctaacgc 1260
agttgcgtcc tgaattcaga ccacatgatc cacagccaca gtccacgata tcgtagcggt 1320
tctgtaaacc ttaacgggtg ctgtgaacat cgcagagctt taatatccac agcagtaaac 1380
ccaaagctta aagatgctgt gcaggcacgt aaacgaggga tatacttgaa cacangcttg 1440
ctgatcgttg tgaaactgct atttgacgga tctgcttttg caatgaaatt cccagaaaaa 1500
aaaagttatg agtataaaat tctgaaaaag agttccaccg tcctcccttt atccgagtct 1560
ttgttcccct tcctggatcc acctgtaatg ttgtgtgatt ataaatttga cgatgagtca 1620
gctgaagaaa tcagggacca ttttatggag atgttggatc acacaattca aatagaagat 1680
ttgggaaatt gcagaggaaa caaacacagc ttgtattgag tcctcctatg aatagtcaag 1740
cttcattgga caacacagat gatgaacaac ccaaaacaac caattaaaac tacaatgtta 1800
ttgaaaattc agcaaaacat aggtgtgatt gcagcattta cagttgcagt ccttgcgtgc 1860
gggtatctcc tttcattact tcagtgatta gggtgaggca caaagagttt cctgtgatca 1920
tccagagaac attgacagac aattatgaat aataaagatg ttaacaatcc atctgtattt 1980
aaaacaccta gccgccagat ctgctgccat gatgcctatt tggtgtgttt ctgattaaaa 2040
tgaaatcacc agctgccttg tttagcctgc tttacattgt aggtggcccg catttccaga 2100
aataacgtta tgcatctaag atggaagctg catgtaacca atcattatta tctattttta 2160
aaagcttcca aatgatggga tatgatcata gattttagtc ttactaatct gaatcacata 2220
ttaatccagg acatttaaaa ctttaacaga 2250
<210> 59
<211> 2963
<212> DNA
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:245193.3:2000MAY01
<400> 59
gtgaggctgg cggtggcgac aaccgaggag gaggggcggg acgccgtgga gcacggcgac 60
cggctgagcg tcatggaggg ctcaggggag cagccgggcc cacaaccaca gcatcccgga 120
gaccaccgca tccgcgacgg cgacttcgtg gtgctgaaac gtgaagatgt gtttaaagca 180
gtacaagtcc agcggagaaa aaaagtaact ttcgaaaaac agtggttcta cctggataac 240
gtcattggcc atagttatgg aactgcattt gaagtgacca gtggaggaag tctacagccc 300
aagaagaaga gggaagagcc tactgcagag actaaagaag cgggcactga taatcgaaat 360
atagttgatg atgggaaatc tcagaaactt actcaagatg acataaaagc tttgaaggac 420
aagggcatta aaggagagga aatagttcag cagttaattg aaaatagtac aacattccga 480
42/ 104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
gacaagacag aatttgccca agataaatat attaaaaaga agaaaaaaaa atatgaagcc 540
atcattactg ttgtgaagcc atccacccgt attctttcaa ttatgtatta tgcaagagaa 600
cctggaaaaa ttaaccacat gaggatacga tacactagcc cagatgttga cgttgggaaa 660
tatccgtgct ggcaacaaaa tgattgtgat ggaaacgtgt gcaggcttgg tgctgggtgc 720
aatgatggaa cgaatgggag gttttggctc cattattcag ctataccctg gaggaggacc 780
tgttcgggca gcaacagcat gttttggatt tcccaaatct tttctcagtg gtctttatga 840
attcccctct caacaaagtg gacagtcttc tacatggaac attttctgcc aagatgttat 900
cttcagagcc caaagacagt gctttggttg aagaaagtaa tggcacactg gaggaaaaac 960
aggcttctga acaagagaat gaagacagca tggcagaggc cccagagagc aaccacccag 1020
aagaccagga aacaatggaa acaatttctc aagatccaga acataagggg cctaaagaga 1080
gaggaagcaa aaaagattat attcaggaaa aacagaggag acaagaagag cagaggaaaa 1140
gacatttaga ggctgccgct ctgctgagtg aaagaaacgc agatgggtgc gttgatggaa 1200
gaaggcagga gactcctcag tgcatgtggg ctctgcttca gacagattgg cattctcttt 1260
ctccttgtct gctttgactc tagtgggacc cgagatgagg attttgtctt gggggttttt 1320
ttaaagaaag gaggctgagg ctggcagggg tggggaattg atgatgctgg tttcagggtt 1380
tcagaagaaa ttgaatcttc tccatcactg catcaagatg ggccctgtgg tcccactgga 1440
tgcaggggat ggggcactca aatgctgcga tacaggctat aacagatatc cacaaagcag 1500
cttatgcagt gttggatttg tttccaggtg atttttttta aaaaatcaag aatgtcatta 1560
aatgcgactt agagttgcca agtaccacaa gagcttctaa cctagttcgc gtttcctaga 1620
aagaaatagc tcatgattgt attctgtttt ggatttctag aatgttatat ttaaatctct 1680
tctctttgtg agtcatgcaa attaaataca tgatcatttt aaatgcattt taaaacctgt 1740
gctccacttt gagggtgtag agaaataatt tgtctggcat tttccttaca gtttaattgt 1800
agctagtcgt ttccacccca ctcccctgct gctgtctttg ctggactttg tggccccttc 1860
aaggccgttt gtggtctact gtcagtacaa agaggtaata ctggaatgga atgggcagga 1920
attcttatgt ctgaatgttg attcttaaac tgcatcccag gaagtagttc ttaacagaat 1980
tctgttgttg tctgcagcct ctgttggaat gctacacaaa actgcgggag aggggagggg 2040
tcatcaacct caggctgtct gaaacctggc tcagaaatta tcaggttttg ccagatcgaa 2100
gtcatcctaa actgctgatg agtggaggtg ggggttatct tctctccggc ttcaccgttg 2160
ccatggacaa ccttaaagca gacaccagcc tcaaatctaa tgcaagcact ttagaatcac 2220
acgagactga ggagcctgca gctaaaaaac gaaaatgccc agagtctgac tcttaaccct 2280
tttgagaatt gctctgaatt ttgttctcag gcattataca gttagtaatt aaactttaaa 2340
tgccattact acttgttttt tcatatccca agaataagaa catgtctatg tacccgtttc 2400
taggaaggag gagtatatgc cttttgtcta tttctgacac aagattgctt tgggccggtc 2460
aaaacctgca accatggggt atgtagtatg accaactgca tttaacaaaa ctcctctaag 2520
tacttctaaa tattctgtgc aaatatcttg agaacttcaa catcctaaaa atgtgtttct 2580
acaagacttt atattttaag ctaagtggaa taatacaacg taactaaaac atggcgggta 2640
ccgaaaggag ggcaattcat ggaagaaatt tcctctgttc attccgttct cttcaaccta 2700
agcaatatgg atgtgtgagt gtgtgattta ttatggtacc aaaaatgtcc accttctttc 2760
ctgcagcgga ataagctttt ttgaaatgct gaggttttat tttaatagtt gacaacctgg 2820
gaaagttctg agtatttatt ttactgctct ttttttgtgc atagaaaggt ttagtagggt 2880
actttttttg cattaatttg ccaatactct tattcatatg ttctaaaaaa agggacctgg 2940
aatttttgtg tactattcaa aaa 2963
<210> 60
<211> 2569
<212> DNA
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:403872.1:2000MAY01
<400> 60
ccaggaggag gcagcggagg aagcagagcg cgggatgggg gcccagcggc atctgtgatc 60
ccgcgcacct ccgccccacg ggcgcgcgca caaacacgga cacacacata cacacactcg 120
cgcacacact cgcacaaaca cacactcgta cacgcccgcg gccgctcgct acgccggctt 180
gctctgggca cgcaagcgga atgcagcagc gcctggagag cgtgtctcgg accgccgcct 240
gaatgtacct cgctcccggg agccggacgg cccagtaggg cgcactggag gacgctccgc 300
tgcgggacgc ttggacagtt ttttgacggt gcagtcttgc tatatggtgt gagaaatggc 360
tgtaggaaac aacactcaac gaagttattc catcatcccg tgttttatat ttgttgagct 420
tgtcatcatg gctgggacag tgctgcttgc ctactacttc gaatgcactg acacttttca 480
ggtgcatatc caaggattct tctgtcagga cggagacttt aatgaagccc ttacccaggg 540
acagaggaag aaagcttcat caccccttct ggtgcctcta ttgtgtgctg gctgccaccc 600
caactgctat tatttttatt ggtgagatat ccatgtattt cataaaatca acaagagaat 660
ccctgattgc tcaggagaaa acattcttgg acggggaatg gctggttcct tgaaccccct 720
tacttcgaag gatcataaga ttcacagggg tgttcgcatt tggacttttt tgctactgac 780
atttttgtaa acgccggaca agtggtcact gggcacttaa cgccatactg ccctgaacgt 840
43/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
gtgtgcaagc ccaactgaca ccagtgcaag actgccaagc gcacccacca ggttagaaac 900
aatgggaaca ttttgtactg gggacctggg aagtgaagta gaaaaggctc ggagatcctt 960
tccctccaaa cacgctgctc tgagcattta ctccgccttt atatgccacg tatctatatt 1020
acaagcacca atcaagacga agagcagtcg actggccaag ccggtggctg tgcctcggaa 1080
ctctctgcgc cagccttcct gacaggcctc caccgggtct ctgagtatcc ggaaccactg 1140
ctcggacgtg attgctggtt tcatcctggg cactgcagtg gcccttgtat tctagggaat 1200
gtgtgtaggt acataacttt aaaggaaacg caaggatctc cagtccggac cacagcactg 1260
aggatcccca cgtcggagta cccctaatgc catcgtccca atggagtagc aaagtccact 1320
ctggataacc tataagtgca ccagagatca cttcttgggt cccaatggcc cggaaggtac 1380
cctgagagcc ggcgcttgaa tgtgtcaacc aaacgctgtt ttttgaaaaa ctagtcgttt 1440
ccccaagttc tatatgcact tccgaaacaa ccaccacggt tgcgtccaat gtcccaaccg 1500
tgggggagcc aaataattaa cggttaattc taaggtatag agaagctata atagttttgg 1560
aacacacttt ttgtaatgag aggagaatga gatgtatagc tttccccgga attttttttt 1620
tttttttggt cagctttaat atatttatgc cagaatttta aaacccaaca caaattttct 1680
tgttcaagcg tgcattgaag aaccacattt attcaatggt tgacgttgtt ttgtgatatt 1740
tgtacacaaa ttttcttttc tcagttttat aaacacagaa gtaaatataa caattcactt 2800
taaactttta ttaccacagt tgctgcctcc tccagaattt ttgaatttta ataaaaggca 1860
aacttttgag ctgcaggaag ggacaatgtc tggttaataa ctaaatctca gagtcaattg 1920
tagaacagac aacaattgtc ttcaagaaag aatgttggca ctcctgatct ccttaaacaa 1980
attgttacgt tcatatagtt tacacatgtg atatattaac caacatgtca ccatagttat 2040
accaaccaat tgtcagagaa ttctggattt ggagggtata tggggttata tgattctttc 2100
ttagataatg gcctctacta aactaactca agatctttct ggaatgtctt ctggcaggca 2160
ggtgccactg tcagcttttc tccaaaaagc aggccaacat cagcctcccc tgtcaactca 2220
acagttttgt atctcatatt atatggacct ttatatgaaa gatgaatatt ttaccagttt 2280
ggcacagtat tattttacag aaaaggaatc agagaatcct acaacatagg gccccagaac 2340
aacagtttca ctttgtggct ttataattat tctaggaatt ttaactgcat ctcatttttc 2400
tagcatggtg agaactaata tgtaactcct tttgattgaa ggagctcttt tgtccgtacc 2460
tatcaagaat gttttcttga cacttccatg ttgggctctt ctcagctttt tttgtacata 2520
tttttttttt ctaaagagaa gaacaaagtt ttcaccaaat tgtccgacg 2569
<210> 61
<211> 2545
<212> DNA
<213> Homo sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:1086294.1:2000MAY01
<220>
<221> unsure
<222> 2124
<223> a, t, c, g, or other
<400> 61
gagcccgagg cggcagcgct cgcggccatc gtgggcccga gctgtgcgcc tcggctcgga 60
gcccggaccg ggcgggggcg ccgacgtgcc tcagcctgct tcgcgaggga ggcgggagtg 120
agcagaaagg cttagggccc agtgggcggg gaaggggggc cgggcctgga tccggcgggg 180
aggccgagcc ggaggccgga ccgtggctcg cgctgtcccc gggacgcgga tcgaacgttg 240
gcggcgcgga tcgcacgtcg gcggccggtg gaacgcggga gctgggcggc gcgcggactg 300
gggccatggc gtctgtgcag gcgtcccgcc gccagtggtg ctacctgtgc gacctgccca 360
agatgccgtg ggccatggtg tgggacttca gcgaggccgt gtgtcgcggc tgcgtgaact 420
tcgagggcgc ggaccgcatc gaactgctca tcgaatgccg cccgccagct caagcgcagc 480
cacgggctcc ccgagggccg ctcgcccggg gcccccggcc cttaagcacc cggccaccaa 540
ggacctggcg gcggcagccg cacaggggcc ccagctgccg cccccgcagg cccagcccca 600
gccgtcaggg accggcggcg gcgtgtcggg ccaggaccgc tatgacaggg ccacatcatc 660
aggccgccgt ccccctgccc tcgcccgcca ctggagtaca actctggggt ccccgcctgg 720
gccaatgggc tgggccgtga ggaggccgtg gctgaggggg cgcgaagggc cttggcttgg 780
ctccatgcct ggtttgatgc cccctgggtt gctggcagct tcagtgtctg gcctgggaag 840
ccgaggcctg acgctggcac ccggcttgag tcctgcccgt cccctcttcg gctccgattt 900
cgagaaagag aagcagcaga ggaatgcgga ctgtctggca gaactgaagc gaggccatgc 960
gaggccgggc agaggaatgg cacgggcgcc ccaaagcagt gcgggaacag ctactggcgc 1020
tgtccgcctg cgccccgttc aatgtgcgct tcaagaagga tcacgggctg gtggggcgag 1080
tgttcgcctt cgatgctaac tgcccgtcct ccaggatacg agttcgagcc tgaagctctt 1140
tcaccgaata cccctgtggt tccggcaatg tgtacgccgg cgtcctggca gtggctcgcc 1200
agatgttcca cgatgctctg cgggagccgg gcaaggcact ggcttcttcg ggcttcaagt 1260
acctcgaata tgaacgccgg'catggatcag gagaatggcg gcagctgggc gagctgctta 1320
441104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
ccgacggcgt ccgaagcttc cgcgagccag ctcccgcgga ggccctgccc ccagcagtac 1380
ccagagcggg gccctggggc tctctgtggc ccacccccgc gagccccatc ccggaacctg 1440
gcgcccacgc cgcgccgtcg caaggcatcc cccgagccgg agggcgaggc ggctgggaag 1500
atgaccaccg aggagcagca gcaacggcac ttgggtggca cccggcggcc ctgtactccg 1560
cgtgagaccc ctcggtgtgc cctcgcccat tgccgccctg aagaatgtgg ccgaagccct 1620
gggccactcg acccaaggac cctgggcgga ggcggggggc ctgtgcgtgc aggtgggcgc 1680
cagccctaac agcctaccac cacgagccca gaccgccaac cccagcatcg cctttgtggc 1740
cgcgcaacag gcgaagcagc aagtcagtcc cacaagcggg ggccgaagct gtcaacgggg 1800
gtggcagcag gcactggggc gacccctggg gcccaccctg tgcttgtacc ctgtgcaggg 1860
agcggctaga agacacccca cttcgtccca gtgcccctcg gtgcccggac acaagttctg 1920
ctttccctgc tcccgggagt tcatcaaggc gcagggcccg gccggggaag gtgtactgcc 1980
cgagcggaga caagtgcccg ctggtcggct cctccgtgcc ctgggccttc atgcagggcg 2040
agatcgccac catccttgct ggagacatca aagttaagaa agaacgggac ccctaggcta 2100
ccactgcctc caggctactg ccgntctgcc cctttgccac ccaccggctg ccgcggataa 2160
attattcccc tccccgaccc agcccagtgc cacctccatc tgggtggaat gaagggagta 2220
tgtacacaga tagaggtggc actggggtaa gatgcattgt gggtgggggg gagaaagctt 2280
gtggctcctg tccgaggggg ggtgtttggg ggtcccttgg ccccctccag tttccctcta 2340
gtcctccttg gcttggcttt gcttgctgct tgtagttagg gggagaaggt gcccccctac 2400
ctccttgaga atgggaccta cctgaaaact ctgctcttta taaactgagt gcaaaagcat 2460
tgtaattcca cacccccgcc acccccctgc gtcgccttct tgctccttca ataaaccgaa 2520
agatgggttt tttttttcaa aaaaa 2545
<210> 62
<211> 2114
<212> DNA
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:337514.3:2000MAY01
<400> 62
agcggctgga gctgggcctt ggccgcgaga ggccggcgaa agctatcttc ctgcaccggc 60
ggccgggtga gggcggtggg agggagcggt gcctgcgctg tggccatgtc tgtgtacgca 120
agggggccgg ggccccgcga agctgtgccc tcaggccggc cccggccgga cacccttacc 180
cctccatggg tccggcagag ggcagtgacc ggcaccttct gtgcgtcctg gactcctctg 240
agaaacagga gagctcaaag gatggctact gacatgcaga ggaagagaag cagcgaatgc 300
cttgatggca cattgactcc ttctgatgga cagagtatgg agagaactga gagccccaca 360
ccaggaatgg cccagggaat ggagccagga gcgggccagg agggtgccat gttcgtccat 420
gcccgttcct acgaggacct gactgagtca gaggatgggg cagcttctgg ggacagccac 480
aaggagggta ccaggggtcc cccgccgctg cctacagaca tgcgccagat cagccaggac 540
tttagcgagc taagcaccca gctgacgggt gtggcccggg acctgcagga ggagatgctg 600
ccaggaagct ctgaggattg gctggaaccc ccaggggcag ttgggcgacc agccacagag 660
ccccccaggg agggcacaac cgagggggat gaggaggatg ccacggaggc atggcgcctg 720
caccagaagc atgtctttgt gctgagtgag gcagggaagc ctgtgtactc ccgctatggg 780
tctgaggagg cactttccag cactatgggt gttatggtgg cccctggtgt ccttcctgga 840
ggcagacaag aacgccatcc gctccatcca tgcagatggc tacaaggtag tattcgtgcg 900
ccggagcccg ctggtgctag tggcggtggc tcgtacgcgg cagtcggcac aagagctggc 960
gcaggagctg ctctacatct actaccagat cctaagcctt cttaccggtg cgcagctgca 1020
gccacatctt ccagcagaag cagaactatg atttgcggcg cctactctcg ggctcagagc 1080
gcatcaccgg acaacctgct gcagctcatg gcacgagacc ccagcttcct gatgggggcg 1140
gcacggtgcc tgcccctggc ggcggccgtg cgcgacactg tgagcgccag cctgcagcag 1200
gcgcgtgcgc gcagcctggt cttctccatc ctgctgggcc cgcaaccagc tcgtggcact 1260
cgtgcgccga aaggaccaat ttctgcaccc catcgacctg cacctgctct tcaacctcat 1320
tagttcctcc tcgtcctttc gcgagggcga ggcctgggac gcccgtggtg cctgcccaaa 1380
ttcaacgcag ccggcttctt ccacgcacac atctcttacc tagatgccta gacactgacc 1440
tactgcctgc tgcttgtctc cactgaccgt gaggacttct ttgcagtctc tgactagcgc 1500
cgccgcttcc aggaagcgcc ttcgcaaagc gcggagccca cctggccctg cgagaggcac 1560
tgcgcacacc ctactacagc gttgcccaag tgggcatccc ctgaccctgc gtacacttcc 1620
tctaataagt cacaagagct ctgggactct tccaccagcc cttgagattg aggccccata 1680
caccagtgaa gaggagcagg agcggctgct ggggcctcta ccagtacttg cacagtcgtg 1740
cccacaatgc ctctcggccc actcaagacc atttactaca cgggccccaa cgagaacctc 1800
ctggcctggg tgacaggcgc ctttgagctc tacatgtgtt acgagccccc tggggaccaa 1860
ggcgtcagcc gtcagtgcca tccataagct gatgcgctgg atccgcaaag aggaagaccg 1920
cctcttcatt ctcacgcccc tcacctattg atgggaatgt gtgcgggctc agccttcctg 1980
gacacactag gtgtgggaag ccataggagc ctcaacgatg ggggctggcc tctcttgccc 2040
gagccagcgg gcagggactg tgggttggta gaatgcatta aagtgctttg gggaagacaa 2100
45/ 104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
aaaaaaaaaa aaaa 2114
<210> 63
<211> 2496
<212> DNA
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:230711.1:2000MAY01
<400> 63
ggcagcatga gccgatcacc cctcaatccc agccaactcc gatcagtggg cgaccaggat 60
gccctggccc ccttgcctcc acctgctccc cagaatccct ccacccactc ttggagaccc 120
tttgtgtgga tctctgcctt ggggcctcag ctgtcttctg gctctgcagc atgtcttggt 180
catggcttct ctgctctgtg tctcccacct gctcctgctt tgcagtctct ccccaggagg 240
actctcttac tccccttctc agctcctggc ctccagcttc ttttcatgtg gtatgtctac 300
catcctgcaa acttggatgg gcagcaggct gcctcttgtc caggctccat ccttagagtt 360
ccttatccct gctctggtgc tgaccagcca gaagctaccc cgggccatcc agacacctgg 420
aaactcctcc ctcatgctgc acctttgtag gggacctagc tgccatggcc tggggcactg 480
gaacacttct ctccaggagg tgtccggggc agtgcgtagt atctgggctg ctgcagggca 540
tgatggggct gctggggagt cccggccacg tgttccccca ctgtgggccc ctggtgctgg 600
ctcccagcct ggttgtggca gggctctctg cccacaggga ggtagcccag ttctgcttca 660
cacactgggg gttggccttg ctggttatcc tgctcatggt ggtctgttct cagcacctgg 720
gctcctgcca gtttcatgtg tgcccctgga ggcgagcttc aacgtcatca actcacactc 780
ctctgcctgt cttccggctc cctttcggta tgtgtgggtc tgggcagggc agtagaggtc 840
agaagggctg gcctggagtg ctcactccat cccctacctt ttggcttctg tctacccctg 900
caaggctggc tcagaaggtt ttgggggagg agttcttttc tcagtctcgc ccctcaggtg 960
ctgatcccag tggcctgtgt gtggattgtt tctgcctttg tgggattcag tgttatcccc 1020
caggaactgt ctgcccccac caaggcacca tggatattgg ctgcctcacc acaggtgagt 1080
ggaaattggc ctttgctgac gcccagagct cttggctgca ggcattctcc atggccttgg 1140
caagcctgcc accagtgtcc ctggggctgc ttatgccctg tgtggccggc tgctggcatt 1200
tggcctcccc ccaaccgtcc aacatgcctg ccagtcggag ggctgagccc tggaggggct 1260
gggacagtgt tgctgggccg ggctgctggg aaggccccat gggcactgca tccagctttc 1320
cccaacgtgg gcaaagtggg tctatatcca ggctggatct cagcaagtgg gctcactata 1380
gtggggctac tctggcgtgg ggctatggac tctcacccca ggtttggctc agctcctcac 1440
caccatccca ctgcctgttg attggtgggg tgcatggggg tagaacccag gcatgtggtc 1500
tttgtctcgc tggattctcc cagcttctac ctggcatgac atagactcct tgggccgaaa 1560
tatcttcatt gcgggcttct ccatcttcat ggccttgctg ctgccaagat ggtttcaggg 1620
aaagccccag tcctgttcag cacaggctgg agccccttgg atgtattact ggcactcact 1680
gctgacacag cccatcttcc tggctggact ctcaggcttc ctactagaga acacgattcc 1740
tggcacacag cttgagcgag gcctaggtca agggctacca tctcctttca ctgcccaaga 1800
ggctcgaatg cctcagaagc ccagggagaa ggctgctcaa gtgtacagac ttcctttccc 1860
catccaaaac ctctgtccct gcatccccca gcctctccac tgcctctgcc cactgcctga 1920
agaccctggg gatgaggaag gaggctcctc tgagccagaa gagatggcag acttggctgc 1980
ctggctcaga gggagccatg ccctgaatct agcagagaag ggtttaggtc cctagaaatg 2040
taccagtaac gccttacttc tgccctggtt aattttagcc cttatactct ctatctgctg 2100
gagagtcagc tcccttaact gttctttctt gtaggcagta ggatatgtgt gtgtgtatta 2160
catgggactg tctagaggtt cctatttccc aatagggtgg gttgcctttc cttgtcttaa 2220
ttaggcctaa ctgttccaga gcagaggcca tgatttagtg gaccatgaat gattgagatt 2280
ttgcgctgtg tactatcaat gccacttgaa gccaagcatt cactttaata cttactgagc 2340
atctcccatt gtgcaaggtc ctggaactac acgggataag acagggtcca tgccgtctcg 2400
aaggcattta cggtttaaaa agacctttgt aattactaac gaaaatgcaa agcagaaagc 2460
agtctgtaat aaagattaaa ataatgccgt gggagc 2496
<210> 64
<211> 1377
<212> DNA
<213> Homo sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:040338.2:2000MAY01
<220>
<221> unsure
<222> 849
46/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
<223> a, t, c, g, or other
<400> 64
gtcgcggcgg cggggaagga ggggtgcttc aggtgcctgc gacctccgcg cctcccggtc 60
ggaagtgccc gaggtggccg cgatggagct gggggagccg ggcgctcggt agcgctggcg 120
ggcaaggcat ggcgccatga ccctgattga aggggatggg tgatgaggtg accgtccttt 180
tactcggtga cttgcctgcc ttactggtgc tggcccttgc ctgaggtctc aacgcacacc 240
gctgagaggc ggggacccac ttgccccagc ctgtcaggga ccccaactgc catcccagcc 300
cagcgcagcc atgggcaggt taccgacagc atgagagggg aggccccagg ggcagagacc 360
cccagcctga gacacagagg tcaagctgca cagccagagc ccatgcacgg ggttcacagc 420
aacaccgcca gccccgggac tccccgcagg agccccatcg tgctacggct gaaattcctc 480
aatgattcag agcaggtggc cagggcctgg ccccactgac accattggct ccttgaaaag 540
gacccagttt cccggccggg aacagcaggt gcgagctcat ctaccaaggg caagctgcct 600
aggcggacga ccaccagacc ctgggcagcc ttcacctccc taccaagtgc gttctccact 660
gccacgtgtc cacgagagtc ggtcccccaa atcccccctg cacgccgggg gtcccgagcc 720
cggccccctc cgggcgtgaa atcggcagcc tgttgttgcc ccctgtgctc ctgctgttgc 780
tgctgctctg gtactgccag atccagtacc ggccctttct tttcccctga ccgccactct 840
gggcctggnc ggcttcaccc tgctcctcag tctcctggcc tttgccatgt accgcccgta 900
gtgcctccgc gggcgcttgg cagcgtcgcc ggcccctccg gacccttgct ccccgcgccg 960
cggcgggagc tgctgcctgc ccaggcccgc cttttcggcc tggcctcttc ccgccgccct 1020
ggagcccagc cctgcgccgc cagaggactc ccgggactgg cggaggcccc gccctgcgac 1080
cgccggggct cggggccacc tcccgggggc tgctgaccct cagccccgca ctgggagtgg 1140
gctcctcggg gtcgggcatc tgctgtcgct cgccttcggc cccgggcaga gccgggccct 1200
cccgggggcc cgtcttagtg ttctgccgga ggaccccacc cgcctccaat ccctgacagc 1260
tccttggggt gagttgggga cgccaggtcg gtgggaggct ggtgaagggg agcggggagg 1320
ggcaaaggag ttccccggaa cccgggcaga ttaaaggaac tgtgaagttt tcaaaaa 1377
<210> 65
<211> 1445
<212> DNA
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:399174.2:2000MAY01
<400> 65
gaaaccaagg acaatgtgtc ctttaaaagt gtaaggttag aaggtgccct gactccagcc 60
gacctggaaa aggacgtgtc ctgcatatct ggaggtggcc cacagggtcc gggaaagatc 120
ggctgccttg cctgcatccc agggcgcttc ccggcctcca ttaagaggtg accattgcat 180
ccacgtgatt tcttttgctc cactatttcc aggcacagtg caactgactc cctcttgaag 240
ctagaatgcc ctgcacaccc gggatggact tctctcccct ttcaaagatc gagtgaagtt 300
atgcaaatgt gaaaggaagg aattgcattt ccagtggtaa cctttgaagg ggaatgacat 360
tgtcacagga cgtcaggagc cacgtggggg gagcccggtg tcctctgagt ctcaacgcca 420
ccttgcattc ccgcttggtg acggtcgatg ggctgtgtcc agcggtgaac gctttacaca 480
aggactctac ggtggggtag gcaagcgcca cttcaatgtg aagacaaatg aactggcgtc 540
tcttgagata tgcccctgcc tccaggacct ctcaggcccc gggccctggt tactgccgtg 600
gaagctgcct gttcagacgt catctctatc accccttgaa gggagacaga gaggtgtttg 660
cgagttggat gttttatctt gtctttcctg attctttgtt agaacacccc cagggcttgg 720
tttttgttct caacctgtga ttagaaataa gatcctaaag tgtcagatct ggaaggccca 780
tgagagctga ggagatcaaa tgcccggagc tcgggagatc agatgacctg gggtgtctgg 840
agccagtggt ggcctcatct gcagcatctt cctctgtcct gcccaccaca gagtccctgc 900
tggccccggg gggcccctct tccgccacag ggcccctgag cattgctgcg tttgtttctc 960
cagctcctcc ttcctgcaga agcagttccc agaggggcaa tttctccagc ctgcctggtt 1020
ggttgtgttg attggttata gttgctcttt caggtgaccg cagaccctct gaaggctgtg 1080
gccgtgggtg tggctctatg gccacctctc tctcttctcc tctcccaggt cgcgtctcct 1140
tcttcacctc ggggtccgag aacctacacc gcgtggagaa ggtccactgg ggcacccgtt 1200
acgccatcac catcgccttc agctgcaacc ccgaccatgg catcgaggac ccagcgttcc 1260
cgtagccagc agccgggcca aggtaacttc aggagggccc gtgtggaggc agccgcgcca 1320
gtcgtgcacc cacccccacg tccacccgct cctgttgcac agagtgcctt aggaattctc 1380
tgattttgat ttgctgacgt gttaatcttt tcatctgtga gtaaatgaag ggaaccagca 1440
aaaaa 1445
<210> 66
<211> 1578
<212> DNA
<213> Homo Sapiens
47/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
<220>
<221> misc_feature
<223> Incyte ID No: LI:197275.5:2000MAY01
<400> 66
cagtgctctt cagcatctgg agtctttgca gaaacagtat ctttttgtgt ccaataagac 60
aggaacccta catgaagcct gtgaacagct cctaaaagaa cagtcggaac ttgttgatct 120
ggctgaaaac attcaacaaa agctttccta ttttaacgaa ttggaaacta ttaacacaaa 180
attgaattcc cctacattgt cggtgaatag tgacggattt atacctatgc tggccaagtt 240
agatgattgt ataacatata tctcatctca tcctaatttt aaagattatc ccatatattt 300
gctgaagttt aaacagtgtc tttctaaagc tttgcacctc atgaagacat atactgtgaa 360
cacactacag accctcacaa gtcagttact gaaaagggat ccttcatctg tacctaatgc 420
agacaatgcc ttcacattat tttatgtgaa atttcgagct gctgccccca aagtcagaac 480
tcttattgaa caaatagaac tgcggtctga aaaaatacct gaataccaac aactgctaaa 540
tgatatccac cagtgttacc ttgatcagcg ggagctcctt ttgggcccta gtattgcttg 600
cactgttgca gagttaacca gccaaaataa tagagatcac tgtgccttgg ttcgtagtgg 660
ctgtgccttc atggttcatg tctgccagga tgaacaccaa ctttacaatg aatttttcac 720
aaaaccaaca tcaaaattag atgagctttt ggagaaactg tgtgtgtcat tgtatgatgt 780
cttcaggcca ttgatcattc atgttattca cttagagact ctgtcggaac tttgtgggat 840
tcttaaaaat gaggtgctga agatcatgtg cagaacaatg ctgagcaact gggggcatcc 900
gcagctggag tcaagcagat gttagaagat gtacaggagc ggctcgtcta ccgaacccac 960
atctatattc agacggacat cacgggctat aaaccagctc ctggagatct ggcatatccc 1020
gataagttag tcatgatgga gcaaattgca cagagtttga aagatgaaca gaagaaggta 1080
ccttcagaag cttcattttc agatgttcac ttagaagaag gagagtctaa cagtctgaca 1140
aaatctggtt caacagaatc cctcaatcct agaccacaga ccacaatttc tccagcagat 1200
cttcatggaa tggtggtatc ctacggttcg aagaactctt gtctgtctct ccaaattata 1260
cagatgcata gatagggcag tgttccaagg attatcacag gaagcattgt ctgcctgcat 1320
tcagtccctt acttggagcg tcagagtcta tcagcaaaaa caagactcag attgatggac 1380
aacttttctt aattaagcac cttttgatac ttcgtgaaca aattgctcca tttcacactg 1440
aattcaccat taaggaaatt tccctggacc tcaagaaaac tagagatgca gcatttaaaa 1500
tcctgaaccc tatgactgtc ccaagatttt ttaggctgaa tagcaacaat gccctgatag 1560
agttcttgtt ggagggta 1578
<210> 67
<211> 1738
<212> DNA
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:336872.1:2000MAY01
<400> 67
aaaatagtca tccttaactg gtttggacca tctttcatta gtaaaatcaa aagcatatgt 60
gcacagtaaa attcctagct gcagacgcag gctcacctcc cacagccaac cccttagccc 120
cttgaactgc tcgcatgagg acctcagaca cacttctcta aacacccctt ttcatatgaa 180
aatactggag gcagagtgtc cttccatttg tgggtttcta tttttatttt tgagacagga 240
tctcagtctg tcacccagcc tgtgatcgca ccactccact ccagcctggg caacagagtg 300
agacttagtc tcaaaaaaaa gggaaggttg aatttttact tcatattcac ccccaattaa 360
cttcagttgg attaaagagc taaaactaga agcaaagttt ttcttctaaa acattggaag 420
acaatattgc attttttata atcaaagggt ctttctgaaa gtgacacaca agtcccccat 480
ctgtaaggga aaagtttgag atttgagtat gcaaattggt attttccata agacaaaaga 540
aagcataaag gaaagcaatg agctgtataa aatattcaca aaatatctat ccgaagatgt 600
atatcagata tattgagaga ccctaacaag atcagtaaga cagaaagaaa ctcacttaaa 660
aaaagtcagt gcgcttttct acattttttc ccaaaataaa aggattggca aagcacataa 720
gcagaccatt catcaaagaa gtaaagatga ctgattaata agaaaaagat ggtaacatca 780
ctaataatca gtaaggccag gcacagttca tgcctgactt tgggatccct tgaacccagg 840
agttcgagac catcctgggc aaaatggcga aaccccatct ctacaaaaaa tacaaaaatt 900
agctgggcgt gatggcacgt gcctgtggtc ccagccgctt ggggggctga ggtgagagga 960
tcacttgagc ccaggagttc aaggctgcag tgagccgtgt ttgcgccact gccctctagc 1020
ctgagtgaca aagtgagaca ctattaaaaa aaaaatcagt aaaatgtaaa tccttgcatt 1080
cctgatgttg atacgcatgg cttctttttt aaaaacgttc agtcttacta gaggttctca 1140
aataattttt tcgagagcgc acagctcccg ggttcattca tattccacat tttggtgttc 1200
aaattcaatg aagtctgctt tttggtcttc ctttgttctg ctaattgttg gggtcacact 1260
ttaacttaat cgctttttgt cggtatctcg gtggaaagct ccacgagagt aattgaattc 1320
tgagaaaccc tctttgtgca ataaataaaa agacacctct ccataggcca tgagtaatat 1380
gttccctctt catagacacc tggcacatat atctgggggc ccacacggat atgttaataa 1440
48/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
taggctcata aatattgcaa ctttcttctt tgccctctgt gtaagaataa agagtttctg 1500
gaatattttc ttggagaaat ctctctttgg ggaattaatt atagacatat aggtgtgtta 1560
acattcccag gcgcaatatt ctagagatcg tccctggtat cccctcttaa tacatggaaa 1620
tttagagtcc aaatcccaca tatgggccag aaaacaataa cactttggga taggaattca 1680
ggttatttta caatcaatta agagttattt tataaacccg ggaaaaaaaa aaaaaagg 1738
<210> 68
<211> 640
<212> DNA
<213> Homo sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:1092901.1:2000MAY01
<400> 68
tttaggaaat agtataggag atacatgatc aagaatttat ataagatggg gttaatcaag 60
aaatgagagt aaaataagaa taataatggt aataattttg aacactgaca aaaggacatt 120
gatgacacag atctactttt ttcaggtctt caaaatgttt cttctatgtc attaggatga 180
acacacattt cacatgttat ctttcaaaag gccttttgtt ttcaagctgg cattggaatc 240
tcagccaaca tctttcttct tctctggcac atttttacat tctttaagga tcacaagcct 300
aaaaaaccat gacctgatca tctgtcactt ggtttctgtc tacatagtga tgctagtcat 360
ggcagcagag ttattgtctc tagacgtgtt tgcgtcacag aattttcaga ataacttcag 420
atgtaaggct gtgttctaca tatacaaggt aatgaggggc ctcttgatct gcaccacctc 480
tctcctgagc atgcttcaga tcatcaccat cagccccagc acctcactgc atagtcgtga 540
aatcggcaga attcccgata agctctccaa ccacgtattt tctgcgtttt tgatccagac 600
ccagatggta ctgctctggc agactcttct ggtactcttc 640
<210> 69
<211> 1950
<212> DNA
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:022387.5:2000MAY01
<400> 69
tgctttgggg tcaggtgtgg agatcagggt cggggaggtc atgaggtagg taggggtcag 60
gatgtggaca gtcatgggct ggtgggtgtg gcagccgtga ggggtgggtg gtggcctggg 120
aggcagggcc tgggcagggc ttctgcactt ctgctgctta cccagccccc tctgggttcg 180
aggactctcc ttgacaaggg ctgagctctc gggcactgcg ttggactcag ctgcctactg 240
ggaggctggg gagaatggac ctgtgagacc ttgtttgtcc tcttccctgc ccagctcttg 300
tagaccccag gcctggctgt ccgcagggcc aggagctgca gccatggcag ccaccagcct 360
cccacatgag ccccagctcc cagccccaca cgcccactcc tttgcccatg tggtgtcagc 420
tctggcctcc gcttccacac atggaccctc agaccttgca catctgttgt ttcccttgca 480
gggcagtgat gatgacatga aatgaggtgg ggtcactcct gtttagggat gagactgggg 540
cccagggagg ggcaggtgtg aagttgctga gggcagaggg agacccaggg ctacctgctc 600
ctaatgacca gcctcacgtt ctccactgct cactccctgc cgttcaccag ctgcatgacc 660
ttgagcagtg cactcaactg taaacagagg tgaaaacact cctttaccaa ctgttttagg 720
ggccactctt gtttgaggcc ttgaacctcc tttcagttcc gtggtggtcc tgagcctctg 780
aatctgggta tggcccctgc tgggtcctgg tctcttaggc agcacgatgg cctccctgct 840
caaggccctg cacccagggg cagattgtgg gaggcccact ggccatggct gggccctatc 900
gcagagagcc tgtcagcacg gccatttcca cacccaggct ggctgggaag caagctacga 960
ggtgctcaaa ggccctctat gtctgcaggt agccccgtcc cacacaggcg aggatcgttg 1020
ggcctcctta gtagccaaag gaactgaggt ccagagcagg gaatgtgttg cccagtgtca 1080
gcatggtctg ctctggggtc aggcgtcttg ccctggtcct aagccacccc aagccaaggc 1140
atgtccctgg gcccatttcc tctctcgagg tcttgggttc cctatttctg atgtgtgtga 1200
aaggaaggcc tgtcctctgg ggtgaccatg aggctcagtg ggaggagctg ccaggcttga 1260
gctgggactt ggcacctggc cagccttttt tctatttcat tgtaccttga tgggctgtca 1320
gttctgaaga gaaaaaatac actaggaatc cattcttcct ccaccattct ccctggcaga 1380
gggaagtgac tacaccccta tggtgtggac atactgacgc tcctccatga agcagcaaag 1440
ttctgttgtt tcaggagact gtgggccttg aggatgtggt agtgacctca ccagaggagg 1500
tggcaattcc taagtgctgc ctggaggcct ctacagagac ataatgttgg agaacttctg 1560
ccacatggca gtgctgggta agacccctct gtccccacca gtgcccttaa ggttatgggt 1620
gttggtaggt ctgtggcctc catttccatg acgatggtgt taaggactca tgtttgtgtc 1680
cccccccaaa gtttatatgt tgaaaccctg acccccagga gggtggtatt aggaggtggg 1740
491104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
gcctttggga ggtgactagg cttaggtgag atcgtgaggg tggggctcgc cgatgagatc 1800
gagtccttat aagaaaagga aggaactaga gcgagatcac tttgtgctgt gtgagcatac 1860
aagaaaactg ccatcttcaa gctgggtgca gtgctcacgc ctgtaatccc agcactggaa 1920
ggccaaggca ttaggattgc atgatccagt 1950
<210> 70
<211> 597
<212> DNA
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:1188334.1:2000MAY01
<400> 70
gggatttgtc ttcttgcact ttattttttc tgaaatgtac attgctagta tttgtgtaag 60
ccaagtggtt aatcttttca taaaaatgca gtcttaagaa atcttaacaa aatttggatt 120
ttaaaaaagt tgatattaga cccagtgaaa gaactacttt ttttactgtt atgttttgtt 180
tttcatgatt ttgtatattc ttcaggacaa gcagtgggaa gagctctgtt atcaatgcaa 240
tgttgtggga taaagttctc cctagtggga ttggccatat aaccaattgc ttcctaagtg 300
ttgaaggaac tgatggagat aaagcctatc ttatgacaga aggatcagat gaaaaaaaga 360
gtgtgaagac agttaatcaa ctggcccatg cccttcacat ggacaaagat ttgaaagctg 420
gctgtcttgt acgtgtgttt tggccagatc atcttcagtg gctattcgat caagttccgg 480
attcttatat gttgcttcaa caaaatgtga tccttcagta acaaactcca gtaactggtc 540
aaagattgca gtaatcgcct tcttagccag cacaaagtgc ttcagtggag aaacagg 597
<210> 71
<211> 963
<212> DNA
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:1188664.1:2000MAY01
<400> 71
gctttcgatg gcctccctag gatggtcatc cagaggataa gccaacgcac atcatcttcg 60
gttctgacag tgaatgtgaa acagaggaga catcgactca ggagcagagc catccaggag 120
aggaatgggt gaaagtaaga agttcaggat gtctctgtgg acattcatct acttcagcag 180
atccccatta cgaacaactg gcaaactcaa cataaaaccc tcctgagagc cccaatgaga 240
cccagggctt gccaggtcac ctcatattga gactacaggg gtcttggaga tttttatata 300
tgaacctata ttctccacaa catctgcagc atgacatcaa tattagtgaa acgctacaaa 360
aactgttctt gcatgtaata actacctccc caaatccagg cttcactgga gagcctctgg 420
attagtgatc ccagaggcca gttagatttc actgagtcag gaatttccac ctgacctgcc 480
atttactcat tcctggtaga tgagtctggg ttactggctt tcaatgtgag ggagaagatt 540
acgttatgaa gggaaatact gcttgtttgc cctctgccta ttaataaatg ttgtgtttcc 600
ttcacaggag tcctatgggt aaaacatcag ggaagctgtt tgatagcagt gatgatgacg 660
aatctgattc tgaagatgac agtaataggt tcaaaattaa acctcagttt gagggcagag 720
ctggacagaa gctcatggat ttacagtcgc actttggcac cgatgacaga ttccgcatgg 780
actctcgatt tctagaaact gacagtgaag aggaacagga agaggtaaat gaaaagaaaa 840
ctgctgagga agaagagctt gctgaagaaa aaaagaaagc cctgaatgtt gtacaaagtg 900
ttttgcaaat caacttaagc aattctacaa acagaggatc agtagctgct aagaaattta 960
agg 963
<210> 72
<211> 1365
<212> DNA
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:247388.1:2000MAY01
<400> 72
tttgccaaaa gttggggtca tccaaagaaa tatctgtcct gtttccagaa gcaacaaagc 60
ttgccttagc aaaggtggaa ccttttcctt cagattcaat ggtgatggtt gtagttcgtc 120
ttaacaagat ctggtcaatg tcctcttcac aaaacttgga gccttcatca tcttcctcca 180
50/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
tgatggctgc atatgctcct tttcttaaaa catcttcaat ctccttctta gagaactgtt 240
ggattccagt aatgttgcca tcccgaccac tcatggattg aagcacagcc ttatccaacc 300
ccaacttgag gctggcctta tcaaacatct ctctctcgta ggaattacga gtgatgaggc 360
ggtacacctt cacagctttg ctctgcccaa ttcgatgaca tcgtgcctgg gcctgcaggt 420
cattttgtgg attccagtct gaatcaaaga tgatgcaggt atcagcagct gtaagattaa 480
taccaagtcc accagcccgg gtacaccagt aagaagacaa agcggtctga gtcaggcttg 540
ctgaagcggt caatggcagc ctgtcgaagg ttgcctctaa ctcgcccatc aatacgttca 600
tataagtacc tcctctggat taaataatcc tctaggatgt ctaggcagcg taccatctga 660
gagaagatca gaactttatg gccaccagct ttaagctttg gaggcaactt gtcaataaga 720
accagtttgc cggctgaacg aaccatggcc tgcaggtgaa aggtcatgag gtataatatg 780
gcaagcttca cggaattctg ttaggatttt ttcttcagca ccagcttttg gaaagagctc 840
actctagctg ctatgataaa caagaacgac cagtgaggaa gttttgaaac tctcctctgc 900
aagagaatgg tggccagcca ggcgtggtgg ttgtcgaatc tgtggcacct gtgggaagtg 960
ggctcagcca cagggactgc catttggatc ccccagcatt ggcaccatac ctaccctggg 1020
ccctaaggtg gccatgcttc tctggatttg cttccctagc agtgagctct agtgcttgca 1080
cacatccctg cccacagcat ggcctgggag cagctgagac tggagggcca gctcatcccg 1240
cgtctgattc ctgtgaagtg ttatcagtcg cctgttatgg agtgctggac ccatgagtgg 1200
cagccttccc tggcagctgg gctgacctgt ctagcttttc cattgctcgc tggttttgtt 1260
cactgtaggg cgtgaggggg tgagtagctg ctggcctcca agtcacatag ctactcatgt 1320
tgtacgctgt tcacagggac ctctaaggat gtacatcatc acaca 1365
<210> 73
<211> 1728
<212> DNA
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:816339.4:2000MAY01
<400> 73
gggctaggtg tgggaaacag ggaagagaac tagaactggg aagtaaagca ttgaagatgt 60
ggactggaat tgctgcaatc tcatggattc aaatttgaat gggatgaggg agttgcttct 120
tatggatgag cacagaaaag tggttttttg agatagaaat tactcctggt gaagatgctg 180
tgatcattgt tgagatgaca acaaagaatt tagaatattc cataaactta ggtgataccg 240
cagctactgg ctttgagagg actgactcca attctgaaag aagttctgtg gataaaatgc 300
tgtcaaacag catcacatgc tacagagaaa tctttctaga aaggaagagt cagttgatgc 360
agcaaacttt attgttctct aagaaattgc cacagcttat cgtaatcttc aaccaccacc 420
accctgatga gtcagtaccc atcgttaacg ttggcgtaaa accctccacc agcaaaaaga 480
ttgttacgca ttttttaacg cagtgatgta tttatcaatt attcattatg ctatttgtac 540
cctttcttaa tagactatgg tatagtgtaa ccataattta tgccctggga aaccaacaaa 600
ttcatgagat tcgctttatt gtagtgctct ggaattgagc ctgcccgggt ttcttgaggt 660
atacctgtgg tatttagtat gttccttgta tataacaccc cattttatag ggtaggaaac 720
taaggcttag agtttgagca attttcccat agataacacc aataaattga gggctgcaga 780
gaccacttaa gtggttctct taacagtagt ctagacatgg acgtaatgag atttggctta 840
ggagtgacaa tggtaaggaa gttaaaggat tcaggaacca aataccagtt attgagaaga 900
aagaatggcc tcaaaaacat cacttctcaa ggaagccttg ataccctcac ccttactaca 960
ctgtatcctc catttgaatg ttgtcaagag ctcttctcac aattgtaaat aataattgtg 1020
taattttgtt ttttttttcc tactttaggt tgctccttga gggcaggaca gttcttatgg 1080
ctttatccgt tgcgtaaggc acagagaggt ctgcgaggtc aaaactattg tcatgatagc 1140
aagatgcctg tctttttcat ttattctcac ggtgtgcaga ggcctacatg atggtgtgat 1200
gacatcctca ttgatgttaa tgaatggtgc tatacttgaa ttttctaagg tgtcattagg 1260
taggtttagg tattgcatac ttgtttttag aaattatttt tttccttttt cccattttta 1320
gaaatcaact cattttttag gttatgcctt cagtaatctt tgcaacctca atattgtgta 1380
atggttactt taaaatactg tagttttctt tgtgcctaag tataaacata agtacatttt 1440
gttgttttgt attgcaatag tggtttaaat attttcccta aatatccaaa tttaaaaagt 1500
ctaaaacttt agaatttaat aaatttattc taaaatattt atatattttt tcatttaaga 1560
atggatcggc ttaaaaacac tgcttctcat ttacttactg gctataccat ctgtatacta 1620
ataaaaaaca agatttgatt tggaaggact gactcaaact aacgaaaata tgaaacctgt 1680
ctttctgctt tggagatatt tacctaatca tgttctgcag tagaataa 1728
<210> 74
<211> 747
<212> DNA
<213> Homo Sapiens
<220>
51/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
<221> misc_feature
<223> Incyte ID No: LI:1188967.1:2000MAY01
<400> 74
atgagcttac agaaagcctg gcttacattt actctgtttg gatttcttcc tcatcaagag 60
actgctgcag tgcctgtcat gtgacagcgg catggacata tgccccaggc tttcctgctg 120
gggtccatcc atgagcctgc aggtgccctc atggagcccc agccctgccc tggtaagctt 180
ggctgagagc ttcctggagg aggagcttcg gctcaaatgc tgtgagctgg agccaagctt 240
gcaggttttc gggagccttg tgggcgatca atctacaatc ccggtggcag ttatgctatg 300
gcgagccgac atctgcaagc tactgtgact cgtgctactg ccaagggccc ccagaggaag 360
tactcttcct tgggcatgaa cccttggacc tttttggcat ggcccaagat ctgtggtgcc 420
cttttggggc aagtaagcat gggtccgggg acgtggttgg gcattttgtg gggccctgtg 480
cgtgacccct tcgcccaaga gcatcctaaa cgacccagtg cctgggactg gagtgcccac 540
agtcagaagg acccaagaca aagcatggga catgaaattc aagagtgaac ttcttcatgc 600
ggaggctgca gctggatcag aggacacaat cccactgtga cagaagtgca agtcagaaga 660
cctggctttt catcccagct ttgaaacttg gaactttttg attgacaaat taataaacct 720
ctttatgccc caggctcctc ctctgtt 747
<210> 75
<211> 1817
<212> DNA
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LT:236230.3:2000MAY01
<400> 75
tcgaagttca tcatccataa tgtatatagt gttagcaagc agggagttgt tattcttgat 60
gacaagtcaa aagaacttcc tcattgggtg ctgtcagcta tgaagtgttt ggcaaattgg 120
cccaactgtt ctgatttgaa gcagcctatg tacttgggat ttgaaaaaga tgtctttaaa 180
accatagctg attactatgg tcacttgaaa gagcctctac ttacatttca tctttttgat 240
gcttttgtca gtgtactggg tttgttacag aaggagaaag tggcagttga agcatttcag 300
atttgctgcc ttctcctacc tcctgaaaat aggagaaagt tacagctatt gatgaggatg 360
atggcaagga tttgcttaaa caaagagatg ccacccctgt gtgatggctt tggtacccga 420
acactgatgg ttcagacatt ttcccgttgc atcttgtgtt ccaaggatga agtggacttg 480
gatgagttat tagctgctag attggtaacg tttctgatgg acaattacca ggaaattctg 540
aaagtccctt_tggccttgca gacctctata gaggagcgtg tggctcatct acgaagagtc 600
cagataaaat acccaggagc tgatatggat atcactttat ctgctccatc attttgccgt 660
caaattagtc cagaggaatt tgaatatcaa agatcatatg ggctctcagg gaacctctgg 720
gcagccttgt tggaggaagt cataacagat gccaaactct ccaacaaaga gaaaaagaag 780
aaactgaagc agtttcagaa atcctatcct gaagtctatc aagaacgatt tcctacacca 840
gaaagtgcag cactttctgt ttcctgaaaa acccaaaccg aaaccacagc tgctaatgtg 900
ggcactaaag aagcctttcc aaccatttcc aaagaactag aagttttcga atgtaataat 960
acttccacag caacaggtgc tagagaccac tgtttgttgt tttgagtgaa tggtggttag 1020
ggggaaagac tttggtggtg gaagaaagaa aagcataaaa caaagactac tgaaatatta 1080
gataaagatt gccttagttt ttaaaaatgt ttggccatta gtatttttat aaaactcaat 1140
gctagtttta aagtgtataa attggttaaa atttatgagt caaatatata gtgataatgt 1200
taacatgttt gtaattgcta cagaatttaa gggtattttt atctctgtgc tctctttttc 1260
atggtgttta ttaaataatt gtgtatatac atccctagct actgatatct ttattatagc 1320
cttaagactt aattttaagt cttaaaaata gccgtgtata cttgaataag aaagacactg 1380
ggtactgtta ctgtgatgct attgacttag tagccaatta tcatttctcc tgtataaatt 1440
ccagttttta ttgctgcaca taaatttttt aatgtcttat attgtgatag ctatgtcttt 1500
tattgcagat ttattggatg ttatgacaga ttttactaaa gctagtgatt tttatgaaca 1560
tatatattag atgcatgatt tacctataag tggagtagat tttcatctgc cctgcaatgg 1620
tataatttca gtcttagcta aaaatggaaa gttgaactgg gataaattct ttggggtacc 1680
cttaggacct ctgattctaa gtcaaatgca aatggggtta aataaaatga ggactacttc 1740
ctttataaat atattttcat ccttttggaa agtaagtgaa atgtaaaata aacttatttt 1800
tttttaaaaa tgccaaa 1817
<210> 76
<211> 2683
<212> DNA
<213> Homo sapiens
<220>
<221> misc feature
521104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
<223> Incyte ID No: LI:246728.3:2000MAY01
<220>
<221> unsure
<222> 2339
<223> a, t, c, g, or other
<400> 76
ttaagaagac agtttagcac agagatggca ccagcctggc cttccctact gtcccagggg 60
agcagagcta gggtcctctt ttaccctccc taaggtcacc cccttcccat ctacacgtcc 120
ctccccaagt tcaagcacat agtcaatcat gaccactcag gagctcagtg agctggggcc 180
atgtccctgt ggcctccagc ccatccgcag gagggtccct tgcagtgaca gcacaaagag 240
tccccctaca gtgaagcccc tgtagggcca gcatggacct tgagagccag gagggaatgg 300
gcctggtgcc actctgttcc cactcccacc taagattcct acccctgtgt tctagcaggt 360
gactcttgat ctggccagcc cacaacaaat acttgaacta ggcagcatgg ggtggttgga 420
ggcctgcaga ggcccactgg gcccacggaa ctgagacata gggctttctc atgaggcctg 480
atcaagctcc cgcaggtatg acctggcctc ctcgcctcgg gctgccttaa agcaccgcta 540
acccacgcca aggggctagg cagggcttcg cggggcctgg cccaaggtct ccagcagagc 600
aataacatct tcccaggttg ggttgccaca gacaccctgc cctggagccc ccagcccatc 660
ccatctggtg ctaccctgtc tgcctggcag cctagcctca cccctcctgt ccggtcatct 720
gggggtcctt ggtaaggatg cagccacatg gggccggttt atgcacctgg gcgagaacct 780
gactggggca ggggatgctc aggggcctgc aggtctccca cagggctgct tttctgcccg 840
cctcaccctg tgggtttgta tttcttgccg ggtcaaaata ggcagtgact cgtgccttcc 900
ctcctcaggg ccggcggcag ggtgtggacc cagctggccg ctggaccgtc cccttcctca 960
ttctccaagc tcatcaacag gtctcagagg aacatttcca taaaaggtgt ggcctggcat 1020
gcagtgctgt ctgcacgctg tcgcttcccc cacagcaacc tgccggtcag ccttaactgg 1080
tgtggaggtc gaggtgggga gggggaggcg ggcttccctc cctggtgtct ggcctctttt 1140
tgctcagccc tcagcacagc cttcagcgtg gagagcgaga ccctgcgtgt cactggggct 1200
tggctgaggt ctcccctgca aggattaaca agtgacttca aggaacccag accccagtct 1260
ggggcggttc taccttcccg gctgggccca gcccccacac cacagtaccc tggccacgct 1320
ccatggcaca aaagcctctt gaggccacag ctcagctatg aagctgatgt ggcttatgtg 1380
cagtctcctc agggaagggg gcagtgatgc catgcatgag atccgctgtg ccataagaaa 1440
gttgcttcct ttagaatttc tggtccaatg cagggaggtg aggcccagcc tcatgcataa 1500
cacatgccca tccaaggaaa agctgtggct aatgcttcca aaacaagtga aaatcttgca 1560
ccaggcccca ggggccatat ctcattccgg ccccagctta ctgagggagg ggacagactg 1620
ctggaggaca atttctccta gttaccacta aggggttaca tggctactca gaatgaaaga 1680
taaattgcca ggcctgttgc aatcgtcttt tttttgagat gggagtcttg ctctgtcgcc 1740
caggctggag tgcagaggtg cgatctcagc tcactgcaac ctccacctcc cgggtcaagc 1800
aattctcctg cctcagcttc ccgagtagct ggaattacag gtgcccacca ccatgcctgg 1860
ctaatttttg tatttttagt agagacgggg tttcaccatg ttggccaggc tggtcttgaa 1920
cacctgacct caaatgatcc gcccacctcg gcctcccaaa gtgttgggat tacaggcgtg 1980
agccacctca ccaggccccg ttgcaatctt actccacttc gtttttcaca ggcagtcccg 2040
ggacatgccc attattaggg cctatttgat aggatgatac tgaggctcag agtcgggggg 2100
gtcacaaggc caaagccaca ccgctagaag ggctcacgga tcccatgcca gctcccgtcc 2160
tcttgggtgg catcaagctt gtgtgatatg aggtcttatg gtctgctcat gacagcctta 2220
aaagcaataa acagatacca acttccagca actttcccaa ctcagcttgc aaaggcttgc 2280
gggggggtcc ctgccctcga gcccataagg tgagcagctt agcccagtgc cgggcccant 2340
gtggagaagg cctgaattgc cctgtgaagc tgggggttgc caggcaggga atattcatgg 2400
aagcccctga ccatgtactc acactgctct tcctcagttc aggggttctt ggatttgctc 2460
aaagttcaac ccaaaatatc ccttttacga ttctcagggg tcccaaccct tccagatcca 2520
atccccttaa ctttacataa gagttcccac aaggctgtga cttcaaactg tgttgtaaac 2580
tgcaacctgc agaatcaaat ttagggttat gttttcagtt gttatcagtc ttacggctat 2640
caagatatta aagagattct tttctggtta tcaaagaaaa aaa 2683
<210> 77
<211> 3328
<212> DNA
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:1190057.1:2000MAY01
<400> 77
ctgcggtggc ggcagcggtg ggagatgccg gggcggccgg cggcaggtcc atgtggcgct 60
cttaggtggg atgccagcgt cctgaaggcg gaggccctgg ccctccgtcc cctgcggcct 120
gggcatggca ttctcccagt cccacgtgat ggccgctcgg cggcaccagc acagccggct 180
53/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
catcatcgag gtggacgagt acagctccaa ccccacccag gccttcacct tctacaacat 240
caaccagggc cgcttccagc caccgcatgt gcagatggtg gacccggtgc ctcacgatgc 300
ccccaaacct ccaggctaca cccgcttcgt ctgcgtctct gatacccact cgaggacgga 360
ccccatccag atgccgtacg gcgacgtgct gatccacgct ggggacttca ctgagctggg 420
gctcccgagc gaggtgaaga agttcaacga gtggctgggc agcctgccct acgagtacaa 480
gatcgtgatc gcaggcaacc acgagctgac ctttgaccag gagttcatgg ccgacctcat 540
caagcaggac ttttactact tcccatctgt gtcgaagctg aagccggaga actatgagaa 600
tgtgcagtcg ctgctgacca actgcatcta ccttcaggac tcggaggtca ccgtgcgggg 660
cttccggatc tatggctccc catggcagcc ctggttctac ggctggggct tcaacctccc 720
gcgaggccaa gccctgctgg agaaatggaa cctcattccc gaaggcgtag acatcctgat 780
aacccatgga ccaccactgg gcttcctgga ctgggtcccc aagaagatgc agcgggtggg 840
ctgtgtggag ctgctcaaca cggtgcagag gcgcgtccag ccgcggttac atgtctttgg 900
ccacatccac gaagggtatg gtgtcatggc agatgggacg accacctatg tgaatgcgtc 960
cgtatgcact gtgaactacc agcccgtgaa cccgcccata gtcatcgacc tccccacacc 1020
ccggaactcc tgactgctcc ccactgcccc tgaccatgca cgcccgtgtc agctccacag 1080
gcctgggccc ggccaactgt tcccttccat gctgagttgc ctgggacgac ccatctggct 1140
gcggggactg ggcctagcag gcaggtcagg gccttggaac gactctttag ccttctgtca 1200
cctggagttg ggaccctgcg catccccatc aggggttctg tgctcattta cgtgtttctg 1260
cgtgtacatc ctgcgtgtac ctcgtttaaa ggacctacta agctcatggc cctgtcatgt 1320
ttgggaaatg actaagatct tcattcttct cccttggacg ccctccctgg ttagggaagc 1380
tgctgcatct tgaatgggtt tcggaagtta cacaaaatct ccctctaacc acgggtctgt 1440
gtggcggcat gcccctggga ttggggtggg tgggaggatt tcgtgagctg caacacagac 1500
agtccctttc gtgcccctcc caagtgaggg aggagacagg cccaaaggcg gaggccctcc 1560
gagggagcat ttagggacat ctcaggaatt cagaccgcac ctggccaggc ccacagctgt 1620
tttgcctggc attgttcccc cctttttctt cccataggca cttttgttta cttgaacaat 1680
gacctgagtg tcctaggcat tcactcggag cctgggatga tgggggcatg gttctacaga 1740
atgagccact ggcattcgtg cccaggacca gtgagagcgt tcccagtcat ggggggatga 1800
cccttggtcc ccacggggaa cacactgctc tgtagaatgc ggtacgcctg gatggaaggg 1860
tctgcaggct taggctgcag caggcctgcc atggcgtgtg aacccatgtg ccagtgcacg 1920
caccgacaca catgcactgc acgcagccgg tcttaattga accaagtggg tcctgtgttt 1980
ctcttttctg ccccgtagtg aggttctgtt ccttaggtgc gggcttaccc ttgcaccggt 2040
tagggattcg tgtcttggca tgcgctgcag cctgagtgaa gcccatggac catgccggcc 2100
cctgtgaatt tggagggtgg ccacagggac ccgagcgggc ccccaggctc ccagcagccc 2160
cacctttgga cagccttctt tttccttctt tgaattagga ctggaggggg tggggccagg 2220
gcggtggtgg gaaccggtag gcccttagat gagggggcag ccagtcaggc atgaatatgg 2280
ggcaagttca gggctcagat tctggtcggt tatttaatat tttggttcat catggacttt 2340
ttctgcattt attttgattt ttaacgttgc attaaagtag taattatttg tcctgaattg 2400
gtgacttttt tttgcacccc tttccgttgt acatctgaga gaagggtgtc actccctcac 2460
ccaggtccca gccctgggaa ccagcctacc gtgagccctt ttgcagatat agactcattt 2520
catcctcaga tggtccttca aggtaggtac tttagtccca ttttagagat gagacgattg 2580
aggccagagg ggtgtggtaa cttgcctggg ggctcacagc acaaaaggag ccgaggcagg 2640
atctgaccct tgttctctgg cgctgactgc cctcactttg ccatgacccg aagttatgtc 2700
cctacaaagc aatgcatggt ccaaggctct ttttattgta tttttatttt taagggtcct 2760
gttcaaaact ggtgtgagct ctgaggagtc cttgaaccct gggtgcagca tccctagcat 2820
cctgggagtc cttttctgcc cacactgagc tgggctcctc gaggggtggg gctgctgtcc 2880
ctggaagcct ggcagcagca ctgtatcggg ttggctgaag ctgagcgccg tggggtgcag 2940
ggctccagga atcccgtttg gctgaagggg ttccctgtag cccgggatgt ttatgaggtc 3000
ctctctgatg ccccaggcgc aggacatgtg tgcgggtgga gaaaagcagg ccctttcagt 3060
gccagctcca ctcaatttct atgtggacca agaacgataa acttaaaaaa tttttttttc 3120
ctaaggtatc ttcagaatat ggtgtatttt tatgtggaaa agaaaagtta tgaaggcagc 3180
tgttacttta agagaaaatt cattagtagt aaaacgaggt atgaagatga cggcgtgctt 3240
ctcaatcatt ttggcataac ttgattgtgg ctgtaattca cacccttttt tggtcaacca 3300
tgtcagacaa taaactcttt gtaaaaag 3328
<210> 78
<211> 2792
<212> DNA
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:221836.3:2000MAY01
<220>
<221> unsure
<222> 2088, 2091, 2093, 2095, 2097, 2099, 2101, 2103, 2105, 2107, 2109,
2113, 2115, 2117, 2119, 2123, 2125, 2129, 2131
541104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
<223> a, t, c, g, or other
<400> 78
catgaagcca cgcatgaaaa tttttctgcg tcaaaagaag gtgactaccc agatgattgc 60
caagagcctg gccaatgtag aatatgatac atataaacct accttcacaa ataagcaggt 120
gagaatcacc tttgggttct cttgcaagag tagtaaccag tttggaataa tgatgtatca 180
taacaaccga ctcataaaat cttttgagaa ggtgtgggtg ccgggtgaag ccaactcgtg 240
tgagaaagtg atggcgagta attggagtca ttgagtgcaa tttcctaaaa cctgcctaca 300
acaaacaaga ctttgagtat accaagggag taccggctaa caataaatgc ccttgcccag 3&0
aagctcaatg cttactggaa gaaaaaaaca tctcaagata attttgagac ctcaactgta 420
gccaggccaa taccgaaggt tcctgaccag acatgggttc agtgtgatga gtgtcttaaa 480
tggagaaagc ttcctgggaa gattgatcca tccatgttac ctgcaagatg gttttgttat 540
tataattccc atccaaagta ccaggagatg ctctgttcca gaggaaccag aaatcactga 600
tgaagacctg tgcttgagca aagctaagaa acaagaacca actgttgagg agaagaagaa 660
gatgcctatg gaaaatgaga accaccaggt attcagtaat ccaccaaaga tccttactgt 720
tcaagaaatg gctggattga ataacaagac aacttggata tgagggaatt catagcccta 780
gtgtgcttcc ttctggtgga gaagaaagca gatcaccatc tcttcaactt aagcctctgg 840
attccagtgt tttacagttt tccagtaagt acaaatggat cctaggtgaa gaaccggtgg 900
agaaacgaag aaggctccag aaatgagatg acaacacctt ctctagatta ttccatgcct 960
gctccttaca ggagggtaga agcacctgtt gcctacccag aaggggagaa cagccatgat 1020
aaatcgagtt ctgagagaag tacaccacca taccttttcc cagaataccc agaagcaagc 1080
aagaatacag gtcagaatag ggaggtttca attctgtatc caggggccaa agaccaacgc 1140
caggggtccc tgcttcctga agaattagaa gatcagatgc caagattggt ggcagaagaa 1200
tctaacagag gtagcacaac cataaacaaa gaagaagtca acaagggacc ttttgtagct 1260
gttgtgggtg ttgccaaagg tgttagagat tcaggagctc ctattcagct tgatcccttg 1320
taacagagag gagcttgctg agagacgaaa agcagttgaa tcctggaacc cagtgcctta 1380
ttctgtggcc tctgctgcaa tccctgctgc agccattggg gagaaagcaa gaggctatga 1440
ggagagcgaa ggtcataata caccaaagtt gaagaaccag agagagctgg aagaattgaa 1500
gagaaccaca gaaaaattgg aacgtgtttt ggctgaaagg aatttgttcc agcaaaaggt 1560
ggaggagctg gaacaggaga ggaatcactg gcagtctgaa ttcaagaaag tccaacatga 1620
attggtgatc tacagtaccc aggaggcgga aggcttgtac tggagcaaga aacacagtgg 1680
attatcgcca agctgaattc ccagatatct gaaagactga gctggaaaga agccaacaga 1740
ggaaaacgca cgagttaaaa gagaaactga aggaaacaga gacacaccct ggaaatgctg 1800
ccacgaaggc tcacggtctc cctacccgga cccccagagg gagatgacct agaaagggct 1860
ttggcacaag cttacgcgcg ctacgtatac cacgtcagca tatctccctt acttctgtcc 1920
tccctcactt ggagcttcgt gagatcgggt atgactcaga aacaagtgga tgggatccct 1980
gtacacggtg ctgggaggca aaatccccat actggattga ggcaccagac tgtataccct 2040
tctcttctct tataattctg tctgttctct tttctctccc tccctcangt ntntntntnt 2100
ntntntntnt ctntntntnt ctntntctna ncctcaccta tatgccttat atagagaatc 2160
tctgtgtaaa tccgtggctc ataatcagtc tcctttttat cagtttttgg gtgtggagaa 2220
agaggccagt tttaaatagg ctttcaagag gtctaggggt cagaaaagca atagtcactt 2280
aagctaggtg acctgaagag ctttaattct tcatgacctg tat,atgtgcg tctattgtat 2340
atctttcttc tgaaatggtg ttgtatatca ttgtagtgtt agatcaatca ggcagatagt 2400
tggtgtccgg tataccaggt attattgggg ggtaagctta acaagtacaa ctcatgtttg 2460
caagccttcg aagtatgtaa caatcgtcgg tggaaatata agaccatata tcacattata 2520
cacaaaagtg tgtgatatgt acaagtgagt ggtacagata tgacatggga agatctgggg 2580
gaggaagttc aaggaaggca ccacaccaga aatggggacc taaattaagg cttaaagaat 2640
gaggcatggc cacactgtca gtgagtgttc tttaggtggt aggactatgg ttgatatttt 2700
ttcttcttcc tatcttcctg cctttttcag attttcaata ttaaacttgt tattcttaca 2760
ttggaaaaaa ataaattgtt tttaaaaaga tc 2792
<210> 79
<211> 918
<212> DNA
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte TD No: LT:334047.3:2000MAY01
<220>
<221> unsure
<222> 380, 419
<223> a, t, c, g, or other
<400> 79
tctttatgta tttttaaaaa aactaattta agttaaatgg cagtaaacca tgataattta 60
55/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
gaaaacatgg tgaaactgag agtgaagaga aatgttcttt acgtaaacca cactgtaaac 120
cataaaactt atttttgtca actgcttttc atgacagtgg ctgggaattt gacatttcta 180
ctacagtagg caaaaataca tgtaaaatac actctcccac ataccacatc acatctctat 240
ttgtatttcc aaactaaaag cattacagcc caaaaaagtg ctgcgtgcac tggtctagtt 300
acaccaagaa gtgtatgttc acaccagcaa caccttaagc tggtatctgt gtggcaaggc 360
cactgctggt ggcccctgan gccaagccct cttcaatgga tccagtttgg ctcaccaana 420
gaaatccact gctctttaac ccaaaaggtg gtaagctttt caatggcctc cagttaccac 480
aagataaaac aaacaaaatt ctcaaacaga ttatgaaacc caactgaagt atccacatga 540
cagcgttcaa tactacctcg ccacttcaaa atgtgtcagc agcaattagc tatgaaaatg 600
agtgttgtga aaattcgcaa tagtttgaaa ctgaatattt taaaactaga tatctttaat 660
atgacagtaa acaatgtgac agaaacatgg ctgtttctct catcttgtct gagatataca 720
ttccatacag gtgactgggt cccataagtt ttctaagaaa aacttttcct ttccacttaa 780
tgatcctaag aagtcagtgc aatctggttc ttctccctgc agaagggtta tttagtttgg 840
gatgtaacat tttacaacaa taatacaaac gtcctgggag aataccacaa taaatgtctc 900
aaaaaccact cagttaat 918
<210> 80
<211> 202
<212> PRT
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Tncyte ID No: LG:223939.1.orf3:2000FEB18
<400> 80
Glu Ile Met Glu Leu Val Leu Val Lys Tyr Gln Gly Lys Asn Trp
1 5 10 15
Asn Gly His Phe Arg Ile Arg Asp Thr Leu Pro Glu Phe Phe Pro
20 25 30
Val Cys Phe Ser Ser Asp Ser Thr Glu Val Thr Thr Val Asp Leu
35 40 45
Ser Val His Val Arg Arg Ile Gly Ser Arg Met Va1 Leu Ser Val
50 55 60
Phe Ser Pro Tyr Trp Leu Ile Asn Lys Thr Thr Arg Val Leu Gln
65 70 75
Tyr Arg Ser Glu Asp Ile His Val Lys His Pro Ala Asp Phe Arg
80 85 90
Asp Ile Ile Leu Phe Ser Phe Lys Lys Lys Asn Ile Phe Thr Lys
95 100 105
Asn Lys Val Gln Leu Lys Tle Ser Thr Ser A1a Trp Ser Ser Ser
110 115 120
Phe Ser Leu Asp Thr Val Gly Ser Tyr Gly Cys Val Lys Cys Pro
125 13 0 135
Ala Asn Asn Met Glu Tyr Leu Val Gly Val Ser Ile Lys Met Ser
140 145 150
Ser Phe Asn Leu Ser Arg Ile Val Thr Leu Thr Pro Phe Cys Thr
155 160 165
Ile Ala Asn Lys Ser Ser Leu Glu Leu Glu Val Gly Glu Ile Ala
170 175 180
Ser Asp Gly Ser Met Pro Thr Asn Lys Trp Asn Tyr Ile Ala Ser
185 190 195
Ser Glu Cys Leu Pro Phe Trp
200
<210> 81
<211> 91
<212> PRT
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LG:397140.1.orf1:2000FEB18
<400> 81
Pro Cys Ala Pro Ile Ser Leu Cys Ala Arg Asp His Met His Met
1 5 10 15
56/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
Gly Glu Cys Leu Cys Ala His Asp Phe Met His Ile Gly Glu Tyr
20 25 30
Leu Cys Ala His Glu His Met His Met Gly Glu Cys Leu Cys Ala
35 40 45
His Glu Tyr Met His Thr Gly Glu Cys Leu Cys Ala His Glu Tyr
50 55 60
Met His Met Gly Ile Cys Leu Cys Ala Arg Asp Tyr Met His Met
65 70 75
Gly Glu Cys Leu Cys Ala Arg Asp Tyr Met His Val Gly Glu Cys
80 85 90
Ser
<210> 82
<211> 197
<212> PRT
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LG:1094205.1.orf3:2000FEB18
<400> 82
Pro Lys Met Ala Ala Pro Pro Gly Glu Tyr Phe Ser Val Gly Ser
1 5 10 15
G1n Val Ser Cys Arg Thr Cys Gln Glu Gln Arg Leu Gln Gly Glu
20 25 30
Val Val Ala Phe Asp Tyr Gln Ser Lys Met Leu Ala Leu Lys Cys
35 40 45
Pro Ser Ser Ser Gly Lys Pro Asn His Ala Asp Ile Leu Leu Ile
50 55 60
Asn Leu Gln Tyr Val Ser Glu Val Glu Ile Ile Asn Asp Arg Thr
65 70 75
Glu Thr Pro Pro Pro Leu Ala Ser Leu Asn Val Ser Lys Leu Ala
80 85 90
Ser Lys Ala Arg Thr Glu Lys Glu Glu Lys Leu Ser Gln Ala Tyr
95 100 105
Ala Ile Ser Ala Gly Val Ser Leu Glu Gly Gln Gln Leu Phe Gln
110 115 120
Thr Ile His Lys Thr Ile Lys Asp Cys_Lys Trp Gln Glu Lys Asn
125 130 135
Ile Val Val Met Glu Glu Val Val Ile Thr Pro Pro Tyr G1n Val
140 145 150
Glu Asn Cys Lys Gly Lys Glu Gly Ser Ala Leu Ser His Val Arg
155 160 165
Lys Ile Val Glu Lys His Phe Arg Asp Val Glu Ser Gln Lys Ile
170 175 180
Leu Gln Arg Ser Gln Ala Gln Gln Pro Gln Lys Glu Ala Ala Leu
l85 190 195
Ser Ser
<210> 83
<211> 98
<212> PRT
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Tncyte ID No: LG:481361.5.orf3:2000FEB18
<400> 83
Pro Ser Gln Gln Cys Lys Val Trp Tyr Glu Ala Ala Thr His Ser
1 5 10 15
Leu Leu Arg Asn Leu Ala Thr Thr Cys Glu Asn Tyr Asn Tyr Phe
20 25 30
Leu G1n Ser Gln His Ile Phe Leu Ile His Ala Ser Thr His Arg
57/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
35 40 45
Lys Met Pro Ile Asn Pro Gln Val Leu Met Ile Thr Pro Glu Val
50 55 60
Ile Gly His Phe His Phe Ile Leu Cys Ile Phe His Cys Phe Pro
65 70 75
Asp Phe Pro Leu Gly Thr Met Ser His Leu Tyr Asp Gln Arg Glu
80 85 90
Arg Tyr Lys Leu Tyr Leu Arg Val
<210> 84
<211> 121
<212> PRT
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LG:981170.1.orf1:2000FEB18
<400> 84
Asp Asp Cys Met Leu Thr His Pro Leu Gln Gly Pro Gly Leu Asp
1 5 10 15
Leu Gly Leu His Cys Ile Leu Ser Asn G1y Leu Ala Gly Ala Pro
20 25 30
Phe Gly Leu Leu Ser Leu Phe Ser Pro Glu Leu Gly Trp Trp Glu
35 40 45
Lys Arg Gly Trp Ser Glu Ser Ile Ser Ile Gln Tle Pro Ala Gly
50 55 60
Ile Thr Leu Gly Val Phe Leu Ala Cys Phe Gly Leu Lys Leu Ser
65 70 75
Tyr Ile Val Tyr Trp Leu Pro Lys Ser Gly Leu Lys Ser Glu Lys
80 85 90
Met Gln Ala Met Asn Pro Ser Ala His Ser Ser Pro Thr Phe Pro
95 100 105
Ala Leu Phe Tyr Leu Gly Gly Gln Trp Lys Gly G1y Glu Ala Met
110 115 120
Pro
<210> 85
<211> 136
<212> PRT
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:197613.1.orf2:2000FEB01
<400> 85
Ala Ser Ser Gly His Ala Pro Leu Ala Ala Ser Thr Arg Lys Ala
1 5 10 15
Pro Gln Ala Glu Cys Gly Met Ile Ser Ile Thr Glu Trp Gln Lys
20 25 30
Ile Gly Val Gly Ile Thr Gly Phe Gly I1e Phe Phe I1e Leu Phe
35 40 45
Gly Thr Leu Leu Tyr Phe Asp Ser Val Leu Leu Ala Phe Gly Asn
50 55 60
Leu Leu Phe Leu Thr Gly Leu Ser Leu Ile Ile Gly Leu Arg Lys
65 70 75
Thr Phe Trp Phe Phe Phe Gln Arg His Lys Leu Lys Gly Thr Ser
80 85 90
Phe Leu Leu Gly Gly Val Val Ile Va1 Leu Leu Arg Trp Pro Leu
95 100 105
Leu Gly Met Phe Leu Glu Thr Tyr Gly Phe Phe Ser Leu Phe Asn
110 115 120
Cys Ser G1y Asp Phe Lys Ala Leu Ala Arg Trp Ser Glu Lys Gln
125 13 0 13 5
58/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
Arg
<210> 86
<211> 71
<212> PRT
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:902682.1.orf3:2000FEB01
<400> 86
Thr Leu Ser Leu Ala Val Ser His Met Val Phe Gly Leu Leu Val
1 5 10 15
His Arg Ser Gln Lys Ser Arg Phe Glu Asn Leu His Leu Asp Phe
20 25 30
Gly Gly Cys Met Glu Met Pro Gly Tyr Pro Gly Arg Ile Leu Leu
35 40 45
Glu Arg Gln Ser Pro Asn Arg Glu Pro Leu Leu Arg Gln Cys Arg
50 55 60
Arg Glu Met Leu Gly Gln Asn Ser G1n Ala Glu
65 ~ 70
<210> 87
<211> 608
<212> PRT
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:212029.1.orf2:2000FEB01
<220>
<221> unsure
<222> 18, 388
<223> unknown or other
<400> 87
Tyr Pro Ala Pro Gln Pro Val Arg Thr Asp Val Ala Val Leu Arg
1 5 10 15
Tyr Gln Xaa Pro Pro Glu Tyr Gly Val Thr Ser Arg Pro Cys Gln
20 25 30
Leu Pro Phe Pro Ser Thr Met Gln Gln His Ser Pro Met Ser Ser
35 40 45
Gln Thr Ser Ser Ala Ser Gly Pro Leu His Ser Val Ser Leu Pro
50 55 60
Leu Pro Leu Pro Met Ala Leu Gly Ala Pro Gln Pro Pro Pro Ala
65 70 75
Ala Ser Pro Ser Gln Gln Leu Gly Pro Asp Ala Phe Ala Ile Val
80 85 90
Glu Arg Ala Gln Gln Met Val G1u Ile Leu Thr Glu Glu Asn Arg
95 100 105
Va1 Leu His Gln Glu Leu Gln Gly Tyr Tyr Asp Asn Ala Asp Lys
110 . 115 120
Leu His Lys Phe Glu Lys Glu Leu Gln Arg Ile Ser Glu Ala Tyr
125 130 135
Glu Ser Leu Val Lys Ser Thr Thr Lys Arg Glu Ser Leu Asp Lys
140 145 150
Ala Met Arg Asn Lys Leu Glu Gly Glu Ile Arg Arg Leu His Asp
155 160 165
Phe Asn Arg Asp Leu Arg Asp Arg Leu Glu Thr Ala Asn Arg Gln
170 175 180
Leu Ser Ser Arg Glu Tyr G1u G1y His Glu Asp Lys Ala Ala Glu
185 190 195
Gly His Tyr Ala Ser Gln Asn Lys Glu Phe Leu Lys Glu Lys Glu
200 205 210
59/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
Lys Leu Glu Met Glu Leu Ala Ala Val Arg Thr A1a Ser Glu Asp
215 220 225
His Arg Arg His Ile Glu Ile Leu Asp Gln Ala Leu Ser Asn Ala
230 235 240
Gln Ala Arg Val Ile Lys Leu Glu Glu Glu Leu Arg Glu Lys Gln
245 250 255
Ala Tyr Val Glu Lys Val°Glu Lys Leu Gln Gln Ala Leu Thr Gln
260 265 270
Leu Gln Ser Ala Cys Glu Lys Arg Glu Gln Met Glu Arg Arg Leu
275 280 285
Arg Thr Trp Leu Glu Arg Glu Leu Asp Ala Leu Arg Thr Gln Gln
290 295 300
Lys His Gly Asn Gly Gln Pro Ala Asn Met Pro Glu Tyr Asn Ala
305 310 315
Pro A1a Leu Leu Glu Leu Val Arg Glu Lys Glu Glu Arg Tle Leu
320 325 330
Ala Leu Glu Ala Asp Met Thr Lys Trp Glu Gln Lys Tyr Leu Glu
335 340 345
Glu Ser Thr Ile Arg His Phe Ala Met Asn Ala Ala Ala Thr Ala
350 355 360
Ala Ala Glu Arg Asp Thr Thr Ile Ile Asn His Ser Arg Asn Gly
365 370 375
Ser Tyr Gly Glu Ser Ser Leu Glu Ala His Ile Trp Xaa Glu Glu
380 385 390
Glu Glu Val Val Gln Ala Asn Arg Arg Cys Gln Asp Met Glu Tyr
395 400 405
Thr Ile Lys Asn Leu His Al~. Lys Ile I1e Glu Lys Asp Ala Met
410 415 420
Ile Lys Val Leu Gln Gln Arg Ser Arg Lys Asp Ala Gly Lys Thr
425 430 435
Asp Ser Ser Ser Leu Arg Pro Ala Arg Ser Val Pro Ser I1e Ala
440 445 450
Ala Ala Thr Gly Thr His Ser Arg Gln Thr Ser Leu Thr Ser Ser
455 460 465
G1n Leu Ala Glu Glu Lys Lys Glu Glu Lys Thr Trp Lys Gly Ser
470 475 480
Ile Gly Leu Leu Leu Gly Lys Glu His His Glu His Ala Ser Ala
485 490 495
Pro Leu Leu Leu Pro Pro Pro Thr Ser Ala Leu Ser Ser Ile Ala
500 505 510
Ser Thr Thr Ala Ala Ser Ser Ala His Ala Lys Thr G1y Ser Lys
515 520 525
Asp Ser Ser Thr Gln Thr Asp Lys Ser Ala Glu Leu Phe Trp Pro
530 535 540
Ser Met A1a Ser Leu Pro Ser Arg Gly Arg Leu Ser Thr Thr Pro
545 550 555
Ala His Ser Pro Val Leu Lys His Pro Ala Ala Lys Gly Thr Ala
560 565 570
Glu Lys Leu Glu Asn Ser Pro Gly His Gly Lys Ser Pro Asp His
575 580 585
Arg Gly Arg Val Ser Ser Leu Leu His Lys Pro Glu Phe Pro Asp
590 595 600
Gly Glu Met Met Glu Va1 Leu Ile
605
<210> 88
<212> 396
<212> PRT
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:249170.1.orf1:2000FEB01
<400> 88
Ser Ala Cys Ala Gly His Ser Leu Ser Pro Ala Ala Met Asp Ala
1 5 10 15
60/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
Ala Leu Leu Leu Asn Val Glu Gly Val Lys Lys Thr Ile Leu His
20 25 30
Gly Gly Thr Gly Glu Leu Pro Asn Phe Ile Thr Gly Ser Arg Val
35 40 45
Ile Phe His Phe Arg Thr Met Lys Cys Asp Glu Glu Arg Thr Val
50 55 60
Ile Asp Asp Ser Arg Gln Val Gly Gln Pro Met His Ile Ile Ile
65 70 75
Gly Asn Met Phe Lys Leu Glu Val Trp Glu Ile Leu Leu Thr Ser
80 85 90
Met Arg Val His Glu Val Ala Glu Phe Trp Cys His Thr Ile His
95 100 105
Thr Gly Va1 Tyr Pro Ile Leu Ser Arg Ser Leu Arg Gln Met Ala
110 115 120
Gln Gly Lys Asp Pro Thr Glu Trp His Val His Thr Cys Gly Leu
125 130 135
Ala Asn Met Phe Ala Tyr His Thr Leu Gly Tyr Glu Asp Leu Asp
140 145 150
Glu Leu Gln Lys Glu Pro Gln Pro Leu Val Phe Val Ile Glu Leu
155 160 165
Leu Gln Val Asp Ala Pro Ser Asp Tyr G1n Arg Glu Thr Trp Asn
170 175 180
Leu Ser Asn His Glu Lys Met Lys Ala Val Pro Val Leu His Gly
185 190 195
Glu Gly Asn Arg Leu Phe Lys Leu Gly Arg Tyr Glu Glu A1a Ser
200 205 210
Ser Lys Tyr Gln Glu Ala Ile Ile Cys Leu Arg Asn Leu Gln Thr
215 220 225
Lys Glu Lys Pro Trp Glu Val Gln Trp Leu Lys Leu Glu Lys Met
230 235 240
Ile Asn Thr Leu Ile Leu Asn Tyr Cys Gln Cys Leu Leu Lys Lys
245 250 255
Glu Glu Tyr Tyr Glu Val Leu Glu His Thr Ser Asp Ile Leu Arg
260 265 270
His His Pro Gly Ile Val Lys Ala Tyr Tyr Va1 Arg A1a Arg Ala
275 280 285
His Ala Glu Val Trp Asn Glu A1a G1u Ala Lys Ala Asp Leu G1n
290 295 300
Lys Val Leu Glu Leu Glu Pro Ser Met Gln Lys Ala Val Arg Arg
305 310 315
Glu Leu Arg Leu Leu Glu Asn Arg Met Ala Glu Lys Gln Glu Glu
320 325 330
Glu Arg Leu Arg Cys Arg Asn Met Leu Ser Gln G1y Ala Thr Gln
335 340 345
Pro Pro Ala G1u Pro Pro Thr Glu Pro Pro Ala G1n Ser Ser Thr
350 355 360
Glu Pro Pro Ala Glu Pro Pro Thr Ala Pro Ser Ala Glu Leu Ser
365 370 375
Ala Gly Pro Pro Ala Glu Pro Ala Thr Glu Pro Pro Pro Ser Pro
380 385 390
Gly His Ser Leu Gln His
395
<210> 89
<211> 109
<212> PRT
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:813218.1.orf1:2000FEB01
<220>
<221> unsure
<222> 4, 7, 13
<223> unknown or other
61/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
<400> 89
Gly Cys Glu Xaa Ile Gly Xaa Phe Met His Tyr Trp Xaa Glu Ser
1 5 10 15
Glu Met Va1 Gln Ser Leu Trp Glu Ser Leu Ala Val Leu G1n Met
20 25 30
Val Lys Arg Arg Ala Thr Ile Trp Pro Ser Asn Ser Pro Tyr Arg
35 40 45
His Met Pro Lys Ile Ile Glu Asn Ile Cys Ser Gly Leu Pro Ser
50 55 60
Leu Gly Pro Leu Pro Leu Tyr Gly Ser Ser Val Phe Thr Leu Leu
65 70 75
Ser Leu Ala Ser Ala Leu Phe Trp Ser Met Phe Val Lys Ala Arg
80 85 90
Ala Glu Leu Leu Leu Ala Val His His Cys Cys Leu Pro Pro Ser
95 100 105
Gln Thr Arg Cys
<210> 90
<211> 94
<212> PRT
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:902522.3.orf2:2000FEB01
<400> 90
Trp Ser Glu Phe Val Ala Ala Phe Leu Ser Leu Val Ala Leu Leu
1 5 10 15
Arg Arg Arg Arg Asn Glu Ala Glu Ala Glu Arg Val Lys Thr Lys
20 25 30
Thr Ala Ala Lys Tyr Gly Leu Ser Ala Gln Pro Arg Leu Va1 Asp
35 40 45
Ile Ile Ala Ala Val Pro Pro Gln Tyr Arg Lys Val Leu Met Pro
50 55 60
Lys Leu Lys Ala Lys Pro Ile Arg Thr Ala Ser Gly Tle Ala Val
65 70 75
Val A1a Val Met Cys Lys Pro His Arg Cys Pro His Ile Ser Phe
80 85 90
Thr Gly Asn Ile
<210> 91
<211> 211
<212> PRT
<213> Homo sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:474304.1.orf2:2000FEB01
<400> 91
Glu Pro Ser Leu Ala Thr Tyr His His Ile Ile Arg Leu Phe Asp
1 5 10 15
Gln Pro Gly Asp Pro Leu Lys Arg Ser Ser Phe Ile Ile Tyr Asp
20 25 30
Ile Met Asn Glu Leu Met Gly Lys Arg Phe Ser Pro Lys Asp Pro
35 40 45
Asp Asp Asp Lys Phe Phe Gln Ser Ala Met Ser I1e Cys Ser Ser
50 55 60
Leu Arg Asp Leu G1u Leu Ala Tyr Gln Val His Gly Leu Leu Lys
65 70 75
Thr Gly Asp Asn Trp Lys Phe Ile Gly Pro Asp Gln His Arg Asn
80 85 90
Leu Tyr Tyr Ser Lys Phe Phe Asp Leu Ile Cys Leu Met Glu Gln
95 100 105
62/104
Gly His Ser Leu Gln His
395
<210>
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
21e Asp Val Thr Leu Lys Trp Tyr Glu Asp Leu Ile Pro Ser Ala
110 115 120
Tyr Phe Pro His Ser Gln Thr Met Ile His Leu Leu Gln A1a Leu
125 130 135
Asp Val A1a Asn Arg Leu Glu Val Ile Pro Lys Ile Trp Lys Gly
140 145 150
Gln Phe Tyr Phe Leu Cys Val Arg Val His Leu Thr Ser Ile Ser
155 160 165
Ser Thr Leu Tle Met Asn Val Leu Thr Leu Leu Leu Gly Met Lys
170 175 180
Thr Ser Ile Leu Thr Glu Pro Asn Val Leu Val Glu Met Tyr Phe
185 190 195
Lys Val Met Cys Ser Cys Cys Met Leu Ala Ile Arg Arg Lys Phe
200 205 210
Cys
<210> 92
<211> 290
<212> PRT
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:027320.1.orf3:2000FEB01
<400> 92
Ser Asp Gly Gly Ser Asp Ala Asp Phe G1y Gly Gly Ser Gly Glu
1 5 10 15
Pro Asp Ser Asp Arg Gly Gly Glu Arg Glu Leu Arg Leu Arg Arg
20 25 30
Gly Glu Leu Gly Gly. Arg Leu Leu Pro Arg Ala Ala G1u Glu Glu
35 40 45
Met Ala Gly Pro Asn Gln Leu Cys Ile Arg Arg Trp Thr Thr Lys
50 55 60
His Val Ala Val Trp Leu Lys Asp Glu Gly Phe Phe Glu Tyr Val
65 70 75
Asp Ile Leu Cys Asn Lys His Arg Leu Asp Gly Ile Thr Leu Leu
80 85 90
Thr Leu Thr Glu Tyr Asp Leu Arg Ser Pro Pro Leu G1u Ile Lys
95 100 105
Val Leu Gly Asp T1e Lys Arg Leu Met Leu Ser Val Arg Lys Leu
110 115 120
Gln Lys Ile His Ile Asp Val Leu Glu Glu Met Gly Tyr Asn Ser
125 130 135
Asp Ser Pro Met Gly Ser Met Thr Pro Phe Ile Ser Ala Leu Gln
140 145 150
Ser Thr Asp Trp Leu Cys Asn Gly Glu Leu Ser His Asp Cys Asp
155 160 165
Gly Pro Ile Thr Asp Leu Asn Ser Asp Gln Tyr Gln Tyr Met Asn
170 175 180
Gly Lys Asn Lys His Ser Val Arg Arg Leu Asp Pro Glu Tyr Trp
185 190 195
Lys Thr Ile Leu Ser Cys Ile Tyr Val Phe Ile Val Phe Gly Phe
200 205 210
Thr Ser Phe Ile Met Val Ile Val His Glu Arg Val Pro Asp Met
215 220 225
Gln Thr Tyr Pro Pro Leu Pro Asp Ile Phe Leu Asp Ser Val Pro
230 235 240
Arg Ile Pro Trp Ala Phe Ala Met Thr Glu Val Cys Gly Met Ile
245 250 255
Leu Cys Tyr Ile Trp Leu Leu Val Leu Leu Leu His Lys His Arg
260 265 270
Tyr Met Ala Val Tyr Gly Arg Asn Tyr Ile Glu Pro Leu Pro Phe
275 280 285
Gly Val Ala Leu Val
290
63/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
<210> 93
<211> 125
<212> PRT
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:228319.1.orf2:2000FEB01
<400> 93
Glu Gln Ala Glu Glu Glu Lys Lys Pro Lys Asp Ser Thr Thr Pro
1 5 10 15
Phe G1u Ser Arg Leu Ser Gln Ser Arg Lys Phe Ser Trp Thr Glu
20 25 30
Tyr Leu Glu Ala Thr Gln Thr Asn Ala Val Pro Ala Lys Val Phe
35 40 45
Lys Met Arg Leu Pro His Gly Phe Leu Pro Asn Met Lys Leu Glu
50 55 60
Val Val Asp Lys Arg Asn Pro Arg Leu Ile Arg Val Ala Thr Ile
65 70 75
Val Asp Val Asp Asp G1n Arg Val Lys Val His Phe Asp Gly Trp
80 85 90
Asp His Lys Tyr Asp Tyr Trp Val Glu Ala Asp Ser Pro Asp Ile
95 100 105
His Pro Ile Gly Leu Cys Asp Val Thr Gly His Pro Leu Glu Va1
110 115 120
Pro Lys Arg Thr Lys
125
<210> 94
<211> 162
<212> PRT
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LG:197267.2.orf2:2000MAY19
<400> 94
Ala Arg Glu Ala Ala Leu Pro Ala Ala Met Arg Glu Gly Gln Glu
1 5 10 15
Met Gly Pro Thr Pro Val Pro Ser Asn Pro Leu Leu His Arg Ser
20 25 30
Phe Pro Cys Trp Pro Arg Gly Trp Ser His Pro Val Pro Ser Asn
35 ~ 40 45
Pro Leu Leu His Arg Ser Phe Pro Cys Trp Pro Arg Gly Trp Ser
50 55 60
His Pro Val Pro Thr Arg Glu Leu Leu Leu Glu Pro Ala Gln Pro
65 70 75
Ala Asp Leu Leu Pro Pro Ala Pro Thr Ala Gly Pro Cys Ser Leu
80 85 90
Ala Ser Trp Met Leu Ser Gln Pro Gly Arg Gly Ser Gln Val Lys
95 100 105
Thr Gly Gly Thr Pro Thr Ala Thr Ala Gln Asp Ala Glu Ala Pro
110 115 120
Leu Pro Asp Cys Asp Leu Cys Leu Ser Pro Ala Pro Val Gly Thr
12 5 13 0 13 5
Trp Gln Pro Arg Ala Lys Ala Gly Trp Ala Gly Asp Pro Arg Asn
140 145 150
Leu Ser Gly Asn Thr Phe Ser Pro Gly Trp Glu Gln
155 160
<210> 95
<211> 181
<212> PRT
<213> Homo Sapiens
64/ 104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
<220>
<221> misc_feature
<223> Incyte ID No: LG:403332.1.orf2:2000MAY19
<220>
<221> unsure
<222> 28
<223> unknown or other
<400> 95
Gly Gly G1u Thr Met Ser Lys Leu Ser Phe Arg Ala Arg Ala Leu
1 5 10 15
Asp Ala Ala Lys Pro Leu Pro Ile Tyr Arg Gly Lys Xaa Met Pro
20 25 30
Asp Leu Asn Asp Cys Val Ser Ile Asn Arg Ala Val Pro Gln Met
35 40 45
Pro Thr Gly Met Glu Lys Glu Glu Glu Ser Glu His His Leu Gln
50 55 60
Arg Ala I1e Ser Ala Gln Gln Val Phe Arg Glu Lys Lys Glu Ser
65 70 75
Met Val Ile Pro Val Pro Glu A1a Glu Ser Asn Val Asn Tyr Tyr
80 85 90
Asn Arg Leu Tyr Lys Gly Glu Phe Lys Gln Pro Lys Gln Phe Ile
95 100 105
His Ile Gln Arg Ile Trp G1y His Tyr Gln Pro Glu Thr Thr Leu
110 115 120
Lys Phe Leu Leu Val Cys Phe Val His Leu Phe Leu Asp His Ser
125 130 135
Ile Ser Phe Asn Leu Gly Cys Arg Ser Ala Gln Gly Ser Val Leu
140 145 150
Arg Lys Ile Phe Cys Phe Ser Phe Leu Pro Lys Gly Lys Leu Arg
155 160 165
Asn Thr Lys Phe Phe Ala Phe Pro Phe Cys Met Ala Asn Leu Phe
170 175 180
Leu
<210> 96
<211> 198
<212> PRT
<213> Homo sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LG:983076.3.orf3:2000MAY19
<400> 96
Trp Asn Leu Met Ser Ile Pro Leu Phe Ser Phe Leu Cys Tyr Gln
1 5 10 15
Arg Asp Leu Glu Pro Tyr Gly Tyr Tyr Leu Glu Asn Glu His Ser
20 25 30
Tyr Ile Tyr Asn Ile Trp Lys Tyr Leu Glu Ser Asn His Glu Tyr
35 40 45
Ser Phe Cys Phe Thr Ser Ile Leu Leu Asn Cys Leu Phe Ile Phe
50 55 60
Cys His His Asn Asn Trp His Pro Val Leu Ala Val Met Ile Val
65 70 75
Pro Asn Ser Cys Val Val Tyr Ala Pro Gly Leu Pro Leu Leu His
80 85 90
Gly Leu Ser Ser Phe Pro Trp Gln Ile Ala Ala Leu Leu Glu Phe
95 100 105
Ile Ser Lys Glu Asn Ala Ile Met Thr Arg Ile Leu Gln G1n Val
110 115 120
Ser Gln Phe Val Ile Leu Ser Val Thr Arg Arg Arg Lys Ile Thr
125 130 135
Leu Thr Lys Gln Val Leu Ile His Cys Tyr Leu Leu Leu Arg Ile
140 145 150
65!104
<212> PRT
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Inc
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
Lys Lys Gly Trp Gly Ile Leu Glu Pro Lys Ile Asp Tyr Phe Lys
155 160 165
Pro Glu Glu His Val Phe Ile Leu Val Ser Val Cys Ser Val Leu
170 175 180
Ser Gly Cys Tyr Cys Phe Ser Ile Leu Pro Ala Arg Arg Cys Leu
185 190 195
Gly Arg Ala
<210> 97
<211> 349
<212> PRT
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LG:216612.3.orf3:2000MAY19
<400> 97
Gly Thr Gly Pro His Gly Ser Ala Pro Arg Pro Pro Pro Val Cys
1 5 10 15
Cys Ala Arg Gly Gly Leu Arg Ser Pro Gly Arg Arg Arg Ala Pro
20 25 30
G1y Ala Gly Gly Glu Met Gly Arg Tyr Ser Gly Lys Thr Cys Arg
35 40 45
Leu Leu Phe Met Leu Val Leu Thr Val Ala Phe Phe Val Ala Glu
50 55 60
Leu Val Ser G1y Tyr Leu Gly Asn Ser I1e A1a Leu Leu Ser Asp
65 70 75
Ser Phe Asn Met Leu Ser Asp Leu Ile Ser Leu Cys Va1 Gly Leu
80 85 90
Ser Ala Gly Tyr Ile Ala Arg Arg Pro Thr Arg Gly Phe Ser Ala
95 100 105
Thr Tyr Gly Tyr Ala Arg Ala G1u Val Val Gly A1a Leu Ser Asn
110 115 120
A1a Val Phe Leu Thr A1a Leu Cys Phe Thr Ile Phe Val Glu Ala
125 130 135
Val Leu Arg Leu Ala Arg Pro Glu Arg Ile Asp Asp Pro Glu Leu
140 145 150
Val Leu Ile Val Gly Val Leu Gly Leu Leu Val Asn Val Val Gly
155 160 165
Leu Leu Ile Phe Gln Asp Cys Ala Ala Trp Phe A1a Cys Cys Leu
170 175 180
Arg Gly Arg Ser Arg Arg Leu Gln Gln Arg Gln G1n Leu Ser G1u
185 190 195
Gly Cys Val Pro Gly Ala Phe G1y Gly Pro Gln Gly Ala Glu Asp
200 205 210
Pro Arg Arg Ala Ala Asp Pro Thr Ala Pro Gly Ser Asp Ser Ala
215 220 225
Val Thr Leu Arg Gly Thr Ser Val Glu Arg Lys Arg Glu Lys Gly
230 235 240
Ala Thr Val Phe Ala Asn Val Ala Gly Asp Ser Phe Asn Thr Gln
245 250 255
Asn Glu Pro Glu Asp Met Met Lys Lys Glu Lys Lys Ser Glu Ala
260 265 270
Leu Asn Ile Arg Gly Val Leu Leu His Val Met Gly Asp Ala Leu
275 280 285
Gly Ser Val Va1 Va1 Val Ile Ile Ile Leu Ser Ser Ala Phe Pro
290 295 300
Leu Ile Lys Glu Thr Ala Ala Ile Leu Leu Gln Met Val Pro Lys
305 310 315
Gly Val Asn Met Glu Glu Leu Met Ser Lys Leu Ser Ala Val Pro
320 325 330
G1y Ile Ser Ser Val His Glu Val His Ile Trp Glu Leu Val Ser
335 340 345
Gly Lys Ile Ile
66/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
<210> 98
<211> 85
<212> PRT
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LG:322465.1.orf3:2000MAY19
<400> 98
Tyr Cys Leu Lys Met Thr Glu Glu Thr Tle Ala Ser Ser Thr Glu
1 5 10 15
Val Tle Leu Thr Ser Gln Met Ser Ser Glu Gly Trp Gln Arg Trp
20 25 ' 30
Gly Lys Ile Lys Ser Asp Gly Gly Gly Asn Ser Gly Val Pro Leu
35 40 45
Gly Trp Ile Glu Gly Phe Ile Asn Val Cys Asp Gly Ile Met Asn
50 55 60
His Asn Ser Glu Ala Phe Pro Pro Leu A1a Phe Phe Trp Phe Leu
65 70 75
Phe Phe Leu G1u Ser Gly Ser Gln Lys Lys
80 85
<210> 99
<211> 81
<212> PRT
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LG:093477.1.orf2:2000MAY19
<400> 99
Val Ala Arg Thr Thr Gly Ala His His His Ala Trp Leu Ser Phe
1 5 10 15
Val Phe Leu Val Glu Met G1y Gly Phe His His Val Gly Gln Thr
20 25 30
Gly Leu Glu Leu Leu Thr Ser Ser Asp Pro Pro Ala Ser Ala Ser
35 40 45
Gln Ser Ala Gly Ile Ile Gly Val Ser His Pro Thr G1n Pro Thr
50 55 60
Thr Asn Ile Asn Ala Val Leu Met Met Tyr Gln Thr His Lys His
65 70 75
Thr Tyr Leu Thr Arg Ser
<210> 100
<211> 433
<212> PRT
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LG:222880.1.orf2:2000MAY19
<400> 100
Pro Pro Arg Arg Pro Cys Pro Arg Ala Pro His Pro Ser Ala Leu
1 5 10 15
Pro Ala Gly Pro Arg Asp Arg Ala Cys Thr Cys Ser G1y Leu Ser
20 25 30
Ala Ser Pro Leu Arg Thr Ser Ser Trp Ser Ser Arg His Ser Ser
35 40 45
Thr Arg Ser Arg Leu Gly Arg Gly Pro Gly Gly Gly Gly Arg Arg
50 55 60
Ser Arg Gly Asp Ala Ser A1a Glu Arg Arg Glu Gly A1a Gly Pro
65 70 75
Gly Arg Gln Ala Ala Ala Ser Ala Met Asn Pro Arg Gly Leu Phe
67/104
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WO 01/62918 PCT/USO1/03465
80 85 90
Gln Asp Phe Asn Pro Ser Lys Phe Leu Tle Tyr Thr Cys Leu Leu
95 100 105
Leu Phe Ser Val Leu Leu Pro Leu Arg Leu Asp Gly Ile Ile Gln
110 115 120
Trp Ser Tyr Trp Ala Val Phe Ala Pro Ile Trp Leu Trp Lys Leu
125 130 135
Leu Val Val Ala Gly Ala Ser Val Gly Ala Gly Val Trp Ala Arg
140 145 150
Asn Pro Arg Tyr Arg Thr Glu Gly Glu Ala Cys Val Glu Phe Lys
155 160 165
Ala Leu Leu Ile Ala Val Gly Ile His Leu Leu Leu Leu Met Phe
170 175 180
Glu Va1 Leu Val Cys Asp Arg Val Glu Arg Gly Thr His Phe Trp
185 190 195
Leu Leu Val Phe Met Pro Leu Phe Phe Val Ser Pro Val Ser Val
200 205 210
Ala Ala Cys Val Trp Gly Phe Arg His Asp Arg Ser Leu G1u Leu
215 220 225
Glu Ile Leu Cys Ser Val Asn Ile Leu Gln Phe Ile Phe Ile Ala
230 235 240
Leu Lys Leu Asp Arg I1e Ile His Trp Pro Trp Leu Val Val Phe
245 250 255
Val Pro Leu Trp Ile Leu Met Ser Phe Leu Cys Leu Val Val Leu
260 265 270
Tyr Tyr Ile Val Trp Ser Leu Leu Phe Leu Arg Ser Leu Asp Val
275 280 285
Val Ala Glu Gln Arg Arg Thr His Val Thr Met Ala Ile Ser Trp
290 295 300
Ile Thr Tle Val Val Pro Leu Leu Thr Phe Glu Val Leu Leu Va1
305 310 315
His Arg Leu Asp Gly His Asn Thr Phe Ser Tyr Val Ser I1e Phe
320 325 330
Val Pro Leu Trp Leu Ser Leu Leu Thr Leu Met Ala Thr Thr Phe
335 340 345
Arg Arg Lys Gly Gly Asn His Trp Trp Phe Gly Ile Arg Arg Asp
350 355 360
Phe Cys Gln Phe Leu Leu Glu Ile Phe Pro Phe Leu Arg Glu Tyr
365 370 375
Gly Asn Ile Ser Tyr Asp Leu His His Glu Asp Ser Glu Asp Ala
380 385 390
Glu Glu Thr Ser Val Pro Glu Ala Pro Lys Ile Ala Pro Ile Phe
395 400 405
Gly Lys Lys Ala Arg Val Val Ile Thr Gln Ser Pro Gly Lys Tyr
410 415 420
Val Pro Pro Pro Pro Lys Leu Asn Ile Asp Met Pro Asp
425 430
<210> 101
<211> 419
<212> PRT
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LG:898320.3.orf3:2000MAY19
<400> 101
Glu Val Trp Asp Cys Pro Gly Asn Ser Arg Val Ser Gly Pro Arg
1 5 10 15
Pro Ile Leu Gly Ala Met Gly Val Ile Gly Ile Gln Leu Val Val
20 25 30
Thr Met Val Met Ala Ser Val Met Gln Lys Ile Ile Pro His Tyr
35 40 45
Ser Leu Ala Arg Trp Leu Leu Cys Asn Gly Ser Leu Arg Trp Tyr
50 55 60
Gln His Pro Thr Glu Glu Glu Leu Arg Ile Leu Ala Gly Lys Gln
68/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
65 70 75
Gln Lys Gly Lys Thr Lys Lys Asp Arg Lys Tyr Asn Gly His Ile
80 85 90
Glu Ser Lys Pro Leu Thr Ile Pro Lys Asp I1e Asp Leu His Leu
95 100 105
Glu Thr Lys Ser Val Thr Glu Val Asp Thr Leu Ala Leu His Tyr
110 115 120
Phe Pro Glu Tyr Gln Trp Leu Val Asp Phe Thr Val Ala Ala Thr
225 13 0 13 5
Va1 Val Tyr Leu Val Thr Glu Val Tyr Tyr Asn Phe Met Lys Pro
140 145 150
Thr Gln G1u Met Asn Ile Ser Leu Val Trp Cys Leu Leu Val Leu
155 160 165
Ser Phe Ala Ile Lys Val Leu Phe Ser Leu Thr Thr His Tyr Phe
170 175 180
Lys Val Glu Asp Gly Gly Glu Arg Ser Val Cys Val Thr Phe Gly
185 190 195
Phe Phe Phe Phe Val Lys Ala Met Ala Val Leu Ile Val Thr Glu
200 205 210
Asn Tyr Leu Glu Phe Gly Leu Glu Thr Gly Phe Thr Asn Phe Ser
215 220 225
Asp Ser Ala Met Gln Phe Leu Glu Lys Gln Gly Leu Glu Ser Gln
230 235 240
Ser Pro Val Ser Lys Leu Thr Phe Lys Phe Phe Leu Ala Ile Phe
245 250 255
Cys Ser Phe Ile Gly Ala Phe Leu Thr Phe Pro G1y Leu Arg Leu
260 265 270
Ala Gln Met His Leu Asp Ala Leu Asn Leu Ala Thr Glu Lys Ile
275 280 285
Thr Gln Thr Leu Leu His Ile Asn Phe Leu Ala Pro Leu Phe Met
290 295 300
Val Leu Leu Trp Val Lys Pro Ile Thr Lys Asp Tyr Ile Met Asn
305 310 315
Pro Pro Leu Gly Lys Glu Ser I1e Pro Leu Met Thr Glu Ala Thr
320 325 330
Phe Asp Thr Leu Arg Leu Trp Leu Ile Ile Leu Leu Cys Ala Leu
335 340 345
Arg Leu Ala Met Met Arg Ser His Leu Gln Ala Tyr Leu Asn Leu
350 355 360
Ala Gln Lys Cys Va1 Asp Gln Met Lys Lys Glu Ala Gly Arg Ile
365 370 375
Ser Thr Val Glu Leu Gln Lys Met Val Ile Ile Pro Gly Val Phe
380 385 390
I1e Gln Asn Leu Ser Leu Pro Tyr Gln Trp Ile Ile Val Tyr Cys
395 400 405
Pro I1e Leu Phe Thr Leu Asn Tyr His Gln Leu Lys Gly Lys
410 415
<210> 102
<211> 127
<212> PRT
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LG:1327047.1.orf1:2000MAY19
<400> 102
Gly Pro Pro Val Thr Phe Gly Asp His Glu Gly Ile Ser Lys Ala
1 5 10 15
Met Gly Asn Val Pro Pro Lys Ala Glu Thr Pro Leu Arg Cys I1e
20 25 30
Leu Glu Asn Trp Asp Gln Leu Asp Ser His Met Leu Arg Asn Lys
35 40 45
Arg Leu Ile Phe Phe Cys Ser Thr Thr Trp Pro Arg Tyr Pro Leu
50 55 60
Gln Gly Gly Glu Thr Trp Pro Pro Glu Gly Ser Ile Asn Tyr Asn
69/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
65 70 75
Thr Ser Leu Gln Leu His Leu Phe Cys Arg Lys Glu Gly Ile Arg
80 85 90
Ser Glu Val Pro Tyr Va1 Gln Thr Phe Phe Ser Leu Arg Asp Asn
95 200 105
Ser Gln Leu Cys Lys Lys Cys Asp Leu Cys Pro Thr Gly Ser Pro
110 115 120
Arg Val Tyr Leu Pro Thr Leu
125
<210> 103
<211> 312
<212> PRT
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LG:235157.21.orf2:2000MAY19
<400> 103
Ser Thr Pro Glu G1y Ile Ala Leu Ala Tyr Gly Ser Leu Leu Leu
1 5 10 15
Met Ala Leu Leu Pro Ile Phe Phe G1y Ala Leu Arg Ser Val Arg
20 25 30
Cys Ala Arg Gly Lys Asn Ala Ser Asp Met Pro Glu Thr Ile Thr
35 40 45
Ser Arg Asp Ala Ala Arg Phe Pro Ile Ile A1a Ser Cys Thr Leu
50 55 60
Leu Gly Leu Tyr Leu Phe Phe Lys Ile Phe Ser Gln Glu Tyr Ile
65 70 75
Asn Leu Leu Leu Ser Met Tyr Phe Phe Val Leu Gly Ile Leu A1a
80 85 90
Leu Ser His Thr Ile Ser Pro Phe Met Asn Lys Phe Phe Pro Ala
95 100 105
Ser Phe Pro Asn Arg Gln Tyr Gln Leu Leu Phe Thr Gln,Gly Ser
110 115 120
Gly Glu Asn Lys Glu Glu I1e Ile Asn Tyr Glu Phe Asp Thr Lys
125 130 135
Asp Leu Val Cys Leu Gly Leu Ser Ser Ile Val Gly Val Trp Tyr
140 145 150
Leu Leu Arg Lys His Trp Ile A1a Asn Asn Leu Phe Gly Leu Ala
155 160 165
Phe Ser Leu Asn Gly Val Glu Leu Leu His Leu Asn Asn Val Ser
170 175 180
Thr Gly Cys Ile Leu Leu Gly Gly Leu Phe Ile Tyr Asp Val Phe
185 190 195
Trp Val Phe Gly Thr Asn Val Met Val Thr Val Ala Lys Ser Phe
200 205 210
Glu Ala Pro Ile Lys Leu Val Phe Pro Gln Asp Leu Leu Glu Lys
215 220 225
Gly Leu Glu Ala Asn Asn Phe Ala Met Leu Gly Leu Gly Asp Va1
23 0 . 235 240
Val Ile Pro G1y Ile Phe Ile Ala Leu Leu Leu Arg Phe Asp Ile
245 250 255
Ser Leu Lys Lys Asn Thr His Thr Tyr Phe Tyr Thr Ser Phe Ala
260 265 270
Ala Tyr Ile Phe Gly Leu Gly Leu Thr Ile Phe Ile Met His Ile
275 280 285
Phe Lys His Ala Gln Leu Arg Val Leu Gly Gly Asn Pro Ala Ser
290 295 300
Tyr Pro Glu Ala His Pro Leu Pro His Asn Ile Arg
305 310
<210> 104
<211> 477
<212> PRT
<213> Homo sapiens
701104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
<220>
<221> misc_feature
<223> Incyte ID No: LG:085713.1.orf1:2000MAY19
<400> 104
Leu Glu Leu Phe Val Phe Ser Ala Phe Ser Met Arg Thr Tyr Val
1 5 10 15
Cys His Ile Cys Ser Ile Ala Phe Thr Ser Leu Asp Met Phe Arg
20 25 30
Ser His Met Gln Gly Ser Glu His Gln I1e Lys Glu Ser Ile Val
35 40 45
Ile Asn Leu Val Lys Asn Ser Arg Lys Thr Gln Asp Ser Tyr Gln
50 55 60
Asn Glu Cys Ala Asp Tyr Ile Asn Val Gln Lys Ala Arg Gly Leu
65 70 75
Glu Ala Lys Thr Cys Phe Arg Lys Met Glu Glu Ser Ser Leu Glu
80 85 90
Thr Arg Arg Tyr Arg Glu Val Val Asp Ser Arg Pro Arg His Arg
95 100 105
Met Phe Glu Gln Arg Leu Pro Phe Glu Thr Phe Arg Thr Tyr Ala
110 115 120
Ala Pro Tyr Asn Ile Ser Gln Ala Met G1u Lys G1n Leu Pro His
125 130 135
Ser Lys Lys Thr Tyr Asp Ser Phe Gln Asp Glu Leu Glu Asp Tyr
140 145 150
Ile Lys Val Gln Lys Ala Arg Gly Leu Asp Pro Lys Thr Cys Phe
155 160 165
Arg Lys Met Arg Glu Asn Ser Val Asp Thr His Gly Tyr Arg Glu
170 175 180
Met Va1 Asp Ser Gly Pro Arg Ser Arg Met Cys Glu Gln Arg Phe
185 190 195
Ser His Glu Ala Ser Gln Thr Tyr Gln Arg Pro Tyr His Ile Ser
200 205 210
Pro Val Glu Ser Gln Leu Pro Gln Trp Leu Pro Thr His Ser Lys
215 220 225
Arg Thr Tyr Asp Ser Phe Gln Asp Glu Leu Glu Asp Tyr Ile Lys
230 235 240
Val G1n Lys Ala Arg Gly Leu Glu Pro Lys Thr Cys Phe Arg Lys
245 250 255
Ile Gly Asp Ser Ser Val Glu Thr His Arg Asn Arg Glu Met Val
260 265 270
Asp Val Arg Pro Arg His Arg Met Leu Glu Gln Lys Leu~Pro Cys
275 280 285
Glu Thr Phe Gln Thr Tyr Ser Gly Pro Tyr Ser Ile Ser Gln Val
290 295 300
Val Glu Asn Gln Leu Pro His Cys Leu Pro Ala His Asp Ser Lys
305 310 315
Gln Arg Leu Asp Ser Ile Ser Tyr Cys Gln Leu Thr Arg Asp Cys
320 325 330
Phe Pro Glu Lys Pro Val Pro Leu Ser Leu Asn Gln Gln Glu Asn
335 340 345
Asn Ser Gly Ser Tyr Ser Val Glu Ser Glu Val Tyr Lys His Leu
350 355 360
Ser Ser Glu Asn Asn Thr Ala Asp His Gln Ala G1y His Lys Arg
365 370 375
Lys His Gln Lys Arg Lys Arg His Leu Glu Glu Gly Lys Glu Arg
380 385 390
Pro Glu Lys Glu Gln Ser Lys His Lys Arg Lys Lys Ser Tyr Glu
395 400 405
Asp Thr Asp Leu Asp Lys Asp Lys Ser Ile Arg Gln Arg Lys Arg
410 415 420
Glu Glu Asp Arg Val Lys Val Ser Ser Gly Lys Leu Lys His Arg
425 430 435
Lys Lys Lys Lys Ser His Asp Val Pro Ser Glu Lys Glu Glu Arg
440 445 450
Lys His Arg Lys Glu Lys Lys Lys Ser Val Glu Glu Arg Thr Glu
455 460 465
71/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
Glu Glu Met Leu Trp Asp Glu Ser I1e Leu Gly Phe
470 475
<210> 105
<211> 105
<212> PRT
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LG:482421.1.orf3:2000MAY19
<400> 105
Arg Glu Asn Tle Cys Ser Gly Leu Ser Pro Arg Pro Pro Ser Leu
1 5 10 15
His Asn Phe Ser Ser Tyr Lys Leu Leu Leu Ala Phe I1e Asn Asn
20 25 30
Ser Phe Leu Leu Glu Gly Leu Ile Arg Ile Phe Lys Glu Glu Glu
35 40 45
Asn Asp Ser Val Ile Lys Gly Gly Met Glu Thr Val Glu Gly Ile
50 55 60
Phe Phe Lys Ala Leu Leu Ile Ser Phe Lys Leu Asn Phe Ala Lys
65 70 75
Ala Arg Asp Asn Ile Lys Glu Lys Leu Tyr Leu Lys Leu Val Ile
80 85 90
Pro Asn Leu Ser Glu Leu Tyr Thr His Gln Arg Gln Tyr Ser Tyr
95 100 105
<210> 106
<211> 213
<212> PRT
<213> Homo sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LG:330944.4.orf1:2000MAY19
<400> 106
G1n Glu Leu Asn Asn Ile Thr Lys Leu Asn Glu His Phe Ser Lys
1 5 10 15
Phe Gly Thr I1e Val Asn Ile Gln Val Ala Phe Lys Gly Asp Pro
20 25 30
Glu Ala Ala Leu Ile Gln Tyr Leu Thr Asn Glu Glu Ala Arg Lys
35 40 45
Ala Ile Ser Ser Thr Glu Ala Va1 Leu Asn Asn Arg Phe Ile Arg
50 55 60
Val Leu Trp His Arg Glu Asn Asn G1u Gln Pro Thr Leu Gln Ser
65 70 75
Ser Ala Gln Leu Leu Leu Gln Gln Gln Gln Thr Leu Ser His Leu
80 85 90
Ser Gln Gln His His His Leu Pro Gln His Leu His Gln G1n Gln
95 100 105
Val Leu Val Ala Gln Ser Ala Pro Ser Thr Va1 His Gly Gly Ile
110 115 120
Gln Lys Met Met Ser Lys Pro Gln Thr Ser Gly Ala Tyr Val Leu
125 130 135
Asn Lys Val Pro Val Lys His Arg Leu Gly His Ala Gly Gly Asn
140 145 150
Gln Ser Asp Ala Ser His Leu Leu Asn Gln Ser Gly Gly Ala Gly
155 160 165
G1u Asp Cys Gln Ile Phe Ser Thr Pro Gly His Pro Lys Met Ile
170 175 180
Tyr Ser Ser Ser Asn Leu Lys Thr Pro Ser Lys Leu Cys Ser Gly
185 190 195
Ser Lys Ser His Asp Val Gln Glu Val Leu Lys Lys Lys Lys Gln
200 205 210
72/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
Ser Gly Arg
<210> 107
<211> 150
<212> PRT
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:223060.1.orf3:2000MAY01
<400> 107
Lys Asn His G1n Tyr Phe Gly Ile Phe Ala Thr Pro Phe Ser Val
1 5 10 15
Asp Ile Tyr Met Leu Pro Gly Asn Phe Glu Met Glu Cys Leu Glu
20 25 30
Leu Gln Ser Asp Val Gln Leu Ile Glu Lys Phe Asp Phe Ala Ser
35 40 45
Leu Leu Asp Phe Cys Lys Thr Cys Leu Pro Asn Asp Lys Tyr Pro
50 55 60
Leu Leu His Asn His Thr Leu Phe Met Ser Leu Leu Leu Gly Ser
65 70 75
Thr Tyr I1e Cys Glu Leu Leu Phe Ser Arg Met Lys Asn Thr Lys
80 85 90
Ser Lys Ile Arg Thr Lys Ile Ser Asp Glu His Leu Glu Asn Ser
95 100 105
Leu Arg Ile Ala Thr Thr Ser Ile Lys Pro Asp Thr Asp Gly Leu
110 115 120
Arg Phe Ser Lys Thr Met Ser Ser Thr Pro Leu Val Leu Cys Cys
125 ° 130 135
Ser Leu Phe Phe Tyr Asn Lys Lys Tyr Gln Lys Ser Ser Glu Val
140 145 150
<210> 108
<211> 298
<212> PRT
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:213087.1.orf2:2000MAY01
<220>
<221> unsure
<222> 197, 200
<223> unknown or other
<400> 108
Ser Arg Arg Ser Ala Ala Met Ala Gly Gly Arg Gly Ala Pro G1y
1 5 10 15
Arg G1y Arg Asp Glu Pro Pro Glu Ser Tyr Pro Gln Arg Gln Asp
20 25 30
His Glu Leu Gln Ala Leu Glu Ala I1e Tyr Gly Ala Asp Phe Gln
35 40 45
Asp Leu Arg Pro Asp Ala Cys Gly Pro Val Lys Glu Pro Pro Glu
50 55 60
Ile Asn Leu Val Leu Tyr Pro Gln Gly Leu Thr Gly Glu G1u Val
65 70 75
Tyr Val Lys Val Asp Leu Arg Val Lys Cys Pro Pro Thr Tyr Pro
80 85 90
Asp Val Val Pro G1u Ile Glu Leu Lys Asn Ala Lys Gly Leu Ser
95 100 105
Asn Glu Ser Val Asn Leu Leu Lys Ser Arg Leu Glu Glu Leu Ala
110 115 120
Lys Lys His Cys Gly Glu Val Met Ile Phe Glu Leu Ala Tyr His
73/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
125 130 135
Val Gln Ser Phe Leu Ser Glu His Asn Lys Pro Pro Pro Lys Ser
140 145 150
Phe His Glu Glu Met Leu Glu Arg Arg Ala Gln Glu Glu Gln G1n
155 160 165
Arg Leu Leu Glu Ala Lys Arg Lys Glu Glu Gln Glu Gln Arg Glu
170 175 180
Ile Leu His Glu Ile Gln Arg Arg Lys Glu Glu Ile Lys Glu Glu
185 190 295
Lys Xaa Arg Lys Xaa Met Ala Lys Gln Glu Arg Leu Glu Ile Ala
200 205 210
Ser Leu Ser Asn Gln Asp His Thr Ser Lys Lys Asp Pro Gly Gly
215 220 225
His Arg Thr Ala A1a Ile Leu His Gly Gly Ser Pro Asp Phe Val
230 235 240
Gly Asn Gly Lys His Arg Ala Asn Ser Ser Gly Arg Ser Arg Arg
245 250 255
Glu Arg Gln Tyr Ser Val Cys Asn Ser Glu Asp Ser Pro Gly Ser
260 265 270
Cys Glu Ile Leu Tyr Phe Asn Met Gly Ser Pro Asp Gln Leu Met
275 280 285
Ala Pro Lys Gly Lys Cys Ile Gly Ser Asp Glu Gln Leu
290 295
<210> 109
<211> 89
<212> PRT
<213> Homo sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:405330.1.orf3:2000MAY01
<400> 109
Tyr Lys Phe Leu Ala Glu Ser Ala Thr Leu Asn Tyr Val Ala Asp
1 5 10 15
Arg Gln Ala Ser Thr Leu Gln Leu G1y Thr Lys Cys Phe His Cys
20 25 30
Arg Ile Ser Ser Arg Leu Lys Thr Glu Arg Leu Val Lys Thr Lys
35 40 45
Cys Leu Lys Arg Val Arg Cys Leu Gly Trp Ala Cys Asp Val Leu
50 55 60
Ser Gly Leu Ala Leu Leu Asp Gly Thr Leu Arg Ser Glu Leu Leu
65 70 75
Glu Asn Leu His Leu Lys Gly Glu Ala Phe Arg Lys G1n Ser
80 85
<210> 110
<211> 771
<212> PRT
<213> Homo sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:350243.2.orf2:2000MAY01
<400> 110
Asn Arg Glu Lys Ile Pro Phe Gln Glu Pro Lys Va1 Ser Pro Va1
1 5 10 15
Pro Leu Pro Leu Pro Ser Pro His Ser Lys Ser Thr Pro Ser Arg
20 25 30
Gln Pro Pro Ser Leu Ala Ala Ser Pro Gly Ser Ser Ser Gly Leu
35 40 45
Thr Ala Thr Val Ala Gln Ala Met Pro Tyr Ser Pro Gln Leu Lys
50 55 60
Pro Ile Gln Pro Ile Ala His Cys Tyr Gly Arg Thr Phe His Ser
65 70 75
74/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
Gln Pro Cys Leu Asp Ser Ser Gln Gly Gln Glu Lys Glu Arg Gln
80 85 90
Ile Ile Glu Gly Ile Phe Lys Gly Thr Cys Lys Ser Ser Asp Pro
95 100 105
Trp Asp Thr Leu Va1 Glu Gln Met Val Ser His Tyr Ser Pro Phe
110 115 120
Arg Glu Ser Ser Gly Asn Gly Met Lys Met Glu Gly Leu Leu Asn
125 130 135
Gly Ser Ser Asp Pro His Gln Ser Arg Leu Ala Ser Ile Lys Ala
140 145 150
Glu Ala Asp Lys Ile Tyr Ser Phe Thr Asp Asn Ala Pro Ser Pro
155 160 165
Ser Ile Gly Gly Ser Ser Arg Leu Glu Asn Thr Thr Pro Thr Gln
170 175 180
Pro Leu Thr Pro Leu His Val Val Thr Gln Asn Gly Ala Glu Ala
185 190 195
Ser Ser Val Lys Thr Asn Ser Pro A1a Tyr Ser Asp Ile Ser Asp
200 205 210
Ala Gly Glu Asp Gly Glu Gly Lys Val Asp Ser Val Lys Ser Lys
215 220 225
Asp Ala Glu Gln Leu Va1 Lys Glu Gly Ala Lys Lys Thr Leu Phe
230 235 240
Pro Pro Gln Pro Gln Ser Lys Asp Ser Pro Tyr Tyr Gln Gly Phe
245 250 255
Glu Ser Tyr Tyr Ser Pro Ser Tyr Ala Gln Ser Ser Pro Gly Ala
260 265 270
Leu Asn Pro Ser Ser Gln A1a Gly Val Glu Ser Gln Ala Leu Lys
275 280 285
Thr Lys Arg Asp Glu Glu Pro Glu Ser Ile G1u Gly Lys Val Lys
290 295 300
Asn Asp Ile Cys Glu Glu Lys Lys Pro Glu Leu Ser Ser Ser Ser
305 310 315
Gln Gln Pro Ser Val Ile Gln Gln Arg Pro Asn Met Tyr Met Gln
320 325 330
Ser Leu Tyr Tyr Asn Gln Tyr A1a Tyr Val Pro Pro Tyr Gly Tyr
335 340 345
Ser Asp G1n Ser Tyr His Thr His Leu Leu Ser Thr Asn Thr Ala
350 355 360
Tyr Arg Gln Gln Tyr Glu Glu Gln Gln Lys Arg Gln Ser Leu Glu
365 370 375
Gln Gln Gln Arg Gly Val Asp Lys Lys Ala Glu Met Gly Leu Lys
380 385 390
Glu Arg Glu Ala Ala Leu Lys Glu G1u Trp Lys Gln Lys Pro Ser
395 400 405
Ile Pro Pro Thr Leu Thr Lys A1a Pro Ser Leu Thr Asp Leu Val
410 415 420
Lys Ser Gly Pro Gly Lys Ala Lys G1u Pro Gly Ala Asp Pro Ala
425 430 435
Lys Ser Val Ile Ile Pro Lys Leu Asp Asp Ser Ser Lys Leu Pro
440 445 450
G1y Gln Ala Pro G1u G1y Leu Lys Val Lys Leu Ser Asp Ala Ser
455 460 465
His Leu Ser Lys Glu Ala Ser Glu Ala Lys Thr Gly Ala Glu Cys
470 475 480
Gly Arg Gln Ala Glu Met Asp Pro Ile Leu Trp Tyr Arg Gln Glu
485 490 495
Ala Glu Pro Arg Met Trp Thr Tyr Val Tyr Pro Ala Lys Tyr Ser
500 505 510
Asp I1e Lys Ser Glu Asp Glu Arg Trp Lys Glu Glu Arg Asp Arg
515 520 525
Lys Leu Lys Glu Glu Arg Ser Arg Ser Lys Asp Ser Va1 Pro Lys
530 535 540
Glu Asp Gly Lys Glu Ser Thr Ser Ser Asp Cys Lys Leu Pro Thr
545 550 555
Ser Glu Glu Ser Arg Leu Gly Ser Lys Glu Pro Arg Pro Ser Val
560 ~ 565 570
His Val Pro Val Ser Ser Pro Leu Thr Gln His Gln Ser Tyr Ile
75/204
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
575 580 585
Pro Tyr Met His Gly Tyr Ser Tyr Ser Gln Ser Tyr Asp Pro Asn
590 595 600
His Pro Ser Tyr Arg Ser Met Pro Ala Val Met Met Gln Asn Tyr
605 610 615
Pro Gly Ser Tyr Leu Pro Ser Ser Tyr Ser Phe Ser Pro Tyr Gly
620 625 630
Ser Lys Val Ser Gly Gly Glu Asp Ala Asp Lys Ala Arg Ala Ser
635 640 645
Pro Ser Val Thr Cys Lys Ser Ser Ser Glu Ser Lys Ala Leu Asp
650 655 660
Ile Leu Gln Gln His Ala Ser His Tyr Lys Ser Lys Ser Pro Thr
665 670 675
Ile Ser Asp Lys Thr Ser Gln G1u Arg Asp Arg Gly Gly Cys Gly
680 685 690
Val Val Gly Gly Gly Gly Ser Cys Ser Ser Val Gly Gly Ala Ser
695 700 705
Gly Gly Glu Arg Ser Val Asp Arg Pro Arg Thr Ser Pro Ser Gln
710 715 720
Arg Leu Met Ser Thr His His His His His His Leu Gly Tyr Ser
725 730 735
Leu Leu Pro Ala Gln Tyr Asn Leu Pro Tyr Ala Ala Gly Leu Ser
740 745 750
Ser Thr Ala I1e Val Ala Ser Gln Gln Gly Ser Thr Pro Ser Leu
755 760 765
Tyr Pro Pro Pro Arg Arg
770
<210> 111
<211> 247
<212> PRT
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:445188.1.orf3:2000MAY01
<400> 111
Val Tyr Ser Glu Asn Met Ser Thr A1a Ile Arg Glu Val Gly Val
1 5 10 15
Trp Arg Gln Thr Arg Thr Leu Leu Leu Lys Asn Tyr Leu Ile Lys
20 25 30
Cys Arg Thr Lys Lys Ser Ser Va1 Gln Glu Ile Leu Phe Pro Leu
35 40 45
Phe Phe Leu Phe Trp Leu Ile Leu Ile Ser Met Met His Pro Asn
50 55 60
Lys Lys Tyr Glu Glu Val Pro Asn Ile Glu Leu Asn Pro Met Asp
65 70 75
Lys Phe Thr Leu Ser Asn Leu Ile Leu Gly Tyr Thr Pro Val Thr
80 85 90
Asn Ile Thr Ser Ser Ile Met Gln Lys Val Ser Thr Asp His Leu
95 100 205
Pro Asp Val Ile Ile Thr Glu Glu Tyr Thr Asn Glu Lys Glu Met
110 115 120
Leu Thr Ser Ser Leu Ser Lys Pro Ser Asn Phe Val Gly Val Val
125 130 135
Phe Lys Asp Ser Met Ser Tyr Glu Leu Arg Phe Phe Pro Asp Met
140 145 150
Ile Pro Val Ser Ser Ile Tyr Met Asp Ser Arg Ala Gly Cys Ser
155 160 165
Lys Ser Cys Glu Ala Ala Gln Tyr Trp Ser Ser Gly Phe Thr Val
170 175 180
Leu Gln Ala Ser Ile Asp Ala Ala Ile Ile Gln Leu Lys Thr Asn
185 190 195
Val Ser Leu Trp Lys Glu Leu Glu Ser Thr Lys Ala Val Ile Met
200 205 210
Gly Glu Thr Ala Val Va1 G1u Ile Asp Thr Phe Pro Arg Gly Val
76/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
215 220 225
Ile Leu Ile Tyr Leu Val Ile Ala Phe Ser Pro Phe Gly Tyr Phe
230 235 240
Leu Ala Ile His Ile Val Ala
245
<210> 112
<211> 98
<212> PRT
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:244378.1.orf1:2000MAY01
<400> 112
Gly Leu Gly Ser Leu Asn Pro Gly Leu Trp Leu Leu Asn Gly Ser
1 5 10 15
Arg Asn Ser Leu Gly Asn Phe Cys Asp Gly Gln Arg Lys Cys Ser
20 25 30
Ser Val Ile Phe Met Asp Glu Ile Asp Ser Phe Gly Ser Ser Glu
35 40 45
Leu Glu Gly Asp Ala Gly G1y Asn Ser Glu Va1 Gln Gln Met Met
50 55 60
Leu Ser Arg Val Ala Leu Arg Pro Pro Arg Val Ser Arg Thr Val
65 70 75
Tyr His Gly Cys Glu Tyr Glu Met Arg Tyr Leu Val Thr Pro Ala
80 85 90
Val Phe Val Ala Gln Gly His His
<210> 113
<211> 51
<212> PRT
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:236574.15.orf1:2000MAY01
<400> 113
Asp Thr Leu Met Lys Thr Trp Thr Ile G1u Trp Ser Arg Asn Ser
1 5 10 15
Pro Leu Ser Leu Thr Tle Thr Val Ala Phe Leu Trp Ser Ser Ser
20 25 30
Ser Pro Arg I1e Pro Lys Thr Ala Ala G1u Phe Ile Lys Ile Lys
35 40 45
Phe Val Asn Val Thr Thr
<210> 114
<211> 94
<212> PRT
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:010100.20.orf3:2000MAY01
<400> 114
Ile Leu Leu Leu G1u Ala Ala Leu Ala Trp Glu Val Leu G1u Trp
1 5 10 15
Glu Ala Tyr Gly Arg Asp Gly Met Arg His Val Lys Phe Leu Lys
20 25 30
Tyr Val Arg Val Ser Cys Leu Ser Met Ser Leu Asn'Phe Phe Ser
35 40 45
Phe Phe Phe Leu Lys Ile Ile Arg Glu Ala Met Asp G1n Leu G1u
77/ 104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
50 55 60
Glu Trp Glu Trp Gly Thr Ile Thr Val Glu Asp Met Va1 Leu Leu
65 70 75
Met Val Trp Val Val Met Val Ser Ile Ser Ser Ser Val Cys Val
80 85 90
Ser Pro His Met
<210> 115
<211> 64
<212> PRT
<2l3> Homo sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:037940.6.orf1:2000MAY01
<400> 1l5
Ala His Ala Glu Asp Ser Val Met Asp His His Phe Arg Lys Pro
1 5 10 15
Ala Asn Asp Ile Thr Ser Gln Leu Glu Ile Asn Phe Gly Asp Pro
20 25 30
Trp Pro Pro Arg Thr Trp Arg Gln Gly Arg Thr Arg Trp Thr Trp
35 40 45
Ala Trp Trp Ala Pro Lys Pro Trp Gln Gln Asp Arg Gln Val Lys
50 55 60
Cys Phe Cys Ser
<210> 1l6
<21l> 238
<2l2> PRT
<213> Homo sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:228550.3.orf2:2000MAY01
<400> l16
Trp Met Val Leu Ser Leu Trp Arg Leu Cys Thr Cys Leu Phe Leu
1 5 10 15
Ala Pro Ser Arg G1n G1y Gly Gly Ser Gln Ala Leu Pro Ser Ser
20 25 30
Met Ala Pro Trp Pro Pro Gly Pro Ser Thr Val Val Va1 Glu Pro
35 40 45
His Gln Trp Pro Leu Gly I1e Arg Leu Asn Ala Gly Gly Thr Phe
50 55 60
Cys Trp Pro Thr Leu Arg Ala Val Met Gln Arg Pro Phe Pro Gln
65 70 75
Ala Cys Val Phe Thr His Leu Pro Ser Leu Ala Phe Ala Val Thr
80 85 90
Gly Arg Glu Glu Pro Ser Arg Asp Pro Trp Trp Pro Thr Cys Gly
95 100 105
Cys His Met Leu Leu Phe Pro Ala Cys Pro Ala Thr Thr His Ala
110 115 120
Leu His Arg Val Arg Trp Ser His Gly Gly Ala Ser Phe Thr Gln
125 130 135
Gln Pro Ser Asn Pro Asp Ala Val Gly Arg Ala Gly Ser Leu Gly
140 145 150
Tyr His His Pro Cys Gly Cys Thr Ala Val Pro Cys Ser Ser Gly
155 160 165
Ser Gly Phe Pro Ala Val Thr Ser Lys Pro Ala Cys Pro Val Cys
170 175 180
Trp Gly Trp Leu Ser Phe Gly Leu Pro Ile Thr Gly Arg Leu Val
185 190 195
Glu Lys Ala Val Pro Arg Gly Arg Thr Arg Pro Arg Arg Gln Leu
200 205 210
78/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
Pro Ala Leu Pro Gln Lys Cys Gln Asp Val His Gln Pro Leu Ala
215 220 225
Arg Ala Arg Ser Arg Gln Ser Thr Val Thr Gly Glu Cys
230 235
<210> 117
<211> 202
<212> PRT
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:027320.1.orf2:2000MAY01
<400> 117
Arg Pro Gly Arg Cys Leu Arg Ala Val A1a Pro Pro Arg Leu His
1 5 ' 10 15
Ser Gly Ser Pro Pro Arg Ala Pro Pro Pro Pro Leu Glu Ala Leu
20 25 30
His Ser Gly Glu Ala Gly Arg Ala Pro Asp Ser Asp Gly Gly Ser
35 40 45
Asp Ala Asp Phe Gly Gly Gly Ser Gly Glu Pro Asp Ser Asp Arg
50 55 60
Gly Gly Glu Arg Glu Leu Arg Leu Arg Arg Gly Glu Leu Gly Gly
65 70 75
Arg Leu Leu Pro Arg Ala Ala Glu Glu Glu Met Ala G1y Pro Asn
80 85 90
Gln Leu Cys Ile Arg Arg Trp Thr Thr Lys His Val Ala Val Trp
95 100 105
Leu Lys Asp Glu Gly Phe Phe Glu Tyr Val Asp Ile Leu Cys Asn
110 115 120
Lys His Arg Leu Asp Gly Ile Thr Leu Leu Thr Leu Thr Glu Tyr
125 13 0 135
Asp Leu Arg Ser Pro Pro Leu Glu Ile Lys Val Leu Gly Asp Ile
140 145 150
Lys Arg Leu Met Leu Ser Val Arg Lys Leu Gln Lys Ile His Ile
155 160 165
Asp Val Leu Glu Glu Met Gly Tyr Asn Ser Asp Ser Thr Met Gly
170 175 180
Ser Met Thr Pro Phe Ile Ser A1a Leu Gln Ser Thr Asp Trp Leu
185 190 195
Cys Asn Gly Glu Leu Ser Pro
200
<210> 118
<211> 172
<212> PRT
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:321475.1.orf2:2000MAY01
<400> 118
Ser Leu Ile Ser Lys Glu Asp Phe Lys Gln Met Ser Pro Gly T1e
1 5 10 15
Ile Gln Gln Leu Leu Ser Cys Ser Cys His Leu Pro Lys Asp Gln
20 ~ 25 30
Gln Ala Lys Leu Pro Pro Thr Thr Leu Glu ,Lys Tyr Gly Tyr Ser
35 40 45
Thr Val Ala Val Thr Leu Leu Thr Leu Gly Ser Met Leu Gly Thr
50 55 60
Ala Leu Val Leu Phe His Ser Cys Glu Glu Asn Tyr Arg Leu Ile
65 70 75
Leu Gln Leu Phe Val Gly Leu Ala Val Gly Thr Leu Ser Gly Asp
80 85 90
Ala Leu Pro Pro Pro Tyr Pro Ser G1y Ser Cys Val Tyr Ile Ser
79/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
95 100 105
Arg Lys Pro Gln Asn Leu Gly I1e Ser Met Lys Ala Lys Val Asn
110 115 120
Ile Trp Lys Leu Met Gly Leu Ile Gly Gly Ile His Gly Phe Val
125 130 135
Leu Asp Arg Thr Asn Val Leu Phe Phe Leu Tyr His.Gln Met Thr
140 145 150
Ser Arg Ala Cys His Trp Leu Met Gly Thr Trp Val Ile Pro Thr
155 160 165
Ile Leu His Ser Thr Leu Asn
170
<210> 119
<211> 166
<212> PRT
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:899552.5.orf1:2000MAY01
<400> 119
Val Asn Ile Lys Ser Pro Gln Pro His Leu Glu Gly Phe His Pro
1 5 10 15
Ala Arg Ala Cys Leu Leu Leu Ser Thr Leu Leu Gly Val Thr Tyr
20 25 30
Glu Cys His Ser Cys Asn Ser Glu Val Pro Thr Lys Pro Arg Ala
35 40 45
Leu Ala Ser Ser Gly Val Arg Pro Leu Phe Arg Val Leu Arg Thr
50 55 60
Ala Val Val Val Gln Val Thr Pro Lys Gly Met Arg Arg Lys Gly
65 70 75
Ser Met Ser Ser Lys Ala Gln Gly Ser Gln Asp Ser Ser Pro Pro
80 85 90
Phe Ser Pro Gly Thr Ser Arg Glu Ala Arg Gly Phe Thr Leu Cys
95 100 105
Thr Phe Leu Leu Leu Leu Lys Cys Pro Ala Val Cys Leu Pro Gly
110 115 120
Gln Lys Phe Gly Ala Thr Gln Ala Gly Leu Thr Met Pro Gln Val
125 130 135
Leu Ile Trp Arg Ala Glu Arg Ser Asp Ala Gly Thr Tyr Lys Glu
140 145 150
Glu Arg Lys Glu Glu Arg Leu Thr Leu Thr Arg Leu Leu Arg Arg
155 160 165
Gly
<210> 120
<211> 194
<212> PRT
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:1071848.1.orf2:2000MAY01
<400> 120
Ala Gly Arg Arg Arg Pro Leu Arg Ser Arg Lys Met Ser Arg Ser
1 5 10 15
Gly Ala Ala Ala G1u Lys Ala Asp Ser Arg Gln Arg Pro Gln Met
20 25 30
Lys Val Asn Glu Tyr Lys Glu Asn Gln Asn Ile Ala Tyr Val Ser
35 40 45
Leu Arg Pro Ala Gln Thr Thr Val Leu Ile Lys Thr Ala Lys Val
50 55 60
Tyr Leu Ala Pro Phe Ser Leu Ser Asn Tyr Gln Leu Asp Gln Leu
65 70 75
80/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
Met Cys Pro Lys Ser Leu Ser Glu Lys Asn Ser Asn Asn Glu Val
80 85 90
Ala Cys Lys Lys Thr Lys Ile Lys Lys Thr Cys Arg Arg Ile Ile
95 100 105
Pro Pro Lys Met Lys Asn Thr Ser Ser Lys Ala Glu Ser Thr Leu
110 115 120
Gln Asn Ser Ser Ser Ala Val His Thr Glu Ser Asn Lys Leu Gln
125 130 135
Pro Lys Arg Thr Ala Asp A1a Met Asn Leu Ser Val Asp Val Glu
140 145 150
Ser Ser Gln Asp Gly Asp Ser Asp Glu Asp Thr Thr Pro Ser Leu
155 160 165
Asp Phe Ser Gly Ile Val Thr Leu Arg Lys Glu Glu Thr Glu Glu
170 175 180
His Ile Arg Lys Arg Arg Leu Phe Cys Phe Ser Ser Val Val
185 190
<210> 121
<211> 313
<212> PRT
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:1072337.2.orf2:2000MAY01
<400> 121
Leu Leu Leu Pro Ala Ala Ser Ala His G1n Thr Ala Thr Gly Pro
1 5 10 15
Ala G1u Gly Phe Trp Gly Pro Pro Va1 Leu Met Leu Lys Arg Ser
20 25 30
Lys Asn Phe G1u Pro Ser Ala Cys His Gly Lys Asn Val Val Val
35 40 45
Thr Ala Asp Cys Ile Val Thr Gln Lys Arg Val Pro Ala Ala Arg
50 55 60
Leu Gly Ile Lys Cys Gln Val Ser Gly Ser His Val Leu Ser Met
65 70 75
Trp Ala Ala Ser Arg Asp Gly Cys Gly Asn Met Ala Gly Arg Ile
80 85 90
Glu Phe Asn Pro I1e Arg Val Arg Thr His Tyr Leu His Thr Ile
95 100 105
Met Lys Leu Glu Leu Glu Ser Lys Arg Gln Val Ser Arg Pro Ala
110 115 120
Ala Pro Asp Glu Glu Pro Ser Pro Thr Ala Ser Cys Ser Leu Thr
125 130 135
Gly Ala Gln Gly Ser G1u Thr G1n Asp Phe Gln Glu Phe Ile Ala
140 145 150
Glu Asn Glu Thr Ala Val Met His Leu Gln Ser Ala Glu Glu Leu
155 160 165
Glu Arg Leu Lys Ala Glu Glu Asp Ser Ser Gly Ser Ser Ala Ser
170 175 180
Leu Asp Ser Ser Ile Glu Ser Leu Gly Val Cys Ile Leu Glu Glu
185 190 195
Pro Leu Ala Val Pro Glu Glu Leu Cys Pro Gly Leu Thr Ala Pro
200 205 210
Ile Leu Ile Gln A1a G1n Leu Pro Pro Gly Ser Ser Val Leu Cys
215 220 225
Phe Thr Glu Asn Ser Asp His Pro Thr Ala Ser Thr Val Asn Ser
230 235 240
Pro Ser Tyr Leu Asn Ser Gly Pro Leu Val Tyr Tyr Gln Val Glu
245 250 255
Gln Arg Pro Val Leu Gly Val Lys Gly Glu Pro Trp Tyr Gly Arg
260 265 270
Arg Leu Ser Leu Phe Pro Lys Gly Glu Gly Ser Glu Cys Leu Leu
275 280 285
Ser Pro Cys Tyr Leu Thr Arg Gly Leu Val Ala Pro Gln Thr Gln
290 295 300
81/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
Leu Pro Ser Val Asn Gln Arg Trp Gly Lys His Pro Pro
305 310
<210> 122
<211> 126
<212> PRT
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:251489.5.orf2:2000MAY01
<400> 122
Gln Lys Phe Pro Met Gly Lys Gly Pro Ser Phe Asn Gln Glu Arg
1 5 10 15
Gly Thr Ser Ser His Leu Pro Pro Pro Thr Lys Val Ala Cys Thr
20 25 30
Ala Ala Ser Thr Ser Arg Ser Thr Gly Ser Thr Trp Glu Asp Gln
35 40 45
Ala Pro Phe Pro Pro Ser Ser Lys Val Ala Asp Glu Asp Glu Ile
50 55 60
Leu Glu Ala Lys Thr Lys Thr Thr Ile Arg Asn Phe Cys Ser Ser
65 70 75
Arg Ile Val Leu Val Asn Gly Val Lys Arg Lys Ser Glu Glu Trp
80 85 90
Lys Asn Lys Ala Lys Ala Ala Cys Ala Glu Lys Leu Lys Arg Leu
95 100 105
Ala Asp Glu Ala Trp His Pro Gly Lys Thr Thr Ile Ser Arg Gly
110 115 120
Asn Gln Gly Lys Gly A1a
125
<210> 123
<211> 911
<212> PRT
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:902018.107.orf2:2000MAY01
<220>
<221> unsure
<222> 55
<223> unknown or other
<400> 123
Thr A1a Trp Gln Cys Gln G1y Arg Va1 Gly Val Ser Pro His Cys
1 5 10 15
Pro Ala Ser Val Gly Gln Pro Asn Thr Va1 Cys Leu Val Val Cys
20 25 30
Val His Met Cys Ala Cys Val Cys Pro Ala G1u G1n Gln Thr Ala
35 40 45
Ala Pro Glu Ser Cys Gly Ala Phe Pro Xaa Tyr Gly Ser Ser Phe
50 55 60
Tyr Ala Leu Glu Glu Lys His Val Gly Phe Ser Leu Asp Val Gly
65 70 75
Glu Ile Glu Lys Lys Gly Lys Gly Lys Lys Arg Arg Gly Arg Arg
80 85 90
Ser Lys Lys Glu Arg Arg Arg Gly Arg Lys Glu Gly Glu Glu Asp
95 100 105
Gln Asn Pro Pro Cys Pro Arg Leu Ser Arg Glu Leu Leu Asp Glu
110 115 120
Lys Glu Pro Glu Val Leu Gln Asp Ser Leu Asp Arg Cys Tyr Ser
125 13 0 135
Thr Pro Ser Gly Tyr Leu Glu Leu Pro Asp Leu Gly Gln Pro Tyr
140 145 150
X21104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
Ser Ser Ala Val Tyr Ser Leu Glu Glu Gln Tyr Leu Gly Leu Ala
15'5 160 165
Leu Asp Val Asp Arg Ile Lys Lys Asp Gln Glu Glu Glu Glu Asp
170 175 180
Gln G1y Pro Pro Cys Pro Arg Leu Ser Arg Glu Leu Leu Glu Val
185 190 195
Val Glu Pro Glu Val Leu Gln Asp Ser Leu Asp Arg Cys Tyr Ser
200 205 210
Thr Pro Ser Ser Cys Leu Glu Gln Pro Asp Ser Cys Gln Pro Tyr
215 220 225
Gly Ser Ser Phe Tyr Ala Leu Glu Glu Lys His Val Gly Phe Ser
230 235 240
Leu Asp Val Gly Glu Asp Gln Arg Arg Lys Glu Glu Gly Glu Glu
245 250 255
Lys Lys Gly Lys Lys Ile Lys Thr His His Ala Pro Gly Leu Ser
260 265 270
Arg Glu Leu Leu Asp Glu Lys Gly Pro G1u Val Leu Gln Asp Ser
275 280 285
Leu Asp Arg Cys Tyr Ser Thr Pro Ser Gly Cys Leu Glu Leu Thr
290 295 300
Asp Ser Cys Gln Pro Tyr Arg Ser Ala Phe Tyr Ile Leu Glu Gln
305 310 315
Gln Arg Val Gly Leu A1a Val Asp Met Asp Glu Ile Glu Lys Tyr
320 325 330
Gln Glu'Val Glu Glu Asp Gln Asp Pro Ser Cys Pro Arg Leu Ser
335 340 345
Gly Glu Leu Leu Asp Glu Lys Glu Pro Glu Val Leu Gln Glu Ser
350 355 360
Leu Asp Arg Cys Tyr Ser Thr Pro Ser Gly Cys Leu Glu Leu Thr
365 370 375
Asp Ser Cys Gln Pro Tyr Arg Ser Ala Phe Tyr Ile Leu Glu Gln
3'80 385 390
Gln Arg Val Gly Leu Ala Val Asp Met Asp Glu I1e G1u Lys Tyr
395 400 405
Gln Glu Val Glu Glu Asp Gln Asp Pro Ser Cys Pro Arg Leu Ser
410 415 420
Arg Glu Leu Leu Asp Glu Lys Glu Pro Glu Val Leu Gln Asp Ser
425 430 435
Leu Gly Arg Cys Tyr Ser Thr Pro Ser Gly Tyr Leu Glu Leu Pro
440 445 450
Asp Leu Gly Gln Pro Tyr Ser Ser Ala Va1 Tyr Ser Leu Glu Glu
455 460 465
Gln Tyr Leu Gly Leu Ala Leu Asp Val Asp Arg Ile Lys Lys Asp
470 475 480
Gln G1u Glu Glu Glu Asp Gln Gly Pro Pro Cys Pro Arg Leu Ser
485 490 495
Arg Glu Leu Leu Glu Val Val Glu Pro Glu Val Leu Gln Asp Ser
500 505 510
Leu Asp Arg Cys Tyr Ser Thr Pro Ser Ser Cys Leu Glu Gln Pro
515 520 525
Asp Ser Cys Gln Pro Tyr Gly Ser Ser Phe Tyr Ala Leu Glu Glu
530 535 540
Lys His Val Gly Phe Ser Leu Asp Val Gly Glu Ile Glu Lys Lys
545 550 555
Gly Lys Gly Lys Lys Arg Arg Gly Arg Arg Ser Lys Lys Glu Arg
560 565 570
Arg Arg Gly Arg Lys Glu Gly Glu Glu Asp Gln Asn Pro Pro Cys
575 580 585
Pro Arg Leu Ser Arg Glu Leu Leu Asp Glu Lys Gly Pro Glu Val
590 595 600
Leu Gln Asp Ser Leu Asp Arg Cys Tyr Ser Thr Pro Ser Gly Cys
605 610 615
Leu Glu Leu Thr Asp Ser Cys Gln Pro Tyr Arg Ser Ala Phe Tyr
620 625 630
Val Leu Glu Gln Gln Arg Val Gly Leu Ala Val Asp Met Asp Glu
635 640 645
Ile Glu Lys Tyr Lys Glu Val Glu Glu Asp Gln Asp Pro Ser Cys
83/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
650 655 660
Pro Arg Leu Ser Arg Glu Leu Leu Asp G1u Lys Glu Pro Glu Val
665 670 675
Leu G1n Asp Ser Leu Asp Arg Cys Tyr Ser Thr Pro Ser Gly Tyr
680 685 690
Leu Glu Leu Pro Asp Leu Gly Gln Pro Tyr Ser Ser Ala Val Tyr
695 700 705
Ser Leu Glu Glu Gln Tyr Leu Gly Leu A1a Leu Asp Val Asp Arg
710 715 720
Ile Lys Lys Asp Gln Glu Glu Glu Glu Asp Gln Gly Pro Pro Cys
725 730 735
Pro Arg Leu Ser Arg Glu Leu Leu Glu Val Val Glu Pro Glu Val
740 745 750
Leu Gln Asp Ser Leu Asp Arg Cys Tyr Ser Thr Pro Ser Ser Cys
755 760 765
Leu Glu Gln Pro Asp Ser Cys Gln Pro Tyr Gly Ser Ser Phe Tyr
770 775 780
Ala Leu Glu Glu Lys His Val Gly Phe Ser Leu Asp Val Gly Glu
785 790 795
Ile Glu Lys Lys G1y Lys Gly Lys Ile Arg Arg Gly Arg Arg Ser
800 805 810
Lys Lys Lys Arg Arg Arg G1y Arg Lys Glu Gly Glu Glu Asp Gln
815 820 825
Asn Pro Pro Cys Pro Arg Leu Asn Ser Val Leu Met Glu Val Glu
830 835 840
Glu Pro Glu Val Leu Gln Asp Ser Leu Asp Arg Cys Tyr Ser Thr
845 850 855
Pro Ser Met Tyr Cys Glu Leu Arg Asp Ser Phe Gln His Tyr Arg
860 865 870
Ser Val Phe Tyr Ser Phe Glu Glu Gln His Ile Ser Phe Ala Leu
875 880 885
Asp Met Asp Asn Arg Phe Phe Thr Leu Thr Val Thr Ser Leu Tyr
890 895 900
Leu Val Phe Gln Met Gly Val Ile Phe Pro Gln
905 910
<210> 124
<211> 198
<212> PRT
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:220495.1.orf1:2000MAY01
<220>
<221> unsure
<222> 191
<223> unknown or other
<400> 124
Arg Phe Trp Leu Pro His Asn Va1 Thr Trp Ala Asp Leu Lys Asn
1 5 10 15
Thr Glu Glu Ala Thr Phe Pro Gln Ala Glu Asp Leu Tyr Leu Ala
20 25 30
Phe Pro Leu Ala Phe Cys T1e Phe Met Val Arg Leu Ile Phe Glu
35 40 45
Arg Phe Val Ala Lys Pro Cys Ala Ile Ala Leu Asn Tle Gln Ala
50 55 60
Asn Gly Pro Gln Ile Ala Pro Pro Asn Ala Ile Leu Glu Lys Val
65 70 75
Phe Thr Ala I1e Thr Lys His Pro Asp Glu Lys Arg Leu G1u Gly
80 85 90
Leu Ser Lys Gln Leu Asp Trp Asp Val Arg Ser Ile Gln Arg Trp
95 100 105
Phe Arg Gln Arg Arg Asn Gln Glu Lys Pro Ser Thr Leu Thr Arg
110 115 120
84/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
Phe Cys Glu Ser Met Trp Arg Phe Ser Phe Tyr Leu Tyr Val Phe
125 13 0 135
Thr Tyr Gly Val Arg Phe Leu Lys Lys Thr Pro Trp Leu Trp Asn
140 145 150
Thr Arg His Cys Trp Tyr Asn Tyr Pro Tyr Gln Pro Leu Thr Thr
155 160 165
Asp Leu His Tyr Tyr Tyr Ile Leu Glu Leu Ser Phe Tyr Gly Ser
170 175 180
Trp Met Leu Phe Ser Val His Trp Ile Ser Xaa Arg Ile Arg Thr
185 190 195
Cys Gly Asp
<210> 125
<211> 205
<212> PRT
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:399478.1.orf3:2000MAY01
<400> 125
Ala Asp Ser Arg Ser Pro Ala Thr Ala Ala Ser Pro Ser Ala Pro
1 5 10 15
Ala Leu Pro Val His Ser Pro Gln Pro Pro Ser Ala Lys Pro Gln
20 25 30
Arg Pro Leu Pro Ser Pro Met Thr Ala Gly Arg Arg Met Glu Met
35 40 45
Leu Cys Ala Gly Arg Val Pro Ala Leu Leu Leu Cys Leu Gly Phe
50 55 60
His Leu Leu Gln Ala Val Leu Ser Thr Thr Val Ile Pro Ser Cys
65 70 75
Ile Pro Gly Glu Ser Ser Asp Asn Cys Thr A1a Leu Val G1n Thr
80 85 90
Glu Asp Asn Pro Arg Val Ala Gln Val Ser Ile Thr Lys Cys Ser
95 100 105
Ser Asp Met Asn Gly Tyr Cys Leu His Gly Gln Cys Ile Tyr Leu
110 115 120
Val Asp Met Ser Gln Asn Tyr Cys Arg Cys Glu Val Gly Tyr Thr
125 130 135
Gly Val Arg Cys Glu His Phe Phe Leu Thr Val His Gln Pro Leu
140 145 150
Ser Lys Glu Tyr Val Ala Leu Thr Val Ile Leu Ile Ile Leu Phe
155 160 165
Leu Ile Thr Val Val Gly Ser Thr Tyr Tyr Phe Cys Arg Trp Tyr
170 175 180
Arg Asn Arg Lys Ser Lys Glu Pro Lys Lys Glu Tyr Glu Arg Val
185 190 195
Thr Ser Gly Asp Pro Glu Leu Pro Gln Val
200 205
<210> 126
<211> 121
<212> PRT
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:229648.2.orf1:2000MAY01
<400> 126
Asp Asp Cys Met Leu Thr His Pro Leu Gln Gly Pro Gly Leu Asp
1 5 10 15
Leu Gly Leu His Cys I1e Leu Ser Asn Gly Leu Ala Gly Ala Pro
20 25 30
Phe Gly Leu Leu Ser Leu Phe Ser Pro Glu Leu Gly Trp Trp Glu
851104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
35 40 45
Lys Arg Gly Trp Ser Glu Ser Ile Ser Ile G1n Ile Pro Ala Gly
50 55 60
Ile Thr Leu Gly Val Phe Leu Ala Cys Met Gly Leu Lys Leu Ser
65 70 75
Tyr Ile Val Tyr Trp Leu Pro Lys Ser G1y Leu Lys Ser Glu Lys
80 85 90
Met Gln Ala Met Asn Pro Ser Ala His Ser Ser Pro Thr Phe Pro
95 100 105
Ala Leu Phe Tyr Leu Gly Gly Gln Trp Lys Gly Gly Glu Ala Met
110 115 120
Pro
<210> 127
<211> 193
<212> PRT
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:025643.2.orf3:2000MAY01
<400> 127
Leu Lys Trp Ile Pro Ser Ser Pro Gly Lys Leu Asn Glu Ala Asp
1 5 10 15
His Asn Gly Asp Leu Ala Leu Arg Ile Leu Ala Pro Leu Thr Thr
20 25 30
Thr Gly Glu Val Asn Cys Gln Pro Arg Trp Leu Val Thr Lys Leu
35 40 45
Met Trp Thr Trp Trp Thr Lys Ser Gly Trp Ser Leu Val Thr Pro
50 55 60
Arg G1y Phe Gln Arg Arg Arg Ser Leu Va1 Leu Pro Leu Ser Tyr
65 70 75
Ile Asn Glu Trp Arg Pro Cys Val Asn A1a Ala Thr Leu Gly Ala
80 85 90
Pro Gly Asp Thr Thr Cys Thr Phe Va1 Gly Leu Cys Thr Ser Ser
95 100 105
Thr Arg Asn Thr Gln Leu Asp Va1 Met Pro G1u Met Ala A1a Asp
110 115 120
Cys Arg Gly Pro Ser Ala Gly Trp Val Pro Thr Pro Asn Met Gln
125 130 135
Asp Ser Lys Gly Arg Thr Pro Val Thr Cys Val Pro Ser Met Ala
140 145 150
Ala Gly Tyr Asp Ile Cys Val Ser Val Ser Cys Ser Ser Arg Lys
155 160 165
G1n Leu Asp Leu Glu Leu Asn Arg Pro Arg Gly Gln Ala Gln Ala
170 175 180
Thr Val Ala Trp Leu Val Gln His Ile Thr Ser Val Phe
185 190
<210> 128
<211> 116
<212> PRT
<213> Homo sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:233942.1.orf2:2000MAY01
<400> 128
Asp Ser Gln Cys Met Arg Ser Gln Pro Arg Glu His Leu Phe Phe
1 5 10 15
Thr Phe Leu Leu Lys Ile His Trp Gly Gly Ile Lys Phe Thr Pro
20 25 30
Lys Lys Phe Ala Trp Ala Lys Ser Leu Gln Val Pro Ser Glu Asn
35 40 45
86/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
Lys Ile Leu Met Ile Phe Phe Phe Phe Trp Leu Leu Gly Arg Asp
50 55 60
Phe Gln His Ser Phe Thr Ile Ser Gln Ile Cys Pro Phe Ser Thr
65 70 75
His Thr G1n Leu Ser His Leu Val Arg Phe I1e Leu Pro Lys G1u
80 85 90
Arg Cys Ser Pro Thr Leu Thr Leu Phe Gln Arg Ala Thr Leu Ser
95 100 105
Gln Pro Gln Gln Pro Cys Gln Glu Lys Ala Arg
110 115
<210> 129
<211> 186
<212 > PRT
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:089158.1.orf1:2000MAY01
<220>
<221> unsure
<222> 29, 36, 38-39, 49
<223> unknown or other
<400> 129
Leu Ser Asp Phe Arg Leu Leu His Leu His Glu Leu Gly His Lys
1 5 10 15
Val Pro Val Met Ser Asn Cys Gln Ser Gly Pro Ser Ile Xaa Arg
20 25 30
Ser Ala Ser Pro Lys Xaa Pro Xaa Xaa Glu Asn Leu Pro G1y Ala
35 40 45
Gln Ala Lys Xaa Trp Val Arg Thr Arg Thr Val Ala Cys Trp Tyr
50 55 60
Cys Arg Asp Ala Ala Ser Val Pro Ser Ser Pro His Arg Pro Arg
65 70 75
Ser Ile Ser Leu Ser Arg Val Gly Leu Leu Leu A1a Ala Thr Gly
80 85 90
Ile Leu Gln Pro Leu Ile Trp Leu Ser Ser Val Ser Glu I1e Ser
95 100 l05
Ile Cys Arg Gly Ser Leu Gly A1a Gln Thr Val Thr Ser Asn Trp
110 115 120
Glu Val Lys Cys Trp Trp Val Lys Phe Thr Ile Val Ser Thr Leu
125 13 0 135
Leu Leu His Phe Leu Pro Ser Ser Gln Lys Met Glu Ser Gln Leu
140 145 150
Leu Glu Thr Leu Met Thr Ser Ser Ser Arg Arg Leu Ala Leu Pro
155 160 . 165
G1n Thr His Asp Thr Ser Thr Thr Glu Pro Ser Ser Leu Asp Pro
170 175 180
His Asp Phe Asp Arg Asn
185
<210> 130
<211> 90
<212> PRT
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:101046.1.orf2:2000MAY01
<400> 130
Thr Tyr Gln Pro Gly Phe Ser Leu Thr Lys Asp Asn Pro Arg Gly
1 5 10 15
Ser Leu Asp Gln Pro His Leu Ser Gly Ser Pro Phe Ser Ser Ser
20 25 30
87/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
Phe Lys Ser Pro Ser Phe Leu Gln Ile Ser Ser Arg Leu Ala Ala
35 40 45
Leu Lys Asp Asn Pro Leu Leu Pro Ala Ala Leu Leu Cys Leu Lys
50 55 60
Gly Lys Gly Leu Ala His Ile Phe Ser Val Trp Pro Pro Pro Pro
65 70 75
Gly His Thr Ala Phe Phe Leu Ala Pro Phe Leu Thr Leu Leu Thr
80 85 90
<210> 131
<211> 167
<212> PRT
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:368676.2.orf1:2000MAY01
<400> 131
Glu Ser Leu Cys His Arg Asp Pro Arg Lys Asn Tle Glu Leu Tyr
1 5 10 15
Val Arg Pro Met Ser Leu Leu Gly Glu Val Gln Leu Gln Pro Ser
20 25 30
Thr Ser Leu Leu Pro Thr Leu Asn Arg Thr Phe Tle Trp Asp Val
35 40 45
Lys Ala His Lys Ser Ile Gly Leu Glu Leu Gln Phe Ser Ile Pro
50 55 60
Arg Met Arg Gln Ile Gly Pro Val Lys Ser Cys Pro Asp Gly Val
65 70 75
Thr Asn Ser Ile Ser Gly Arg Ile A1a Ala Thr Val Val Arg I1e
80 85 90
Gly Thr Phe Cys Ser Asn Gly Thr Val Ser Arg Ile Gln Asp Ala
95 100 105
Arg Arg Ser Glu Asn Gly Leu Thr Pro Pro Met Gly Ser Thr Pro
110 115 120
Glu Asn Val Ser Gly Phe Ser Ile Glu Thr Arg Ser Ser Ile Lys
125 130 135
Arg Leu'Cys Ile Ile Glu Ser Val Phe Glu Gly G1u Gly Ser Ala
140 145 150
Thr Leu Asn Val Cys Gln Leu Pro Thr Lys Ala Pro Leu Arg Met
155 160 165
Ser Ser
<210> 132
<211> 249
<212> PRT
<213> Homo sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:238713.1.orf2:2000MAY01
<400> 132
Val Lys Leu Lys Glu Leu Phe Asn Arg Ile Leu Arg Asn Gln Ala
1 5 10 15
Ser Val Met Gln Lys Arg Lys Thr Glu Lys Leu Lys Gln Glu Gln
20 25 30
Lys Gly Gln Pro Arg Thr Val Ser Pro Ser Thr Ile Arg Asp Gly
35 40 45
Pro Ser Ser Ala Pro Ala Thr Pro Thr Lys Ala Pro Tyr Ser Pro
50 55 60
Thr Thr Ser Lys Glu Lys Lys Ile Arg Ile Thr Thr Asn Asp Gly
65 70 75
Arg Gln Ser Met Val Thr Leu Lys Ser Ser Thr Asn Phe Phe Glu
80 85 90
881104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
Leu Gln Glu Ser Ile Ala Arg Glu Phe Asn Ile Pro Pro Tyr Leu
95 100 105
Gln Cys Ile Arg Tyr Gly Phe Pro Pro Lys Glu Leu Met Pro Pro
110 115 120
Gln Ala Gly Met Glu Lys Glu Pro Val Pro Leu Gln His Gly Asp
125 130 135
Arg Ile Thr Ile Glu Ile Leu Lys Ser Lys Ala Glu Gly Gly Gln
140 145 150
Ser Ala Ala Ala His Ser Ala His Thr Val Lys Gln Glu Asp Ile
155 160 165
Ala Val Thr Gly Lys Leu Ser Ser Lys Glu Leu Gln G1u Gln Ala
170 175 180
Glu Lys Glu Met Tyr Ser Leu Cys Leu Leu Ala Thr Leu Met Gly
185 190 195
Glu Asp Val Trp Ser Tyr Ala Lys Gly Leu Pro His Met Phe Gln
200 205 210
Gln Gly Gly Val Phe Tyr Ser Ile Met Lys Lys Thr Met Gly Met
215 220 225
Ala Asp Gly Lys His Cys Thr Phe Pro His Leu Pro Gly Lys Thr
230 235 240
Phe Val Tyr Asn Ala Ser Glu Asp Arg
245
<210> 133
<211> 110
<212> PRT
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:720928.1.orf3:2000MAY01
<400> 133
Thr Phe Thr His Met His Ile Ile Thr Gly Thr Gln Thr Phe Thr
1 5 10 15
His Met His Ile Ile Thr Gly Thr Gln Thr Tyr Thr His Met His
20 25 30
Ile Leu Met Gly Thr Gln Thr Phe Thr Arg Met His Ile Leu Met
35 40 45
Gly Thr Gln Thr Phe Thr His Met His Met Leu Met Gly Thr Gln
50 55 60
I1e Phe Thr Tyr Met His Lys Ile Met Gly Thr Gln Thr Phe Thr
65 70 75
His Met His Met Ile Thr Gly Thr Gln Thr Tyr Gly Ser Thr Gly
80 85 90
Leu Trp Ala His Ser Leu Gln His Lys His Thr Asp Val Pro Pro
95 100 105
Ile Phe Leu Arg Val
110
<210> 134
<211> 225
<212> PRT
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:221874.1.orf2:2000MAY01
<400> 134
Ile Gln Pro Ser Val Ser Lys Asn Asp Tyr Gln Asn Gly Val Cys
1 5 10 15
Phe Val Arg Leu Gly Thr Met Ser Leu Ser Thr Glu Gly Glu Glu
20 25 30
Glu Thr Val Thr Thr Leu Asp Tyr Ser His Cys Ser Phe Arg Thr
35 40 45
Ser Ser Gly Lys Arg Phe Leu Leu Leu Lys Lys Leu Leu Glu Glu
X9/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
50 55 60
Leu Tyr Leu Asp Ala Asn Gln Ile Glu Glu Leu Pro Lys Gln Leu
6S 70 75
Phe Asn Cys Gln Ser Leu His Lys Leu Ser Leu Pro Asp Asn Asp
80 85 90
Leu Thr Thr Leu Pro Ala Ser I1e Ala Asn Leu Ile Asn Leu Arg
95 100 105
Gly Thr Gly Cys Gln Gln Glu Trp Asn Thr Gly Val Ser Arg Lys
110 115 120
Leu Ser Lys Ile Val Lys Cys Leu Thr Ile Val Glu A1a Ser Val
125 130 135
Asn Pro Ile Ser Lys Leu Pro Asp Gly Phe Ser Gln Leu Leu Asn
140 145 150
Leu Thr Gln Leu Tyr Leu Asn Asp Ala Phe Leu Glu Phe Leu Pro
155 160 165
Ala Asn Phe Gly Arg Leu Thr Lys Leu Gln Ile Leu Glu Leu Arg
170 175 180
Glu Asn Gln Leu Lys Met Leu Pro Lys Thr Met Asn Arg Leu Thr
185 190 195
Gln Leu Glu Arg Leu Asp Leu Gly Ser Asn G1u Phe Thr Gly Ser
200 205 210
Ala Leu Lys Val Arg
215
<210> 135
<211> 198
<212> PRT
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LT:1143545.3.orf2:2000MAY01
<400> 135
Ala Glu Cys Gln Ala Thr Pro Pro Ala Val Trp Val Val Pro Arg
1 5 10 15
Leu Ala Thr Leu Arg Arg Arg Gly Ser Gln Ser Phe Ser Ala Trp
20 25 30
Thr Ala Leu Val Arg Arg Gly Pra Leu Arg Met Gly A1a Ala Arg
35 40 45
Arg Tyr Pro Asp Ser Met Glu Ala Pro Thr Arg Ile Arg Asp Thr
50 55 60
Pro Glu Asp Ile Va1 Leu G1u Ala Pro Ala Ser Gly Leu Ala Phe
65 70 75
His Pro Ala Arg Gly Pro Tyr Trp Leu Gln Gly Thr Trp Thr Gly
80 85 90
Thr Cys Ser Ser Phe Pro Thr Leu Ala Lys Arg Glu Lys Pro Arg
95 100 105
Ser Ser Gly His Gln Val Thr Ile Ser Arg Pro Ser Glu Leu Trp
110 115 120
Ala Phe Ser Glu Asp Gly Gln Lys Leu Ile Thr Val Ser Lys Asp
125 130 135
Lys Ala Ile His Val Leu Asp Val G1y Ala Gly Pro Thr G1y Lys
140 145 150
Thr Cys Phe Pro Arg Leu Met Val Pro Pro Ser Ile Val Phe Cys
155 160 165
Trp Trp Met Arg Met Phe Trp Pro Leu Gly Met Thr Pro Gly Gly
170 175 180
Ile Arg Ser Leu Gly Pro Ala Glu Gly Gly Pro Leu Asn Gly Tyr
185 190 195
Glu Ala Thr
<210> 136
<211> 147
<212> PRT
<213> Homo Sapiens
90/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
<220>
<221> misc_feature
<223> Incyte ID No: LI:1143605.1.orf1:2000MAY01
<400> 136
Thr Tyr Ser Ile Trp Ala Ser Ser Cys Lys Asn Lys Ala Glu Cys
1 5 10 15
Asn Glu Leu His Pro Ser Val Ser Val Val Gln Ile Leu A1a Phe
20 25 30
Ile Leu Ile Arg Asn Ile Pro Gly Tyr Ala Arg Ser Va1 Tyr Ser
35 40 45
Ser Phe Phe Ala Trp Phe Gly Lys Ile Ser Leu Glu Leu Phe Ile
50 55 60
Cys Gln Tyr His Ile Trp Leu Ala Ala Asp Thr Arg Gly Tle Leu
65 70 75
Val Leu Ile Pro Gly Lys Pro Tyr Ala Gln His His Cys Gln His
80 85 90
Phe His Ile Cys Leu Cys G1y His Met Lys Phe Leu Arg Ser Leu
95 100 105
Met Ile Leu His Arg Leu Leu Phe Ala Lys Asp Asn Ser Ser Leu
110 115 120
Leu Lys Arg Leu Ala Cys Ile Ala Ala Phe Phe Phe Cys Gly Leu
125 13 0 13 5
Leu Ile Leu Ser Ser Ile Gln Asp Lys Ser Lys His
140 145
<210> 137
<211> 153
<212> PRT
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:474069.7.orf1:2000MAY01
<220>
<221> unsure
<222> 60
<223> unknown or other
<400> 137
Arg Ser Cys Val Leu Asn Ser Asp His Met Ile His Ser His Ser
1 5 10 15
Pro Arg Tyr Arg Ser Gly Ser Val Asn Leu Asn Gly Cys Cys Glu
20 25 30
His Arg Arg Ala Leu Ile Ser Thr Ala Val Asn Pro Lys Leu Lys
35 40 45
Asp Ala Val Gln Ala Arg Lys Arg Gly Ile Tyr Leu Asn Thr Xaa
50 55 60
Leu Leu Ile Val Val Lys Leu Leu Phe Asp Gly Ser Ala Phe Ala
65 70 75
Met Lys Phe Pro Glu Lys Lys Ser Tyr Glu Tyr Lys Ile Leu Lys
80 85 90
Lys Ser Ser Thr Val Leu Pro Leu Ser Glu Ser Leu Phe Pro Phe
95 100 105
Leu Asp Pro Pro Val Met Leu Cys Asp Tyr Lys Phe Asp Asp Glu
110 115 120
Ser Ala Glu G1u Ile Arg Asp His Phe Met Glu Met Leu Asp His
125 130 135
Thr Ile Gln Ile Glu Asp Leu Gly Asn Cys Arg Gly Asn Lys His
140 145 150
Ser Leu Tyr
<210> 138
<211> 279
<212> PRT
91/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:245193.3.orf1:2000MAY01
<400> 138
Val Arg Leu Ala Val Ala Thr Thr Glu Glu Glu Gly Arg Asp Ala
1 5 10 15
Val Glu His Gly Asp Arg Leu Ser Val Met Glu Gly Ser Gly Glu
20 25 30
Gln Pro Gly Pro Gln Pro Gln His Pro G1y Asp His Arg Ile Arg
35 40 45
Asp Gly Asp Phe Val Val Leu Lys Arg Glu Asp Val Phe Lys Ala
50 55 60
Val Gln Val Gln Arg Arg Lys Lys Val Thr Phe Glu Lys Gln Trp
65 70 75
Phe Tyr Leu Asp Asn Val I1e Gly His Ser Tyr Gly Thr Ala Phe
80 85 90
Glu Val Thr Ser Gly Gly Ser Leu Gln Pro Lys Lys Lys Arg Glu
95 100 105
Glu Pro Thr Ala Glu Thr Lys G1u Ala Gly Thr Asp Asn Arg Asn
110 115 120
Ile Val Asp Asp Gly Lys Ser Gln Lys Leu Thr Gln Asp Asp Ile
125 130 135
Lys Ala Leu Lys Asp Lys Gly Ile Lys Gly Glu Glu Ile Va1 Gln
140 145 150
Gln Leu Ile Glu Asn Ser Thr Thr Phe Arg Asp Lys Thr Glu Phe
155 160 165
Ala Gln Asp Lys Tyr Ile Lys Lys Lys Lys Lys Lys Tyr Glu Ala
170 175 180
Ile Ile Thr Val Va1 Lys Pro Ser Thr Arg Ile Leu Ser Ile Met
185 190 195
Tyr Tyr Ala Arg Glu Pro Gly Lys Ile Asn His Met Arg Ile Arg
200 205 210
Tyr Thr Ser Pro Asp Val Asp Val Gly Lys Tyr Pro Cys Trp Gln
215 220 225
Gln Asn Asp Cys Asp Gly Asn Val Cys Arg Leu Gly Ala G1y Cys
230 235 240
Asn Asp Gly Thr Asn G1y Arg Phe Trp Leu His Tyr Ser Ala Ile
245 250 255
Pro Trp Arg Arg Thr Cys Ser Gly Ser Asn Ser Met Phe Trp Ile
260 265 270
Ser Gln Ile Phe Ser Gln Trp Ser Leu
275
<210> 139
<211> 138
<212> PRT
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:403872.1.orf1:2000MAY01
<400> 139
Pro G1y Gly Gly Ser Gly Gly Ser Arg Ala Arg Asp Gly G1y Pro
1 5 10 15
Ala Ala Ser Val Ile Pro Arg Thr Ser Ala Pro Arg Ala Arg Ala
20 25 30
Gln Thr Arg Thr His Thr Tyr Thr His Ser Arg Thr His Ser His
35 40 45
Lys His Thr Leu Val His A1a Arg Gly Arg Ser Leu Arg Arg Leu
50 55 ' 60
Ala Leu Gly Thr G1n Ala Glu Cys Ser Ser Ala Trp Arg Ala Cys
65 70 75
Leu Gly Pro Pro Pro Glu Cys Thr Ser Leu Pro Gly Ala Gly Arg
92/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
80 85 90
Pro Ser Arg Ala His Trp Arg Thr Leu Arg Cys G1y Thr Leu Gly
95 100 105
Gln Phe Phe Asp Gly A1a Val Leu Leu Tyr Gly Val Arg Asn Gly
110 115 120
Cys Arg Lys Gln His Ser Thr Lys Leu Phe His His Pro Val Phe
125 130 135
Tyr Ile Cys
<210> 140
<211> 347
<212> PRT
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:1086294.1.orf1:2000MAY01
<400> 140
Gln Gly His Ile Ile Arg Pro Pro Ser Pro Cys Pro Arg Pro Pro
1 5 10 15
Leu Glu Tyr Asn Ser Gly Val Pro Ala Trp Ala Asn Gly Leu Gly
20 25 30
Arg Glu Glu Ala Val Ala Glu Gly Ala Arg Arg Ala Leu A1a Trp
35 40 45
Leu His Ala Trp Phe Asp Ala Pro Trp Val Ala Gly Ser Phe Ser
50 55 60
Val Trp Pro Gly Lys Pro Arg Pro Asp Ala G1y Thr Arg Leu Glu
65 70 75
Ser Cys Pro Ser Pro Leu Arg Leu Arg Phe Arg Glu Arg Glu Ala
80 85 90
Ala Glu Glu Cys Gly Leu Ser Gly Arg Thr Glu Ala Arg Pro Cys
95 100 105
Glu Ala Gly Gln Arg Asn Gly Thr Gly Ala Pro Lys Gln Cys Gly
110 115 120
Asn Ser Tyr Trp Arg Cys Pro Pro A1a Pro Arg Ser Met Cys Ala
125 130 135
Ser Arg Arg Ile Thr Gly Trp Trp Gly Glu Cys Ser Pro Ser Met
140 145 150
Leu Thr Ala Arg Pro Pro G1y Tyr Glu Phe Glu Pro Glu Ala Leu
155 160 165
Ser Pro Asn Thr Pro Val Val Pro Ala Met Cys Thr Pro Ala Ser
170 175 180
Trp Gln Trp Leu Ala Arg Cys Ser Thr Met Leu Cys Gly Ser Arg
185 190 195
Ala Arg His Trp Leu Leu Arg A1a Ser Ser Thr Ser Asn Met Asn
200 205 210
Ala Gly Met Asp Gln Glu Asn Gly Gly Ser Trp Ala Ser Cys Leu
215 220 225
Pro Thr Ala Ser Glu Ala Ser Ala Ser Gln Leu Pro Arg Arg Pro
230 235 240
Cys Pro Gln Gln Tyr Pro Glu Arg Gly Pro Gly Ala Leu Cys Gly
245 250 255
Pro Pro Pro Arg Ala Pro Ser Arg Asn Leu Ala Pro Thr Pro Arg
260 265 270
Arg Arg Lys Ala Ser Pro Glu Pro Glu Gly Glu Ala Ala Gly Lys
275 280 285
Met Thr Thr Glu Glu Gln Gln Gln Arg His Leu Gly Gly Thr Arg
290 295 300
Arg Pro Cys Thr Pro Arg Glu Thr Pro Arg Cys Ala Leu Ala His
305 310 315
Cys Arg Pro Glu Glu Cys Gly Arg Ser Pro G1y Pro Leu Asp Pro
320 325 330
Arg Thr Leu Gly Gly Gly Gly Gly Pro Val Arg Ala Gly Gly Arg
335 340 345
Gln Pro
93/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
<210> 141
<211> 440
<212> PRT
<213> Homo sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:337514.3.orf1:2000MAY01
<400> 141
Ser Gly Trp Ser Trp Ala Leu Ala Ala Arg Gly Arg Arg Lys Leu
1 5 10 15
Ser Ser Cys Thr Gly Gly Arg Val Arg Ala Val Gly Gly Ser Gly
20 25 30
Ala Cys Ala Val Ala Met Ser Val Tyr Ala Arg Gly Pro Gly Pro
35 40 45
Arg G1u Ala Val Pro Ser Gly Arg Pro Arg Pro Asp Thr Leu Thr
50 55 60
Pro Pro Trp Val Arg Gln Arg Ala Val Thr Gly Thr Phe Cys Ala
65 70 75
Ser Trp Thr Pro Leu Arg Asn Arg Arg Ala Gln Arg Met Ala Thr
80 85 90
Asp Met Gln Arg Lys Arg Ser Ser Glu Cys Leu Asp Gly Thr Leu
95 100 105
Thr Pro Ser Asp Gly Gln Ser Met Glu Arg Thr Glu Ser Pro Thr
110 115 120
Pro Gly Met Ala Gln Gly Met Glu Pro Gly Ala Gly Gln Glu Gly
125 130 135
Ala Met Phe Val His Ala Arg Ser Tyr Glu Asp Leu Thr Glu Ser
140 145 150
Glu Asp Gly Ala Ala Ser Gly Asp Ser His Lys Glu Gly Thr Arg
155 160 165
Gly Pro Pro Pro Leu Pro Thr Asp Met Arg Gln Ile Ser Gln Asp
170 175 180
Phe Ser Glu Leu Ser Thr Gln Leu Thr Gly Val Ala Arg Asp Leu
185 190 195
Gln G1u Glu Met Leu Pro Gly Ser Ser Glu Asp Trp Leu Glu Pro
200 205 210
Pro Gly Ala Val Gly Arg Pro Ala Thr G1u Pro Pro Arg Glu Gly
215 220 225
Thr Thr Glu Gly Asp Glu Glu Asp Ala Thr Glu Ala Trp Arg Leu
230 235 240
His Gln Lys His Val Phe Val Leu Ser G1u Ala Gly Lys Pro Val
245 250 255
Tyr Ser Arg Tyr Gly Ser Glu Glu Ala Leu Ser Ser Thr Met Gly
260 265 270
Val Met Val Ala Pro Gly Val Leu Pro Gly Gly Arg G1n G1u Arg
275 280 285
His Pro Leu His Pro Cys Arg Trp Leu Gln Gly Ser Ile Arg Ala
290 295 300
Pro Glu Pro Ala Gly Ala Ser G1y Gly Gly Ser Tyr Ala Ala Val
305 310 315
Gly Thr Arg Ala Gly Ala Gly Ala Ala Leu His Leu Leu Pro Asp
320 325 330
Pro Lys Pro Ser Tyr Arg Cys A1a Ala Ala Ala Thr Ser Ser Ser
335 340 345
Arg Ser Arg Thr Met Ile Cys Gly Ala Tyr Ser Arg Ala Gln Ser
350 355 360
Ala Ser Pro Asp Asn Leu Leu Gln Leu Met Ala Arg Asp Pro Ser
365 370 375
Phe Leu Met Gly Ala Ala Arg Cys Leu Pro Leu Ala Ala Ala Val
380 385 390
Arg Asp Thr Val Ser Ala Ser Leu Gln Gln Ala Arg Ala Arg Ser
395 400 405
Leu Val Phe Ser Ile Leu Leu Gly Pro Gln Pro Ala Arg Gly Thr
94/ 104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
410 415 420
Arg Ala Pro Lys G1y Pro Ile Ser Ala Pro His Arg Pro Ala Pro
425 430 435
Ala Leu Gln Pro His
440
<210> 142
<211> 386
<212> PRT
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:230711.1.orf3:2000MAY01
<400> 142
Pro Ala Arg Ser Tyr Pro Gly Pro Ser Arg His Leu Glu Thr Pro
1 5 10 15
Pro Ser Cys Cys Thr Phe Val Gly Asp Leu Ala Ala Met Ala Trp
20 25 30
Gly Thr Gly Thr Leu Leu Ser Arg Arg Cys Pro Gly Gln Cys Val
35 40 45
Val Ser Gly Leu Leu Gln Gly Met Met Gly Leu Leu Gly Ser Pro
50 55 60
Gly His Val Phe Pro His Cys Gly Pro Leu Val Leu Ala Pro Ser
65 70 75
Leu Val Val Ala Gly Leu Ser Ala His Arg Glu Val Ala Gln Phe
80 85 90
Cys Phe Thr His Trp Gly Leu Ala Leu Leu Val Ile Leu Leu Met
95 100 105
Val Val Cys Ser G1n His Leu Gly Ser Cys Gln Phe His Val Cys
110 115 120
Pro Trp Arg Arg Ala Ser Thr Ser Ser Thr His Thr Pro Leu Pro
125 130 135
Val Phe Arg Leu Pro Phe Gly Met Cys Gly Ser Gly Gln Gly Ser
140 145 150
Arg Gly Gln Lys Gly Trp Pro Gly Val Leu Thr Pro Ser Pro Thr
155 160 165
Phe Trp Leu Leu Ser Thr Pro Ala Arg Leu Ala Gln Lys Val Leu
170 175 180
Gly Glu Glu Phe Phe Ser Gln Ser Arg Pro Ser Gly Ala Asp Pro
185 190 195
Ser Gly Leu Cys Val Asp Cys Phe Cys Leu Cys Gly Ile Gln Cys
200 205 210
Tyr Pro Pro Gly Thr Val Cys Pro His Gln Gly Thr Met Asp Ile
215 220 225
Gly Cys Leu Thr Thr Gly Glu Trp Lys Leu Ala Phe Ala Asp Ala
230 235 240
Gln Ser Ser Trp Leu Gln A1a Phe Ser Met Ala Leu Ala Ser Leu
245 250 255
Pro Pro Va1 Ser Leu Gly Leu Leu Met Pro Cys Val Ala Gly Cys
260 265 270
Trp His Leu Ala Ser Pro Gln Pro Ser Asn Met Pro Ala Sex Arg
275 280 285
Arg Ala Glu Pro Trp Arg Gly Trp Asp Ser Val Ala Gly Pro G1y
290 295 300
Cys Trp Glu Gly Pro Met Gly Thr Ala Ser Ser Phe Pro Gln Arg
305 310 315
Gly G1n Ser Gly Ser Ile Ser Arg Leu Asp Leu Ser Lys Trp Ala
320 325 330
His Tyr Ser Gly Ala Thr Leu Ala Trp Gly Tyr Gly Leu Sex Pro
335 340 345
Gln Val Trp Leu Ser Ser Ser Pro Pro Ser His Cys Leu Leu Ile
350 355 360
Gly Gly Val His Gly Gly Arg Thr Gln Ala Cys Gly Leu Cys Leu
365 370 375
Ala Gly Phe Ser G1n Leu Leu Pro Gly Met Thr
95/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
380 385
<210> 143
<211> 198
<212> PRT
<213> Homo sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:040338.2.orf1:2000MAY01
<400> 143
His His Trp Leu Leu Glu Lys Asp Pro Val Ser Arg Pro Gly Thr
1 5 10 15
Ala Gly Ala Ser Ser Ser Thr Lys Gly Lys Leu Pro Arg Arg Thr
20 25 30
Thr Thr Arg Pro Trp Ala Ala Phe Thr Ser Leu Pro Ser Ala Phe
35 40 45
Ser Thr Ala Thr Cys Pro Arg Glu Ser Val Pro Gln I1e Pro Pro
50 55 60
Ala Arg Arg Gly Ser Arg Ala Arg Pro Pro Pro Gly Val Lys Ser
65 70 75
Ala A1a Cys Cys Cys Pro Leu Cys Ser Cys Cys Cys Cys Cys Ser
80 85 90
Gly Thr Ala Arg Ser Ser Thr Gly Pro Phe Phe Ser Pro Asp Arg
95 100 105
His Ser Gly Pro Gly Arg Leu His Pro Ala Pro Gln Ser Pro Gly
110 115 120
Leu Cys His Val Pro Pro Val Val Pro Pro Arg Ala Leu Gly Ser
125 130 135
Val Ala Gly Pro Ser Gly Pro Leu Leu Pro Ala Pro Arg Arg G1u
140 145 150
Leu Leu Pro Ala Gln Ala Arg Leu Phe Gly Leu Ala Ser Ser Arg
155 160 165
Arg Pro Gly Ala Gln Pro Cys Ala Ala Arg Gly Leu Pro Gly Leu
170 175 180
Ala Glu Ala Pro Pro Cys Asp Arg Arg Gly Ser Gly Pro Pro Pro
185 190 195
Gly Gly Cys
<210> 144
<211> 116
<212> PRT
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:399174.2.orf2:2000MAY01
<400> 144
Pro Leu Lys Gly Asn Asp Ile Val Thr Gly Arg Gln Glu Pro Arg
1 5 10 15
Gly Gly Ser Pro Val Ser Ser Glu Ser Gln Arg His Leu Ala Phe
20 25 30
Pro Leu Gly Asp Gly Arg Trp Ala Val Ser Ser Gly Glu Arg Phe
35 40 45
Thr Gln Gly Leu Tyr Gly Gly Val Gly Lys Arg His Phe Asn Val
50 55 60
Lys Thr Asn Glu Leu Ala Ser Leu Glu Ile Cys Pro Cys Leu G1n
65 70 75
Asp Leu Ser Gly Pro Gly Pro Trp Leu Leu Pro Trp Lys Leu Pro
80 85 90
Val Gln Thr Ser Ser Leu Ser Pro Leu Glu Gly Arg Gln Arg Gly
95 100 105
Val Cys Glu Leu Asp Val Leu Ser Cys Leu Ser
110 115
96/104
CA 02418496 2003-02-04
WO 01/62918 PCT/USO1/03465
<210> 145
<211> 307
<212> PRT
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:197275.5.orf2:2000MAY01
<400> 145
Ser Ala Leu Gln His_Leu Glu Ser Leu Gln Lys Gln Tyr Leu Phe
1 5 10 15
Val Ser Asn Lys Thr Gly Thr Leu His Glu Ala Cys Glu Gln Leu
20 25 30
Leu Lys Glu Gln Ser Glu Leu Val Asp Leu Ala Glu Asn I1e Gln
35 40 45
Gln Lys Leu Ser Tyr~Phe Asn Glu Leu Glu Thr Ile Asn Thr Lys
50 55 60
Leu Asn Ser Pro Thr Leu Ser Val Asn Ser Asp Gly Phe Ile Pro
65 70 75
Met Leu Ala Lys Leu Asp Asp Cys Ile Thr Tyr Ile Ser Ser His
80 85 90
Pro Asn Phe Lys Asp Tyr Pro Ile Tyr Leu Leu Lys Phe Lys Gln
95 100 105
Cys Leu Ser Lys Ala Leu His Leu Met Lys Thr Tyr Thr Val Asn
110 115 120
Thr Leu Gln Thr Leu Thr Ser Gln Leu Leu Lys Arg Asp Pro Ser
125 130 135
Ser Val Pro Asn Ala Asp Asn Ala Phe Thr Leu Phe Tyr Val Lys
140 145 150
Phe Arg Ala Ala A1a Pro Lys Val Arg Thr Leu Ile Glu Gln Ile
155 160 165
Glu Leu Arg Ser Glu Lys Tle Pro Glu Tyr Gln Gln Leu Leu Asn
170 175 180
Asp Ile His Gln Cys Tyr Leu Asp Gln Arg Glu Leu Leu Leu Gly
185 190 195
Pro Ser Ile Ala Cys Thr Val A1a Glu Leu Thr Ser Gln Asn Asn
200 205 210
Arg Asp His Cys A1a Leu Va1 Arg Ser Gly Cys Ala Phe Met Val
215 220 225
His Val Cys Gln Asp Glu His Gln Leu Tyr Asn Glu Phe Phe Thr
230 235 240
Lys Pro Thr Ser Lys Leu Asp Glu Leu Leu Glu Lys Leu Cys Val
245 250 255
Ser Leu Tyr Asp Val Phe Arg Pro Leu I1e Ile His Val Ile His
260 265 270
Leu G1u Thr Leu Ser Glu Leu Cys Gly Ile Leu Lys Asn Glu Val
275 280 285
Leu Lys Ile Met Cys Arg Thr Met Leu Ser Asn Trp Gly His Pro
290 295 300
G1n Leu Glu Ser Ser Arg Cys
305
<210> 146
<211> 85
<212> PRT
<213> Homo Sapiens
<220>
<221> misc_feature
<223> Incyte ID No: LI:336872.1.orf2:2000MAY01
<400> 146
Ser Ser Thr Gly Leu Asp Leu Leu Val Lys Ser
Leu His Ser Lys
1 5 10 15
Ala Tyr His Ser Lys Ile Ser Arg Arg Arg Leu
Val Pro Cys Thr
20 25 30
97/104
DEMANDE OU BREVET VOLUMINEUX
LA PRESENTE PARTIE DE CETTE DEMANDE OU CE BREVET COMPREND
PLUS D'UN TOME.
CECI EST LE TOME 1 DE 2
~~ TTENANT LES PAGES 1 A 224
NOTE : Pour les tomes additionels, veuillez contacter 1e Bureau canadien des
brevets
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THIS IS VOLUME 1 OF 2
CONTAINING PAGES 1 TO 224
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NOTE POUR LE TOME / VOLUME NOTE:
