Note: Descriptions are shown in the official language in which they were submitted.
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SPECIFICATION
Human Immunoglobulin VH Gene Segments and DNA Fragments
Containing the Same
TECHNICAL FIELD
This invention relates to novel human immunoglobulin
VH gene segments and DNA fragments containing the same.
The segments and DNA fragments according to the present
invention are useful for producing human antibodies using
a mammalian host by a genetic engineering process.
BACKGROUND ART
Immunoglobulins are composed of the L chains and H
chains, each of which consists of a variable region (V
region) and a constant region (C regs.on) that has a
structure common to immunoglobulin molecules.. What
determines the antigenic specificity of an antibody is
the V region. The V region of the H chain is encoded by
V, D (diversity) and J (joining) genes (The gene of the H
chain is expressed by placing a suffix "H", like "VH").
One of the important reasons why the V regions of
immunoglobulins are highly diverse and can provide
antibodies which specifically binds to infinite number of
antigens is the rearrangement of V, D and J genes. That
is, there are a plurality of V genes, D genes and J
genes, respectively and they are randomly combined in
somatic cells to form a gene encoding a single mRNA.
Since the combination is randomly selected, wide variety
of immunoglobuiin V regions are provided.
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On the other hand., antibodies currently employed for
therapies of various diseases are those originated from
animals other than human, such as mouse. However, if
these antibodies are administered to human, since the
antibodies are of exogenous origin, an immunological
response occurs in the human body to present allergy and
to neutralize the, antibodies. To overcome this problem,
it is desired to use antibodies originated from human for
the therapies 'for human. Further, if a human antibody is
industrially produced using human as the host and using a
human-originated antigen, a problem of immunological
tolerance is brought about, so that this approach
employing the known method is very difficult. Thus, the
production of human immunoglobuli:ns by a genetic
engineering process using an animal as a host is now
being developed '(for example, Japanese Laid-open PCT
Application (Kohyo) No. 4-504365; Proc. Natl. Acad. Sci.
USA, Vol. 86, pp.5898-5902, August 1989; Proc. Natl.
Acad. Sci. USA, Vol. 87, pp.5109-5113, July 1990;
Genomics 8, 742-750 {1991)). However, in the
conventional methods in which human immunoglobulin genes
are expressed in host animals other than human, there is
a problem that the number of human VH segments provided
for the genetic recombination is very small, so that the
diversity of the expressed human immunoglobulins is
limited. Even if only one VH segment is recombined, the
diversity of the ~immunoglobulin is assured to some degree
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because of the combination with D and J genes. However,
as mentioned above, since the diversity of
immunoglobulins is determined by the rearrangement
(random combination) of V gene segments, the more the
human VH segments, recombined, the higher the diversity of
the immunoglobulins expressed. If the diversity of
immunoglobulins is increased, not only antibodies against
a number of antigens can be formed, but also the
possibility of forming an antibody having a high
specificity to a given antigen is promoted. Therefore,
it is important for therapies and diagnoses to recombine
VH segments as many as possible.
DISCLOSURE OF THE INVENTION
Accordingly, an object of the present invention is
to provide a DNA fragment comprising a plurality of human
immunoglobulin VH segments. Another object of the
present invention is to provide a novel human
immunoglobulin VH segments.
The present inventors intensively studied and succeed
in determining human immunoglobulin H chain V region gene
segments having a size of about 800 kb and in determining
DNA sequences of 64 human VH segments contained therein.
This made it possible to provide this DNA fragment of 800
kb and various DNA fragments contained therein, thereby
completing the present invention.
That is, the present invention provides a DNA
fragment having a size of about 800 kbp and having the
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structure shown in Fig.. 1. It should be noted that in
Fig. 1, the 64 human VH segments are those having DNA
sequences shown in Sequence ID Nos. l, 2, ... 63, and 64,
respectively, in the order from downstream (i.e., from
the side near the Jg gene).
The present invention also provides DNA fragments
containing at least two consecutive functional human VH
segments which are contained in said DNA fragment of
about 800 kb according to the present invention.
The present invention further provides DNA fragments
Y20, Y103, Y21, Y6, Y-24, M131, M118, M84 and 3-31, which
have been deposited.
The present invention still further provides DNA
fragments consisting essentially of at least two optional
DNA fragments linked in an optional order, each of which
contains at least two consecutive functional human VH
segments contained in the DNA fragment of about 800 kb
according to the present invention.
The present invention still further provides DNA
fragments consisting essentially of at least two DNA.
fragments selected from the group consisting of DNA
fragments Y20,~Y103, Y21, Y6, Y-24, M131, M118, M84 and
3-31 which have been deposited, which are linked in an
optional order.
The present invention still further provides novel
human immunoglobulin VH segments having DNA sequences
shown in Sequence ID Nos. f, 7, 8, 9, 10, 11, 12, 13, 14,
_5_
15, 16, 17, 18; 19, 20, 21, 22, 23, 24, 25, 26, 27, 29,
30, 31, 32, 33, 34, 35; 36, 37, 38, 40, 41, 42, 43, 44,
45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 63 and 64,
respectively.
By the present invention, novel human immunoglobulin
VH segments and DNA fragments containing the same were
provided. The DNA fragment of about 800 kb according to
the present invention contains as many. as 64 human
immunoglobulin VH segments. Thus, by producing human
immunoglobulins by a host animal using this DNA fragment,
the diversity of the produced human immunoglobulin is
largely increased, when compared with the conventional
methods.
BRIEF DESCRIPTION OF THE DRAWINGS
Fig. 1 shows a genetic map of the DNA fragment of about
0.8 Mb according to the present invention:
. Fig. 2 shows the results of Southern hybridization
of a representative DNA inserted in YAC.
Fig..3A shows the results of Southern hybridization
of the fragment digested with restriction enzymes Mlu I
and Not I.
Fig. 3B shows a physical map of a YAC clone
constructed based on the results shown in Fig. 3A.
Fig. 4 shows a genetic map of YAC clone Y6.
BEST MODE FOR CARRYING OUT THE INVENTION
The present inventors prepared a library by
inserting the DNA partially digested with Eco RI into YAC
~:~~2~'~'~
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by the method detailed in the examples hereinbelow
described, which DNA was originated from human
lymphoblastoid cell line transformed by EB virus, and
succeeded in determining the structure of human VH gene
region having a size~of.about 800 kbp using the above-
mentioned library. The structure is shown in Fig. 1. In
Fig. 1, the genetic map is shown on the four thick solid
lines. The right side of each solid line~is .the 3' side
and the left end of the upper most solid line continues
to the right end of the second solid line. In the DNA
fragment shown in Fig. 1, there exist C genes, JH genes
and D genes in the order mentioned from the 3' end.
Subsequent to the D genes, there are 64 vH segments. The
DNA sequences of~all of these 64 VH segments have been.
determined as described in the examples below, and
Sequence ID Nos. ~1, 2, ... 63, 64 were assigned to~the 64
VH segments in the order from downstream. Among these VH
segments, the functional VH segments which are thought to
encode polypeptides are indicated by solid rectangles.
On the other hand, those which have the general features
of the known Vg segments but do not presently encode
polypeptides because of the termination codons contained
therein, that is, pseudo VH segments are indicated by
hollow rectangles. Immediately below the genetic map,
restriction maps by Eco RI and Hind III are shown. The
restriction.sites are indicated by short perpendicular
lines. The short lines to which ends circles are
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attached are those whose order is not determined, and the
dotted boxes indicate the regions in which Eco RI sites have
not been determined. In Fig. 1, the symbol which looks like
"Y" indicates the sites at which two restriction sites are
close. In Fig. 1, restriction sites of Mlu I are indicated by
hollow triangles and restriction sites of Not I are indicated
by solid triangles. The fragments inserted in the clones
employed for determining the structure of the DNA fragment are
shown thereunder. The structure of the 3' side farther than
the 3' end shown in Fig. 1 is known and described in Ravetch,
J.V. et al., (1981) Cell, Vol. 27, pp. 583-591.
Among the DNA fragments inserted in the clones shown
in Fig. 1, the yeasts containing Y20, Y103, Y21, Y6 and Y24
inserted in YAC have been deposited with National Institute of
Bioscience and Human-Technology, Agency of Industrial Science
and Technology of 1-3, Higashi 1-chome, Tsukuba-shi, Ibaraki,
305, Japan, under Accession Numbers FERM BP-4272, FERM BP-4275,
FERM BP-4273, FERM BP-4271 and FERM BP-4274, respectively. The
E. coli cells containing M131, M118, M84 and 3-31,
respectively, inserted in cosmids have been deposited with
National Institute of Bioscience and Human-Technology, Agency
of Industrial Science and Technology of 1-3, Higashi 1-chome,
Tsukuba-shi, Ibaraki, 305, Japan, under Accession Numbers FERM
BP-4279, FERM BP-4278, FERM BP-4277 and FERM BP-4276,
respectively.
The DNA fragment having a size of about 800 kbp shown
in Fig. 1 can be prepared by linking these
_g-
deposited DNA fragments by known~methods. That is, a DNA
fragment A and a DNA fragment B.whose DNA sequence at its
terminal region overlaps with the DNA sequence of the
terminal region of DNA fragment A (i.e., the~DNA sequence
of the 3' region of DNA fragment A is identical to the
DNA sequence of the 5' region of DNA fragment B) can be
easily ligated by a method exploiting genetic
recombination in the yeast.cells. More particularly, DNA
fragments A and B are inserted in separate YAC vectors,
and the resulting recombinant YAC vectors. are introduced
in separate mating type yeast cells, respectively. The
resulting yeast cells are then fused. By this, genetic
recombination occurs in the yeast host to form a YAC
having a DNA fragment in which DNA fragment A and DNA
fragment B are ligated, Which has only one overlapping
region located at the terminal regions of DNA fragments A
and B. The thus formed recombinant YAC can easily be
selected using the auxotrophy encoded in the YAC as a
marker. This method is well-known in the art, and is
described in, for example, Japanese Laid-open PCT
Application (ICohyo) No. 4-504365; Proc. Natl. Acad. Sci.
USA, Vol. 87, pp.9913-9917, December 1990; Science Vol.
250, p.94, Proc. Natl. Acad. Sci. USA, Vol. 89, pp.5296-
5300, June 1992; and Nucleic Acid Research, Vol. 20, No..
12, pp.3135-3138. Since the terminal regions of each of
the deposited 8 DNA fragments overlap the respective
terminal regions of the adjacent DNA fragments, they can
~~.~~~'~''~
_g-
be ligated sequentially by the method described above.
Although DNA fragments 3-31, M84, M118 and M-131 are
cloned in cosmid vectors,.they can be kept in an
artificial.chromosome in the yeast cell by cutting the
recombinant cosmid with a restriction enzyme having a
restriction site only in the cosmid vector, and ligating
a YAC vector to the ends of the digested recombinant
cosmid vector. Further, by the above-described method,
the digested recombinant vector can be ligated to a YAC
clone of other regions. It should be noted that even if
the above-mentioned 9 deposited fragments are ligated, a
gap of about 4 kb still remains. A DNA fragment which
fills the gap can be easily prepared by the method
described below. That is, as shown in Fig. 1, since the
Hind IIh fragment including the region of the gap is
relatively large, this Hind III fragment can be obtained
by completely digesting human genome by Hind III,
electrophoresing the resultant, selecting~DNA fragments
having sizes of about 15 kb, detecting the desired
fragment with a probe, and recovering the detected-
desired fragment. The probe used here can be isolated as
follows. That is, the DNA fragments located at the both
ends of the gap are subcloned using a plasmid and DNA
fragments which do not contain a repetitive sequence are
prepared therefrom. The thus obtained fragments are then
used for screening of the library. Only those detected
by the probes which are the DNA fragments at both ends of
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the. gap are isolated.
As.described above, the DNA.fragment of about 800
kbp shown in Fig. 1 was provided according to the present
invention. The fragments consisting of the DNA region
included in this DNA fragment can also be used for
producing human immunoglobulin by a genetic engineering
method. More particularly, to increase the diversity of
human immunoglobulin produced by a genetic engineering
method, it is preferred to incorporate a fragment
containing human VH segments as many as possible.
However, if the fragment contains at least two human VH
segments, the diversity to some degree is given during
rearrangement, so that the fragment can be employed.
Thus, DNA fragments consisting of a region containing at
least two consecutive functional VH segments, which
region is contained in the DNA of about 800 kb shown in
Fig. l can be employed and are useful. The number of the
functional VH segments contained in.such DNA fragments is
at least two, and is preferably not less than 6. The
more the number of the functional VH segments, the higher
the diversity of the human immunoglobulin produced, so
that the more pref erred . Thus , the preference i s
increased when the number of the functional VH segments
is 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,
21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32 and 33,
with the order mentioned. Among these fragments,
although those having large molecular weights are cloned
2~~~~'~'~
into YAC vector, small fragments having a size of about
not more than 50 kb are not.necessarily cloned into YAC
vector, but can be. cloned into cosmid vectors and plasmid
vectors.
Such DNA fragments can be prepared since the
information disclosed.in Fig. 1 and Sequence ID Nos. 1 -
64 is available: That is, for example,.a DNA fragment
containing not less than two functional VH segments can
be.obtained by partially digesting human genome with an
appropriate restriction enzyme such as Eco RI or Hind
III, separating the resulting fragments by
electrophoresis, and selecting a DNA fragment containing
not less than two desired functional VH segments using
not~less than two probes each of which hybridizes with
one of the not less than two desired functional VH
segments. Alternatively, amplification by PCR may be
employed in place of the detection by the probes. In
this case, since the entire DNA sequences of the
functional VH segments are known, the DNA sequences of
the primers which should be used are also known, so that
the PCR can be carried out easily.
The present invention further provides DNA fragments
consisting essentially of optional DNA fragments each of
which contains not less than two functional VH segments
which are ligated in optional orders. That is, by
ligating a plurality of the DNA fragments each containing.
not less than two functional VH segments, the number of
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VH segments in the DNA fragment can be increased when
compared. with the case. where only one such DNA fragment
containing not less thin two VH segments is used, so that
the diversity of the produced immunoglobulin can be
increased accordingly. The DNA fragments are not
necessarily consecutive, and optional DNA fragments may
be ligated in an optional order. In cases where there is
no overlapping region between two,.DNA fragments to be
ligated, the above-described method for ligating the DNA
fragments having an overlapping region cannot be applied.
However, two DNA fragments having no overlapping region
can also be ligated by the method as follows.
The left arm~vector region and the right arm vector
region of a YAC clone containing not less than two
functional VH segments are recovered by the method of
Hermanson et al (1991) (Nucleic Acids. Res.,l9; 4943-
4948). A plasmid (pICL) which has a sequence homologous
with the ampicillin-resistant marker (AMP) in the left
arm vector region of the YAC, a marker (Lys) which
reverse the lysine auxotrophy to the wild type, and a
multiple cloning.site immediately downstream Lys; and a
plasmid (PLUS) which has a sequence homologous with YAC4
region in the right arm vector region of the YAC, the
above-mentioned Lys, a kanamycin-resistant marker (KAN),
and a multiple cloning site immediately downstream the
KAN are linearized and then introduced into yeast cells
containing YAC by a conventional method. The plasmids
2~.~~~'~'~
pICL and pLUS cause recombination in the yeast cells at
an appropriate frequency, thereby being recombined with
the left arm vector region and the right arm vector
region of the YAC. The yeast cells carrying such a YAC
are selected by using an appropriate selection medium and
the YAC in the selected yeast cells is then cut with. an
appropriate restriction enzyme which has a restriction
sites ~n the multiple cloning.sites of the above-
mentioned plasmids: By the operation described above,
DNA fragments containing the left end or the right end of
the DNA fragment originated from human contained in the
YAC are recovered as plasmids. After amplifying the thus
obtained plasmids in E. coli by a conventional method,
the recovered plasmids are digested with a restriction
enzyme and then ligated by ligase. The thus ligated DNA
fragment is then ligated to the left arm vector region or
the right arm vector region of the YAC and introduced
into yeast cells carrying the YAC. These YAC vectors
causes recombination at a certain frequency between the
intrinsic left arm or.right arm vector regions and the
left end or right end region of the DNA fragment
originated from human. By selecting the resulting
recombinant vectors, a YAC clone containing a DNA
fragment originated from human, which left end is ligated
to the right end of another DNA fragment originated from
human, and a YAC clone containing a DNA fragment
originated from human, which right end is ligated to the
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left end of another DNA fragment originated from human
are recovered. Since these YAC clones have the structure
in which the left end or the right end of a DNA
originated from human is ligated to the right end or the
left end of another DNA originated from human, they can
be recombined with a YAC clone having a sequence in the
ligated DNA fragments by the method described above.
Further, by optionally ligating the above-described
eight actually deposited DNA fragments in an optional
order, a large fragment containing a number of VH
segments can be prepared.
By the present invention, the DNA sequences of the
64 VH segments contained in the fragment of about 800 kbp
shown in Fig. 1 were determined. As described in detail
in the examples below, among these, 50 VH segments are
novel segments which have DNA sequences that have not
hitherto been known. These novel human immunoglobulin VH
segments include pseudo segments which do.not encode a
polypeptide. Even a pseudo segment has an utility
because it may function as a donor of gene conversion in
the somatic cell level.
The fiuman.immunoglobulin VH segments and the DNA
fragments containing the same according to the present
invention can be used for producing human immunoglobulins
in a mammalian host as described in, for example,
Japanese Laid-open PCT Application (Rohyo) No. 4-504365.
Examples
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The present invention will now be described in more
detail by way of examples thereof. It should be noted
that the present invention is not limited to the
following examples.
Example 1 ~ Determination of Structure of DNA Fragment of
about 8 0 0. kbp .
(1) Library Used for Screening
The human YAC library screened was constructed from
DNA of an Epstein-Barr virus-transformed human
lymphoblastoid cell line CGM1 (T. Imai and M.V. Olson,
genomics, 8, 297-303 (1990)). Eco RI partial digests of
CGM1 DNA were ligated to pYAC4 vector (D. Burke and M.V.
Olson, in "Guide to Yeast Genetics and Molecular Biology"
(C.~Guthrie arid G.R. Fink, eds), p.253, Academic Press,
Orlando, 1991), and introduced into AB1380 yeast host
strain (D. Burke and M.V. Olson, in "Guide to Yeast
Genetics and Molecular Biology" (C. Guthrie and G.R.
Fink, eds), p.253, Academic~Press, Orlando, 1991). The
library consisted of 15,000 independent clones with mean
YAC size of about 360 kb. The library thus contained the
equivalent of approximately 1.8 haploid human genomes.
DNA rearrangement in immunoglobulin H chain (IgFi) locus
was first checked by Southern hybridization.using the
human D and Jg probes. The result showed that an allele
kept germline configuration while the other was VDJ
rearranged.
(2) Primers~used for PCR-based Screening
21~~~ ~'~
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For PCR-based screening of human VH YAC clones,
oligonucleotide primers for VH-LII and VH-I families, the
first and the second largest VH families, were
synthesized. VH region segments of immunoglobulins
contain two hypervariable regions (CDR1 and CDR2) and
three framework regions (FR1, FR2 and FR3) (E.A. Rabat et
al., Sequences of Proteins of Immunological Interest.,
Fifth edition, NIH publications, Washington D.C. (1991)).
Nucleotide sequences of the framework regions are highly
conserved within the same family, suggesting the
possibility of oligonucleotide synthesis is for consensus
primers corresponding to the framework regions. For this
purpose, nucleotide sequences of FR1, FR2 and~FR3 regions
in all the known VH sequences were aligned for
comparison. Nucleotide sequences corresponding to the
first 8 amino acid residues of the FR1 region had
extremely high conservation not only within the same
family but also between VH-I and VH-III families, which
enabled the synthesis of a.forward primer F-univ common
for the two families as shown in Table 1. Sequences for
family-specific reverse primers Were independently chosen
from conserved sequences in the FR2 region so that 3'-
half of .the primer sequence has 100$ identity~to known VH
segments and, in particular, 3'-most nucleotide
corresponds to the first letter of the highly
conserved/invariant amino acid residues. More
particularly, F-univ and I-R, and F-univ and III-R were
._
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used as primers for the screening. The-DNA sequences of
the primers are shown in Table 1.
(3) Optimal PCR Condition Check ,
Analytical experiments were carried out to determine
the optimal condition for specific amplification. A
reaction mixture (5 ul) was prepared in accordance with
the protocol recommended by Perkin-Elmer/Cetus. Thermal
cycling was performed using a DNA Thermal Cycler
(Perkin-Elmer/Cetus). Reactions were carried out using
25 ng of template human DNA under various annealing
temperatures (55°C, 58°C, 60°C and 62°C) and
cycles (25,
30, and 35 cycles).. As a result, it was found that the
reaction under high annealing temperature, namely 94°C, 1
minute - 62°C, 2 minutes - 72°C, 2 minutes, regardless of
cycles, produced specific amplification in human DNA
sample~but not in.yeast strain AB1380 DNA. PCR under low
annealing temperature sometimes gave false positive
signals in negative control and therefore could not be
used. Thus, the PCR was carried out under the above-
described conditions.
(4) Polymerase Chain Reaction (PCR)
PCR-based first screening was performed using
synthesized oligonucleotide primers described above
against seven multi-filter DNA pools each of which
represents the.DNA from 1920 colonies (20 x.96-well) as
described (E. D. Green and M.v. Olson, Proc. Natl. Acad.
Sci. USA, 87, 1213-1217 (1990)). Positive multi-filter
2~~2~ ~'~
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pools were divided into five pools each of which consists
of 384 colonies (4 x 96-well), and further screened by
the same procedure. 25 ng.each of YAC pool.DNAs Were
used for reaction. DNA of CGM1 whose DNA.was used to
construct the YAC library, and of the yeast strain AB1380
were included during the PCR analysis as positive and
negative controls, respectively. After the
amplification, the entire sample was analyzed by
electrophoresis in 10% polyacrylamide gels containing 15%
glycerol and visualized by ethidium bromide staining.
(5) Colony Hybridization
After PCR-based first and second screening, the
location of the positive. clone within the 384-clone array
was established by conventional colony hybridization.
The nylon filters consisting of 384 YAC clones were
prepared by a known method (D. Burke and M.V. Olson, in
"Guide to Yeast Genetics and Molecular Biology" (C.
Guthrie and G.R. Fink, eds), p.253, Academic Press,
Orlando., 1991). V266BL (Y~ Nishida, et al., Proc. Natl.
Acad. Sci. USA, 79, 3833-3837 (1992)) and VHBV (M.
Rodaira et al., J. Mol. Biol., 190, 529-541(1986)) were
used for probes representative for human VH-I and VH-III
families, respectively. These probes were labeled (5 x
105 cpm) with 32P-dCTP using Oligolabeling Rit
(Pharmacia) and subjected to colony hybridization
according to standard procedure (D. Burke, et al.,
supra). After the hybridization fox 12 hours at 65°C,
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filters were' washed twice with 2xSSC (lxSSC is 0.15 M
NaCl-15 mM sodium citrate) for 10 minutes at room
temperature, then twice with 0.2xSSC-0.1% SDS for 30
minutes at 65°C. Filters were exposed overnight and
corresponding positive YAC clones were picked up for
further characterization.
(6) Insert Check by Colony PCR
To test the presence of specific DNA sequence in
isolated YACs, simple and rapid rescreening of colony-
purified clones was carried out by using PCR without. DNA
purification (E. D. Green and M.V. Olson, Proc. Natl.
Acad. Sci. USA, 87, 1213-1217 (1990)). That is, the
positive yeast clones were streaked onto AFiC plates and
grown. Four each of single colonies from each clone were
transferred by toothpick into 5 ~cl of PCR mixture
described above. PCR and following gel electrophoresis
were performed for identification of the amplified bands
under.the same condition as that used for screening. In
most of'the clones, all of the four colonies gave rise to
specific amplification of DNA fragments.
(7) Sizing of YAC Clones Using PFGE
Many researchers claimed that some YACs are clonally
unstable due to intrachromosomal rearrangement during the
growth in culture resulting in size variation of the
human DNA insert. This artifact is considered to be
often mediated by repetitive sequences or tandem repeat
of homologous DNA sequences in the insert DNA. Since VH
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locus contains a number of homologous DNA fragments
consisting of VR gene segments and their flanking
regions, such kind of rearrangement can take place at
considerable frequency. An additional problem is the
presence of single yeast containing more than one insert
YACs. In order to exclude the artifact clones for
subsequent analysis and to identify YAC clones with.
multiple insert, the sizes of the YAC clones were first
determined by pulse field gel electrophoresis (PFGE).
The same four VH-positive single colonies checked by PCR
were selected from 17 colonies originating from a single
well, and miniprepared from 5 ml culture in AHC medium to
give Iow-gelling temperature agarose blocks by~a known
method (D. Burke et al.., su ra). Appropriate sized piece
of agarose block was used for 'sizing the YACs by~PFGE
with a Pulsaphor*(Pharmacia) or a Crossfield*(ATTO,
Tokyo, Japan) gel electrophoresis apparatus at 60 second
pulse time. Concatamerized lambda DNA was also loaded as
a size standard. After the electrophoresis, DNAs were
transferred to nitrocellulose filter and subjected to
Southern hybridization using pBR322 plasmid as a probe.
Typical result is shown in Fig. 2. AlI of the four
colonies selected from each of clones Y21, Y22 and Y24
having DNA inserts with a size of 300 kb, 330 kb and 310
kb, respectively exhibited the same size, so that they
seemed to have no recombination. On the other hand,
since four colonies selected from clone Y23 had DNA
*Trade-mark
. . _.
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inserts with different sizes, the insert of the clone Y23
looked rather unstable due to frequent recombination.
Therefore, the colony which did not cause recombination
was selected for the subsequent analysis. All but 3
clones including clone Y23 of 17 VH-carrying YAC clones
including the analyzed VH~displayed instability of human
inserts. Subsequent analysis revealed that such
recombination took place regardless of the number of VH
segments in the insert DNA, indicating some other factors
might be involved in homologous recombination. From 14
stable YAC clones among the 17 YAC clones containing VH,
Y20, Y103, Y21, Y6 and Y24 were selected and used for the
subsequent physical mapping.
(8) Physical Mapping of YAC Clones with Rare Site
Endonucleases
Gel blocks were prepared from the YAC clones after
sizing and were used for physical map construction by
PFGE. In general, detailed physical map using several
enzymes might be required for long-range YAC analysis.
In this example, however, only two rare-site restriction
enzymes (i.e., restriction enzymes whose restriction
sites occur relatively rarely), namely Not I and Mlu _I,
were used for overlapping analysis of the YAC clones
mainly by the~following two reasons: 1) VH-carrying YAC
clones can be arrayed.with several other information such
as comparison of the'size or the pattern of the fragments
hybridized with VH probes or non-repetitive probes
~~~z~~~
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isolated from VH-carrying cosmid clones, 2) it is
necessary to subclone the YACs into cosmids fox detailed
structural analysis including construction of physical
maps using ordinary restriction enzymes.
Gel blocks digested in completion with Not I.or Mlu
I were electrophoresed with a PFGE apparatus using.a
pulse time of 30 to 60 seconds depending on the length of
YAC. Mixtures of lambda phage DNA, its Xho I digests and
Hind III digests were also used as low molecular weight
size markers. Southern filters were first hybridized .
with total human large molecular. DNAs for detection of
all restricted fragments. The sizes of detected bands
were summed up to fit the length of undigested yAC
insert. Filters were hybridized consecutively with
pBR322 DNA probes corresponding to each of the pYAC4
arms. A P'vu II and Bam HI double digest of pBR322
results in a 2.67-kb and 1.69-kb fragments which
hybridize specifically to the left (trp) and the right
(ura) end of YACs, respectively. Filters were also
hybridized with six VH family-specific probes for the
presence of VH segments in digested DNA fragments.
Origin of VH family-specific probes for VH_II, VH_IV~
VH-V and VH-VI families, respectively, are; VCE-1 (N.
Takahashi et al., Proc. Natl. Acad. Sci. USA, 81, 5194-
5198 (1984)), V71-2 (R~H. Lee et al., J. Mol. Biol., 195,
761-768 (1987)), 5-1R1 (J.E. Berman~et al., EMBO J. 7,
727-1051 (1988) and 6-1R1 (J.E. Berman et.al., EMBO J. 7,
=23-
?27-1051 (1988)).
In order to array Not I and Mlu I fragments detected
by the complete digestion experiments, hybridization
experiments using partially digested YAC DNA were carried
out. Analytical experiment was necessary to determine
the optimal condition for partial digestion since the
efficiency of the restriction enzyme reaction is highly
dependent on the purity of DNA. In the DNA preparation
in this example, 6-hour incubation with 1 unit of
restriction enzyme was, in most cases, sufficient for
complete digestion of a gel block (about 500 ng of DNA).
Partial cleavage of DNA was achieved by varying the time
of digestion as follows: ~ .
1. Dialyze three gel flocks (about 50 ~1 each volume
containing about 1 ~cg of DNA, stored in~0.5 M EDTA (pH
8.0)) fvr 1 hour against 50 ml of distilled water at room
temperature with gentle agitation. Repeat this step for
complete removal of EDTA.
2. Equilibrate the blocks with 10 ml appropriate
digestion buffer at 37°C for 30 minutes.
3. Transfer each block to 250-ul reaction mixture
containing 1 unit each of restriction enzyme in lx
digestion buffer.
4. Incubate all three tubes for 10 minutes, 30 minutes
and 1 hour at 37oC.
5. Stop the reaction by adding 100 ~cl of 0:5 M EDTA
(pH 8.0).
.,.
-24-
6. Equilibrate the blocks with appropriate gel
electrophoresis buffer 2 - 3 times over a 1 hour period
and immediately perform PFGE using an appropriate pulse
time.
Filters were.hybridized with the above-described
right- or left-end probe of YAC vector and~the size of
the hybridized restriction fragments was determined by
comparison with size standards (Fig. 3A). Results from
complete and partial digestion experiments were combined
to construct a physical map of YAC clones shown in Fig.
3B. Mapped clones were thus linked and classified into
several contigs.
(9) Isolation of Insert-terminal Sequences from YACs
After isolated YAC clones were classified into
several contigs based on their restriction maps, insert-
terminal DNA segments were isolated from both ends of
each contig to synthesize oligonucleotide primers. As is
often pointed out, considerable percentage (up to 30%) of
YAC clones in libraries contain noncontiguous DNA
segments spliced together resulting in "chimeric clone".
Since no good strategies have been developed to exclude
coligation artifact during the construction of the
library, it is necessary to check this possibility with
appropriate method after isolation of YAC clones. In
this example, the strategy to investigate the possibility
by using PCR with synthesized insert-terminal primers was
taken. The reason is that the synthesized primers would
-25-
be useful not only to investigate chimeric clones but
also to register resulting sequences as sequence tagged
sites (STS) for rescreening the YAC library by PCR. In
addition, they could be used to look for overlaps between
contigs~which could not be found by comparison of their
restriction maps.
For isolation of insert-terminal YAC segments,
several different methods can be employed including more
sophisticated and rapid method by inverse PCR and the
Vectorette system (J. H. Riley et al.., Nucleic Acids Res.,
18,.2887-2890 (1990.)). However, in this example, a
rather classical way, that is, to subclone the fragments
with plasmid or lambda phage vectors was taken. High
molecular weight DNA from YAC clones was digested with
restriction enzymes which have recognition sites both in
right- and left-arm sequences. Gel electrophoresis was
performed in a 0.7~ agarose gel and Southern filter was
hybridized with a 0.62-kb Hind III - Sal I fragment of
pBR322 DNA (TetR) which specifically hybridizes with
insert-vector boundary sequence of pYAC4 vector. The DNA
fractions of interest were recovered from the gel using
DES1 paper and ligated to either EMBL4 or pUCl9 vector
depending on the insert size. Isolated fragments with
EMBL4 vector were subcloned into pUCl9 vector for
subsequent sequencing. The chain. termination method~'with
M13 forward or reverse primer was used for sequencing
these plasmid clones. Sequences for insert-terminal
1
-26-
primers were provided from the non-repetitive portion in
the resulting sequence.
PCR experiments were achieved.to investigate the
above-mentioned artifact using primers at the both ends
of YAC-DNA against the DNA_from a human~mouse somatic ,
cell hybrid GM10479 line (Colier Institute) which carries
human chromosome 14 alone in which the human IgH locus
exists. DNA from CGM1 cells (source of YAC library) and
Rag cells (mouse cell) were also used as positive and
negative controls, respectively. PCR was carried out in
25- ~1 reactions according to a known method (H.S. Rim
and O. Smithies, Nucleic Acids Res., 16, 8870-8903
(1988)). 200 ng each of DNA was used for the regction.
Incubations containing DNAs from GM10479, CGM1 and Rag,
respectively were subjected to 35 to 40 cycles at 95°C, 1
minute - 55 to 62°C, 2 minutes = 72°C, 2 minutes
according to the condition optimized by analytical
experiment using CGM1 DNA. The YAC clones of which
either of the two insert-terminal primers gave no
specific amplification against GM10479 were concluded to
be chimeric clones. Only one contig neither of which
primers gave~amplified bands was turned out to cover
orphan VH locus on chromosome 16.
(10) Cosmid Subcloning and Construction of Physical Maps
Isolation of~large chromosomal region using YAC
system is advantageous for the. initial step of physical
mapping. However, subsequent step to analyze large DNA
-27-
fragments in YAC can be problematic since exogenous DNA
inserts cannot be. easily separated from yeast chromosomal
DNA and fragments up to several hundred kb are difficult
to handle without mechanical shearing. In order to map
VH segments of a.large DNA fragment containing VH
segments, detailed restriction map using common 6bp-site
restriction enzyme is necessary. For this purpose, YAC
clones were subcloned into cosmids. Cosmid libraries
were constructed from whole YAC DNA without previous
separation of cloned DNA from host chromosome. There are
two major reasons for this: 1) separation of intact
insert DNA and.their manipulation are difficult, 2) 4000
independent colonies are sufficient for complete coverage
of ,YAC insert since the genome size of.yeast is about 1,5
x 104 bp, 1/200 of that of human.
In general, there are two major difficulties in the
construction of cosmid libraries. The first is self-
ligation of vector DNAs, resulting in generation of
clones carrying no inserts of foreign DNA, and 'the second
is insertion of more than one DNA fragments in a single
vector, namely co-ligation artifact. To overcome these
problems, great efforts have been made including
construction of better-designed vectors with two cos
sites and modified method for ligation.such as partial
filling of vector and insert DNAs (J. Sambrook et al., A
Laboratory Manual, Cold Spring Harbor Laboratory Press,.
Cold Spring Harbor, N.Y. (1989)). Size fractionated
-28-
insert DNA usually contains smaller DNA molecules trapped
among larger molecules especially when excess amount of
DNA was loaded in the preparative gel. Alkaline
phosphatase treatment of insert DNA is effective in order
to exclude the co-ligation between inserts but gives rise
to polymerized vector DNA during the ligation step, which
causes high background of empty colonies under the
antibiotic selection. In this example, however, less .
than 5 gig of YAC DNA was sufficient for insert
preparation and thus preparative gel electrophoresis was
successful without contamination of smaller DNA
fragments. Most of the cosmid libraries were thus
constructed with minimal steps in combination with
alkaline phosphatase-treated cosmid vector and partially
digested DNA of exact size range for cosmid~insert (from
35 kb to 45 kb).
p1 Preparation of Yeast DNA Containing YAC
Since large DNA fragments are required as starting
material for preparing the DNA, extraction of DNA from
yeast cells with minimal shear damage is one of the most
critical steps. Obviously, the best way is to manipulate
DNA in-gel because DNA is fully protected from shear
damage. The present inventors found, however, that
gentle extraction of DNA in liquid from.yeast- cells gives
sufficient length of. DNA (>200 kb) for partial digestion
and subsequent size fractionation. In addition, liquid
DNA is easier to control the condition for partial
~1~~~~~
-29-
digestion than gel block DNA. With a simple and rapid (6
hours for total procedure) method described below, about
50 ~g of large size DNA. (>200 kb) can be routinely
purified from 100-ml. yeast culture.
(i) Spin down~yeast cells and wash them with TE (10 mM.
Tris HC1 (pH 8.0) - 1 mM EDTA) twice.
(ii) Resuspend the cells in 20 m1 of 0.1 M EDTA (pH 7.5),
1 M sorbitol, 0.2 mg/ml of Zymolyase 100T (ICN
Cat#152270), 15 mM 2-mercaptoethanol. Incubate at 37oC
for 1 hour to form spheroplasts.
(iii) Spin down the spheroplasts and resuspend in 9' ml of
0.1 M Tris HC1 (pH 7.5), 50 mM EDTA (pH 7.5).
(iv) Add 1 ml (1/10 final volume) of 10% SDS and mix
gently. Incubate at 60°C for 10 to 20 minutes.
(v) Add 1/3 volume of 4 M potassium acetate and mix
gently. Leave on ice for 30 minutes.
(vi) Centrifuge at 2000xg for 30 minutes and transfer the
supernatant to a new tube. Add 3 volumes of isopropanol
and mix gently. Leave at room temperature for 10 to 20
minutes for precipitation of DNA.
(vii) Centrifuge again at 2000xg for 30 minutes and
discard supernatant. Dissolve the pe~.let in 10 ml of
water.
From~this step onwards, care should be taken not to
give shear damage to the DNA.
(viii) Extract with phenol twice and with CIAA
(chloroform:isoamyl alcohol = 24:1) twice followed by
-30-
ethanol.precipitation at room temperature for 1'p to 20
minute s ~.
(ix) Centrifuge at 2000xg for 30 minutes. Rins~ the
pellet with 70% ethanol and dry up the pellet.
(x) Dissolve with l.ml of TE. ~
p Vector DNA Preparation
Lorist 2 DNA was linearized by digestion with Hind
III or Bam HI. Linearized~DNA was dephosphoryl~ted by
treatment with bacterial alkaline phosphatase. Small
aliquots of DNA before and after phosphatase treatment
were used for test ligation for phosphatase treatment
according to a known method (J. Sambrook et al.,, su ra).
~3 Insert DNA Preparation
Analytical experiment of partial digestion of yeast
DNA was performed according to standard procedure (J.
Sambrook et al., su ra) to determine the optimal enzyme
concentration and reaction time. Preparation ofi size-
fractionated DNA from the gel was achieved with~LGT
agarose and ~ agarase I. This very gentle methbd
resulted in high recovery (>90%) of fractionateca DNA
without degradation. Scaled up cleavage reactiqn was
done using 5 ug of DNA with optimal enzyme
concentration. Digested samples were loaded in ;a
preparative gel of 0.5% LGT agarose (Bio Rad preparative
grade) at about 1 V/cm overnight. Linearized lambda DNA
and its Xho I-digests which give 35-kb and 15-kt~~bands
were also loaded as size markers. After visualixing~the
~~.~2~7'~
=31-
DNA under ultraviolet transilluminater, a small slice~of
agarose containing the fraction ranging from 35 kb to 45
kb was cut out. Recovery of the DNA from the gel slice
was achieved using ~ agarase I (NEB) as follows:
(i) Equilibrate the gel block with water for complete
removal of gel electrophoresis buffer.
(ii) Transfer the block to a new tube and add 1/9 volume
of. lOx ~ agarase I buffer.
(iii) Melt the gel at 68°C for 10 minutes. Cool to 40°C
and incubate the molten agarose at 40°C for 1 hour with
optimal number of units of ~ agarase I.
(iv) Adjust the salt concentration of the solution to 0.5
M~NaCl for ethanol precipitation. Chill on ice for 10
minutes.
(v) Centrifuge at 15,OOOxg for 15 minutes to pellet any
remaining undigested carbohydrates.
(vi) Transfer the DNA-containing supernatant to a new
tube. Precipitate the DNA with 3 volumes of ethanol at
-80°C for 10 minutes.
(vii) Centrifuge at 15,OOOxg for 15 minutes and remove
the supernatant. Rinse the pellet with 70% ethanol and
dry up the pellet.
(viii) Resuspend the pellet in appropriate volume of
water for subsequent manipulation.
With this method,~in average 100 to 300 ng of size-
fractionated DNA can be recovered.
~ Ligation, in vitro Packaging and Infection to ~ i
~~ ~2~~
-32-
This process was performed according to standard
procedure ,(J. Sambrook et al., supra). By using lambda
inn packaging kit (Nippon Gene) and ED8768 host strain,
about 10,000 colonies were obtained from 25 ng of ligated
DNA.
~.Screening of Cosmid Libraries
Initial screening was carried out using Hind III-
partial cosmid libraries. About .10,000 colonies (500
colonies per ~lOcm plate x20) were plated on LB plates
containing 50 ~g/ml of kanamycin so that single colonies
can be picked up after first screening. Colonies were
then lifted from~the plates with X8.2 cm detergent-free
nitrocellulose membranes (Advantec Toyo Membrane) and
subjected to colony hybridization. Three different kinds
of probes were used for screening, namely mixture of six
VH-family specific probes to isolate VH-containing cosmid
clones, YAC vector probes (TetR gene segment of pBR322,
described above) for isolation of insert-terminal cosmid
clones, and total human DNA for any remaining cosmid
clones. In average, 50 to 100 clones from a YAC clone
with approximately 300-kb insert were isolated with the
probes.
~ Construction.of Cosmid Contigs
DNA from cosmid clones.was isolated by the alkaline
lysis method by a conventional method (J. Sambrook et
al., su ra). Purified cosmid DNAs were digested with Eco
RI or Hind III and subjected to agarose gel
-33-
electrophoresis for restriction mapping. Overlaps
between clones were easily. found by comparinglrestriction
patterns among cosmid clones. Ordered cosmid clones were
then cleaved with Eco. RI or Hind III and loaded in a 0.7~
agarose gel. Southern filters were hybridized with six
VH-family specific probes for identification of location
and number of VH segments in cosmid clones. Filters were
washed three times for 30 minutes under standard
conditions (at 50°C in lxSSC, 0.1% SDS) followed by
stringent conditions (at 65°C in O.IxSSC, 0.1~ SDS).
Location of VH segments were determined by comparison
between hybridization pattern of cosmids and their
physical maps.
Theoretically, approximately 50 independent cosmid
clones (about 7 fold of the whole YAC insert) would be
sufficient to cover the whole YAC insert of 300 kb in
length. However, the distribution of cosmid clones were
uneven and there still remained a few gaps. The clones
corresponding to the gaps could not be isolated even
after screening of Sau 3AI partial. library or chromosomal
walking by using the probes isolated from the edge of
each contig. Regions not present in the cosmid libraries
were subcloned with phage or plasmid vectors by isolation'
of DNA fragments of required size from YAC DNA as shown
in Fig. 4. After the complete physical map was
constructed, the present inventors found out that this
was not due to the nonrandom distribution of restriction
-34-
sites within the YAC insert. The presence of some
classes of sequences such as pahindromic.or tandem repeat
DNA might make these regions unclonable or under-
represented by using cosmid system. The complete
physical map of the 0.8-Mb region constructed in this
example is shown in Fig. 1 as mentioned above. The
distance.from JH of each VH segment shown in Fig. 1 and
the sizes of Eco RI and Hind III fragments are shown in
Table 3.
Example 2 Construction of Cosmid Clones
A cosmid library was constructed from human high
molecular DNAs as follows:
3-31: High molecular DNAs obtained ,from human placenta
were partially digested with Tag ~I and the resultant was
subjected to electrophoresis on 0.5~ agarose gel. The 35
- 45-kb bands were recovered by using DEAF paper. The
recovered DNAs were treated with alkaline phosphatase and
the resultant was ligated to cosmid vector pJBB which.had
been completely digested with a.restriction enzyme Cla I.
The ligation product was subjected to in vitro packaging
and the resultant was infected to host E. coli 490A,
followed by the screening by the conventional colony
hybridization to obtain the clone.
M131, M84 and M118: These fragments were obtained by
the same method as for 3-31 except that the DNA used was
human pro B cell line FLEB14-14, the vector and the host
E.- coli used were Lorist 2 and ED8767, respectively, the
CA 02162577 2000-10-20
76432-1
-35-
combination of restriction enzymes employed was Xba I and
Hind III, and the edges of the fragments were modified by
the partial repairing. The partial repairing was carried
out according.to a known method (J. Sambrook, E.F.
Fritsch and T. Maniatis, 1989, Molecular Cloning; a
Laboratory Manual, Cold Spring Harbor Laboratory Press,
Cold Spring Harbor, N.Y.).
Example 3 Sequencing Analysis of VH Segments
Instead of sequencing subcloned VH-containing DNA
fragments using vector primers, VH family-specific
oligonucleotide primers were synthesized. As mentioned
above, nucleotide sequences of FR regions of VH.segments
are highly conserved within the same family, so the
present inventors selected consensus sequences from the
conserved portions and synthesized family-specific
oligonucleotide primers for sequence analysis. For this
purpose, automated fluorescence-based sequencing system
Model 373A developed by Applied Biosystems was employed.
Dye-Deoxy*terminator sequencing kit supplied from the
same company using fluorescent-dye labeled dideoxy
nucleotides was suitable for our purpose~since
synthesized VH-specific primers could be directly used
without fluorescence-label.
(I) Subcloning of VH-containing Restriction Fragments
In order to use VH-family specific primers for
sequencing, it is essential to subclone VH-containing DNA
fragments so that each plasmid contains only one VH
*Trade-mark
kb was cut out. Recovery of th
76432-1 ca o2i62s~~ Zooo-io-2o
-36-
segment. Several other 6bp-site enzymes than Eco RI and
Hind III were used to isolate single VH-carrying DNA
fragments. Plasmid DNA of the subcloned fragments was
isolated by alkaline lysis method followed by
ult=acentrifugation twice to obtain high~quality DNA
samples for accurate sequences.
(2) Oligonucleotide Synthesis for Sequencing
To select consensus sequences for VH family-specific
oligonucleotide primer synthesis, nucleotide sequences of
framework regions and axon-intron boundaries of the known
VH segments were aligned by family. Attention was paid
so that 3'-half of them have 100% identities to reference
sequences and 3'-most nucleotide corresponds to the first
or the second letter of highly conserved/iwariant amino
acid residues. Nineteen additional primers were designed
for five VH families as shown in Table 1 (described
below).
(3) Sequencing Reaction and Gel Electrophoresis
The sequencing reaction was performed by PCR using
Dye-Deoxy terminator sequencing kit (ABI) according to
manufacturer's instruction. Gel electrophoresis and
detection of signals were done in the sequencing
apparatus according to the users manual of the system.
In average, sequences of over 350 bases were obtained
from each reaction.
(4) Evaluation of Synthesized VH Family-specific Primers
The primers F-univ and I-R were first' chosen to
*Trade-t~k
21~2~'~~
-37-
sequence VH-I segments. As shown in Table 2, they
annealed 11 of 12 VH_I segments analyzed. It i~s to be
noted that all of 6 functional VH-I segments could be
sequenced with these two primers. Two more primers, I-
NF1 and I-NR1 were designed for V1-14P and V1-27P
segments. These two primers were also used for. some
other VH segments to verify their sequences obtained by
first two primers (Table 2).
Eight primers were designed and used for sequencing
VH-III family segments. The first sequencing reaction of
each VH segment was performed with F-univ and III-R
primers. They annealed more. than $0$ of the VH_III
.segments analyzed (25/30 for F-univ and 24/30 for III=
R)(Table 2). Importantly, again, all the functional VH-
. III segments with one exception could be sequenced with
this combination of primers, suggesting that they would
be good for most of VH-III cDNA. Based on the nucleotide
sequences obtained from first experiment, six additional
primers (III-F3, III-R3, III-F4, III-R4, III-NF1 and
III-F2) were designed and appropriate combination among
them were used for further analysis. Among these, III-R3
and III-F4 were used to determine the sequence of 5'
regulatory region and 3' flankii-ig region, respectively.
V3-29P and v3-32P were pseudogenes with extensive
divergence in their sequences and thus all but III-NF1
failed to anneal these two VH segments. Sequences of
V3-25P, V3-44P and V3-63P were determined using M13
~~.~~~'~'~
-38-
vector primers from their internal restriction~sites.
Five each of synthesized primers were used to
determine the sequences of VH segments belonging to VH-
III VH-IV and VH-V families. Since VH segments belonging
to each of these three families are highly homologous
with each other, it was thought that four each of the
primers are.enough for most. of the VH segments belonging
to these smaller VH families. In fact,~all four VH-II
family-specific primers annealed three VH-II segments
(V2-5, V2-lOP and V2-26). In brief, in total 11 primers
(F-univ and I-R for VH-I; II-R1, II-F2 and II-R2 for VH-
II% F-univ and IiI-R for VH-III% IV-R1, IV-F2 and IV-R2
for VH-IV% V-R2 and V-R3 for VH~V) would be sufficient
for sequencing most of the VH segments belonging to five
VH families. The II-F1, III-NF2 and IV-F1 primers
contain intron sequences and thus cannot be used for cDNA
sequencing.
By this procedure, the DNA sequences of the 64 VH
segments were determined and they are shown in Sequence
ID Nos. 1 - 64 as mentioned above. The distance of each
VH segment from JH and the sizes of Eco RI and Hind III
fragments are summarized in Table 3.
(5) Transcriptional Polarities of VH Segments
The strategy for sequencing VH segments with
family-specific primers was not suitable for
determination of transcriptional polarities of the VH
segments because it did not require restriction map of
..._
-39-
single VH-containing subcloned fragments. The. present
inventors could not determine orientations of all the VH
segments within this region for that reason. The present
inventcsrs found, however, that 8 regions containing 21'VH
segments-were already isolated in cosmid or phage clones
since sequences.between corresponding VH segments as well
as their restriction maps were identical with each other.
As the relative orders of these 21 VH segments within
these clones are identical to those in the 0.8-Mb region,
it was concluded that the orientation of these 21 VH
segments are the same as those of the JH segments.
- ~~.~"~~7'~
-40-
Table 1 V" family-specific primers~used for screening and sequencing
family name sequence(5'to 3' ) X location direction
I, 13, F univ AGGTGCAGCTGGTGCAGTCTG 1-8 ~ forward
V - .
I I R ~CCAGGGGCCTGTCGCACCCA 36-42 reverse
-
I N F TGGGGCCTCAGTGAAGGTCTCCTG 14-22 forward
- 1
I N R GATCC(A/G)TCCCATCCACTCAAG45-51 reverse
- 1
II II F 1 TGTCTTCTCCACAGGGGTCTT intron-(-2)forward
-
II F 2 GGGAAGGCCCTGGAGTGGCT 42-48 forward
-
IL R 1 GTGCAGGTCAGCGTGAGGGT 17-23 reverse
-
II R 2 TGGTTTTTG.GAGGTGTCCTTGG 70-77 reverse
-
III III R CACTCCAGCCCCTTCCCTGGAGC 40-47 reverse
-
III F 3 GTGAGGTTCAGCTGGTGGAGT (-1)-7 forward
-
III R 3 AGCTGAACCTCACACTGGAC (-3)-4 reverse
-
111 F 4 AAGGGCCGATTCACCATCT 64-70 forward
-
II< R 4 TTGTCTCTGGAGATGGTGAA 68-73 reverse
-
II< N F TGAGACTCTCCTGTGCAGCCTCTG 18-26 forward
- 1
Ill N F TCT(T/C)TGTGTTTGCAGGTGT intron-(-3)forward
- 2
IV F 1 TCTGTTCACAGGGGTCCTGTC ntron-(-1) forward
- i
N F 2 TCCGGCAGCCCCCAGGGAA 37-43 forward
-
Iv R 1 GCAGGTGAGGGACAGGGT 17-22 reverse
-
IV R 2 CAGGGAGAACTGGTTCTTGGA 74-80 reverse
-
V V R 1 CCCGGGCATCTGGCGCACCCA 36-42 reverse
-
V R 2 GCTGCTCCACTGCAGGTAGGC 78-82R reverse
-
V R 3 CTTCAGGCTGCTCCACTGCAG 74-83 reverse
-
X Locations of the primers are indicated as amino acid residue number
according to Kabat et al. Bases with redundancy are shown in the
parentheses. Directions relative to coding sequence are also shown.
~~.~w~~~
-41-
Table 2 List of useful primers for sequencing V" clones
VH-, primers VH-,m primers VH_", primers
V" segments
univ R NFI NRI univ R F3 R3 F4 R4 NF1 NF2 FI Rl F2 R2
V" I 1-2 + +
1-3 + +
1-8 + + .
1-12P + +
I-14P - + +
1-17P + ~ + + +
1-18 + + +
1-24P + + + +
1-27P + - + +
1-40P + +
1-45 + +
1=46 +. +
VH DI 3-6P - + - + - + + +
3-7 + + + +
3-9 + + +
3-11 + + + +
3-13 + - + + + +
3-15 + + + +
3-16P + + + +
3-19P + + +
3-20 + + + + +
3-21 + + + + +
3-22P + + +
3-23 + + + : + +
3-29P _ _ _ _ _ ~..
3-30 + + + + +
3-32P _ _ _ _ _ _ + _
3-33 + + + + +
3-35 + +
3-36P - + +
3-37P + - +
3-38P + +
3-41P + +
3-42P. + - + +
3-43 ~ + + .
3-47P + +
3-48 + +
3-49 + +
3-50P + +
3-52P~ + +
3-53 + +
3-54P + + +
3-64 + +
yH Iv 4-4 + + + +
+ + - +
4-34 + + + +
4-39
4-55P
-42-
Table 3
V " kb from . Fragment size(kb)
1H EcoRI Hind I~
6-1 75 0. 9 25
1-2 125 7. 2 12. 5
1-3 150 , 3.4 l.'7
4-4 160 5.1 8. 0
2-5 175 5. 4 16. 0
3-6P 185 11. 8 16. 0
3-7 190 ~ 2.2 5.0
1-8 215 3. 8 2. 0
3-9 230 2.6 5.4
2-lOP 235 13.5 18.5
3-11 245 1. 6 18. 5
1=12P 250 4.5 2.8
3-13 260 1.7 5.8
1-14P 275 2.9 13.0
3-15 280 4.8 13.0
3-16P 290 5.4 1.8
1-17P 295 5.4+1.6 10.2
1-18 315 3. 4 8. 8
3-19P 330 4.3 ~ 14.7
3-20 345 11.8 12.8
3-21 360 2. 2 6. 8
3-22P 385 5.7 7.0
3-23 395 2.0 5.7
1-24P 410 3.0 5.2
3-25P 420 10.0 7.3
2-26 430 8.1 6.6
1-27P 450 8.3 11.3
4-28 455 8.3 5.4
3-29P 460 3.5 5.8
3-30 470 9. 8 6, 8
4-31 475 10. 3 13. 0
3-32P 485 13.3 5.6
3-33 490 13.3 6.8
4-34 505 11.5 16.2
3-35 520 5.3 3.2
3-36P 525 5.3 5.7
3-37P 540 7.5 13.2
3-38P 545 8.0 15.4
4-39 555 7.0 15.4
__ -
-43-
Table 3 (continued)
V " kb from Fragment size(kb)
JH EcoRI Hind
IB
1-40P 560 1.4 3.2
3-41P 580 4.4 11.9
3-42P 590 - 3:0 3.8
3-43 600 6.5 8.1
3-44P 610 8.8 17.0
1-45 635 10.7 2.7
1-46 640 2.0 4.6
3-47P 650 2.7 10.5
3-48 670 2.7 3.9
3-49 690 1.6 16.5
3-50P 695 10.0 16.5
5-51 710 8. 0 11.
0
3-52P 715 4.0 11.0
3-53 725 ~ 8.3 6.3
3-54P 730 6.4- 15.4
4-55P 735 3.9 15.4
1-56P 740 3.4 15.4
3-57P 745 9.7 6.6
1-58P 750 8.3 17.5
4-59 755 8. 3 17.
5
3-60P 760 0.8+3.0 17.5
4-61 770 8. 1 9. 0
3-62P 'l75 4..6 9.0
3-63P 780 8.9 6.2
3-64 790 4.4 >7.4
~,1~~~'~
SEQUENCE ID N0. : 1 .
SEQUENCE LENGTH . 1 4 2 9
SEQUENCE TYPE : nucleic acid
STRANDEDNESS : double
TOPOLOGY : 1 inear
MOLECULE TYPE : Genomic DNA .
ORIGINAL SOURCE : Homo sa iens
IMMEDIATE SOURCE: hucian lymphoblastoid cell line CGMI
SEQUENCE DESCRIPTION
CTGATCTATG AATAAGGGTA TATAGACCAG TTTGGCCTGA TGTAGGGAAC GCCAAAGTGC 60
TGGAATTTCA GAGTCATCAC ACCCAGGGGC CCTGCCTCTG AGCTCCTCTT TGCATCCAAT 120
CTGCTGAAGA ACATGGCTCT AGGGAAACCC AGTTGTAGAC CTGAGGGCCC CGGCTCTTCA 180
ATGAGCCATC TGCGTCCCGG GGCCTTATAT CAGCAAGTGA CGCACACAGG CAAATGCCAG 240
GGTGTGGTTT CCTGTTTAAA TGTAGCCTCC CCCGCTGCAG AACTGCAGAG CCTGCTGAAT 300
TCTGGCTGAC CAGGGCAGTC ACCAGAGCTC CAGACA ATG TCT GTC TCC TTC CTC 354
Met Ser Val Ser Phe Leu
1 5
ATC TTC CTG CCC GTG CTG GGC CTC CCA TGG G GTCAGTGTCA GGGAGATGCC 405
Ile Phe Leu Pro Val Leu Gly Leu Pro Trp
15
GTATTCACAG CAGCATTCAC AGACTGAGGG GTGTTTCACT TTGCTGTTTC CTTTTGTCTC 465
CAG GT GTC CTG TCA CAG GTA CAG CTG CAG CAG TCA GGT CCA GGA CTG 512
Gly Val Leu Ser Gln Val Gln Leu Gln Gln Ser Gly Pro Gly Leu
25 30
GTG AAG CCC TCG CAG ACC CTC TCA CTC ACC TGT GCC ATC TCC GGG GAC 560
Val Lys Pro Ser Gln Thr Leu Ser Leu Thr Cys Ala Ile Ser Gly Asp
35 40 45
AGT GTC TCT AGC AAC AGT GCT GCT TGG AAC TGG ATC AGG CAG TCC CCA 608
2~ ~~~'~'~
Ser Val Ser Ser Asn Ser Ala Ala Trp Asn Trp Ile Arg Gln Ser Pro
50 55 60
TCG AGA GGC CTT GAG TGG CTG GGA AGG ACA TAC TAC AGG TCC AAG TGG 656
Ser Arg Gly Leu Glu Trp Leu Gly Arg Thr Tyr Tyr Arg Ser Lys Trp
65 70 75
TAT AAT GAT TAT GCA GTA TCT GTG AAA AGT CGA ATA ACC ATC AAC CCA 704
Tyr Asn Asp.Tyr Ala Val Ser Val Lys Ser Arg Ile Thr Ile Asn Pro
80 85 ' 90 95
GAC ACA TCC AAG AAC CAG TTC TCC CTG~CAG CTG AAC TCT GTG ACT CCC ?52
Asp Thr Ser Lys Asn Gln Phe Ser Leu GIn Leu Asn Ser Val Thr Pro
100 105 110
GAG GAC ACG GCT GTG TAT TAC TGT GCA AGA GA CACAGTGAGG GGAAGTCAGT 804
Glu Asp Thr Ala Vat Tyr Tyr Cys Ala Arg
115 120
GTGAGCCCAG ACACAAACCT CCCTGCAGGG ATGCTCAGGA CCCCAGAAGG CACCCAGCAC 864
TACCAGCGCA GGGCCCAGAC CAGGAGCAGG TGTGGAGTTA AGCCAAAATG GAACTTCTTG 924
CTGTGTCTTA AACTGTTGTT GTTTTTTTTT TTTTTTTGGC TCAGCAACAG AGATCATAGA 984
AAACCCTTTT TCATATTTTT CAAATCTGTT CTTAGTCTAA TGGAGATTCT CTAATATGTG 1044
ACATTGTTTT TCTCTTGCTT GTTTTTGGAA TTCTTTGTCT TTGACTTTTG ACAACTTGAC 1104
TTTTGACAGT GTGCCTCAAA GAAGTTCTAT TTTGGGTTCT GTGAACCTCC TGGATCTGGG 1164
AAGTTTTCAG CTATGATTTC ATTAAACGTG TTTTCTACAC CATTTCCCTA CTTCTTTCCA 1224
ATACCCATAA TGCAAATATT TGTTCACTTA ATTGTGTCCC ATAAATGCCT GGGGATTTTC 1284
TTCATTCCTT TTTACTCTTT TTTTCTTTTT A1'TCATCTGC CTGAATTATT TCAAAAGATC 1344
TGTCTTCAAC TTCAGAAACT CTTTGGCTTG GCCTAGTCTA ATCTTGAAGG TCTCAATTGT 1404
ACTTTTAATT TCATTCATTG AATTC 1429
SEQUENCE ID HO.: 2
SEQUENCE LENGTH . 5 1 2
SEQUENCE TYPE : nucleic acid
STRANDEDNESS : double
TOPOLOGY : l inear
MOLECULE TYPE : Genomic DNA
ORIGINAL SOURCE : Homo sa iens
IMMEDIATE SOURCE: human lymphoblastoid cell line CGMI
SEQUENCE DESCRIPTION
~TGAGAGCTCC GTTCCTCACC ATG GAC TGG ACC TGG AGG ATC CTC TTC TTG GTG 53
Met Asp Trp,Thr Trp Arg Ile Leu Phe Leu Val
1 5 10
GCA GCA GCC ACA G GTAAGAGGCT CCCTAGTCCC AGTGATGAGA AAGAGATTGA 106
Ala Ala Ala Thr
15
GTCCAGTCCA GGGAGATCTC ~CACAG 162
ATCCACTTCT GA
GTGTTCTCTC GCC
CAC
TCC
Gly
Ala
His
Ser
CAGGTG CAGCTGGTG CAGTCTGGG GCTGAGGTGAAGAAG CCTGGGGCC 210
GlnVal GlnLeuVal GlnSerGly AlaGluValLysLys ProGlyAla
20 25 30 35
TCAGTG AAGGTCTCC TGCAAGGCT TCTGGATACACCTTC ACCGGCTAC 258
SerVal LysValSer CysLysAla SerGlyTyrThrPhe ThrGlyTyr
40 45 50
TATATG CACTGGGTG CGACAGGCC CCTGGACAAGGGCTT GAGTGGATG 306
TyrMet HisTrpVal ArgGlnAla.ProGlyGlnGlyLeu GluTrpMet
55 . 60 65
GGATGG ATCAACCCT AACAGTGGT GGCACAAACTATGCA CAGAAGTTT 354
GlyTrp IleAsnPro AsnSerGly GlyThrAsnTyrAla GlnLysPhe
70 75 80
CAGGGC AGGGTCACC ATGACCAGG GACACGTCGATCAGC ACAGCCTAC 402
GlnGly ArgValThr MetThrArg AspThrSerIleSer ThrAlaTyr
85 90 ~ 95
~1.~25 ~ "~
ATG GAG CTG AGC AGG CTG AGA TCT GAC GAC ACG GCC GTG TAT TAC TGT 450
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
100 105 110 115
GCG AGA GA CACAGTGTGA AAACCCACAT CCTGAGGGTG TCAGAAACCC AAGGGAGGAG 508
Ala Arg
GCAG
512
SEQUENCE ID NO.: 3
SEQUENCE LENGTH . 4 9 6
SEQUENCE TYPE : nucleic acid
STRANDEDNESS : double
TOPOLOGY : 1 inear
MOLECULE TYPE : Genomic DNA
ORIGINAL SOURCE : Homo sa iens
IMMEDIATE SOURCE: human lymphoblastoid cell line CGMI
SEQUENCE DESCRIPTION
CACAACTCCT CACC ATG GAC TGG ACC TGG AGG ATC CTC TTT TTG GTG GCA 50
Met Asp Tcp Thr Trp Arg Ile Leu Phe Leu Val Ala
1 5 10
GCA GCC ACA G GTAAGGGGCT GCCAAATCCC AGTGAGGAGG AAGGGACTGA 100
Ala Ala Thr
AGCCAGTCAA GGGGGCTTCC ATCCACTCCT GTGTCTTCTC TACA G GT GTC CAC TCC 156
Gly Val His Ser
CAG GTT CAG CTG GTG CAG TCT GGG GCT GAG GTG AAG AAG CCT GGG GCC 204
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
25 30 35
TCA GTG AAG GTT TCC TGC AAG GCT TCT GGA TAC ACC TTC ACT AGC TAT 252
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
40 X45 50
GCT ATG CAT TGG GTG CGC CAG GCC CCC GGA CAA AGG CTT GAG TGG.ATG 300
Ala Met His Trp Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Met
55 60 65
GGA TGG AGC AAC GCT GGC AAT GGT AAC ACA AAA TAT TCA CAG GAG TTC 348
Gly Trp Ser Asn Ala Gly Asn Gly Asn Thr Lys Tyr Ser Gln Glu Phe
70 75 RO
CAG GGC AGA GTC ACC ATT ACC AGG GAC ACA TCC GCG AGC ACA GCC TAC 396
Gln Gly Arg Val Thr Ile Thr.Arg Asp Thr Ser Ala Ser Thr Ala Tyr
85 90 95
ATG GAG CTG AGC AGC CTG AGA TCT GAG GAC ATG GCT GTG TAT TAC TGT 444
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Met Ala Val Tyr Tyr Cys
100 105 110 115
GCG AGA GA CACAGTGTGA AAACCCACAT CCTGAGAGTG TCAGAAACCC CAGG 496
Ala Arg
SEQUENCE ID N0. : 4
SEQUENCE LENGTH . 6 5 0
SEQUENCE TYPE : nucleic acid
STRANDEDNESS : double
TOPOLOGY : 1 inear
MOLECULE TYPE : Genomic DNA
ORIGINAL SOURCE : Homo sapiens
IMMEDIATE SOURCE : human lymphoblastoid cell line CGMI
SEQUENCE DESCRIPTION
CACAGGAAAC CACCACACAT TTCCTTAAAT TCAGGGTCCA GCTCACATGG 50
GAAATACTTT CTGAGACTCA TGGACCTCCT GCACAAGAAC ATG AAA CAC CTG TGG 105
Met Lys His Leu Trp
1 5
TTC TTC 156
CTC CTG
CTG GTG
GCA GCT
CCC4AGA
T GTGAGTGTCT
CAAGGCTGCA
Phe Phe
Leu Leu
Leu Val
Ala Ala
Pro Arg
_ 10 15
GACATGGGATATGGGAGGTG TCTGTTCACA216
CCTCTGATCC
CAGGGCTCAC
TGTGGGTCTC
G GG GTC G A CTG 264
CT TCC GTG
CAG
GTG
CAC
CTG
CAG
GAG
TCG
GGC
CCA
GG
Trp Val u r Gln Va1 y Pro y Leu
Le Se Gln Leu Gln Gl Val
Glu Ser Gl
20 25 30
AAG CCT GAGACC CTG TCC ACC TGC GTCTCT GGC TCC 312
TCG CTC ACT GGT
Lys Pro GluThr Leu Ser Thr Cys ValSer Gly Ser
Ser Leu Thr Gly
35 40 45
ATC AGT TACTAC TGG AGC ATC CGG CCCGCC AAG GGA 360
AGT TGG CAG GGG
Ile Ser TyrTyr Trp Ser Ile Arg ProAla Lys Gly
Ser Trp Gln Gly
50 55 ~ 60
CTG GAG ATTGGG CGT ATC ACC AGT AGCACC TAC AAC 408
TGG TAT GGG AAC
Leu Glu IleGly Arg Ile Thr Ser SerThr Tyr Asn
Trp Tyr Gly Asn
65 70 75
CCC TCC AAGAGT CGA GTC ATG TCA GACACG AAG AAC 456
CTC ACC GTA TCC
Pro Ser LysSer Arg.Val Met Ser AspThr Lys Asn
Leu Thr Val Ser
80 85 90 95
CAG TTC CTGAAG CTG AGC GTG ACC GCGGAC GCC GTG 504
TCC TCT GCC ACG
GIn Phe LeuLys Leu Ser Val Thr AlaAsp Ala Vat
Ser Ser Ala Thr
100 105 Iln
TAT TAC TGT GCG AGA GA CACAGTGAGG GGAGGTGAGT GTGAGCCCAG 551
Tyr Tyr Cys Ala Arg
lI5
ACACAAACCT CCCTGCAGGG AGGCGGAGGG GACCGGCGCA GGTGCTGCTC AAGACCAGCA 611
GGGGGCGCGC GGGGCCCACA GAGCAAGAGG CCGGGTCAG 650
SEQUENCE ID NO.: 5
2~~~5~~
-50-
SEQUENCE LENGTH . 6 1 3
SEQUENCE TYPE : nucleic acid
STRANDEDNESS : doubl.e
TOPOLOGY : 1 inear .
MOLECULE TYPE : Genomic DNA
ORIGINAL SOURCE : Homo sa iens
IMMEDIATE SOURCE: human lymphoblastoid cell line CGMI
SEQUENCE DESCRIPTION
CCAGCTCCAC CCTCCTCTGG GTTGAAAAAG CCGAGCACAG GTACCAGCTC ACTGACTCCT 60
GTGCACCACC ATG GAC ACA CTT TGC TCC ACG CTC CTG CTG CTG ACC ATC 109
Met Asp Thr Leu Cys Ser Thr.Leu Leu Leu Leu Thr Ile
1 5 10
CCT TCA T GTGAGTGCTG TGGTCAGGGA CTCCTTCACG GGTGAAACAT CAGTTTTCTT 166
Pro Ser
GTTTGTGGGC TTCATCTTCT TATGCTTTCT CCACAG GG GTC TTG TCC CAG ATC 219
Trp Val Leu Ser Gln Ile
ACC TTGAAGGAG TCTGGTCCTACG CTGGTG CCC ACACAGACC CTC 267
AAA
Thr LeuLysGlu SerGlyProThr .LeuValLysPro ThrGlnThr Leu
30 35
ACG CTGACCTGC ACCTTCTCTGGG TTCTCACTCAGC ACTAGTGGA GTG 315
Thr LeuThrCys ThrPheSerGly PheSerLeuSer ThrSerGly Val
40 45 50
GGT GTGGGCTGG ATCCGTCAGCCC CCAGGAAAGGCC CTGGAGTGG CTT 363
Gly ValGlyTrp IleArgGlnPro ProGlyLysAla LeuGluTrp Leu
55 60 65
GCA CTCATTTAT TGGAATGATGAT AAGCGCTACAGC CCATCTCTG AAG 411
Ala Leu. Ile Tyr Trp Asn Asp Asp Lys Arg Tyr Ser Pro Ser Leu Lys
2~.~~~'~"~
70 75 51 80 85
AGC AGG CTC ACC ATC ACC AAG GAC ACC TCC AAA AAC CAG GTG GTC CTT 459
Ser Arg Leu Thr IIe Thr Lys Asp Thr Ser Lys Asn Gln Val VaI Leu
90 95 100
ACA ATG ACC AAC ATG GAC CCT GTG GAC ACA GCC ACA TAT TAC TGT GCA 507
Thr Met Thr~Asn Met Asp Pro Val Asp Thr Ala Thr Tyr~Tyr Cys Ala
105 110 115
CAC AGA C CACAAAGACA CAGCCCAGGG CACCTCCTGT ACAAAAACCC AGGCTGCTTC 564
His Arg
TCATTGGTGC TCCCTCCCCA CCTCTGCAGA ACAGGAAAGT CTGTCTGCT 613
SEQUENCE ID NO.: 6
SEQUENCE LENGTH . 5 9 4
SEQUENCE TYPE : nucleic acid
STRANDEDNESS : double
TOPOLOGY : 1 inear
MOLECULE TYPE : Genomic DNA
ORIGINAL SOURCE : Homo sa iens
IMMEDIATE SOURCE : human lymphoblastoid cell line CGMI
SEQUENCE DESCRIPTION
ACAGGATTCA CC ATG GAG TTG GGG CTG AGG TGG GTT TTC CTT GCT GCT ATT 51
Met Glu Leu Gly Leu Arg Tcp Val Phe Leu Ala Ala Ile
1 5 10
TTA AAA G GTGATTTATG GTTAACTAGA GCTATTGAGT GTGAATGGAC ATAAGTGAGC 108
Leu Lys
GAAACAGTGG ATATGTGTGG CAGTTTCTTA CCAGGATGTC TCTGTGTTTG CAG GT GTC 166
Gly Val
CAG TGT GAG ATG CAG CTG GTA GAG TCT GGA GCA AAC TTG ACA AAG CCT 214
-52-
GlnCys GluMetGln LeuValGlu SerGlyAlaAsn LeuThrLysPro
20 25 30
GGGTGT CCCTGAGAC TCTCCTGTG CAGCCTCTGCAT TCACCTTCAGTA 262
GlyCys Pro Asp SerProVal GlnProLeuAsp SerProSerVal
35 40 45
GCCATA GCACGCACT GGGTCCCCC AGGCTCCAGGGA AGGGTCTGCAGT 310
AlaIle AlaArgThr GlySerPro ArgLeuGlnGly ArgValCysSer
50 55 60
GGGTCC CAGTTATTA GTGGTAGTG GTAGTACA TGT ACTACGCAGACT 358
C
GlySer GlnLeuLeu ValValVal YalValProCys ThrThrGlnThr
65 70 75 80
CTGTGA AGGGCCGAT TCACCATTT CCAGAGACAATA CCAAAAACTCAC 406
Leu ArgAlaAsp SerProPhe ProGluThrIle ProLysThrHis
85 90 95
TGTATC TGCAAATGA ACAGACTGA GGGCAGAGGATG CAGCTGCATATG 454
CysIle CysLys ThrAsp ly GlnArgMet GlnLeuHisMet
G
100~ 105
ACTCTG TGAGAGA AGAAGTCAGT GTGAGCCCAG 507
TACGGTAAGG ACACAAACCT
ThrLeu Glu
110
CCCTTCAGGG ACCTGGGAC AGCCTGG GACACTGTGCA CT 567
T AACCAGGGAA GTGCTGACCC
CAGGGGCAAG GCAGGTGCT 594
T ACAAGGG
SEQUENCE ID NO.: 7
SEQUENCE LENGTH . 8 7 7
SEQUENCE TYPE : nucleic acid
STRANDEDNESS : double
T OPOLOGY : 1 i near
MOLECULE TYPE : Genomic DNA
-53-
ORIGINAL
SOURCE
: Homo
sapiens
IMMEDIATE line
SOURCE: CGMI
human
lymphoblastoid
cell
SEQUENCE
DESCRIPTION
ACAGCCTATTCCTCCAGCAT CCCACTAGAG CTTCTTATATAGTAGGAGAC ATGCAAATAG 60
GGCCCTCCCTCTACTGATGA AAACCAACCC AACCCTGACCCTGCAGGTCT CAGAGAGGAG 120
CCTTAGCCCTGGACTCCAAG GCCTTTCCAC TTGGTGATCAGCACTGAGCA CAGAGGACTC 180
ACC ATG TTG GGG CTG AGC TGG GTT GTTGCT TTA 229
GAA TTC CTT ATT GAA
G
Met Glu Leu Gly Leu Ser Trp Val~ ValAla Leu
Phe Leu Ile Glu
1 5 10 15
GTGATTCATGGAAAACTAGG AAGATTGAGT GTGTGTGGATATGAGTGTGA GAAACAGTGG289
ATTTGTGTGGCAGTTTCTGA CCTTGGTGTC TCTTTGTTTGCAGGT CAGTGT 343
GTC
Gly GlnCys
Val
GAG GTG CTG GTG GAG TCT GGG GGA GTCCAG GGGGGG 391
CAG GGC TTG CCT
Glu Val Leu Val Glu Ser Gly Gly ValGln GlyGly
Gln Gly Leu Pro
20 25 30 35
TCC CTG CTC TCC TGT GCA GCC TCT ACCTTT AGCTAT 439
AGA GGA TTC AGT
Ser Leu Leu Ser Cys Ala Ala Ser ThrPhe SerTyr
Arg Gly Phe Ser
40 45 . 50
TGG ATG TGG GTC CGC CAG GCT CCA GGGCTG TGGGTG 487
AGC GGG AAG GAG
Trp Met Trp Val Arg Gln Ala Pro GlyLeu TrpVal
Ser Gly Lys Glu
55 60 65
GCC AAC AAG CAA GAT GGA AGT GAG TATGTG TCTGTG 535
ATA AAA TAC GAC
Ala Asn Lys Gln Asp Gly Ser Glu TyrVal SerVal
Ile Lys Tyr Asp
70 75 80
AAG GGC TTC ACC ATC TCC AGA GAC AAGAAC CTGTAT 583
CGA AAC GCC TCA
Lys Gly Phe Thr Ile Ser Arg Asp LysAsn LeuTyr
Arg Asn Ala Ser
85 90 95
CTG CAA AAC AGC CTG AGA GCC GAG GTG TACTGT 631
ATG GAC ACG GCT TAT
Leu Gln Asn Ser Leu Arg Ala Glu Val TyrCys
Met Asp Thr Ala Tyr
~~~~5"~'~
w
100 105 110 115
GCG AGA GA CACAGTGAGG GGAAGTCAGT GTGAGCCCAG ACACAAACCT CCCTGCAGGG 689
Ala Arg
GTCCCTTGGG ACCACCAGGG GGCGACAGGG CATTGAGCAC TGGGCTGTCT CCAGGGCAGG 749
TGCAGGTGCT GCTGAGGGCT GGCTTCCTGT CGCGGTCTGG GGCTGCCTCG TCGTCAAATT 809
TCCCCAGGAA CTTCTCCAGA TTTACAATTC TGTACTGACA TTTCATGTCT CTAAATGCAA 869
TACTTTTT 877
S EQUENCE I D N0. : 8
SEQUENCE LENGTH . 5 6 4
SEQUENCE TYPE : nucleic acid
STRANDEDNESS : double
TOPOLOGY : 1 inear
MOLECULE TYPE : Genomic DNA
ORIGINAL SOURCE : Homo sa iens
IMMEDIATE SOURCE: human lymphoblastoid cell line CGMI
SEQUENCE DESCRIPTION
CACTCCACCA ACCACATCTG TCCTCTAGAG AAAACCCTGT GAGCACACCT CCTCACC 57
ATG GAC TGG ACC TGG AGG ATC CTC TTC TTG GTG GCA GCA GCT ACA A I03
Met Asp Trp Thr Trp Arg Ile Leu Phe Leu Val Ala Ala Ala Thr
1 5 10 15
GTAAGGGGCT TCCTAGTCTC AAAGCTGAGG AACGGATCCT GGTTCAGTCA AAGAGGATTT 163
TATTCTCTCC TGTGTTCTCT CCACAG GT GCC CAC TCC CAG GTG CAG CTG GTG 215
Ser Ala His Ser Gln Val Gln Leu Val
CAG TCT GGG GCT GAG GTG AAG AAG CCT GGG GCC TCA GTG AAG GTC TCC 263
Gl.n Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
~ 30 35 40
T GC AAG GCT TCT GGA TAC ACC TTC ACC AGT TAT GAT ATC AAC TGG GTG 311
-55-
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr Asp Ile Asn Trp Val
45 50 ~ 55
CGA CAG GCC ACT GGA CAA GGG CTT GAG TGG ATG GGA TGG ATG AAC CCT 359
Arg Gln Ala Thr Gly Gln Gly Leu Glu Trp Met Gly Trp Met Asn Pro
60 65 70
AAC AGT GGT AAC ACA GGC TAT GCA CAG AAG TTC CAG GGC AGA GTC ACC .407
Asn Ser Gly Asn Thr Gly Tyr Ala Gln Lys Phe Gln Gly Arg.Val Thr
75 ~ 80 85
ATG ACC AGG AAC ACC TCC ATA AGC ACA GCC TAC ATG GAG CTG AGC AGC 455
Met Thr Arg Asn Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Ser
90 ~ 95 100
CTG AGA TCT GAG GAC ACG GCC GTG TAT TAC TGT GCG AGA GG CACAGTGTGA 506
Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg
105 110 115
AAAACCACAT CCTCAGAGAG TCAGAAACCC CTAGGGGAGA AGGCAGCTTC TGCTGGGC 564
SEQUENCE ID N0. : 9
SEQUENCE LENGTH . 6 4 0
SEQUENCE TYPE : nucleic acid
STRANDEDNESS : double
TOPOLOGY : t inear
MOLECULE TYPE : Genomic DNA
ORIGINAL SOURCE : Homo sa iens
IMMEDIATE SOURCE : human lymphoblastoid cell line CGMI
SEQUENCE DESCRIPTION
CAAATAGGGC CCTCCCTCTG CTGATGAAAA CCAGCCCAGC CCTGACCCTG CAGCTCTGGG 60
AGAGGAGCCC CAGCCCTGAG ATTCCCAGGT GTTTCCATTC AGTGATCAGC ACTGAACACA 120
GAGGACTCAC C ATG GAG TTG GGA CTG AGC TGG ATT TTC CTT TTG GCT ATT 170
Met Glu Leu Gly Leu Ser Trp Ile Phe Leu Leu Ala IIeI
TTA GTGAGTGGAC 227
AAA ATGAGTGGAT
G
GTGATTCATG
GAGAAATAGA
GAGATTGAGT
.
Leu
Lys
15
TTGTGTGGCA GTTTCTGACC C TGTTTGCA G T G T 279
TTGGTGTCT TG G GTC TG
GA
Gl y l n s
Va Gl Cy
GAA GTG CTG GTGGAGTCTGGG GGAGGCTTGGTA GAGCCTGGC AGG 327
GAG
Glu Val Leu ValGluSerGly GlyGlyLeuVal ln ProGly Arg
Gln G
20 25 ~ ~ 3Q 35
TCC CTG CTC TCCTGTGCAGCC TCTGGATTCACC TTTGATGAT TAT 375
AGA
Ser Leu Leu SerCysAlaAla SerGlyPheThr PheAspAsp Tyr
Arg
40 45 50
GCC ATG TGG GTCCGGCAAGGT CCAGGGAAGGGC CTGGAGTGG GTC 423
CAC
Ala Met Trp ValArgGlnAla ProGlyLysGly L.euGluTrp Val
His
55 60 65
TCA GGT AGT TGGAATAGTGGT AGCATAGGCTAT GCGGAGTCT GTG 471
ATT
Ser Gly Ser TrpAsnSerGly SerIleGlyTyr AlaAspSer Val
Ile
70 75 80
AAG GGC TTC ACCATCTCCAGA GAGAACGCCAAG AACTCCCTG TAT 519
CGA.
Lys Gly Phe ThrIleSerArg AspAsnAlaLys AsnSerLeu Tyr
Arg
85 90 95
CTG CAA AAC AGTCTGAGAGCT GAGGAGACGGCC TTGTATTAG TGT 567
ATG
Leu Gln Asn SerLeuArgAla GluAspThrAla LeuTyrTyr Cys
Met
100 105 110 115
GCA AAA CAGTGAGG GGAAGTCAGC. GAGAGCCCAG 617
GAT ACAAAAACCT
A
CA
Ala Lys
Asp
CCTGCAGGAA 640
GACAGGAGGG
GCC
SEQUENCE ID NO.: 1 0
SEQUENCE LENGTH . 6 3 0
y .
-57-
SEQUENCE TYPE : nucleic acid
STRANDEDNESS : double
TOPOLOGY : 1 inear .
MOLECULE TYPE : Genomic DNA
ORIGINAL SOURCE : Homo sa iens
IMMEDIATE SOURCE: human lymphoblastoid cell line CGMI
SEQUENCE DESCRIPTION
AGCTCCACCC TTCTCTGTGT TGAAAAGCCG AGCATGGGGA CCTAGTTCAG TGACTCCTGC 60
GCCCCACCAC ATG GAG CTT TAC TCC ACG CTT CTC CTG CTG ACT GTC CCT 109
Met GIu Leu Tyr Ser Thr Leu Leu Leu Leu Thr Val Pro
1 5 m
TCC T GTGAGTTCAG TGGTCAGGGA ATCCTTCAGG GGTGAAACAC CTGTTCTTTT 163
Ser
CTTTGTGGGC TTCATCTTCT TATGCTTTCT CCACAG GG GTC TTA TCC CAG GTC 216
Trp Val Leu Ser Gln Val
15 ~n
ACCTTG AAGGAGTCT GGTCCTGCA CTGGTG CCCACA CAGACCCTC 264
AAA
ThrLeu LysGluSer GIyProAla LeuValLysProThr GlnThrLeu
25 30 35
ATGCTG ACCTGCACC TTCTCTGGG TTCTCACTCAGCACT TCTGGAATG 312
MetLeu ThrCysThr PheSerGly PheSerLeuSerThr SerGlyMet
40 45 . 50
GGTGTG GGTTAGATC TGTCAGCCC TCAGCAAAGGCCCTG GAGTGGCTT 360
GlyVal Gly Ile CysGlnPro SerAlaLysA1aLeu GluTrpLeu
55 60 65
GCACAC ATTTATTAG AATGATAAT AAATACTACAGCCCA TCTCTGAAG 408
Ala His Ile Tyr Asn Asp Asn Lys Tyr Tyr~Ser Pro Ser Leu Lys
70 75 80
AGT AGG CTC ATT ATC TCC AAG GAC ACC TCC AAG AAT GAA GTG GTT CTA 456
Ser Arg Leu Ile Ile Ser Lys Asp Thr Ser Lys Asn Glu Val Val Leu
85 90 95
ACA GTG ATC AAC ATG .GAC ATT GTG GAC ACA GCC ACA CAT TACTGTGCAA 505
Thr Val Ile Asn Met Asp Ile Val Asp Thr Ala Thr His
100 , 105 110
GGAGACCACA GAGACAGAGC CCAGGGTGCC TCTTGTACAA GACCCAGGCT GCTTCTCAGT 565
GGCGCTCCCT CCCCACCTCT GCAGAACAGG AAAGTGTGGC TGAGATGCCA TTTCCTGTCA 625
GGGTC 630
SEQUENCE ID NO.: 1 1
SEQUENCE LENGTH . 7 1 5
SEQUENCE TYPE : nucleic acid
STRANDEDNESS : double
TOPOLOGY : 1 inear
MOLECULE TYPE : Genomic DNA
ORIGINAL SOURCE : Homo sa .iens
IMMEDIATE SOURCE : human lymphoblastoidline CGMI
cell
SEQUENCE DESCRIPTION
CACCCCAGGC~TTTACACTTT ATGCTTCCGG GTGTGGAATT GTGAGCGGAT60
CTCGTATGTT
AACAATTTCA CACAGGAAAC AGCTATGACC CAAGCTTGCA TGCCTGCAGG120
ATGATTACGC
TCGACTCTAG AGGATCCCCG GGTACCGAGC AGGAGTTTCC ATTCGGTGAT180
TCGAATTCCC
CAGCACTGAA CACAGAGGAC TCACC ATG GAG CTG AGC TGG GTT 232
TTT GGG TTC
Met Glu Phe Gly Leu Ser Trp Val
Phe
1 5
CTT GTT GCT ATA ATA AAA G GTGATTTATG 281
GAGAACTAGA GACATTGAGT
Leu Val Ala Ile Ile Lys
15
GGACGTGAGT GAGATAAGCA GTGAATATAT CTGACTAGGT TGTCTCTGTG341
GTGGCAGTTT
TTTGCAG GT GTC CAG TGT CAG GTG CAG 389
CTG GTG GAG~TCT GGG GGA GGC
'~~.~~~7'~
-59-
Gly Val Gln Cys Gln Val Gln Leu Val Glu Ser Gly Gly Gly
20 25
TTGGTC AAGCCTGGAGGG TCCCTGAGACTC TCCTGTGCAGCC TCTGGA 437
LeuVal LysProGlyGly SerLeuArgLeu SerCysAlaAla SerGly
30 35 40 ~ 45
TTCACC TTCAGTGACTAC TACATGAGCTGG ATCCGCCAGGCT CCAGGG 485
PheThr PheSerAspTyr TyrMetSerTrp IleArgGlnAla ProGly
50 55 60
AAGGGG CTGGAGTGGGTT TCATACATTAGT AGTAGTGGTAGT ACCATA 533
LysGly Leu.GluTrpVal SerTyrIleSer SerSerGlySer ThrIle
65 70 75
TACTAC GCAGACTCTGTG AAGGGCCGATTC ACCATCTCCAGG GACAAC 581
TyrTyr AlaAspSerVal LysGlyArgPhe ThrIleSerArg AspAsn
80 ~ ~
85 90
GCCAAG AACTCACTGTAT CTGCAAATGAAC AGCCTGAGAGCC GAGGAC 629
Ala Lys Asn Ser Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp
95 100 105
ACG GCC GTG TAT TAC TGT GCG AGA GA CACAGTGAGG GGAAGTCAGT 675
Thr Ala Val Tyr Tyr Cys Ala Arg
110 115
GTGAGCCCAG ACACAAACCT CCCTGCAGGG GGTCCCTTGG 715
SEQUENCE ID NO.: 1 2
SEQUENCE LENGTH . 6 6 0
SEQUENCE TYPE : nucleic acid
STRANDEDNESS : double
TOPOLOGY : 1 inear
MOLECULE TYPE : Genomic DNA
ORIGINAL SOURCE : Homo sa iens
~1~~~ ~'~
-so-
IMMEDIATE SOURCE: human lymphoblastoid cell line CGMI
SEQUENCE DESCRIPTION .
GGATTGGGCT TTGAGCTAAG GANAGGCTTT GTCNNATGAA TATNCGAATA TACTGATATC 60
CACTGAGNTG AATATGTTCT GTNCCCTGAG AGAATCACCT GAGAGAATCC CCTGAGAGCA 120
CATCTCCTC ATG GNC TGG ACC TAC AAG ATC CTC TTC .TTG GTG GCA GCA GCC 171
Met Xaa Trp Thr Tyr Lys Ile Leu Phe Leu Val Ala Ala Ala
1 5 10
ACA G GTAAGCAGTT CCCAGGTCCA AGTAATGAGG AGGGGATTGA GTCCAGTCAA 225
Thr
15
GGGGGCTTTC ATCCACTCCT GTGTCCTCCC CACAG GT GCC CAC TCC CAG GTG CAG 280
Gly Ala His Ser Gln Val Gln
CTG GTG CAA TCT GGG GCT GAG GTG AAG AAG CCT GGG GCC TCA GTG AAG 328
Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys
25 30 ~ 35
GTCTCC TGCAAGGCT TCTGGATAC ACCTTCACCTAC TGCTACTTGCAC 376
ValSer CysLysAla SerGlyTyr ThrPheThrTyr CysTyrLeuHis
40 45 50
TGGGTA TGACAGGCC CCTGGACAA GGGCTTGAATGG ACAGGATTTTAG 424
TrpVal GlnAla ProGlyGln GlyLeuGluTrp ThrGlyPhe
55 60 65
TTATTT GAGAGATTT TTCATACAA CATTTATTCTGT AAGCAAATTTCA 472
LeuPhe GluArgPhe PheIleGln HisLeuPheCys LysGlnIleSer
70 75 80
GGGATT GTAGAATGA ATCATATTA ACAAATCTGACA CAGAACTTCCTC 520
GlyIle ValGlu IleIleLeu ThrAsnLeuThr GlnAsnPheLeu
85 . 90 95
TGA ATC AAT CTT TGT AAA CAT .CAA TTT CTG AAT CAA TGT TGT NAA TAT 568
-sl-
Ile Asn Leu Cys Lys His Gln Phe Leu Asn Gln Cys Cys Xaa Tyr
100 105 1.10
TTC AGA ACA CAA GCA CAA NTT CAC ATT TNA ACT CTA CfiT TNA TCT CTA 616
Phe Arg Thr Gln Ala Gln Xaa His Ile Xaa Thr Leu Leu Xaa Ser Leu
115 120 125 130
TTT AAA ANA TAT CAA AAA NTC TCA TCN NGT GCA TGT AAC GTT TG 660
Phe Lys Xaa Tyr Gln Lys Xaa Ser Ser Xaa Ala Cys Asn Val
135 140
SEQUENCE ID NO.: 1 3
SEQUENCE LENGTH . 8 1 9
SEQUENCE TYPE : nucleic acid
STRANDEDNESS : double
TOPOLOGY : 1 inear
MOLECULE TYPE : Genomic DNA
ORIGINAL SOURCE : Homo sa iens
IMMEDIATE SOURCE : human lymphoblastoid cell line CGMI
SEQUENCE DESCRIPTION
AATAAAAAAA TGATAGTTGT TAAATGTTTA TCGCAGAACA ATTCCAAATA AGGCAGCATT 60
TTCCCCAAAT ACAATCATTG TCATCCAAAA TCCCCCAGGA CGCTCTCATC TACTCTGCCC 120
CTGCCTTCAC CTCAGATGTC CCACCCCAGA GCTTGCTATA TAGTAACAGA CATGCAAATA 180
GTTGACTCCC TCTCCTGATG AAAACCAGCC CAGCCCTGAC CCTGCAGCTC TGGGAGTGGA 240
GCCCCAGCCT TGGGATTCCC~AAGTGTTTGT ATTCAGTGAT CAGGACTGAA CACACAGGAC 300
TCACC ATG GAG TTG GGG CTG AGC TGG GTT TTC CTT GTT GCT ATA TTA GAA 350
Met Glu Leu Gly Leu Ser Trp Val Phe Leu Val Ala Ile Leu Glu
1 5 10 15
G GTGATTCATG GAGAACTAGA GATATTGAGT GTGAATGGGC ATGAATGAGA 401
GAAACAGTGG GTATGTGTGG CAATTTCTGA CTTTTGTGTC TCTGTGCCTT GCAG GT 457
Gly
-62-
GTC CAG TGT GAG GTG CAT CTG GTG GAG TCT GGG GGA GGC TTG GTA CAG 505
Val Gln Cys Glu Val His Leu Val Glu Ser Gly Gly Gly Leu Val Gln
20 25 30
CCT GGG GGG GCC~CTG AGA CTC TCC TGT GCA GCC TCT GGA TTC ACC TTC 553
Pro Gly Gly Ala Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe
35 40 45
AGT AAC TAC GAC ATG CAC TGG GTC CGC CAA GCT ACA GGA AAA GGT CTG 601
Ser Asn Tyr Asp Met His Trp Val Arg Gln Ala Thr Gly Lys Gly Leu
50 55 ~ 60
GAG TGG GTC TCA GCC AAT GGT ACT GCT GGT GAC ACA TAC TAT CCA GGC 649
Glu Trp Val Ser Ala Asn Gly Thr Ala Gly Asp Thr Tyr Tyr Pro Gly
65 70 75 80
TCC GTG AAG GGG CGA TTC ACC ATC TCC AGA GAA ~AAT GCC AAG AAC TCC 697
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Glu Asn Ala Lys Asn Ser
85 90 95
TTG TAT CTT CAA ATG AAC AGC CTG AGA GCC GGG CAC ACG GCT GTG TAT 745
Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Gly Asp Thr Ala Val Tyr
100 105 . 110
TAC TGT GCA AGA GA CACAGTGAGG GGAAGTCAGT ATGAGCCCAG ACACAAACCT 799
Tyr Cys Ala Arg
115
CCCTGCAGAA TGCCTGGGGG 819
SEQUENCE ID NO. : 1 4
SEQUENCE LENGTH . 8 1 6
SEQUENCE TYPE : nucleic acid
STRANDEDNESS : double
TOPOLOGY : 1 inear
MOLECULE TYPE : Genomic DNA
~~.~2~ ~~.
ORIGINAL SOURCE : Homo Sapiens
IMMEDIATE SOURCE : human lymphoblastoid cell line CGMI
SEQUENCE DESCRIPTION
AGNGANGAAG GNAGTGATCA CTGTGATCTT TTCNCCAAGT TCACCATTTC NCTGAAGGTG 60
AGGACAGGTC CTCCTGCATG TGTTCAAACA AAAGNNNNAG AGACTACCTG GTAAGTGAGG 120
TGCTCACCTG GTTCTGGATG TTTGGTCTGT CTCCTCCCCT CTGTTGCCCC ACACAAGGTC 180
AGCCCACTCT TTCCAGGTCC GAAGAAGAGA GCACAGGTTT GTCCTGATTA TATGACTCAC 240
CCAGCTTCTG ATGAGTCTCC TGTTGCCAGC GTCCATGGCC TCAGTGAAGG TCTCCTGCAA 300
AGCTCTGGAT ACACCTTCGC CAGCTACGAC ATTCACTGTG TGTGACAGGC CCCTGGATAA 360
GGGTTTGANT GGATGGTAGG GAGCTACTCT GGCAATGGTA ACACAGGCTA TGCACAGAAG 420
TTTCAGGGCA GAGTCACCAT GACCAGGGAC ACGTCCACGA GCACAGCCTA CATGGAGCTG 480
AGCAGTCAGA GATCTGAGGA CATAGATGTG TACTACTGTG CGANACACAC AGTGTGACAN 540'
CCCACATCCT GAGAGAGTCA GAAATCCTGA GGGAGGTGGC AGCAGTGCTA GGCTTGAGAG 600
ATGACAGGGA TTTTATTTGC TTTNNCGGCT TTTTTTNGNN AGCGAGGTTA NTTCATTACA 660
GANNNNNGGA AAATAGAAAT GTGTATGGAC TCTAATTATG TGGGAAATTT CCATACAACT 720
TTGGTTCTCT TNGNNNNTTC AGGGGTNGGA NNCAATCAAT TAATAACCTG ATAAAGATTC 780
GAGTCGTACC CNGGATCCCT GNTTGGCCTG AGNATA . 816
SEQUENCE ID NO.: 1 5
SEQUENCE LENGTH . 5 3 5
SEQUENCE TYPE : nucleic acid
STRANDEDNESS : double
TOPOLOGY : l inear
MOLECULE TYPE : Genomic DNA
ORIGINAL SOURCE : Homo Sapiens
IMMEDIATE SOURCE: human lymphoblastoid cell line CGMI
SEQUENCE DESCRIPTION
CACAGAGGAC TCACC ATG GAG TTT GGG CTG AGC TGG ATT TTC CTT CCT GCT 51
Met Glu Phe Gly Leu Ser Trp Ile Phe Leu Pro Ala
1 5 10
ATT TTA AAA G GTGATTTATG GAGAACTAGA GAGATTAAGT GTGAGTGGAC 101
Ile Leu Lys
GTGAGTGAGA GAAACAGTGG ATATGTGTGG CAGTTTCTGA TCTTAGTGTC TCTGTGTTTG 161
CAGGT 208
GTC
CAG
TGT
GAG
GTG
CAG
CTG
GTG
GAG
TCT
GGG
GGA
GCC
TTG
Gly
Yal
Gln
Cys.
Glu
Val
Gln
Leu
Val
Glu
Ser
Gly
Gly
Ala
Leu
20 25 30
GTAAAGCCT GGGGGG TCCCTTAGACTC TCC GCAGCC TCTGGATTC 256
TGT
ValLysPro GlyGly SerLeuArgLeu Ser AlaAla SerGlyPhe
Cys
35 . 40 45
ACTTTCAGT AACGCC TGGATGAGCTGG GTC CAGGCT CCAGGGAAG 304
CGC .
ThrPheSer AswAla TrpMetSerTrp Val GlnAla ProGlyLys
Arg
50 55 60
GGGCTGGAG TGGGTT GGCCGTATTAAA AGC ACTGAT GGTGGGACA 352
AAA .
GlyLeuGlu TrpVal GlyArg.IleLys Ser ThrAsp GlyGlyThr
Lys
65 70 i5
ACA GAC TAC GCT GCA CCC GTG AAA GGC AGA TTC ACC ATC TCA AGA GAT 400
Thr Asp Tyr Ala A,la Pro Val Lys Gly Arg Phe Thr Ile Ser Arg Asp
80 85 90
GAT TCA AAA AAC ACG CTG TAT CTG CAA ATG AAC AGC CTG AAA ACC GAG 448
Asp Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Lys Thr Glu
95 100 105 110
GAC ACA GCC GTG TAT TAC TGT ACC ACA GA CACAGTGAGG GGAGGTCAGT 497.
Asp Thr Ala Val Tyr Tyr Cys Thr Thr
115
GTGAGCCCGG ACACAAACCT CCCTGCAGGG GCGCGCGG 535
~~~~'~
SEQUENCE ID NO.: 1 6
SEQUENCE LENGTH . 5 4 2
SEQUENCE TYPE : nucleic acid
STRANDEDNES$ : double
TOPOLOGY : 1 inear
MOLECULE TYPE : Genomic DNA
ORIGINAL SOURCE : Homo sa iens
IMMEDIATE SOURCE : human lymphoblastoid cell line CGMI
SEQUENCE DESCRIPTION
ATTGGGTCAA CAGCAATAAA CAAATTACC ATG GAA TTT GGG CTG AGC TGG GTT 53
Met Glu Phe Gly Leu Ser Trp Yal
1 5
TTT CTT GCT GGT ATT TTA AAA G GTGATTCATG GAGAACTAAG GATATTGAGT 105
Phe Leu Ala Gly Ile Leu Lys
15
GAGTGGACAT GAGTGAGAGA AACAGTGGAT ATGTGTGGCA GTTTCTGACC AGGGTGTCTC 165
TGTGTTTGCA G GT GTC CAG TGT GAG GTA CAA CTG GTG GAG TCT GGG GGA 214
Gly Val Gln Cys Glu Val Gln Leu Val G!u Ser Gly Gly
25
GGC TTG GTA CAG CCT GGG GGG TCC CTG AGA CTC TCC TGT GCA GCC TCT 262
Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser
35 40
GGA TTC ACC TTC.AGT AAC AGT GAC ATG AAC TGG GCC CGC AAG GCT CCA 310
Gly Phe Thr Phe Ser Asn Ser Asp Met Asn Trp Ala Arg Lys Ala Pro
45 50 55 60
GGA AAG GGG CTG GAG TGG GTA TCG GGT GTT AGT TGG AAT GGC AGT AGG 358
Gly Lys Gly Leu Glu Trp Val Ser Gly Val Ser Trp Asn Gly Ser Arg
65 70 75
ACG CAC TAT GTG GAC TCC GTG AAG CGC CGA TTC ATC ATC TCC AGA GAC 406
i
E
Thr His Tyr~Val Asp Val Arg Arg Ile Ile Ser Arg
Ser. Lys Phe Asp
g0 g5 90
AAT TCC AGG AAC TCC TAT CAA AAG AGA CGG AGA GCC 454
CTG CTG AAC GAG'
Asn Ser Arg Asn Ser Tyr Gln Lys Arg Arg Arg Ala
Leu Leu Asn Glu
95 100 105
GAC ATG GCT GTG TAT TGT AGA AA 503
TAC GTG TCCTGTGAGG
GGACACAAGT
Asp Met Ala Val~ Cys Arg
Tyr Tyr Val
110 115
GCGAGCCCAG ACACAAACCT
CCTGCAGGAA CACTGGGCG
SEQUENCE ID NO.:
1 7
SEQUENCE LENGTH .
9 1
SEQUENCE TYPE : nucleicacid
STRANDEDNESS : double
TOPOLOGY : 1 inear
MOLECULE TYPE : GenomicDNA
ORIGINAL SOURCE :
Homo Sapiens
IMMEDIATE SOURCE lymphoblastoid line CGMI
: human cell
SEQUENCE DESCRIPTION
ACATCCCTCC TCTATAGAAGCCCTGAGAG CACC ATG GAC TGT 56
C CACAGCTCCT ACC
Met Asp Cys Thr
1
TGG GGG ATC CTC TTC TTG GTG GCA TCT NCC ACA G GTAAGGGGCT 100
Trp Gly Ile Leu Phe Leu Val Ala Ser Xaa Thr '
5 10 I5
CCCAAGTCCT AGTGATGAGG AGGGGATTGA GTCCAGTCAA GGGGGCTTTT ATCATCTCCT 160
CCCTTCTCCT CACAG AT GTC CAT TCC CAG GTT CAG CTG TTG CAG CCT GGG 210
Asp Val His Ser Gln Val Gln Leu Leu Gln Pro Gly
20 25
~~~.~~5'~
-67-
GCT GAGGTGAAG AAGCCTGCGTCC TCAGTGAAGGTC TCCTGGCCA GGC 258
Ala GluValLys LysProAlaSer SerValLysVal SerTrpPro Gly
30 35 40
TTC CAGATACAC GTTCACCAAATA CTTTACACAGTG GGTGCGACA GGG 306
Phe GlnIleHis LeuHisGlnIle LeuTyrThrVal GlyAlaThr Gly
45 50 55
CCC TGGACAAGG GCATAGTGGTTG GGATGCATCAAC CCTTACAAT GAT 354
Pro TrpThrArg Ala TrpLeu GlyCysIleAsn ProTyrAsn Asp
60 65 70
AAC ACACACTAC GCACAGAAGTTC CGGCGCAGAGTC ACCATTACC AGT 402
Asn ThrHisTyr AlaGlnLysPhe ArgGlyArgVal ThrIleThr Ser
75 80 85 90
GAC AGGTCCGTG AGG-ACAGCCTAC ATGGAGCTGAGC AGTCTGAGA TCT 450
Asp ArgSerVal SerThrAlaTyr MetGluLeuSer SerLeuArg Ser .
95 100 105
GAA GACATGGTC GTGTATTCCTGT GTGAGAGA CACAGTGCGA 502
AAACCCACAT
Glu AspMetVal ValTyrSerCys ValArg
110 116
CCTGAGAGTG TCAGAAACCC CAGGAAGGAG GCACCTGTGC TGACACAGAG GGAGATGACA 562
AAGATTATTA GATTAACGAT TTTCTTAGA ~ 591
SEQUENCE ID NO.: 1.8
SEQUENCE LENGTH . 5 3 9
SEQUENCE TYPE : nucleic acid
STRANDEDNESS : double
TOPOLOGY : I inear
MOLECULE TYPE : Genomic DNA
ORIGINAL SOURCE : Homo sapiens
IMMEDIATE SOURCE : human lymphoblastoid cell line CGMI
SEQUENCE DESCRIPTION
_6g_
CAAAGACCCC TCCTTGGGAG AATCCCCTAG ATCACAGCTC CTCACC ATG GAC TGG 55
Met Asp Trp
. 1
ACC 102
TGG
AGC
ATC
CTT
TTC
TTG
GTG
GCA
GCA
CCA
ACA
G GTAACGGACT
Thr
Trp
Ser
Ile
Leu
Phe
Leu
Val
Ala
Ala
Pro
Thr
10 15
CCCCAGTCCC GCCAGTCATGTGAGACTTCA CCCACTCCTG162
AGGGCTGAGA
GAGAAACCAG
TGTCCTCTCC.ACAG 211
GT
GCC
CAC
TCC
CAG
GTT
CAG
CTG
GTG
CAG
TCT
GGA
Gly Ala His Ser G ln Val
Gln Leu
Val Gln
Ser Gly
20 25
GCT GTG AAG AAG CCT GGG TCA GTG GTC TCC TGC AAG 259
GAG GCC AAG~ GCT
Ala Val Lys Lys Pro Gly Ser Val Val Ser Cys Lys
Glu Ala Lys Ala
30 35 40
TCT TAC ACC TTT ACC AGC GGT ATC TGG GTG CGA CAG 307
GGT TAT AGC GCC
Ser Tyr Thr Phe Thr Ser Gly Ile Trp Val Arg Gln
Gly Tyr Ser Ala
45 50 55
CCT CAA GGG CTT GAG TGG GGA TGG AGC GCT TAC AAT 355
GGA ATG ATC GGT
Pro Gln G1y Leu Glu Trp Gly Trp Ser Ala Tyr Asn
Gly Met Ile Gly
60 65 70 75
AAC AAC TAT GCA CAG AAG CAG GGC GTC ACC ATG ACC 403
ACA CTC AGA ACA
Asn Asn Tyr Ala Gin Lys Gln Gly Val Thr Met Thr
Thr Leu Arg Thr
80 85 90
GAC TCC ACG AGC ACA GCC ATG GAG AGG AGC.CTG AGA 451
ACA TAC CTG TCT
Asp Ser Thr Ser Thr Ala Met Glu Arg Ser Leu Arg
Thr Tyr Leu Ser
95 100 105
GAC GCG AGA CACAGTGTGA AAACCCACAT503
GAC GA
ACG
GCC
GTG
TAT
TAC
TGT
Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg
~~.~~~ 1 6
110 115
-69-
CCTGAGGGTT TCAGAAACCC CAGGGAGGAG GCAGCT ~ 539
SEQUENCE ID NO.: 1 9
SEQUENCE LENGTH . 7 2 7
SEQUENCE TYPE : nucleic acid
STRANDEDNESS : double
TOPOLOGY : I inear
MOLECULE TYPE : Genomic DNA
ORIGINAL SOURCE : Homo sapiens
IMMEDIATE SOURCE : human lymphoblastoid cell line CGMI
SEQUENCE~DESCRIPTION
AGATTTAAGA ACCTTGCACC TGGTACCCGT TGCTCTTCTT GTAACCATTT GTCTTTTAAG 60
TTGTTTATCA CTCTGTAACT ATTTTGATTA TTTTGATTCT TGCATGTTTT TACTTCTGTA 120
AAATTATTAC ATTTGAGTCC CTCTCCCCTT CCTAAACCTA GGTATAAAAT TTACTCGAGC 180
CCCTTCCTCG TGGCCGAGAG AATTTTGAGC ATGAGCTGTC TCTTTGGCAG CCGGCTTAAT 240
AAAGGACTCT TAATTCGTCT CAAAGTGTGG CGTTTTCTTA ACTCACCTGG GTACAACAGT 300
GCAGCTGGTG GAGTCTGGGG GAGGCTTGGT AGAGCCTGGG GGGTCCCTGA GACTCTCCTG 360
TGCAGCCTCT GGATTCACCT TCAGTAACAG TGACATGAAC TGGGTCCGCC AGGCTCCAGG 420
AAAGGGGCTG GAGTGGGTAT CGGGTGTTAG TTGGAATGGC AGTAGGACGC ACTATGGAGA 480
CTCTGTGAAG GGCCGATTCA TCATCTCCAG AGACAATTCC AGGAACTTCC TGTATCAGCA 540
AATGAACAGC CTGAGGCCCG AGGACATGGC TGTGTATTAC TGTGTGAGAA ACACTGTGAG 600
AGGACGGAAG TGTGAGCCCA GACACAAACC TCCTGCAGGA ACGTTGGGGG AAATCAGCTG 660
CAGGGGGCGC TCAAGACCCA CTCATCAGAG TCAACCCCAG AGCAGGTGCA CATGGAGGCT 720
GGGTTTT 727
SEQUENCE ID NO.: 2 0
SEQUENCE LENGTH . 5 1 4
SEQUENCE TYPE : nucleic acid
-70-
STRANDEDNESS
: double
TOPOLOGY: 1 inear
MOLECULETYPE : Genomic DNA
ORIGINALSOURCE : Homo sapiens
IMMEDIATE lineCGMI
SOURCE
: human
lymphoblastoid
cell
SEQUENCE. DESCRIPTION
GGACTCGCC C TGG 48
ATG GTT TTC
GAG CTT GTT
TTT GCT ATT
GGG
CTG
AG
Met Glu Phe Gly Leu r Trp a Ile
Se Val Phe
Leu Val
Al
1 5 .
i0
TTA G GTGATTGATG GATCAATAGAGATGTTGAGT 105
AAA GTGAGTGAAC
ACGAGTGAGA
Leu
Lys
15
GAAACAGTGG CCAGGGTGTCTCTGTGTTTG 163
ATTTGTGTGG CAG
CAGTTTCTGA GT
GTC
Gly Val
CAG GAG GTG CAG CTG GTG TCT GGG GGT GTG CGG CCT 211
TGT GAG GGA GTA
Gln Glu Val Gln Leu Val Ser Gly~GlyGly Val Arg Pro
Cys Glu Val
20 25 30
GGG TCC CTG AGA CTC TCC GCA GCC GGA TTC TTT GAT 259
GGG TGT TCT ACC
Gly Ser Leu Arg Leu Ser Ala Ala Gly Phe Phe Asp
Gly Cys Ser Thr
35 40 45 -
GAT GGC ATG AGC TGG GTC CAA GCT GGG AAG CTG GAG 307
TAT CGC CCA GGG
Asp Gly Met Ser Trp Val Gln Ala Gly Lys Leu Glu
Tyr Arg Pro Gly
50 55 60 65
TGG TCT GGT ATT AAT TGG GGT GGT ACA GGT GCA GAC 355
GTC AAT AGC TAT
Trp Ser Gly Ile Asn Trp Gly Gly Thr Gly Ala Asp
Val Asn Ser Tyr
70 75 80
TCT AAG GGC CGA TTC ACC TCC AGA AAC GCC AAC TCC 403
GTG ATC GAC AAG
Ser Lys Gly Arg Phe Thr Ser Arg Asn Ala Asn Ser
Val Ile Asp Lys
85 90 95
-71-
CTG TAT CTG CAA ATG AAC AGT CTG AGA GCC GAG GAC ACG GCC TTG TAT 451
Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr
100 105 110
CAC TGT GCG AGA GA CACAGTGAGG GGAAGCCAGT GAGAGCCCAG ACACAAACGT 505.
His Cys Ala Arg
115
CCCTGCAGG 514
SEQUENCE ID N0. : 2 1
SEQUENCE LENGTH . 5 1 9
SEQUENCE TYPE : nucleic acid
STRANDEDNESS : double
TOPOLOGY : 1 i near
MOLECULE TYPE : Genomic DNA
ORIGINAL SOURCE : Homo sa iens
IMMEDIATE SOURCE: human lymphoblastoid cell line CGMI
SEQUENCE DESCRIPTION
AGGATTCACC ATG GAA CTG GGG CTC CGC TGG GTT TTC CTT GTT GCT AT'T 49
Met Glu Leu Gly Leu Arg Trp Val Phe Leu Val Ala Ile
1 5 10
TTA GAA G GTGAATCATG GAAAAGTAGA GAGATTTAGT GTGTGTGGAT ATGAGTGAGA 106
Leu Glu
I5
GAAACGGTGG ATGTGTGTGA CAGTTTCTGA CCAATGTCTC.TCTGTTTGCA G GT GTC 162
Gly Yal
CAG TGT GAG GTG CAA CTG GTG GAG TCT GGG GGA GGC CTG GTC AAG CCT 210
Gln Cys Glu Val Gln Leu Val Glu Ser Gly.Gly Gly Leu Val Lys Pro
20 25 30
GGG GGG TCC CTG AGA CTC TCC TGT GCA GCC TCT GGA TTC ACC TTC AGT 258
~~~25'~'~
-72-
GlyGly SerLeuArg LeuSerCysAla AlaSerGlyPhe ThrPheSer
35 40 ~ 45
AGCTAT AGCATGAAC TGGGTCCGCCAG GCTCCAGGGAAG GGGCTGGAG 306
SerTyr SerMetAsn TrpValArgGln AlaProGlyLys GlyLeuGlu
50 55 60 65
TGGGTC TGATCCATT AGTAGTAGTAGT AGTTACATATAC TACGCAGAC 354
TrpVal SerSerIle SerSerSerSer SerTyrIleTyr TyrAlaAsp
70 75 80
TCAGTG AAGGGCCGA TTCACCATCTCC AGAGACAACGCC AAGAACTCA 402
SerVal LysGlyArg PheThrIleSer Arg~AspAsnAla LysAsnSer
85 90 95
CTGTAT CTGCAAATG AACAGCCTGAGA GCCGAGGACACG GCT~GTGTAT 450
LeuTyr LeuGlnMet ~AsnSerLeuArg AlaGluAspThr AlaValTyr
100 105 110
TACTGT GCGAGAGA CACAGTGAGG ACACAAACCT 504
GGAAGTCAGT
GTGAGCCCAG
TyrCys AlaArg
115
CCCTGCAGGG 519
GTCCC
SEQUENCE ID NO.: 2 2
SEQUENCE LENGTH . 6 0 6
SEQUENCE TYPE : nucleic acid
STRANDEDNESS : double
TOPOLOGY : 1 inear
MOLECULE TYPE : Genomic DNA
ORIGINAL SOURCE : Homo sapiens
IMMEDIATE SOURCE: human lymphoblastoid cell line CGMI
SEQUENCE DESCRIPTION
CTACAGCTCT GGGAGAGGAC CCCCAGCCCT GGGATTTTCA GATGTTTTCA TTTGGTGATC 60
2~.6~~'~'~
-73-
AGGACTGAAC ACAGAGGACT 111
CACC ATG~GAG
TCA TGG CTG AGC
TGG GTT TTT
Met Glu Ser Trp
Leu Ser Trp
Val Phe
1 5
CTT GCC GCT ATT 160
TTA AAA G GTAATTCATT
GAGAACTATT GAAATTGAGT
Leu Ala Ala Ile Leu
Lys
15 . .
GTGAGCGGAT AAGAGTGAGA CAGTTTCTGA CCAGGGTTTC220
GAAACAGTGG ATACGTGTGG
TTTTTGTTTG C AG GT GTC 271
CAG TGT
GAG GTG
CAT CTG
GTG GAG
TCT GGG
GGA
Gly Val n Cys Glu Val
Gl His Leu Val
Glu Ser Gly
Gly.
20 25
GCC TTG GTACAG CCT GGG TCC CTG AGA TCC TGT GCA GCC 319
GGG CTC TCT
Ala Leu ValGln Pro Gly Ser Leu Arg Ser Cys Ala Ala
Gly Leu Ser
30 35 40
CGA TTC ACCTTC AGT TAC TAC ATG AGC GTC CGC CAG GCT 367
TAC GGG CCC
Gly Phe ThrPhe Ser Tyr Tyr Met Ser Val Arg Gln Ala
Tyr Gly Pro
45 50 55 ~ 60
GGG AAG GGGCTG GAA GTA GGT TTC ATT AAC AAA GCT AAT 415
TGG AGA GGT
GIy Lys GlyLeu Glu Val Gly Phe Ile Asn Lys Ala Asn
Trp Arg Gly
65 70 75
GGG ACA ACAGAA TAG ACG TCT GTG AAA AGA TTC ACA ATC~TCA463
ACC GGC
~Gly Thr ThrGlu Thr Thr Ser Val Lys Arg Phe Thr Ile
Gly Ser
. 80 85 90
AGA GAT GATTCC AAA ATC ACC TAT CTG ATG AAG AGC CTG 511
AGC CAA AAA
Arg Asp AspSer Lys Ile.Thr Tyr Leu Met Lys Ser Leu
Ser Gln Lys
95 100 105
ACC GAG GACACG GCC T.AT TAC TGT GA CACAGTGAGG 556
GTG TCC AGA
Thr Glu AspThr Ala Tyr Tyr Cys Ser
Val Arg
110 115
GGAGGTC AGTGTGAGCCCGG GCGCGCGGGG 606
ACACAAACCT
CCCTGCAGGG
-74-
SEQUENCE ID NO.: 2 3
SEQUENCE LENGTH . 5 1 4
SEQUENCE TYPE : nucleic acid
STRANDEDNESS : double
TOPOLOGY : l inear
MOLECULE TYPE : Genomic DNA
ORIGINAL. SOURCE : Homo sa iens
IMMEDIATE SOURCE: human lymphoblastoid cell line CGMI
SEQUENCE DESCRIPTION
GAACTCACC ATG GAG TTT GGG CTG AGC TGG CTT TTT CTT GTG GCT AAA 48
Met Glu Phe Gly Leu Ser Trp Leu Phe Leu Val Ala Lys
1 5 10
ATA AAAG GAGAAATAGA AAAATTGAGT 105
GTAATTCATG GTGAATGGAT
AAGAGTGAGA
I Lys
I
a
15
GAAACAGTGG TTTTTGTTTG 160
ATACGTGTGG~CAGTTTCTGA CAG
CCAGGGTTTC GT
Gl y
GTC CAGTGTGAG GTGCAGCTG TTGGAGTCTGGG~GGA GGCTTGGTA CAG 208
Val GlnCysGIu ValGlnLeu LeuGluSerGlyGly GlyLeuVal Gln
20 25 30
CCT GGGGGGTCC CTGAGACTC TCCTGTGCAGCCTCT GGATTCACC TTT 256
Pro Gly.GlySer LeuArgLeu SerCysAlaAlaSer GlyPheThr Phe
35 ~ 40 . 45
AGC AGCTATGCC ATGAGCTGG GTCCGCCAGGCTCCA GGGAAGGGG CTG 304
Ser SerTyrAla MetSerTrp ValArgGlnAlaPro GlyLysGly Leu
50 55 ~ 60
GAG TGGGTCTCA GCTATTAGT GGTAGTGGTGGTAGC ACATACTAC GCA 352
Glu TrpValSer AlaIleSer GlySerGlyGlySer ThrTyrTyr Ala
-75-
65 70 75 80
GACTCC GTGAAGGGC CGGTTCACCATC TCCAGAGACAAT TCCAAGAAC 400
.
AspSer Va LysGly ArgPheThr~Ile SerArgAspAsn SerLysAsn
l
85 90 95
ACGCTG TATCTGCAA ATGAACAGCCTG AGAGCCGAGGAC ACGGCCGTA 448
ThrLeu TyrLeuGln MetAsnSerLeu ArgAlaGluAsp ThrAlaVal
. 100 105 110
TATTAC TGTGCGAAA GA CACAGTGAGG 495
GGAAGTCATT
GTGAGCCCAG
TyrTyr CysAlaLys
115
ACACAAA CCTCCCTGCAG G 514
SEQUENCE ID N0. : 2 4
SEQUENCE LENGTH . 6 0 0
SEQUENCE TYPE : nucleic acid
STRANDEDNESS : double
TOPOLOGY : 1 inear
MOLECULE TYPE : Genomic DNA
ORIGINAL SOURCE : Homo sapiens
IMMEDIATE SOURCE : human lymphoblastoid cell tine CGMI
SEQUENCE DESCRIPTION
CCCAGAGACC ATCACACAAC AGCCACATCC CTCCCCTACA GAAGCCCCCA GAGCGCAGCA 60
CCTCACC ATG GAC TGC ACC TGG AGG ATC CTC TTC TTG GTG GCA GCA GCT 109
Met Asp Cys Thr Trp Arg Ile Leu Phe Leu Val Ala Ala Ala
1 5 10
ACA G GCAAGAGAAT CCTGAGTTCC AGGTCTGATG AGGGGACTGG GTCCAGTTAA 163
Thr
GTGGTGTCTC ATCCACTCCT CTGTCCTCTC CACAG GC ACC CAC GCC CAG GTC CAG 218
r,..
-76-
Gly Thr His Ala Gln Val Gln
CTG GTA CAG GGG GAGGTG.AAG AAGCCTGGGGCC TCAGTGAAG 266
TCT GCT
Leu Yal Gln Gly GluValLys LysProGlyAla SerValLys
Ser Ala
~ 30 35
GTC TCC TGC GTT GGATACACC CTCACTGAATTA TCCATGCAC 314
AAG TCC
Val Ser Cys Val GlyTyrThr LeuThrGluLeu SerMetHis
Lys Ser
40 45 50
TGG GTG CGA GCT GGAAAAGGG CTTGAGTGGATG GGAGGTTTT 362
CAG CCT
Trp Val Arg Ala GlyLysGly LeuGluTrpMet GlyGlyPhe
Gln Pro
55 60 65. 70
GAT CCT GAA GGT ACAATCTAC GCACAGAAGTTC CAGGGCAGA 410
GAT GAA
Asp Pro Glu Gly ThrIleTyr AlaGinLysPhe GlnGlyArg
Asp Glu
75 80 85
GTC ACC ATG GAG ACATCTACA GACACAGCCTAC ATGGAGCTG 458
ACC GAC
Val Thr Met Glu ThrSerThr AspThrAlaTyr MetGluLeu
Thr Asp
90 95 ~ 100
AGC AGC CTG TCT GACACGGCC GTGTATTACTGT GCAACAGA 505
AGA GAG
Ser Ser Leu Ser AspThrAla ValTyrTyrCys AlaThr
Arg Glu
105 110 115
CACAGTGTGA CCACAT G TGAGGAATGAGGCAGCTGTG565
AAAC CCTGAGAGC TCAGAAACCC
CTGAGGCTGA ATGACA A TTT 600
GGAG GGATTTATG AG
SEQUENCE ID : 2
NO: 5
SEQUENCE LENGTH
. 6 5 5
SEQUENCE TYPE: nucleicacid
STRANDEDNESS
: double
TOPOLOGY :
1 inear
MOLECULE TYPEGenomicDNA
:
ORIGINAL SOURCE : Homo sapiens
-77-
IMMEDIATE SOURCE : human lymphoblastoid cell line CGMI
SEQUENCE DESCRIPTION
ATTCACGTTT TCGAGCTCGG TACCCGGGGG ATCCTCTAGA GTCGACCTGC AGCTCTGGGA 60
GAGGAGCCCA GCCCCCGAAT TCCCAGGTGT TTTCATCTGG TGATCAGCAC CGAACA.CAGA 120
GGACTCACCA TGG AGT TTG TGC TGA GCT GGG TTT TCC TTG TTG CTA TTT TAA 172
Trp Ser Leu Cys Ala Gly Phe Ser Leu Leu Leu Phe
1 5 10
AAC GTGATCTATA GAGAACTAGA GATATTGAGT ATGAATGGAT ATGAGTGAGA 225
Asn
AACAGTGGAT ACGTGTGGCA GTTTCTGACC GGGGTGTCTC TGTGTTTGCA G.GTA TCC 282
Yal Ser
AGT GTG AGA.TGC AGC TGG TGG AGT CTG GGG GAG GCT TGC AAA AGC CTG 330
Ser Yal Arg Cys Ser Trp Trp Ser Leu Gly Glu Ala Cys Lys Ser Leu
20 25 30
CGTGGT CCCCGAGACTCT CCTGTGCAGCCT CTCAATTCA CCTTCAGTA 378
ArgGly ProArgAspSer ProValGlnPro LeuAsnSer ProSerVal
35 40 45
GCTACT ACATGAACTGTG TCCGCCAGGCTC CAGGGAATG GGCTGGAGT 426
AlaThr Thr ThrVal SerAlaArgLeu GlnGlyMet GlyTrpSer
50 55 60
TGGTTT GACAAGTTAATC CTAATGGGGGTA GCACATACC TCATAGACT 474
TrpPhe AspLysLeuIle LeuMetGlyVal AlaHisThr Ser Thr
65~ 70 75
CCGGTA AGGACCGATTCA ATACCTCCAGAG ATAACGCCA AGAACACAC 522
ProVal ArgThrAspSer IleProProGlu IleThrPro ArgThrHis
80 85 90
TTCATC TGCAAATGAACA GCCTGAAAACCG AGGACACGG CCCTCTATT 570
PheIIe ~CysLys Thr Ala LysPro ArgThrArg ProSerIle
-78-
95 100 105
AGT GTA CCA GAG A CACAGTGAGG GGAGGTCAGT GTGAGCCCAG ACACAAACCT 623
Ser Val Pro Glu
110
CCCTGCAGGC ATGCAAGCTT GGCACTGACC GT 655
SEQUENCE ID NO.: 2 6
SEQUENCE LENGTH . 5 4 6
SEQUENCE TYPE : nucleic acid
STRANDEDNESS : double
TOPOLOGY : 1 inear
MOLECULE TYPE : Genomic DNA
ORIGINAL SOURCE : Homo sa iens
IMMEDIATE SOURCE : human lymphoblastoid cell line CGMI
SEQUENCE DESCRIPTION
AGTGACTCCT GTGCCCCACC ATG GAC ACA CTT TGC TAC ACA CTC CTG CTG CTG 53
Met Asp Thr Leu Cys Tyr Thr Leu Leu Leu Leu
1 5 . 10
ACC ACC CCT TCC T GTGAGTGCTG TGGTCAGGGA CTTCCTCAGA AGTGAAACAT 106
Thr Thr Pro Ser
CAGTTGTCTC CTTTGTGGGC TTCATCTTCT TATGTCTTCT CCACAG GG GTC TTG TCC 163
Trp Val Leu Ser
CAG GTC ACC TTG AAG GAG TCT GGT CCT GTG CTG GTG AAA CCC ACA GAG 211
Gln Val Thr Leu Lys Glu Ser Gly Pro Val Leu Val Lys Pro Thr Glu
25 30 35
ACC CTC ACG CTG ACC TGC ACC GTC TCT GGG~TTC TCA CTC AGC AAT GCT 259
21625~'~
-79-
ThrLeu TheLeuThr CysThrValSer GlyPheSerLeu SerAsnAla
40 45 ~ 50
AGAATG GGTGTGAGC TGGATCCGTCAG CCCCCAGGGAAG GCCCTGGAG 307
ArgMet GlyValSer TrpIIeArgGln ProProGlyLys AlaLeuGlu
55 60 65
TGGCTT GCACACATT TTTTCGAATGAC GAAAAATCCTAC AGCACATCT 355
TrpLeu AlaHisIle PheSer~AsnAsp GluLysSerTyr SerThrSer
70 75 80
CTGAAG AGCAGGCTC ACCATCTCCAAG GACACCTCCAAA AGCCAGGTG 403
LeuLys SerArgLeu ThrIleSerLys AspThrSerLys SerGlnVal
85 90 95
GTCCTT ACCATGACC AACATGGACCCT GTGGACACAGCC ACATATTAC 451
ValLeu ThrMetThr AsnMetAspPro ValAspThrAla ThrTyrTyr
100 105 110 115
TGTGCA CGGATAC TGCCTCCTGT 504
CACAGAGACA ACAAGAACCT
CAGCCCAGGA
Cys Ala Arg Ile
AGCTGCATCT CAGTGGTGCT CCCTCCCTAC CTCTGCAGAA CA 546
SEQUENCE ID NO.: 2 7
SEQUENCE LENGTH . 5 8 7
SEQUENCE TYPE : nucleic acid
STRANDEDNESS : double
TOPOLOGY : I inear
MOLECULE TYPE : Genomic DNA
ORIGINAL.SOURCE : Homo sapiens
IMMEDIATE SOURCE : human lymphoblastoid cell line CGMI
SEQUENCE DESCRIPTION
TGAGAGCATC ATCCAACAAC CACAACTCTC CTCAGAAGAA GCCCCTAGAC CACAGCACCT 60
~c,~~w~~~
-80-
CAAC ATG TAC TGG ACC TGG AGG ATC CTC TTC TTG GTG GCA GCA GCA ACA 109
Met Tyr Trp Thr Trp Arg Ile Leu Phe Leu Val Ala Ala Ala Thr
1 5 10 15
G GTAAGGGACC TCCCAGTCAC CGGGCTGAGA GAGAAACCAG GCCAGTCAAG 160
TGAGACTTCA CGCACTCCTG TCTCCTCTCC ACAG GT GTC CAC TCA CAG GTG CAG 214
Gly Val His Ser Gln Val Gln
CTG GTG CAG~TCT GGG CCT GAG GTG AAG AAG CCT GGA GCC TCA TTG AAG 262
Leu Val Gln Ser Gly Pro Glu Val Lys Lys Pro Gly Ala Ser Leu Lys
30 35
GTT TCC TGC AAG GCT TCT GGA TAC ACC TTC ACA AGC TAT GCT ATC AGC 310
Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr~Ser Tyr Ala Ile Ser
40 45 ~ 50
TGGGTA TGACAGGCC CATGGACAAGGG CTTGAGGAAATG GGATGGATC 358
TrpVal GlnAla HisGlyGlnGly LeuGluGluMet GlyTrpIle
55 60 65
AACACC AACACTGGG AACCTAACGTAT GCCCAGGGCTTC ACAGGACGG 406
AsnThr AsnThrGly AsnLeuThrTyr AlaGlnGlyPhe ThrGlyArg
70 75 80 85
TTTGTC TTCTCCATG GACACCTCCGTC AGCATGGCATAT CTTCATATC 454
PheVal PheSerMet AspThrSerVal SerMetAlaTyr LeuHisIle
90 ~ 95 100
AGCAGC CTAAAGGCT GAGGACACGTGC AAGAGGCACAGTGTGG AAACCCACAT 507
SerSer LeuLysAla GluAspThrCys LysArg
105 110
CCTGAGAGAA CCAGAAATCC CTGAGCTGAG GCAGTGACAG
567
TGAGGGAGGA
GGCAGCTGTG
GGACAACGTG GCTGCACCCT 587
SEQUENCE ID NO.: 2 8
-81-
SEQUENCE LENGTH
. 6 2 4
SEQUENCE TYPE : acid
nucleic
STRANDEDNESS : double
TOPOLOGY : 1 inear
MOLECULE TYPE : DNA
Genomic
ORIGINAL SOURCE
: Homo sapiens
IMMEDIATE SOURCE: lymphoblastoid lineCGMI
human cell
SEQUENCE DESCRIPTION
CATCCCTTTT CACCTCTCCA CCACCCACATGCAAATCTCA 60
TACAGAGGCA CTTAGGCACC
CAAGGGAAAC CATCACACAT TCAGGGTCCTGCTCACATGG 120
TTCCTTAAAT GAAATACTTT
CTGAGAGCTC TGGACCTCCT ATG CAC TGG TTC CTC 174
GTGCAAGAAC AAA CTG TTC
Met His Trp Phe Leu
Lys Leu Phe
1 5
CTG CTG GTG GCA AGA CAAGGCT GCA GACATGGAGA 226
GCT CCC T GTGAGTGTCT
Leu Leu Val Ala Arg
Ala Pro
15
TATGGGAGGT GCCTCTGAGC CTGTGGGTCT CTCTGTTCAC GTC 283
CCAGGGCTCA AG
GG
Trp Val
CTG TCC CAG GTG CAG TCG CCAGGACTG GTG CCT 331
CAG CTG GAG GGC AAG
Leu Ser Gln Val Gln Ser ProGlyLeu Val Pro
Gln Leu Glu Gly Lys
25 30
TCG GAC ACC CTG ACC GCT TCTGGTTAC TCC AGC 379
TCC CTC TGC GTC ATC
Ser Asp Thr Leu Thr Ala SerGlyTyr Ser Ser
Ser Leu Cys Val Ile
35 40 45
AGT AGT AAC.TGG TGG CGG CCCGCAGGG AAG CTG 427
TGG GGC ATC CAG GGA
Ser Ser Asn Trp Trp Arg ProProGly Lys Leu -
Trp Gly Ile Gln Gly
50 55 60 . 65
GAG TGG ATT GGG TAT AGT AGCACCTAC TAC CCG 475
TAC ATC TAT GGG AAC
Glu Trp Ile Gly Tyr Ser SerThrTyr Tyr Pro
Tyr Ile Tyr Gly Asn
-82-
70 75 80
TCC CTC AAG AGT CGA GTC ACC ATG TCA GTA GAC ACG TCC AAG AAC CAG 523
Ser Leu Lys Ser Arg Val Thr Met Ser Val Asp Thr Ser Lys Asn Gln
85 90 . 95
TTC TCC CTG AAG CTG AGC TCT GTG ACC GCC GTG GAC ACG GCC GTG TAT 571
Phe Ser Leu Lys Leu Ser Ser Val Thr Ala Val Asp Thr Ala Val Tyr
100 ~ 105 110
TAC TGT~GCG AGA AA CACAGTGAGG GGAGGTGAGT GTGAGCCCAG ACACAAACC 624
Tyr Cys Ala Arg
115
SEQUENCE ID N0. : 2 9
SEQUENCE LENGTH . 3 0 4
SEQUENCE TYPE : nucleic acid
STRANDEDNESS : double
TOPOLOGY : 1 inear
MOLECULE TYPE : Genomic DNA
ORIGINAL SOURCE : Homo Sapiens
IMMEDIATE SOURCE : human lymphoblastoid cell line CGMI
SEQUENCE DESCRIPTION
GTCAGATACA CCATGCAGAC TCTGTGAAGG GCAGATTCTC CATCTCCAAA GACAATGCTA 60
AGAACTCTCT GTATCTGCAA ATGAACAGTC AGAGAACTGA GGACATGGCT GTGTATGGCT 120
GTACATAAGG TTCCAAGTGA GGAAACATCG GTGTGAGTCC AGACACAAAA TTTCCTGCAA 180
AAAGAAGAAA GGAGTCTGGG CCAAAGGGGA CACTCAGCAC TCACAAAACA GGTGCAGCCC 240
CACGGCAGGT GCAGATGGAG GGAGGGTAAG GGCTGNTTTC CTTCAGGATC TGTGGGTTTC 300
CTCT 304
SEQUENCE ID NO.: 3 0
SEQUENCE LENGTH . 5 1 2
SEQUENCETYPE ,: nucleic acid
STRANDEDNESS
: double
TOPOLOGY: 1 inear.
MOLECULETYPE : Genomic DNA .
ORIGINALSOURCE : Homo sapiens
IMMEDIATE lineCGMI
SOURCE:
human.lymphoblastoid
cell
SEQUENCEDESCRIPTION
GGACTCACC C 51
ATG CTC
GAG GTT
TTT GCT
GGG CTT
CTG TTA
AGC
TGG
GTT
TT
Met Glu Phe Gly Leu r Trp e
Se Val Ph Leu
Val
Ala
Leu
Leu
1 5 1 0
AGA CTGAGT C ATGAGTGAGA 105
G GTGATTCATG GTGAGTGAA
GAGAAATAGA
GAGA
A rg
15
AAAACTGGAT TTGTGTGGCA TTTTCTGATAACGGTGTCCTTCTGTTTGCA GT GTC 161
G
Gly Val
CAG CAG GTG CAG CTG GTG TCT GGG GGC GTG CAG CCT 209
TGT GAG GGA GTC
Gln Gln Val Gln Leu Val Ser Gly Gly Val Gln Pro
Cys Glu Gly Val
20 25 30
GGG TCC CTG AGA CTC TCC GCA GCC GGA TTC TTC AGT 257
AGG TGT TCT ACC
Gly Ser Leu Arg Leu.Ser Ala Ala Gly Phe Phe Ser
Arg Cys Ser Thr
35 40 45
AGC GGC ATG CAC TGG GTC CAG GCT GGC AAG CTG GAG 305
TAT CGC CCA GGG
Ser Gly Met His Trp Val Gln Ala Gly Lys Leu Glu
Tyr Arg Pro Gly
50 55 60 65
TGG GCA GTT ATA TCA TAT GGA AGT AAA TAC GCA .GAC 353
GTG GAT AAT TAT
Trp Ala Val Ile Ser Tyr Gly Ser Ly5 Tyr Ala Asp
Val Asp Asn Tyr
70 75 80
TCC AAG GGC CGA TTC ACC TCC AGA AAT TCC AAC ACG 401
GTG ATC GAC AAG
Ser Lys Gly Arg Phe Thr Ser Arg Asn Ser Asn Thr
Val Ile Asp Lys
85 90 95
CTG TAT CTG CAA ATG AAC AGC CTG AGA GCT GAG GAC ACG GCT GTG TAT 449
Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr
100 105 110
TAC TGT GCG AGA GA CACAGTGAGG GGAAGTCATT GTGCGCCCAG ACACAAACCT 503
Tyr Cys Ala Arg
.115
CCCTGCAGG ~ 512
SEQUENCE ID NO.: 3 1
SEQUENCE LENGTH . 6 3 1
SEQUENCE TYPE : nucleic acid
STRANDEDNESS : double
TOPOLOGY : linear
MOLECULE TYPE : Genomic DNA.
ORIGINAL SOURCE : Homo sapiens
IMMEDIATE SOURCE : human lymphoblastoid cell line CGMI
SEQUENCE DESCRIPTION
CATCCCTTTT CACCTGTCCA TAGAGAGGCA CCAGCCACAT GCAAATCTCA CTTAGGCACC 60
CACAGAAAAC CGCCACACAT TTCCTTAAAA TCAGGGTCCT GCTCACATGG GAAATACTTT 120
CTGAGAGTCC TGGACCTCCT GTGCGAGAAC ATG AAA CAC CTG TGG TTC TTC CTC 174
Met Lys His Leu Trp Phe~Phe Leu
1 5
CTG CTG GTG GCA GCT CCC AGA T GTGAGTGTCT CAAGGCTGCA GACATGGAGA 226
Leu Leu Val Ala Ala Pro Arg
15
TATGGGAGGT GCCTCTGATC CCAGGGCTCA CTGTGTGTCT CTCTGTTCAC AG GG GTC 283
Trp Val
CTG CCC CAG GTG CAG CTG CAG GAG TCG GGC CCA GGA CTG GTG AAG CCT 331
w
LeuPro GlnValGln LeuGln GluSer GlyProGlyLeu ValLysPro
20 25 30
TCACAG ACCCTGTCC CTCACC TGTACT GTCTCTGGTGGC TCCATCAGC 479
SerGln ThrLeuSer LeuThr CysThr ValSerGlyGly SerIleSer
35 40 45
AGTGGT GGTTACTAC TGGAGC TGGATC CGCCAGCACCCA GCGAAGGGC 427
SerGly GlyTyrTyr TrpSer TrpIle ArgGlnHisPro GIyLysGly
50 55 ~ 60 65
CTGGAG TGGATTGGG TACATC TATTAC AGTGGGAGCACC TACTACAAC 475
LeuGlu TrpIleGly TyrIle TyrTyr SerGlySerThr TyrTyrAsn
70 75 80
CCGTCC CTCAAGAGT CGAGTT ACCATA TCAGTAGACACG TCTAAGAAC 523
ProSer LeuLysSer ArgVal ThrIle SerValAspThr SerLysAsn
85 90 95
CAGTTC TCCCTGAAG CTGAGC TGTGTG ACTGCCGCGGAC ACGGCCGTG 571
GlnPhe SerLeuLys LeuSer SerVal ThrAlaAlaAsp ThrAlaVal
100 105 110
TATTAC TGTGCGAGA GACACAGTGAGG 618
GGAGGTGAGT
GTGAGCCCAG
TyrTyr CysAlaArg
115
ACACAAACCT CCC 631
SEQUENCE ID NO.: 3 2.
SEQUENCE LENGTH . 3 4 1
SEQUENCE TYPE : nucleic acid
STRANDEDNESS : double
TOPOLOGY : 1 inear
MOLECULE TYPE : Genomic DNA
ORIGINAL SOURCE : Homo sapiens
~,.~-
_86_
IMMEDIATE SOURCE: human lymphoblastoid cell line CGMI
SEQUENCE DESCRIPTION
ACCAGTCTCC AGGCAAGGGG CTGGAGTGAG TAATAGATAT AAAAGATGAT GGAAGTCAGA 60
TACACCATGC AGACTCTGTG AAGGGCAGAT TCTCCATCTC CAAAGACAAT GCTAAGAACT 120
CTCTGTATCT GCAAATGAAC ACTCAGAGAG CTGAGGACGT~GGCCGTGTAT GGCTATACAT I80
AAGGTCCCAA GTGAGGAAAT ATCGGTGTGA GTCCAGACAC AACATTTCCT GCAAAAAGAA 240
GAAAGGAGTC TGGGCCGAAG GGGACACTCA GCACTCACAA AACAGGTGCA GCCCCACGGC 300
AGGTGCAGAT GGAGGGAGGG TAAGGGCTGC TTTTCCTTCA G 341
SEQUENCE ID NO.: 3 3
SEQUENCE LENGTH . 5 8 3
SEQUENCE TYPE : nucleic acid
STRANDEDNESS : double
TOPOLOGY : 1 inear
MOLECULE TYPE : Genomic DNA
ORIGINAL SOURCE ~: Homo sapiens
IMMEDIATE SOURCE: human lymphoblastoid cell line CGMI
SEQUENCE DESCRIPTION
TGAACACAGA GGACTCACC ATG-GAG TTT GGG CTG AGC TGG GTT TTC CTC GTT 52
Met Glu Phe Gly Leu Ser Trp Val Phe Leu Val
1 5 10
GCT CTT TTA AGA G GTGATTCATT GGAGAAATAG AGAGACTGAG.TGTGAGTGAA 105
Ala Leu Leu Arg
CATGAGTGAG AAAAACTGGA TTTGTGTGGC ATTTTCTGAT AACGGTGTCC TTCTGTTTGC 165
AG GT GTC CAG TGT CAG GTA CAG CTG GTG GAG TCT GGG GGA GGC GTG 211
Gly Val Gln Cys Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val
25 30
GTC CAG CCT GGG AGG TCC CTG AGA CTC TCC TGT GCA GCG TCT GGA TTC 259
Val Gln Pro Gly Arg Ser Leu Arg Leu Ser.Cys Ala Ala Ser Gly Phe
,'
1~~~ ~ '~
35 40 45 .
ACCTTCAGTAGC TATGGCATG CACTGG GTCCGCCAG GCTCCAGGC AAG 307
ThrPheSerSer TyrGlyMet HisTrp ValArgGln AlaProGly Lys
50 55 60
GGGCTGGAGTGG GTGGCAGTT ATATGG TATGATGGA AGTAATAAA TAC 355
GlyLeuGluTrp ValAlaVal IleTrp TyrAspGly SerAsnLys Tyr
65 70 75
TATGCAGACTCC GCGAAGGGC CGATTC ACCATCTCC AGAGACAAT TCC 403
TyrAlaAspSer AlaLysGly ArgPhe ThrIleSer ArgAspAsn Ser
80 85 90
ACGAACACGCTG TTTCTGCAA ATGAAC AGCCTGAGA GCCGAGGAC ACG 451
ThrAsnThrLeu PheLeuGln MetAsn SerLeuArg AlaGluAsp Thr
95 100 105 110
GCTGTGTATTAC TGTGCGAGA GAC GAGGTCATTG TGCGCCCAGA 505
ACAGTGAGGG
AlaValTyrTyr CysAlaArg
115
CACAAACCTC CCTGCAGGAA G CAGGGGGGGC TCAGGAGCCA
565
CGCTGGCGG AAATCAGCTG
CTGATCAGAG TCAGCCCT ~ 583
SEQUENCE ID NO.: 3 4
SEQUENCE LENGTH .: 6 8 7
SEQUENCE TYPE : nucleic acid
STRANDEDNESS : double
TOPOLOGY : l inear
MOLECULE TYPE : Genomic DNA
ORIGINAL SOURCE : Homo sapiens
IMMEDIATE SOURCE : human lymphoblastoid cell line CGMI
SEQUENCE DESCRIPTION
AAAAGACTGG GCCCTCCCTC ATCCCTTTTT ACCTATCCAT ACAAAGGCAC CACCCACATG 60
CAAATCCTCA CTTAGGCACC CACAGGAAAT GACTACACAT ~TTCCTTAAAT TCAGGGTCCA 120
GCTCACATGG GAAGTGCTTT CTGAGAGTCA TGGACCTCCT GCACAAGAAC ATG AAA 176
Met Lys
1
CAC CTG TGG TTC TTC CTC CTC CTG GTG GCA GCT CCC AGA T GTGAGTGTCT 226
His Leu Trp Phe.Phe Leu Leu Leu Yal Ala Ala Pro Arg
10 15
CAGGAATGCG GATATGAAGA TATGAGATGC TGCCTCTGAT CCCAGGGCTC ACTGTGGGTT 286
TCTCTGTTCA CAC GG GTC CTG TCC CAG GTG CAG CTA CAA CAG TGG GGC GCA 337
Trp Val Leu Ser Gln Val Gln Leu Gln Gln Trp Gly Ala
20 25
GGA CTG TTG AAG CCT TCG GAG ACC CTG TCC CTC ACC TGC GCT.GTC TAT 385
Gly Leu Leu Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ala Val~Tyr
30 35 40
GGTGGG TCCTTCAGT GGTTACTACTGG AGCTGGATCCGC CAGCCCCA 433
C
GlyGly SerPheSer GlyTyrTyrTrp SerTrpIleArg GlnProPro
45 50 55 60
GGGAAG GGGCTGGAG TGGATTGGGGAA ATCAATCATAGT GGAAGCACC 481
GlyLys GlyLeuG1-uTrpIleCly~GluIleAsnHisSer GlySerThr
65 70 75
AACTAC AACCCGTCC CTCAAGAGTCGA GTCACCATATCA TA GACACG 529
G
AsnTyr AsnProSer LeuLysSerArg ValThrIleSer ValAspThr
80 85 90
TCCAAG AACCAGTTC TCCCTGAAGCTG AGCTCTGTGACC GCCGCGGAC 577
SerLys AsnGlnPhe SerLeuLysLeu SerSerValThr AlaAlaAsp
95 100 105
ACGGCT GTGTATTAC TGTGCGAGAGG 623
CACAGTGAGG
GGAGGTGAGT
ThrAla ValTyrTyr CysAlaArg
110 115
~~~~~'~~
GTGAGCCCAG ACAAAAACCT CCCTGCAGGT AGGCAGAGGG GGCGGGCGCA GGTACTGCTC. 683
AAGA 687
SEQUENCE ID NO.: 3 5
SEQUENCE LENGTH . 7 0 0
SEQUENCE TYPE : nucleic acid
STRANDEDNESS : double
TOPOLOGY : I inear
MOLECULE TYPE : Genomic DNA
ORIGINAL SOURCE : Homo sapiens
IMMEDIATE SOURCE: human lymphoblastoid cell line CGMI
SEQUENCE DESCRIPTION
AAATAGGAGA CATNCAAATA GGCCCCCCCC TTTCCTGATA AAAAGCAGCC CAGTCCTGAC 60
CCTGCAGCCC TGGGAGAGAA GCACCAGCCC TGGGATTCTC AGGTGTTTCC ACTTTGTCAT 120
CAGCAACAAA CAAATTACC ATG GAA TTT GGG CTG AGC TGG GTT TTC CTT GCT 172
Met Glu.Phe Gly Leu Ser Trp Val Phe Leu. Ala
1 5 10
GCT ATT TTA AAA G GTGATTCATG AAGAACTAAG GATATTGAGT GAGTGGACAT 225
Ala Ile Leu Lys
GAGTGAGAGA AACAGTGGAT TTGTGTGGCA GTTTCTGACC AGGGTGTCTC TGTGTTTGCA 285
G GT GTC CAG TGT GAG GTG CAG CTG GTG GAG TCT GGG GGA GGC TTG GTA 333
Gly Val Gln Cys Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
25 30
CAG CCT GGG GGA TCC CTG AGA CTC TCC TGT GCA GCC TCT GGA TTC ACC 381
Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala.Ser Gly Phe Thr
35 40 45
TTC AGT AAC AGT GAC ATG AAC TGG GTC CAT CAG GCT CCA GGA AAG GGG 429
'..-
i
~A
-90-
PheSer AsnSerAsp MetAsnTrpVal GlnAlaPro LysGly
His Gly
50 ~ 55 60
CTGGAG TGGGTA.TCG GGTGTTAGTTGG GGCAGTAGG CACTAT 477
AAT ACG
LeuGlu TrpValSer GlyValSerTrp GlySerArg HisTyr
Asn Thr
65 70 75
GCAGAC TCTGTGAAG GGCCGATTCATC TCC.AGAGAC TCCAGG 525
ATC AAT
AlaAsp SerValLys GlyArgPheIle SerArgAsp SerArg
Ile Asn
80 85 90 95
AACACC CTGTATCTG CAAACGAATAGC AGGGCCGAG ACGGCT 573
CTG GAC
AsnThr LeuTyrLeu GlnThrAsnSer ArgAlaGlu ThrAla
Leu Asp
100 105 110
GTGTAT TACTGTGTG AGAAA CCAG 623
CACTGTGAGA
GGTCGGAAGT
GTGAGC
ValTyr TyrCysVal Arg
115
ACACAAACCT CCTGCAGGAA AGGGGGCGCT CAGGACCCAC
683
CGTTGGGGGA
AATCAGCTGC
TCATCAGAGT CAACCCC 700
SEQUENCE ID NO.: 3 6
SEQUENCE LENGTH . 8 0 6
SEQUENCE TYPE : nucleic acid
STRANDEDNESS : double
TOPOLOGY : 1 inear
MOLECULE TYPE : Genomic DNA
ORIGINAL SOURCE : Homo sapiens
IMMEDIATE SOURCE: human lymphoblastoid cell line CGMI
SEQUENCE DESCRIPTION
TGACACTAAC TCCCCCAGGA TCTCACATCT GCTCTGGANA CGGCTCTCCT GTTGTCCCTA 60
CCCCAGAGCT TGCTATAGAG GAGGAGACAT CCACATAGGG.CCCTCNCTTG TCCTGATGAA 120
AACCAGCCTT GCCTGCGTCT ACGGGAGAAG AGCCCCAGTC CAGAAGTACC AGGGGTTTCC 180
...
-91-
ATTTGGTGGT CAGGTCTCTG AACACAGAGG ACTCACT ATG GAG TTT GGG CTG AGC . 235
Met Glu Phe Gly Leu Ser
1 5 ~
TGGGGT TTCCATGTT GCTAATGTA AAAG GTGACTCATG 283
GAGAACTAGA
TrpGly PheHisVal AlaAsnVal Lys
10 15
GATATTGAGT GAAACAGTGG ATATGTGTGG
TCTGA343
GTGAGTGGAC CAGGT
ACAAGTGAGA
CCAGGGTGTC GT GAG TG 394.
TGTGTGTGTT GTC GTG ~
TGCAG CAG CAC
TGT CTG
G
Gly Glu al
Val Val
Gln His
Cys Leu
V
20
GAGTCT TTGGGAGGC TTGTTATAG CCTGGG CCCTGA GACTTT CTT 442
GGT
GluSer LeuGlyGly LeuLeu ProGly Pro AspPhe Leu
Gly
25 30 35
TTGCAG CCTCTGGAT TCACCTTTA GTACCT TTAGGT ACTGGA TGA 490
TTA
LeuGln ProLeuAsp SerProLeu ValPro LeuGly ThrGly
Leu
40 ~ 45 50
GCTGGG TCCATCAGG CTCCTGGGA AAGGGC AGTAGG TCTCAT TTA 538
TGG
AlaGly SerIleArg LeuLeuGly LysGly SerArg SerHis Leu
Trp
55 60 65
TGAGTT GTTGTGTAG GTAGCACAA GCTATG ACTCTG TGAAGG GTC 586
CAG
Val VatVal ValAlaGln AlaMet ThrLeu Arg Val
Gln
70 75 80
GATTCA CCCTCTCCA GAGATGATG CCAAGA CACTGT ATCTGC AAA 634
AAT
AspSer ProSer.ProGluMetMet ProArg HisCys IleCys Lys
Asn
85 90 95
TGAACA GCGTCAGAG CCGAGGATA GGTCTG ATTACT GTGGTG G 680
TGT
Thr Ala Ser Glu Pro Arg Ile Gly Leu Cys Ile Thr Val Val
100 105 110
CATTGTGTGC ATCCCTTGTT TAGGTACATG CAGAGATGCT GCTTTGGTGT GTTCAGGGGC 740
a'~r
-92-
TCCTGTTTTG GGGACACCAA TTTTGGAGTT TGCAGTATCC TTGAGTCCAG TACGTTCATG. 800
GTGGCA ~ 806
SEQUENCE ID NO.: 3 7
SEQUENCE LENGTH . 5 0 0
SEQUENCE TYPE : nucleic acid
STRANDEDNESS : double
TOPOLOGY : 1 inear
MOLECULE TYPE : Genomic DNA
ORIGINAL SOURCE : Homo sa iens
IMMEDIATE SOURCE: human lymphoblastoid cell line CGMI
SEQUENCE DESCRIPTION
GGAATCACC ATG TTG TTT GGA CTG AGC TGG CCG TTC CGA TTT ACT ATT TTA 51
Met.Leu Phe Gly Leu Ser Trp Pro Phe Arg Phe Thr Ile Leu
1 5 10
AGG G GTGACACGTG AAGCACTACA GATATTGCTC'GTGAGTGGAT ATTAGAGAAA 105
Arg
CAGTGGATAT GTGTGGCAGT TTCTGACCAG GATGTCTCTG TGTTTACAG GT GTG CAG 162
Gly Val Gln
TAT GAG GTG CAG CTG GTA GAG TCT GGG GGA GAC TTG GTA CAG CTG TGG 210
Tyr Glu Yal Gln Leu Val Glu Ser Gly Gly Asp Leu Val Gln Leu Trp
25 30
TGG GTC CTG AGA CTC TCA TGT GCA GCC TGT GGA TTC ATC TTG AGA AGC 258
Trp Val Leu Arg Leu Ser Cys Ala Ala Cys Gly Phe Ile Leu Arg Ser
35 40 45 50
AAC TGG TCC CAC CGG GCT TCA CGA AAG GGG CTG GCA TGG AAT GAC ATG 306
Asn Trp Ser His Arg Ala Ser Arg Lys Gly Leu Ala Trp Asn Asp Met
55 60 65
-98-
GTC TCA TAC ATT AGT GCT AGT GGT GGT AGT CTA TAC TAT GCA GAC ACT 354
Val Ser Tyr Ile Ser Ala Ser Gly Gly Ser Leu Tyr Tyr Ala Asp Thr
70 75 80
GAA GGG TAG ATT CAC CAT CTC TAG AGA CAA TGG CAA GAA CAT GCT GTT 402
Glu Gly Ile His His Leu Arg Gln Trp Gln Glu His Ala Val
85 90 ~ 95
CTT GCA AAT GAA CAG TCT GAG AGA TGA GGA CTC GGT TGT GTT GAG AGA 450
Leu Ala Asn Glu Gln Ser Glu Arg Gly Leu Gly Cys Val Glu Arg
100 105 ' 110
CATGGTGAGG GGAAAATCAG TATGAGCCCA GCCAGAACTC TCCCTGCAGG 500
SEQUENCE ID NO.: 3 8
SEQUENCE LENGTH . 5 0 7
SEQUENCE TYPE : nucleic acid
STRANDEDNESS : double
TOPOLOGY : 1 inear
MOLECULE TYPE : Genomic DNA
ORIGINAL SOURCE : Homo sapiens
IMMEDIATE SOURCE : human lymphoblastoid cell line CGMI
SEQUENCE DESCRIPTION ' '
CAACTCATC ATG CAG TTT GTG CTG AGC TGG GTT TTC CTT GTT GGT ATT TTA 51
Met Gln Phe Val Leu Ser Trp Val Phe Leu Val Gly Ile Leu
1 5 10
AAA G GTGATTCATG GAGAACTACA GATGTTGAGT GTGAGTGGAC ATGAGTGAGC 105
Lys
CAAACAGTGG GTTTGTGTGG CAGTTTCTGA CCTGGTGTCT CTGTGTTTAC AG GT GTC 162
Gly Val
CAG TGT GAG GTG CAG CTG GTG GAG TCT GGG GGA GGC TTG GTA CAG CCT 210
.._
_g4_
Gln Cys. Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
20 25 30
AGG GGG TCC CTG AGA CTC TCC TGT GCA GCC TCT GGA TTC ACC GTC AGT 258
Arg.Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Val Ser
35 40 45
AGC AAT GAG ATG AGC TGG ATC CGC CAG GCT CCA GGG AAG GGG CTG GAG 306
Ser Asn Glu Met Ser Trp Ile Arg Gln Ala Pro Gly Lys Gly Leu Glu
50 55 60 65
TGG GTC TCA TCC ATT AGT GGT GGT AGC ACA TAC TAC GCA GAC TCC AGG 354
Trp Val Ser Ser Ile Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Arg
70 75 80
AAG GGC AGA TTC ACC ATC TCC AGA~GAC AAT TCC AAG AAC ACG CTG.TAT 402
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
85 90 95
CTT CAA ATG AAC AAC CTG AGA GCT GAG GGC ACG GCC GCG TAT TAC TGT 450
Leu Gln Met Asn Asn Leu Arg Ala Glu Gly Thr Ala Ala Tyr Tyr Cys
100 105 110
GCC AGA TA TACACAGAGG GGAAGTCATT GTGCGCCCAG ACACAAACCT 498
Ala Arg _
115
CCCTGTAGG 507
SEQUENCE ID NO.: 3 9
SEQUENCE LENGTH . 8 0 0
SEQUENCE TYPE : nucleic acid
STRANDEDNESS : double
TOPOLOGY : 1 inear
MOLECULE TYPE : Genomic DNA
ORIGINAL SOURCE : Homo sapiens
-95-
IMMEDIATE SOURCE : human lymphoblastoid cell line CGMI
SEQUENCE DESCRIPTION
AGAAGAGGAC TCTGGGCTTG GAGAGGGGAG CCCCCCAAGA AGAGAAACTT GATTCTCCAA 60
AGGGCACAGC CAGCATTCTC CTCCCAGGGT GAGCTCCAAA AGACTGGCGC CTCTCTCATC 120
CCTTTTCACT GCTCCGTACA AACGCACNCA CCCCCATGCA AATCCTCACT TAGGGGCCCA 180
CAGGAAGCCA CCACACATTT CCTTAAATTC AGGTCCAACT CATAAGGGAA ATGCTTTCTG 240
AGAGTCATGG ATCTCATGTG CAAGAAA ATG AAG CAC CTG TGG TTC TTC CTC CTG 294
Met Lys His Leu Trp Phe Phe Leu Leu
1 5
CTG GTG GCG GCT CCC AGA T GTGAGTGTTT CTAGGATGCA GACATGGAGA 343
Leu Vat Ala Ala Pro Arg
10~ 15
TATGGGAGGC TGCCTCTGAT CCCAGGGCTC ACTGTGGGTT TTTCTGTTCA CAG GG GTC 401
Trp Bal
CTG TCC CAG CTG CAG CTG CAG GAG TCG GGC CCA GGA CTG GTG AAG CCT 449
Leu Ser Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val. Lys Pro
20 25 30
TCG GAG ACC CTG TCC CTC ACC TGC ACT GTC TCT GGT GGC TCC ATC AGC 497
Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser
35 40 45
AGT AGT AGT TAC TAC TGG GGC TGG ATC CGC CAG CCC CCA GGG AAG GGG 545
Ser Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly
50 55 60 65
CTG GAG TGG ATT GGG AGT ATC TAT TAT AGT GGG AGC ACC TAC TAC AAC 593
Leu Glu Trp Ile Gly Ser Ile.Tyr Tyr Ser Gly Ser Thr Tyr Tyr Asn
70 75 80
CCG TCC CTC AAG AGT CGA GTC ACC ATA TCC GTA GAC ACG TCC AAG AAC 641
Pro Ser Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn
85 90 95
CAG TTC TCC CTG AAG CTG AGC TCT GTG ACC GCC GCA GAC ACG GCT GTG 689
Gln Phe Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val
100 105 110
TAT TAC TGT GCG AGA CA CACAGTGAGG GGAGGTGAGT GTGAGCCCAG 736
Tyr Tyr Cys Ala Arg
115
ACAAAAACCT CCCTGCAGGG AGGCTGAGGG GGCGGTCGCA GGTGCAGCTC AGNGCCAGCA 796
GGGG 800
SEQUENCE ID NO.: 4 0
SEQUENCE LENGTH . 9 7 0
SEQUENCE TYPE : nucleic acid
STRANDEDNESS : double
TOPOLOGY : I inear
MOLECULE TYPE : Genomic DNA
ORIGINAL SOURCE : Homo sapiens
IMMEDIATE SOURCE : human lymphoblastoid cell line CGMI
SEQUENCE DESCRIPTION
CACAACCTCC ATGAAAAACA ACATAGAAAT TTCTCAAAGA.ACTAAAATTA GAATTACCAT 60
TTCTTCCAGT AAGCTGTCCC AGTAGGCATG TTCCTCCCAA ACTTTTATNT CAGAGAATGT 120
TGCCTGCACT CATATGTTTA TTTCAACACC ATTTTCAATA GAAAAGTCAA ATAATCTAAG 180
TGTCAATCAG TGGATGATTA GATAAAATAT GATATNNATG TAAATCATNG GAATACTATG 240
CAGCCAGTAT GGTATGAATT CAGTNGTGAN NCCNAGCCCC TGGACAAGNN GGCTTGAGTG 300
GATGGGATGG ATCATCACCT ACACTGGGAA CCCAACATAT ACCAACGGCT TCACAGGACG . 360
GGTTTCTATT CTCCATGGGA CACCTCTGTC AGCATGGCGT ATCTGAAGAT CAGCAGCGTA 420
AAGGCTGAGG ACACGGCCGC GTATGACTGT ATGAGAGACA CAGGGTGGAA ACCCACATCC 480
CGAGGGAGTC AGAAACCCCG GGGGAGGAGC CACCTGTTCT GACCTGAGNC AGTGGTCCAA 540
NCAGTNTCTT TAACNTCCAT ATGATCTCAT TTTTGCATCA TCTTCTACTT TTATATTAGC 600
TAAGAACTTG GGGTAGACAG GTGCTCCTAA GAGATCCTTA ACTTGCCCAT TTTCATGGGT 660
TTTCCAGAAG ACGTGAGAAG CCACTTTGTT ANCAAAGCAT CCCAAATCCA TGCCCTGTTN 720
CTAGATACAT .GTGAGCCCAT TTCCTGGTCT TTGCTTAACT GACAAGCTCT CATCAGTGCA 780
CCTGGGCTAA TTTCACATCA GGTAGAGGAA CGCGTTATAA AGGAAAGCTA ATGTTGTAAT 840
AGCAATTCCT GCTTAAAAAC CTTCAGCTTC ATTGTTTTTG TGTAATCCAT CANCAAATTA 900
TGTTAGTTCA AGGTTCTCAA TGGGAGTTTC TAATAAATAG AAAGGATGTA TAAAGCTTGN 960
CACTGNCCGT 970
SEQUENCE ID N0. : 4 1
SEQUENCE LENGTH . 8 1 9
SEQUENCE~TYPE : nucleic acid
STRANDEDNESS : double
TOPOLOGY : linear
MOLECULE TYPE : Genomic DNA
ORIGINAL SOURCE : Homo sapiens
IMMEDIATE SOURCE : human lymphoblastoid cell line CGMI
SEQUENCE DESCRIPTION
CCCCACTCTC TCCTCAGNCG TCCCATCCCA GAGCTTGGCA TTGTAGTAGG AGACATCCAA 60
ATAGAGCCCT CCCTCTGCTT ATGAAAACCA GCCCAGCCCT GACCCTGCAG CTGTGGGAGA 120
GGAGCCCCAG CCCTGGGATT TTCAGGTGCT TTCATTTTGT GATCAGGACT GAACACAGAG 180
GATTCACC ATG GAG TCA TGG CTG AGC TGG GTT TTT CTT GCC GCT~ATT TTA 230
Met Glu Ser Trp Leu Ser Trp Val Phe Leu Ala Ala Ile Leu
1 5 ~ ~ 10
AAA G GTAATTCATT GAGAACTATT GAAATTGAGT GTGAGTGGAT AAGAGTGAGA 284
Lys
TAAACAGTGG ATACGTGTGG CAGTTTCTGA CCAGGGTTTC TTTGTGTTTG CAG GT GTC 342
Gly Val
CAG TGT GAG GTG CAG CTG GTG GAG TCT GGG GGA GGC TTG GTC CAG CCT 390
Gln Cys Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Yal Gln Pro
w ~ ~ 6 2 5'~'~
20 25 30
GGGGGGTCC CTGAGACTC TCCTGTGCA GCCTCAGGATTC TCCTTTAGT 438
GlyGlySer LeuArgLeu SerCysAla AlaSerGlyPhe SerPheSer
35 40 45
AGCTATGGC ATGAGCTGG GTCCGCCAG GCTCCAGGGAAG GGGCTGGAG 486
SerTyrGly MetSerTrp ValArgGln AlaProGlyLys GlyLeuGlu
50 ~ 55 60 65
TGAGTGGCA CATATCTGG AATGATGGA AGTCAGAAATAC TATGCAGAC 534
ValAla HisIleTrp AsnAspGly SerGlnLysTyr TyrAlaAsp
70 75 . . 80
TCTGTGAAG GGCCGATTC ACAATCTCC GAGACAATTCTA AGAGCATGC 582
SerValLys~GlyArgPhe ThrIleSer GluThrIleLeu ArgAlaCys
85 90 ~ 95
TCT ATC TGC AAA TGG ACA GTC TGA AAG CTA AGG ACA CGG CCA TGT ATT 630
Ser Ile Cys Lys Trp Thr Val Lys Leu Arg Thr Arg Pro Cys Ile
100 105 110
ACT GTA CCA GA CACAGTGAGA GGAAGTCCGT GTGAGCCCAG ACACAAACCT 681
Thr Val Pro
CCCTGCAGGG GCACGCGGGG CCACCAGAGG GTGCCCAGGA TCCCCTGAAG ACAGGGACAG 741
NCCAAAGGCA GGTGCAGATG GNTGTCAAGA GGGTCTTGTG GCTTCGTCTA CATCTAACTG 801
GTTTCCTGGG TGAGCCTC 819
SEQUENCE ID N0. : 4 2
SEQUENCE L$NGTH . 4 7 1
SEQUENCE TYPE : nucleic acid
STRANDEDNESS : double
TOPOLOGY : 1 inear
MOLECULE TYPE : Genomic DNA
ORIGINAL SOURCE :Homo sapiens
~~~~w~~~
-99-
IMMEDIATE SOURCE : human lymphoblastoid cell line CGMI
SEQUENCE DESCRIPTION
TTGTAGGTGA TTTATGGAGA ATGAGAGATG TTGAGTGCGA GTGGACATGA GTGAGAGAAA 60
CAGTAGATAT GTGTGCCCGT TTCTGACCAG GGTGTCTCTG TGTTTGCAGG CGTCCAGCGT 120
GAGGCGCAGC TGGTGGAGTC TGGGGGAGAC TTGGTACAAC CTGGGTGGGT CCCCGAGACT 180
CTCATTTGCA GCTTCTAGAT TCACCTTCAG TGACTTCTGA ATGCACTGGA TCCGCCAGGC 240
TTCTGGGAAA GGGCTGGAGT GGGTTGGCCG TATTAGAACC AAACGTAACA GTTACACGAC 300
AGAATGCGCT GCATCTGTGA AAGGCAGGTT CACCATCTCA AGAGATGATT CAAAGAACAC 360
ACTGTATCTG CAAGTGAATA CCCTGAAAAC CGAGTACACG GCCATCTATT ACTGTACTAG 420
AGACAGTGAG GGGGAGGTTA ACGTAGGCCC ATACACAAAT CTCCCTGCAG G 471
SEQUENCE ID N0. : 4 3
SEQUENCE LENGTH . 8 7 0
SEQUENCE TYPE : nucleic acid
STRANDEDNESS : double
TOPOLOGY : 1 inear
MOLECULE TYPE : Genomic DNA
ORIGINAL SOURCE : Homo s_apiens
IMMEDIATE~SOURCE: human lymphoblastoid cell line CGMI
SEQUENCE DESCRIPTION
CATCTGTTAC AGAACTCATT ATATAGTAGG AGACATCCAA ATNGGGTCCC TCCCTCTGCT 60
GATGAAAACC AGCCCAGCCC TGACCCTGCA GCTCTGGGAG AGGAGCCCCA GCCCTGAGAT 120
TCCCAGGTGT TTCCATTCGG TGATCAGCAC TGAACACAGA GAACGCACC ATG GAG TTT 178
Met Glu Phe
1
GGA CTG AGC TGG GTT TTC CTT GTT GCT ATT TTA AAA G GTGATTCATG 225
Gly Leu Ser Trp Val Phe Leu Val Ana Ile Leu Lys
10 15
GATAAATAGA GATGTTGAGT GTGAGTGAAC ATGAGTGAGA GAAACAGTGG ATATGTGTGG 285
.,_
-100-
CAGTGTCTGA CCAGGGTGTC TCTGTGTTTG CAG GT GTC CAG TGT GAA GTG CAG 338
Gly Val Gln Cys Glu Val Gln
20
CTGGTG GAGTCTGGG GGAGTCGTG GTACAGCCTGGGGGG TCCCTGAGA 386
LeuVal GluSerGly GlyVaIVal ValGinProGlyGly SerLeuArg
25 30 35
CTCTCC TGTGCAGCC TCTGGATTC ACCTTTGATGATTAT ACCATGCAC 434
LeuSer CysAlaAla SerGlyPhe ThrPheAspAspTyr ThrMetHis
40 45 50
TGGGTC CGTCAAGCT CCGGGGAAG GGTCTGGAGTGGGTC TCTCTTATT 482
T Val ArgGlnAla ProGlyLys GlyLeuGluTrpYal SerLeuIle
rp
55 60 65 70
AGTTGG GATGGTGGT AGCACATAC TATGCAGACTCTGTG AAGGGCCGA 530
SerTrp AspGlyGly SerThrTyr TyrAlaAspSerVal LysGlyArg
75 80 85
TTC ACC ATC TCC AGA GAC AAC AGC AAA AAC TCC CTG TAT CTG CAA ATG 578
Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Ser Leu Tyr Leu Gln Met
90 95 100
AAC AGT CTG AGA ACT GAG GAC ACC GCC TTG TAT TAC TGT GCA AAA GAT 626
Asn Ser Leu Arg Thr Glu Asp Thr Ala Leu Tyr Tyr Cys Ala Lys Asp
105 110 115
A CACAGTGAGG GGAAGTCAGC GAGAGCCCAG ACAAAAACCT CGCTGCAGGA 677
AGACAGGAGG GGCCTGGGCT GCAGAGGCCA CTCAAGACAC ACTGAGCATA GGGTTAACTC 737
TGGGACAAGT TGCTCAGGAA GGTTAAGAGC TGGTTTCCTT TCAGAGTCTT CACAAATTTC 797
TCCATCTAAC AGTTTCCCCA GGAACCNGTC TAGATCTGTG ATCTTGGATC TGCTGAAACT 857
GCCTGTGTCA CCT ~ 870
SEQUENCE ID N0. : 4 4
SEQUENCE LENGTH . 5 2 9
-101-
SEQUENCE TYPE : nucleic acid
STRANDEDNESS : double
TOPOLOGY : 1 inear
MOLECULE TYPE : Genomic DNA
ORIGINAL SOURCE : Homo sa iens
IMMEDIATE SOURCE : human lymphoblastoidline CGMI
cell
SEQUENCE DESCRIPTION
TCCCCGGGTA CCGAGCTCAA GTGCCAGGAT TTTCACTTGG TGATCAGAAC60
TCCCAGGTGT
TTAACACAGA GGACTCACC ATG TTG TTT 112
GGG CTG AGC TGG GCT TTC CTT GTT
Met Leu Phe Gly Leu Ser Trp Ala Phe
Leu Val
1 5 10
ACT ATT TTA AGA G GTGATTCATG AAGAACTACA 165
GATATTGTTT GTGAGTGGAT
Thr Ile Leu Arg
15
ATTAGAGAAA CAGTGGATAT GTGTGGCAGT GATTTCTCTG TGTTTGCAG224
TGCTGACCAG
GT GTG CAG TAT GAG GTG CAG CTG GTA TTT TTT TTT TTT 271
GAG TCT TTT
Gly Val Gln Tyr Glu Val Gln Leu Val Phe Phe Phe Phe
Glu Ser Phe
20 25 30
TTT CAC TTT TTA GCG AAC ATC CAT GGG AAT AAT GGG TTG 319
TTA CAA GCT
Phe His Phe Leu Ala Asn Ile His Gly Asn Asn Gly Leu
Leu Gln Ala
35 40 45
TTT CTT CCA ACA CTT TAC AGA CAC CAT TCC CCT TGC TTA 367
CAA TTT TAA
Phe Leu Pro Thr Leu Tyr Arg His His Ser Pro Cys Leu
Gln Phe
50 55 60
GGT TTT TAA CCA GAA GAA TGC TGT CAT TCC TGT TCT TTT 415
CAT CTT AGG
.._
-102-
Gly Phe Pro Glu Glu Cys Cys His His Leu Ser Cys Ser Phe Arg
65 70 75
AAG AAT GCC CCC TCA ACT CAT CTC CAC TTG TCT GCA TGT ATT TCT ATT 463
Lys Asn Ala Pro Ser Thr His Leu His Leu Ser Ala Cys Ile Ser Ile
80 85 90
TGT CTT GGA CGT TCC CAA CAG CCT CNC GAA CAC TCA CCT CAC CCT ACA 511
Cys Leu Gly Arg Ser Gln Gln Pro Xaa Glu His Ser Pro His Pro Thr
95 100 105
ATG CTG CTC GAG GGG GTG ~ 529
Met Leu Leu Glu Gly Val
110 ~ 115
SEQUENCE ID NO.: 4 5
SEQUENCE LENGTH . 7 4 8
SEQUENCE TYPE : nucleic acid
STRANDEDNESS : double
TOPOLOGY : 1 inear
MOLECULE TYPE : Genomic DNA
ORIGINAL SOURCE : Homo Sapiens .
IMMEDIATE SOURCE : human lymphoblastoid cell line CGMI
SEQUENCE DESCRIPTION
CAGGATCAGG GCTTGAGTCA TCAGCATCTC ACTCTTGCAA~AGNCTGATGT GTCGTTTGTC 60
TTCCCTTTCT TATCATCGAC CAGGCTTTGA GCTATGAAAT GCCCTGTCTC ATCAATATNC 120
AAATAACCTG AGATCGACTG AGGTAAATAT GGATATGTCT GTGCCCTGAG AGCATCACCC 180
AACAAACCAC ATCCCTCCTC TAGAGAATCC CCTGAAAGCA CAGCTCCTCA CC ATG GAC 238
Met Asp
1
TGG ACC TGG AGA ATC CTC TTC TTG GTG GCA GCA GCC ACA G GTAAGGGGCT 288
Trp Thr Trp Arg Ile Leu Phe Leu Val Ala Ala Ala Thr
~~ ~~~'~7
-103-
10 15
CCCAAGTCCC AGTGATGAGG AGGGGATTGA GTCCAGTCAA GGTGGCTTTT ATCCACTCCT 348
GTGTCCCCTC CACAG AT GCC TAC TCC CAG ATG CAG CTG GTG CAG TCT GGG 398
Asp Ala Tyr.Ser Gln Met Gln Leu Val Gln Ser Gly
20 25
GCTGAG GTG.AAG ACTGGGTCCTCA GTG GTTTCC TGCAAGGCT 446
AAG AAG
AlaGlu ValLysLys ThrGlySerSer ValLysYalSer CysLysAla
30 35 40 .
TCCGGA TACACCTTC ACCTACCGCTAC CTGCACTGGGTG CGACAGGCC 494
SerGly TyrThrPhe ThrTyrArgTyr LeuHisTrpVal ArgGlnAla
45 50 55
CCCGGA CAAGCGCTT GAGTGGATGGGA TGGATCACACCT TTCAATGGT 542
ProGly GlnAlaLeu GluTrpMetGly TrpIleThePro PheAsnGly
60 65 70 75
AACACC AACTACGCA CAGAAATTCCAG GACAGAGTCACC ATTACCAGG 590
AsnThr AsnTyrAla GlnLysPheGln AspArgValThr IleThrArg
80 85 90
GACAGG TCTATGAGC ACAGCCTACATG~GAGCTGAGCAGC CTGAGATCT 638
AspArg SerMetSer ThrAlaTyrMet GluLeuSerSer LeuArgSer
95 100 105
GAGGAC ACAGCCATG TATTACTGTGCA AGATA 690
CACAGTGTGA
AAACCCACAT
Glu~Asp ThrAlaMet TyrTyrCysAla Arg
110 115
CCTGAGACCG GCAGCTTCAC TGAATGAGGA 748
TCAGAAACCC GGTTACAG
CAAGGAGGAG
SEQUENCE ID NO:: 4 6
SEQUENCE LENGTH . 7 9 9
SEQUENCE TYPE : nucleic acid
.._
-104-
STRANDEDNESS : double
TOPOLOGY : linear
MOLECULE TYPE : Genomic DNA
ORIGINAL SOURCE : Homo Sapiens
IMMEDIATE SOURCE: human lymphoblastoid cell line CGMI
SEQUENCE DESCRIPTION
CATTTCTTCA AAGCAGGATT AGGGCTTGGA CCATCAGCAT CCCACTCCTG TGTGGCAGAT 60
GGGACATCTA TCTTCTTTCT CCAACCTCGA TCAGGCTTTT GAGGTATGAA ATAATCTGTC 120
TCATGAATAT GCAAATAACC TTACATCTAC TGAGGTAAAT ATGGATACAT CTGGGCCCTG 180
AAAGCATCAT CCAACAACCA CATCCCTTCT CTACAGAAGC CTCTGAGAGG AAAGTTCTTC 240
ACC ATG GAC TGG ACC TGG~AGG GTC TTC~TGC~TTG CTG GCT GTA GCT CCA G 289
Met Asp Trp Thr Trp Arg Val Phe Cys Leu Leu Ala Val Ala Pro
1 5 10 15
GTAAAGGGCC AACTGGTTCC AGGGCTGAGG AAGGGATTTT TTCCAGTTTA GAGGACTGTC 349
ATTCTCTACT GTGTCCTCTC CGCAG GT GCT CAC TCC CAG GTG CAG CTG GTG CAG 403
Gly Ala His Ser Gln Val Gln Leu Val Gln
20 25
TCT GGG GCT GAG GTG AAG AAG CCT GGG GCC TCA GTG AAG GTT TCC TGC 451
Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys
30 35 40
AAG GCA TCT GGA TAC ACC TTC ACC AGC TAC TAT ATG CAC TGG GTG CGA 499
Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr Tyr Met His Trp Val Arg
45 50 55
CAG GCC CCT GGA CAA GGG CTT GAG TGG ATG GGA ATA ATC AAC CCT AGT 547
Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly Ile Ile Asn Pro Ser
60 65 70
GGT GGT AGC ACA AGC TAC GCA CAG AAG TTC CAG GGC AGA GTC ACC ATG 595
Gly Gly Ser Thr Ser Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Met
75 80 85
.... r ~;
ACC AGG GAC ACG ACG AGC GTC TAC GAG CTG AGC AGC CTG
TCC ACA TG 643
A
Thr Arg Asp Thr Thr Ser Val Tyr Glu Leu Ser Ser
Ser Thr Met eu
L
90 95 100 105
AGA TCT GAG GAC GCC GTG TAC TGT AGA GA CACAGTGTGA 691
ACG TAT GCG
Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg
lI0 115
GAAACCACAT CCTCAGAGTG TCAGAAACCC TGAGGGAGGA GTCAGCTGTG CTGAGCTGAG 751
AAAATGACAG GGGTTATTCA GTTTAAGACT GTTTAGAAAA CGGGTTAT 799
SEQUENCE ID NO.: 4 7
SEQUENCE LENGTH . 6 2 7
SEQUENCE TYPE : nucleic acid
STRANDEDNESS : double
TOPOLOGY : 1 inear
MOLECULE TYPE : Genomic DNA
ORIGINAL SOURCE : Homo sa iens
IMMEDIATE SOURCE: human lymphoblastoid cell line CGMI
SEQUENCE DESCRIPTION
CCAAATAAAC ACATTAAATG TCAAGATACG CCCAAAAACT TATCTGCCTG ACCCCCTAGT 60
TGTCTCCGTA ATTTTTGGAT GAAAACCAGC CCACCCCTGA CCCTGCTGCT CTGGGAGAGG 120
AGCCCCAGCC TTGGGATTCC CAAGTGTTTG CATTCAGTGA TCAGGACTGA ACACACAGGA 180
CTCACC AGG GAG TTT GTG CTA AGC TGG GTT TTC CTT GTT GCT ATA TTA 228
Arg Glu Phe Val Leu Ser Trp Val Phe Leu Val Ala Ile Leu
1 5 10
AAA T GTGATTCATG GAGAACTAGA GAGATTGAGT GTGAGTTACA TGAGTGAGAG 282
Lys
AAACAGTGGA TATGTTTGGC AATTTCTGAC TTTTGTGTCT CTGTGTTTGC AG GT GTC 339
Cys Val
2~s~~~~r
-106-
CAGTGT GAGGATCAGCTG GTGGAGTCT GGGGGAGGCTTG GTACAGCCT 387
GlnCys GluAspGlnLeu ValGluSer GlyGlyGlyLeu ValGlnPro
20 25 30
GGGGGG TCCCTGAGACCC TCCTGTGCA GCCTCTGGATTC GCCTTCAGT 435
GlyGly SerLeuA.rgPro SerCysAla AlaSerGlyPhe AlaPheSer
35 40 45
AGC~TAT GTTCTGCACTGG GTTCGCCGG GCTCCAGGGAAG GGTCCGGAG 483
SerTyr ValLeu~HisTrp ValArgArg AlaProGlyLys GlyProGlu
50 55 60 65
TGGGTA TCAGCTATTGGT ACTGGTGGT GATACATACTAT GCAGACTCC .531
TrpVal SerAlaIleGly ThrGlyGly AspThrTyrTyr AlaAspSer
70 75 80
GTGATG GGCCGATTCACC ATCTCCAGA GACAACGCCAAG AAGTCCTTG 579
Val Met Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Lys Ser Leu
85 90 95
TAT CTC AAA TGA ACA GCC TGA TAG CTG AGG AGA TGG CTG TGT ATT ATG 627
Tyr Leu Lys Thr Ala Leu Arg Thr Trp Leu Cys Ile Met
100 105 110
SEQUENCE ID NO.: 4 8
SEQUENCE LENGTH .- 7 4 3
SEQUENCE TYPE : nucleic acid
STRANDEDNESS : double
TOPOLOGY : 1 inear
MOLECULE TYPE : Genomic DNA
ORIGINAL SOURCE : Homo sapiens
IMMEDIATE SOURCE: human lymphoblastoid cell line CGMI
SEQUENCE DESCRIPTION
AAGGGTCCCC ACCCTAGAGC TTGCTATATA GTAGGAGATA TCCAAATAGG NCCCTCCCTC 60
TACTGATGAA AACCCAACCC AACCCTGACC CTGCAGCTCT CAGAGAGGTG CCTTAGCCCT 120
GGATTCCAAG GCATTTCCAC TTGGTGATCA GCACTGAACA CAGAGGACTC ACC ATG 176
Met
1
GAG TTG GGG CTG TGC TGG GTT TTC CTT GTT GCT ATT TTA GAA G 219
Glu Leu Gly Leu Cys Trp Val Phe Leu Val Ala Ile Leu Glu
5 10 15
GTGATTCATG GAAAACTAGA ATGAGTGAGA GAAACAGTGG279
GAGATTTAGT
GTGTGTGGAT
ATATGTGTGG CAGTTTCTGA C CAGGT GTCCAGTGT 333
CCTTGGTGT TCTTTGTTTG
Gly ValGlnCys
GAG GTGCAGCTG GTGGAGTCTGGGGGA GGCTTGGTACAG CCTGGGGGG 381
Glu ValGlnLeu ValGluSerGlyGly GlyLeuYalGln ProGlyGiy
20 25 30 35
TCC CTGAGACTC TCCTGTGCAGCCTCT GGATTCACCTTC AGTAGCTAT 429
Ser LeuArgLeu SerCysAlaAlaSer GlyPheThrPhe SerSerTyr
40 45 50
AGC ATGAACTGG GTCCGCCAGGCTCCA GGGAAGGGGCTG GAGTGGGTT 477
Ser MetAsnTrp ValArgGlnAlaPro GlyLysGlyLeu GluTrpVal
55 60 65
TCA TACATTAGT AGTAGTAGTAGTACC ATATACTACGCA GACTCTGTG 525
Ser TyrIleSer SerSerSerSerThr IleTyrTyrAla AspSerVal
70 75 80
AAG GGCCGATTC ACCATCTCCAGAGAC AATGCCAAGAAC TCACTGTAT 573
Lys GlyArgPhe ThrIleSerArgAsp AsnAlaLysAsn SerLeuTyr
85 90 95
CTG CAAATGAAC AGCCTGAGAGCCGAG GACACGGCTGTG TATTACTGT 621
Leu GlnMetAsn SerLeuArgAlaGlu AspThrAlaVal TyrTyrCys
100 105 110 115
GCG AGAGA CAGACACAAACCT 679
CACAGTGAGG CCCTGCAGGG
GGAGGTCAGT
GTGACAC
-108-
Ala Arg
GTCCGCAGGA CCACCAGGGG GCGACAGGAC ACTGAGCACG GGGCTGTCTC CAGGGCAGGT 739
G CAG 743
SEQUENCE ID NO.: 4 9
SEQUENCE LENGTH . 7 6 3
SEQUENCE TYPE : nucleic acid
STRANDEDNESS : double
TOPOLOGY : 1 i near
MOLECULE TYPE : Genomic DNA
ORIGINAL SOURCE : Homo sapiens
IMMEDIATE SOURCE : human lymphoblastoid cell line CGMI
SEQUENCE DESCRIPTION
TCACCCAACT CCTCCAGGCA CAGTCATCTT ATCTGGCGCC GTCCTCTCGT CAGNTGTCCC 60
ACCCCAGAGC TTGGTATATA GTAGGAGACA TNCAAATAAG GCCCTCCCTC TGCTGATGAA 120
AATGAGCCCA GCCCTGACCC TGCAGCTCTG GGAGAGGAGC CCCANCCGTG AGATTCCCAG 180
GAGTTTCCAC TTGGTGATCA GCACTGAACA CAGACCACCA~ACC ATG GAG TTT GGG 235
Met Glu Phe Gly
1
CTT AGC TGG GTT TTC CTT GTT GCT ATT TTA AAA G GTAATTCATG 279
Leu Ser Trp Val Phe Leu Val Ala Ile Leu Lys
10 15
GTGTACTAGA GATACTGAGT GTGAGGGGAC ATGAGTGGTA GAAACAGTGG ATATGTGTGG 339
CAGTTTCTGA CCTTGGTGTT TCTGTGTTTG CAG GT GTC CAA TGT GAG GTG CAG 392
Gly Val Gln Cys Glu Val Gln
CTG GTG GAG TCT GGG GGA GGC TTG GTA CAG CCA GGG CGG TCC CTG AGA 440
Leu Val Glu Ser Gly Gly Gly.Leu Val Gln Pro Gly Arg Ser Leu Arg
30 35
CTC TCC TGT ACA GCT TCT GGA TTC ACC TTT GGT GAT TAT GCT ATG AGC 488
~ ~. ~ 2 5'~'~
-109-
LeuSer CysThrAla SerGlyPheThr PheGlyAspTyr AlaMetSer
40 45 50
TGGTTC CGCCAGGCT CCAGGGAAGGGG CTGGAGTGGGTA GGTTTCATT 536
TrpPhe ArgGlnAla ProGlyLysGly LeuGluTrpVal GlyPheIle
55 60 65 70
AGAAGC AAAGCTTAT GGTGGGACAACA GAATACACCGCG TCTGTGAAA 584
ArgSer LysAlaTyr GlyGlyThrThr GluTyrThrAla SerValLys
75 80 85
GGCAGA TTCACCATC TCAAGAGATGGT TCCAAAAGCATC GCCTATCTG 622
Gly~Arg PheThrIle SerArgAspGly SerLysSerIle .AlaTyrLeu
90 95 100
CAAATG AACAGCCTG AAAACCGAGGAC ACAGCCGTGTAT TACTGTACT 680
GlnMet AsnSerLeu LysThrGluAsp ThrAlaValTyr TyrCysThr
105 110 115
AGAGA ACACAGACCT 735
CACAGTGNGG CCCTGCAGGC
GGAGGTCAAT
GTGAGCCCAG
A
rg
CCGCACAGAG 763
CCACCAGGGG
GCGCTAGG
SEQUENCE ID NO.: 5 0
SEQUENCE LENGTH . 2 8 3
SEQUENCE TYPE : nucleic acid
STRANDEDNESS : double
TOPOLOGY : 1 inear
MOLECULE TYPE : Genomic DNA
ORIGINAL SOURCE : Homo sa iens
IMMEDIATE SOURCE : human lymphoblastoid cell line CGMI
SEQUENCE DESCRIPTION
TGGCTCACC ATG GAG TTA GGG CTG AGC TGG GTT TCC CTT GTC ATT ATA 48
Met Glu Leu Gly Leu Ser Trp Val Ser Leu Val Ile Ile
..._
-110-
1 ~ 5 10
TTA AAA G GCGAATAATG GAGAACTTGA GATATGGAGT GTGAGTGGAT ATGAGTGAAG 105
Leu Lys
AAACAGTGAT TCTGTGTGGC AGGTTCTGAC~TCAGATGTCC TCTGTGCTTG TAG GT GTC 163
Gly Val
TAG TGT GGG GTG CAG ATG GTG GAG TCT TGG GGA GAG TTG GCA CAA NCT 211
Cys Gly Val Gln Met Val Glu Ser Trp Gly Glu Leu Ala Gln Xaa
25 30
GAA TGT GCC TGA GAC TCT GCC GTG CAT CCT CTG AAT CCA CCT TCT GTA 259
Glu Cys Ala Asp Ser Ala Val His Pro Leu Asn Pro~Pro Ser Val
35 40 45
GCT ACT AGA TCA GCT GAA TCT GCC ~ 283
Ala Thr Arg Ser Ala Glu Ser Ala
50 55
SEQUENCE ID NO.: 5 1
SEQUENCE LENGTH . 7 0 0
SEQUENCE TYPE : nucleic acid
STRANDEDNESS : double
TOPOLOGY : 1 inear
MOLECULE TYPE : Genomic DNA
ORIGINAL SOURCE : Homo sa iens
IMMEDIATE SOURCE : human lymphoblastoid cell line CGMI
SEQUENCE DESCRIPTION
AGGTTCTGGG TTATAAACNC TGTAGACTCC TCCCTTCAGG GCAGGNTGAC CAACTATGCA 60
AATGCAAGTG GGGGCCTCCC CACTTAAACC CAGGGCTCCC CTCCACAGTG AGTCTCCCTC 120
ACTCCCCAGC TGGGATCTCA GGGCTTCATT TTCTGTCCTC CACCATC ATG GGG TCA 176
Met Gly Ser
..._
~1~~ ~~
-111-
1
ACC GCCATC GCCCTC~CTC GCTGTTCTC CAAG GTCAGTCCTG 223
CTC CTG
Thr AlaIle AlaLeuLeu AlaValLeu Gln
Leu Leu
10 15
CCGAGGGCTT GAGGTCACAG GGAGAACGG GCCCCTGATT 283
A GTGGAAAGGA CAAATTTTGT
GTCTCCCCCA CAG GA TC GT TCC 334
G T GAG
GTG
CAG
CTG
GTG
CAG
TCT
GGA
GCA
G ly al ys Ser lu ln
V C G Val Leu
G Val
Gln
Ser
Gly
Ala
20 25
GAG GTGAAAAAG CCCGGGGAG CTGAAGATC TCCTGT AAG GGT 382
TCT TCT
Glu ValLysLys ProGlyGlu LeuLysIle SerCys Lys Gly
Ser Ser
30 35 40
GGA TACAGCTTT ACCAGCTAC ATCGGCTGG GTGCGC CAG ATG 430
TGG CCC
Gly TyrSerPhe ThrSerTyr IleGlyTrp ValArg Gln Met
Trp Pro
45 50 55 60
GGG AAAGGCCTG GAGTGGATG ATCATCTAT CCTGGT GAC TCT 478
GGG GAT
Gly LysGlyLeu_GluTrpMet IleIleTyr ProGly Asp Ser
Gly Asp
65 70 75
ACC AGATACAGC CCGTCCTTC.CAAGGCCAGGTC ACCATC TCA GCC 526
GAC
Thr ArgTyrSer ProSerPhe GlyGlnYal ThrIl~e Ser Ala
Gln Asp
0 $5 90
AAG TCCATCAGC ACCGCCTAC CAGTGGAGC AGCCTG AAG GCC 574
CTG TCG
Lys SerIleSer ThrAlaTyr GlnTrpSer SerLeu Lys Ala
Leu Ser
95 100 105
GAC ACCGCCATG TATTACTGT AGACA A GAAACCAGCC 623
GCG CACAGTGAG
Asp ThrAlaMet TyrTyrCys Arg
Ala
110 115
CCGAGCCCGT GGTGCAGAAT GAGCTGCTAG 683
CTAAAACCCT AGACTCACTC
CCACACCGCA
CCCAGGGGCC AT 700
TCTCT
-." ,
-112-
SEQUENCE ID NO.: 5 2
SEQUENCE LENGTH . 7 6 7
SEQUENCE TYPE : nucleic acid
STRAND):DNESS : doub 1 a
TOPOLOGY : 1 inear
MOLECULE TYPE : Genomic DNA
ORIGINAL SOURCE : Homo sa iens .
IMMEDIATE SOURCE : human lymphoblastoid cell line CGMI
SEQUENCE DESCRIPTION
ACACTCACCT GCTCTGGGCT CCTCCAAACT CTCCTCAGGA TTCCCCACCC CAGAGCTTGC 60
TATATAGTAG GAGACATCCA AACAAGAGCC NAAACCTCTG CTGATGAAAA GCAGCCCAGC 120
CCTGACCCTG CAGCTCTGGG AGAGGAGCCC CAGCTCCAGG ATTCCCAGGT CTTTCCATTT 180
AGTCTTCAGG GCTGAGCACA GAGGACTCAC C ATG GAG TCT GGG CTG AGC TGG 232
Met Glu Ser Gly Leu Ser Tcp
1 5
GTT TTC CTT GTT GCT ATT TTG AAA G GTGATTCATG GGGAATGAGT 277
Val Phe Leu Val Ala Ile Leu Lys
15
TGAATGTAAG TGAATATGAG TGAGAGAAAC AGTGGATGTG TGCGGCAGTT TCTGACCAGG 337
GTGTCTCTGT GTTTGCAG GT GTC CAG TGT GAG GTG CAG CTG GTG GAG TCT 387
Gly Val Gln Cys Glu Val Gln Leu Val Glu Ser
25
GGG TGA GGC TTG GTA CAG CCT GGA GGG TCC CTG AGA CTC~TCC TGT GCA 435
Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala
. 35 40
GCC TCT GGA TTC ACC TTC AGT AGC TCC TGG ATG CAC TGG GTC TGC CAG 483
Ala Ser Gly Phe The Phe Ser Ser Ser Trp Met His Trp Val Cys Gln
45 50 55
GCT CCG GAG~AAG GGG CTG GAG TGG GTG GCC GAC ATA AAG TGT GAC GGA 531
-..
-113-
AlaPro GluLys Leu GluTrpValAla AspIleLysCys AspGly
Gly
60 65 70
AGTGAG AAATAC GTA.GACTCTGTGAAG GGCCGATTGACC ATCTCC 579
TAT
SerGlu LysTyr Val AspSerValLys GlyArgLeuThr IleSer
Tyr
75 80 85
AGAGAC AATGCC AAC TCCCTCTATCTG CAAGTGAACAGC CTGAGA 627
AAG
ArgAsp AsnAla Asn SerLeuTyrLeu GlnValAsnSer LeuArg
Lys
90 95 100 105
GCTGAG GACATG GTG TATTACTGTGTG AGAGG 672
ACC CACAGTGAGG
AlaGlu AspMet Val TyrTyrCysVal Arg
Thr
I10 115
GGAGGTCAGT TGAGCCCAG CCTGCAG GGGCATCTGGA GC GGGGG732
G ACACAAACCT CACAA
CGCTCAGGAT CACAGAGGG CCCA 767
A ACAGGGGCAG
C
SEQUENC$ ID NO.: 5 3
SEQUENCE LENGTH . 7 2 4
SEQUENCE TYPE : nucleic acid
STRANDEDNESS : double
TOPOLOGY : 1 inear
MOLECULE TYPE : Genomic DNA
ORIGINAL SOURCE : Homo sapiens
IMMEDIATE SOURCE: human lymphoblastoid cell line CGMI
SEQUENCE DESCRIPTION
CCATTCGGTG ATCAGCACTG AACACAGAGG ACTCACC ATG GAG TTT TGG CTG AGC 55
Met Glu Phe Trp Leu Ser
1 5
TGG GTT TTC CTT GTT GCT ATT TTA AAA G GTGATTCATG GAGAACTAGA 103
Trp Val Phe Leu Val Ala Ile Leu Lys
15
GATATTGAGT GTGAGTGAAC ACGAGTGAGA GAAACAGTGG ATATGTGTGG CAGTTTCTAA 163
CCAATGTCTC.TGTGTTTGCA G ~GT GTC CAG TGT GAG GTG CAC CTG GTG GAG 213
Gly Val GIn Cys Glu Val Gln Leu Val Glu
20 25
TCTGGAGGAGGC TTGATCCAG CCTGGG TCCCTG AGACTCTCC TGT 261
GGG
SerGlyGlyGly LeuIleG~InProGlyGlySerLeu Ai-gLeuSer Cys
30 35 ~ 40
GCAGCCTCTGGG TTCACCGTC AGTAGCAACTACATG AGCTGGGTC CGC 309
AlaAlaSerGly PheThrVal SerSerAsnTyrMet SerTrpYal Arg
45 50 55
CAGGCTCCAGGG AAGGGGCTG GAGTGGGTCTCAGTT ATTTATAGC GGT 357
GlnAlaProGly LysGlyLeu GluTrpYalSerVal IleTyrSer Gly
60 65 70
GGTAGCACATAC TACGCAGAC TCCGTGAAGGGCCGA TTCACCATC TCC 405
GlySerThrTyr TyrAlaAsp SerValLysGlyArg PheThrIle Ser
75 80 g5
AGAGACAATTCC AAGAACACG CTGTATCTTCAAATG AACAGCCTG AGA 453
Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg
90 95 100 105
GCC GAG GAC ACG GCC GTG.TAT TAC TGT GCG AGA GA CACAGTGAGG 498
Ala Glu Asp Thr Ala Val Tyr Tyr Cys A~la Arg
110 . 115
GGAAGTCATT GTGCGCCCAG ACACAAACCT CCCTGCAGGA ACGCTGGGGG GAAATCAGCG 558
GNAGGGGGCG CTCAGGAGCC ACTGATCAGA GTCAGCCCCG GAGGCAGGTG CAGATGGAGG 618
CTGATTTCCT TGTCAGGATG TGGGGACTTT TGTCTTCTTC TGACGGGTTC CCCAGGGGAA 678
CCTCTCTAAG TTTAGCATTC TGTGCCTATG AACGTCTTCT CTAAGT 724
SEQUENCE ID NO.: 5 4
SEQUENCE LENGTH . 7 0 6
-115-
SEQUENCE TYPE : nucleic acid
STRANDEDNESS : double
TOPOLOGY : 1 inear
MOLECULE TYPE : Genomic DNA
ORIGINAL SOURCE : Homo sa iens
IMMEDIATE SOURCE: human lymphoblastoid cell line CGMI
SEQUENCE DESCRIPTION
CTTGCTATAC AGTAGGAGAC ATGCNAATAG GTTTCTCCCT CTGCTGATGA CCAGTCCTGA 60
CCCCATAGCT.CTGGGAGAGA AGCGCCAGCC CTGGGATTCC CAGGGGTTTC CATTTGGTGA 120
TCAGGACTAA AGACAGAGGA CCCACC ATG GAG CTT GGG CTG AGC TGG GTT TTC 173 .
Met Glu Leu .Gly Leu Ser Trp Val Phe
.1 5
ACT GTT ACT GTT TTA AAA G GTGAACTAGA GAGATTGAGT GTGAATGGAT 222
Thr Val Thr Vat Leu Lys
15
ACACTTGAGA GAAACAGTGG ATATGTCTGG AACTTTCTGA CCAGGACACC TACAAGTTTG 282
CAG GT GTC CAG TGT GAG GTA CAG CTG GTG GAG TCT GAA GAA AAC CAA 329
Gly Val Gln Cys Glu Val Gln Leu Val Glu Ser Glu Glu Asn Gln
25 30
AGA CAA CTT GGG GGA TCC CTG AGA CTC TCC TGT GCA GAC TCT GGA TTA 377
Arg Gln Leu Gly Gly Ser Leu Arg Leu Ser Cys Ala Asp Ser Gly Leu
35 40 45
ACC TTC AGT AGC TAC TGA ATG AGC TCA GAT TCC CAA GCT CCA GGG AAG 425
Thr Phe Ser Ser Tyr Met Ser Ser Asp Ser Gln Ala Pro Gly Lys
50 55 60
GGG CTG GAG TGA GTA GTA GAT ATA TAG TAG GAT AGA AGT CAG CTA TGT 473
Gly Leu Glu Val Val Asp Ile Asp Arg Ser Gin Leu Cys
65 70
TAT GCA CAA TCT GTG AAG AGC AGA TTC ACC ATC TCC AAA GAA AAT GCC 521
-116-
Tyr Ala Gln Ser.Yal Lys Ser Arg Phe Thr Ile Ser Lys Glu Asn Ala
75 80 85 90
AAG AAC TCA CTC TGT TTG CAA ATG~AAC AGT CTG AGA GCA GAG GGC ACG 569
Lys Asn Ser Leu Cys Leu Gln Met Asn Ser Leu Arg Ala Glu Gly Thr
95 . 100 ~ 105
GCC GTG.TAT TAC TGT ATG TGA GT CACCAGGTAA GAAGACATCA GTGTGATCAC 622
Ala Val Tyr Tyr Cys Met
110
AGACACAGAA TTTCCTGAAA TAAGGGAGGA GTCTGGGCTA AAAGGGCACT CAGGACCCAC 682
AGAAAACAGC GGAAGCTCTA GGGC 706
SEQUENCE ID NO:: 5 5
SEQUENCE LENGTH . 8 0 0
SEQUENCE TYPE : nucleic acid
STRANDEDNESS : double
TOPOLOGY : 1 inear
MOLECULE TYPE : Genomic DNA
ORIGINAL SOURCE : Homo sa iens
IMMEDIATE SOURCE: human lymphoblastoid cell line CGMI
SEQUENCE DESCRIPTION
GGAAGAGANC TTGATTCTCA AGAGGGCACA GCCAGCTTCC TACTCCCAGG GCAAGCCCCA 60
AAAGACTGGG NCCTCCCTCC TCCCTTTTCA CCTGTCCATA CAAAGTCACC GCCCACATGC 120
AAATCCTCAC TTAGGCACCT ACAGGAAACC AGCACACATT TCCTTAAATT TGGGATCCAG 180
CTCACATGGG AAATACTTTC TGAGACTCAT GGGCCTCCTG CACAAGAAC ATG AAA CAC 238
Met Lys His
I
CTG TGG TTC TTC CTC CTG CTG GTG GCA GCT CCC AGA T GTGAGTGCCT 285
Leu Trp Phe Phe Leu Leu Leu Val Ala Ala Pro Arg
10 15
,.
-117-
CAGGGATCCA GACCTGAAGA TATGAGATGC TGCCTCTCAT CCCAGGGCTC ACCGTGGTTC 345
TCTCTGTTCA CAG GG GTC CTG TCC CAG GTG CAG CTG CAG GAG TCG GGC CCA 396
Trp Val Leu Ser Gln Val Gln Leu Gln Glu Ser Gly Pro
20 25
GGA CTGGTG CCTTCGGAG.ACCCTGTCC.CTC GCT GTC 444
AAG ATC TCT
TGC
Gly LeuValLys ProSerGlu LeuSerLeu Ile Ala ValSer
Thr Cys
30 35 40
GGT GACTCCATC AGCAGTGGT TGGTGAATC TGG CGC CAGCCC 492
AAG GTC
Gly AspSerIle SerSerGly Trp Ile Trp Arg GlnPro
Asn Val
45 50 55
CCA GGGAAGGGG CTGGAGTGG GGGGAAATC CAT AGT GGGAGC 540
ATT CAT
Pro GlyLysGly LeuGluTrp GlyGluIle His Ser GlySer
Ile His
60 65 70 75
ACC TACTACAAC CCGTCCCTC AGTCGAATC ACC TCC GTAGAC 588
AAG ATG
Thr TyrTyrAsn ProSerLeu SerArgIle Thr Ser ValAsp
Lys Met
80 85 90
ACG TCCAAGAAC CAGTTCTAC AAGCTGAGC TCT ACC GCCGCG 636
CTG GTG
Thr SerLysAsn GlnPheTyr LysLeuSer Ser Thr AlaAla
Leu Val
95 100 105
GAC ACGGCCGTG TATTACTGT AGATACACA~GTG GGAGGTGAGT 685
GCG AGG
Asp ThrAtaVal TyrTyrCys Arg Thr Val
Ala Tyr Arg
110 115 120
GTGAGCCCAG CACAAACCT AGGCAGAGGG GGNGGGCACA
745
A CCCTACAGAT GGTGCTGCTC
AGGANCAACA AGCCCGAGGN CCGGGTCANG 800
GGGGGCGCGC AGCAG
GANGNCACAG
SEQUENCE ID NO.: 5 6
SEQUENCE LENGTH : 4 2 9
SEQUENCE TYPE : nucleic acid
STRANDEDNESS : double
-,.
-118-
TOPOLOGY : linear
MOLECULE TYPE :. Genomic DNA
ORIGINAL SOURCE : Homo sa iens ,
IMMEDIATE SOURCE : human lymphoblastoid cell line CGMI
SEQUENCE DESCRIPTION
AGGAATTGGG CTATTCAATG CATCCTTCGT GAATATGCAA ATCACTAAGG TTAATACAGA 60
TATCTCTGTG CCGTGAGAGC ATCACCCAAC AACCACACCC CTCCTTGGAG AATCCCTAGA 120
TCACAGCTCC TCACC ATG GAC TGG ACC TGG AGC ATC CTC TTC TTG GTG GCA 171
Met Asp Trp Thr Trp Ser Ile Leu Phe Leu Val Ala
1 5 10
GCA GCA ACA G GTAAGGACTC CCCAGTCCCA GGGCTGAGGG AGAAACCAGG 221
Ala Ala Thr
CCAGTCATGT GAGACTTCAC CCACTGCTGT CTCCTCTCCA CAG GT GCC CAC TCC CGA 278
Gly Ala His Ser Arg
GTG CAG CTG GTG CAG TCT GGG CCT GAG GTG AAG CAG CCT GGG GCC TCG 326
Val Gln Leu Val Gln Ser Giy Pro Glu Val Lys Gln Pro Gly Ala Ser
30 35
GCG AAG GTC TCC TGC AAG GTG TCT GGT TAA ACT GTC ATC ACC TAT GGT 374
Ala Lys Val Ser Cys Lys Val Ser Gly Thr Val Ile Thr Tyr Gly
40 45 50
ATG AAT TGG ATA CGA. CAG ACC CCA GGA CAG GGG CTT GAG TGG ATG GGA 422
Met Asn Trp Ile Arg Gln Thr Pro Gly Gln Gly Leu Glu Trp Met Gly
55 60 65
TGG ATC C 429
Trp Ile
SEQUENCE ID N0. : 5 7
SEQUENCE LENGTH . 4 6 2
~~~2~'~'~
-lI9-
SEQUENCE TYPE : nucleic acid
STRANDEDNESS :double
TOPOLOGY : I inear
MOLECULE TYPE : Genomic DNA
ORIGINAL SOURCE : Homo sa iens
IMMEDIATE SOURCE : human lymphoblastoid cell line CGMI
SEQUENCE DESCRIPTION
CATCAGTTGC GCTCAGGAGT TTTAGAACAG CCTGGCAACA CATTTAGATC TGGGCTTCCC 60
TTCTCATCAC CCTCAATATT AGTGTCCCTT GTGAATCAGG TCCAGCTGCG GCTGTTCCAC 120
ATGGGGCCGT TCTTCCATTT CCTCAGTGTT TGCAGAAGTC CTGTGTGAAG TTTATTGATG 180
GAGTCAGAGG CAGAAAATTG TACAGCCCAG TGGTTCACTG AGACTCTCCT GCAAAGGCTC 240
TGATTTCACC TTTACTGGCT ACAGCATGAG CTTGGTCCAG CAGGCTTCAT GACAGGGATT 300
GGTGTGGGTG GAAACAGTGA.GTAGTCAAGT GGGAGTTCTC AGAGTTACTC TCCATGAGTA 360
CAAATAAATT AACAGTCCCA AGCGACACCT TTTCATGTGC AGTCTACCTT ACAATGACCA 420
ACCTGAAAGT CCAAGGACAA GGCTGTGTAT TACTGTGAGG GA ~ 462
SEQUENCE ID NO.: 5 8
SEQUENCE LENGTH . 6 2 9
SEQUENCE TYPE : nucleic acid
STRANDEDNESS : double
TOPOLOGY : 1 inear
MOLECULE TYPE : Genomic DNA
ORIGINAL SOURCE : Homo sapiens
IMMEDIATE SOURCE: human lymphoblastoid cell line CGMI
SEQUENCE DESCRIPTION
AGGGTCTTCA GCTATGAAAT GCTCTGACTC ATGAATATGC AAATAACCTG AGATGCACTG 60
AGGTAAATAT GGATATTTGT CAGCCCTGAG AGCATCATCC AGAAACCACA TCCCTCCGCT 120
AGAGAAGCCC TGACGGCACA GTTCCTCACT ATG GAC TGG ATT TGG AGG ATC CTC 174
Met Asp Trp Ile Trp Arg Ile Leu
._
-120-
1 5
TTC TTGGTGGGA GCAGCGACA G AGTGATGAGG 226
GCAAGGAGAT
GCCAAGTCCC
Phe LeuValGly AlaAlaIle
15
AGGGGAT TGA GTGTTCTCTC CACAG 283
GTCCAGTCAA GT
GGTGGCTTTC
ATCCACTCCT
Gly
GCC CACTCCCAA ATGCAGCTG GTGCAGTCTGGGCCTGAG GTGAAGAAG 331
Ala HisSerGln MetGlnLeu ValGlnSerGlyProGlu ValLysLys
20 25 30
CCT GGGACCTCA GTGAAGGTC TCCTGCAAGGCTTCTGGA TTCACCTTT 379
Pro GlyThrSer ValLysVaI .SerCysLysAlaSerGly PheThrPhe
35 40 45
ACT AGCTCTGCT GTGCAGTGG GTGCGACAGGCTCGTGGA CAACGCCTT 427
Thr SerSerAla ValGlnTrp ValArgGlnAlaArgGly GlnArgLeu
50 55 60
GAG TGGATAGGA TGGATCGTC GTTCGCAGTGGTAACACA AACTACGCA 475
Glu TrpIleGly TrpIleVal ValGlySerGlyAsnThr AsnTyrAla
65 70 75 80
CAG AAGTTCCAG GAAAGAGTC ACCATTACCAGGGACATG TCCACAAGC 523
Gln LysPheGln GluArg.ValThrIleThrArgAspMet SerThrSer
85 90 95
ACA GCCTACATG GAGCTGAGC AGCCTGAGATCCGAGGAC ACGGCCGTG 571
Thr AlaTyrMet GluLeuSer SerLeuArgSerGluAsp ThrAlaVal
100 105 110
TAT TACTGTGCG GCAGA CCTGAGA GTG 618
CACAGTGTGA
AAACCCACAT
Tyr Tyr~CysAla Ala
115
TCAGAAACGC 629
C
2 ~. 62 ~? ?
-121-
SEQUENCE ID NO.: 5 9
SEQUENCE LENGTH . 6 2 2
SEQUENCE TYPE : nucleic acid
STRANDEDNESS : double
TOPOLOGY : 1 inear
MOLECULE TYPE : Genomic DNA
ORIGINAL SOURCE : Homo sa i.ens
IMMEDIATE SOURCE : human lymphoblastoid cell
line CGMI
SEQUENCE.DESCRIPTION
CCTCCTTTTT CACCTCTCCA TACAAAGGCA CCACCCACAT ACTTAAGCAC60
GCAAATCCTC
CCACAGGAAA CCACCACACA TTTCCTTAAA TTCAGGTTCC GGAAATACTT120
AGCTCACATG
TCTGAGAGCT CTGGACCTCC TGTGCAAGAA C ATG AAA TTC TTC 172
CAT CTG TGG
Met Lys His Leu Trp Phe Phe
1 ~ 5
CTT CTC CTG GTG GCA GCT CCC AGA T GTGAGTATCT 217
CAGGGATCCA
Leu Leu Leu Val Ala Ala Pro Arg
15
GACATGGGGA TATGGGAGGT GCCTCTGATC CCAGGGCTCA CTCTGTTCAC277
CTGTGGGTCT
AG GG GTC CTG TCC CAG GTG CAG CTG CAG GAG GA CTG 326
TCG GGC CCA G GTG
Trp Val Leu Ser Gln Val Gln Leu Gln Glu Ser ly Leu
Gly Pro G Val
25 30
AAG CCT TCG GAG ACC CTG TCC CTC ACC TGC ACT GGC TCC 374
GTC TCT GGT
Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Gly Ser
Val Ser Gly
35 40 45
GTC AGT AGT TAC TAC TGG AGC TGG ATC CCG CAG AAG GGA 422
CCC CCA GGG
Val Ser Ser Tyr Tyr Trp Ser Trp Ile Arg Gln Lys Gly
Pro Pro Gly
50 55 60
CTG GAG TGG ATT GGG TAT ATC TAT TAC AGT GGG TAC AAC 470
AGC ACC AAC
Leu Glu Trp Ile Gly Tyr Ile Tyr Tyr Ser Gly Tyr Asn
Ser Thr Asn
__ ~2~~2~'~'~
65 -122-
70 , 75
CCCTCCCTC. AAG CGA GTC ATA GTA GAC ACG AAG AAC 518
AGT ACC TCA TCC
ProSerLeu Lys Arg Val Ile Val Asp Thr Lys Asn
Ser Thr Ser Ser
80 85 90 95
CAGTTC.TCC CTG CTG AGC GTG GCT GCG GAC GCC GTG 566.
AAG TCT ACC ACG
GlnPheSer Leu Leu Ser Val Ala Ala Asp Ala Val
Lys Ser Thr Thr
100 105 110
TATTACTGT GCG GA CACAGTGAGG GTGAGCCCAGACAAAAACC
AGA GGAGGTGAGT 622
TyrTyrCys Ala
Arg
115
SEQUENCE ID NO.: 6 0
SEQUENCE LENGTH . 5 8 8
SEQUENCE TYPE : nucleic acid
STRANDEDNESS : double
TOPOLOGY : linear
MOLECULE TYPE : Genomic DNA
ORIGINAL SOURCE : Homo sa iens
IMMEDIATE SOURCE: human lymphoblastoidline CGMI
cell
SEQUENCE DESCRIPTION
CCCGGGATTC CCAGCTGTCT CCACTTGGTC AACACAGAAG ACACACC 57
ATGAACACTG
ATG GAG TCT GGG CTG AGC TGG ATT GCA GTT TTA AAA 103
TTC CTT GTT G
Met Glu Ser Gly Leu Ser Trp Ile Ala Val Leu Lys
Phe Leu Val
1 5 10 15
GTGATTTATG GAGAATAGAC ACACTGAGTG TAAGTGAGAG AAACAGTGGA163
TGACTGGACA
TTTGTGTGGC AGTTTCTGAC CAGGGTGTCT A GG TGT CCA GTG 228
CCGTGTTTGC TGA
Gly Cys Pro Val
GGT GCA GCT GGT GGA GTC TGG GGG .AAA GAC TGG GGG 266
AGG CTT AGT GTC
Gly Ala Ala Gly Gly Val Trp Gly Lys Asp Trp Gly
Arg Leu Ser Val
20 25 -123-
30 35
TCT GAGACTCTC CTGTGCAGC TGG CACCTT CAGTAGCTC TGC 314
CTC ATT
Ser GluThrLeu LeuCysSerLeu Trp HisLeu Gln Leu Cys
Ile
40 45 50
TAT GCACTGGGT CCACCAGGCTCC AGG GGGTTT GGAGTGGGT CTC 362
AAA
Tyr AlaLeuGly ProProGlySer Arg Gly.PheGlyValGly Leu
Lys
55 60 65
AGT TATTAGTAC AAGTGGTGATAC CGT CTACAC AGACTC.TGT GAA 410
' ACT
Ser Tyr Tyr LysTrp Tyr Arg LeuHis ArgLeuCys Glu .
Thr
70 75 80
GGG CTGATTCAC CATCTCTAGAGA CAA CCAGAA TTCACTGTA TCT 458
TGC
Gly LeuIleHis HisLeu Arg Gln ProGlu PheThrVal Ser
Cys
85 90 95
GCA GAACAG CCTGAGAGCCGA CGA GGCTGT GTATTACTG TGT 506
AAT CAT
Ala GluGln ProGluSerrg Arg GlyCys ValLeuLeu Cys
Asn A His
100 105 110
GAA AGA CGCAGTGAGA AGTCAGTGTG AGCCCAGACA CAAACCTCCT GCAGGGTACC 562
Glu Arg
TGGGACAACC AGGGAAAGCC TGGGAC 5gg
S EQUENCE I D N0. : 6 1
SEQUENCE LENGTH . 1 2 1 2
SEQUENCE TYPE : nucleic acid
S TRANDEDNESS : doub 1 a
TOPOLOGY : 1 inear
MOLECULE TYPE : Genomic DNA
ORIGINAL SOURCE : Homo sa iens
IMMEDIATE SOURCE: human lymphoblastoid cell line CGMI
SEQUENCE DESCRIPTION
~~.~5'~
CCTCCTTTTT CACCTCTCCG TACAAAGGCA CC ~ CACAT GCAAATCCTT ACTTAAGCAC 60
CCACAGGAAA CCACCACACA TTTCCTTAAA TTCAGGTTCC AGCTCACATG GGAAATACTT 120
TCTGAGAGCC TGGACCTCCT GTGCAAGAAC ATG.AAA CAC CTG TGG TTC TTC CTC 174
Met Lys His Leu Trp Phe Phe Leu
1 5
CTC CTG GTG GCA GCT CCC AGA T GTGAGTGTCT CAGGGATCCA GACATGGGGG 226
Leu Leu Val Ala Ala Pro Arg
15
TATGGGAGGT GCCTCTGATC CCAGGGC'fCA CTGTGGGTCT CTCTGTTCAC AG GG GTC 283
Trp Val
CTG TCC CAG GTG CAG CTG CAG GAG TCG GGC CCA GGA CTG GTG AAG CCT 331
Leu Ser Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro
25 sn
TCGGAG ACCCTGTCC CTCACCTGCACT GTCTCTGGT GGCTCCGTC AGC 379
SerGlu ThrLeuSer LeuThrCysThr ValSerGly GlySerVal Ser
35 40 45
AGTGGT AGTTACTAC TGGAGCTGGATC CGGCAGCCC CCAGGGAAG GGA 427
SerGly SerTyrTyr TrpSerTrpIle ArgGlnPro ProGlyLys Gly
50 55 60 65
CTGGAG TGGATTGGG TATATCTATTAC AGTGGG~AGC ACCAACTAC AAC 475
LeuGlu TrpIleGly TyrIleTyrTyr SerGlySer ThrAsnTyr Asn
70 75 80
CCCTCC CTCAAGAGT CGAGTCACCATA TCA.GTAGAC ACGTCCAAG AAC 523
ProSer LeuLysSer ArgYalThrIle SerYalAsp ThrSerLys Asn .
. 85 90 95
CAGTTC TCCCTGAAG CTGAGCTCTGTG ACCGCTGCG GACACGGCC GTG 571
GlnPhe SerLeuLys LeuSerSerVal ThrAlaAla AspThrla Val
A
100 105 110
TATTAC TGTGCGAGA GA GTGAGCCCAG 618
CACAGTGAGG
GGAGGTGAGT
-I25-
Tyr Tyr Cys Ala Arg
115
GACACAAACC TCCCTCATGG ACGCGGAGGG GACCGGCGCA GGTGCTGCTC AGGACCAGCA 678
GGTGGCGCGC GGGGCCCCCA GAGCATGAGG CCGGGTCAGG-ACAGGTGCAG GGAGGGCTTC 738
CTCATCTGCT CACTGGTCTC CGTCCTCGCC AGCACCTCGC TGTCACCAGG GCTCCTCTTT 798
CTTTATTATC TGTGGTTCTG CTTCCTCACA TTCTTGTGCC AGGAAAGAAA CGAGGAAGAC 858
GGGTTTTCGT CTATAGTTGA AGCTTTTACT AGGATCTTGC CTACAAGTTC CTGCATGACC 918
CATTATAACT TATCGATTAA AAAATATATA TTCTAATGCT TCTCACCATC TCTTGATTTG 978
TATCATCAAC TGAATTGTAC CCTCTTTGAA ATTCATATGA,TGAAACCTTA AATTCAATGG 1038
ATCTATATTG GAATTTTAAT GAAATAATTA AGGTTAAATG TGGTCATAAT TGTAAGACCC 1098
TAATGCAATA GACGTGTTGT CTTTATAAGA AGAGGAAGAG ACACCAGAGA CCTCTCACTT 1158
TTCACGTGCA GGCAGAGAAG AGGCCATGTG GAGAGATAGT GCACTAGAAG GTGG 1212
SEQUENCE ID NO.: 6 2
SEQUENCE LENGTH . 5 6 0
SEQUENCE TYPE : nucleic acid
STRANDEDNESS : double
TOPOLOGY : 1 inear
MOLECULE TYPE : Genomic DNA
ORIGINAL SOURCE : Homo sa iens
IMMEDIATE SOURCE : human lymphoblastoid cell line CGMI
SEQUENCE DESCRIPTION
GATCAGCACT GAACACAGAG GACTCACC ATG GAG TTT GGG CTG AGC TGG GTT 52
Met Glu Phe Gly Leu Ser Trp Val
1 5
TTC CTT GTT GCT AAT TTA AGA G GTGATTCATA GATAAATAGA GATGTTGAGT 104
Phe Leu Val Ala Asn Leu Arg
15
GGGAGTGGAC ATGAGTGAGA GAAACAGTGG ATGTGTGTGG CAGTTTCTGA CCTTGGTGTC 164
~~.62~'~~'~
TTTGTGTTTG CAG GT GTC CAG TGT GAG GTG CAG CTG GTG GAG TCT GGG GAA 215
Gly Yal Gln Cys Glu Val Gln Leu VaI Glu Ser Gly Glu
20 25
GGC TTGGTCCAG CCTGGGGGG TCCCTGAGACTC TCCTGTGCA GCCTCT 263
Gly LeuVal.GlnProGlyGly SerLeuArgLeu SerCysAla AlaSer
30 35 40
GGA TTCACCTTC AGTAGCTCT GCTATGCAGTGG GTCCGCCAG GCTCCA 311
Gly PheThrPhe SerSerSer AlaMetHisTrp ValArgGln AlaPro
45 50 55 60
AGA AAGGGTTTG TAGTGGGTC TCAGTTATTAGT ACAAGTGGT GATACC 360
Arg LysGlyLeu TrpVal SerValIleSer ThrSerGly AspThr
65 70 75
GTA CTCTACACA GAGTCTGTG AAGGGCCGATTC ACCATCTCC AGAGAC 407
Val LeuTyrThr AspSerVal LysGlyArgPhe ThrIleSer ArgAsp
g5 90
AAT GCCCAGAAT TCACTGTCT CTGCAAATGAAC AGCCTGAGA GCCGAG 455
Asn AlaGlnAsn SerLeuSer LeuGlnMetAsn SerLeuArg AlaGlu
95 100 105 .
GGC ACAGTTGTG TACTACTGT GTGAAAGA TGAGA TCAGTGTG 504
CGCAG AG
Gly ThrValVal TyrTyrCys ValLys
110 115
AGCCCAGACA TGGGACAATC AGGGAAAG CC 560
CAAACCTCCT TGGGAC
GCAGGGTACC
SEQUENCE ID NO.: 6 3
SEQUENCE LENGTH . 5 1 5
SEQUENCE TYPE : nucleic acid
STRANDEDNESS : double
TOPOLOGY : linear
MOLECULE TYPE': Genomic DNA
2~~~ ~ '~
-127-
ORIGINAL SOURCE : Homo sa iens
IMMEDIATE SOURCE: human lymphoblastoid cell
line CGMI
SEQUENCE DESCRIPTION
GAGCTCACT ATG GGG TTT GAG CTA ACC AGA ATT TTT GCTATT 51
CTT GTT TTA
Met Gly Phe Glu Leu Thr Arg Ile Phe Leu Val AlaIle
Leu
1 5 10
AAA G GTGACTCATA GAGAAATAGA GTGAGTGAGA GTGAGTGGAT 105
ATAAGTGAGA
Lys
15
AAAACAGTAG ATGTGTTTGG CAGTTTCTGA CCAGGACGTT CAGGT 163
TGTGTATTTT GTT
Gly
Val
CAG TGT GAG GTG GAG CTG ATA,GAG TCC ATA GAG 211
GGC CTG AGA CAA CTT
Gln Cys Glu Val Glu Leu Ile Glu Ser Ile Glu
Gly Leu Arg Gln Leu
20 25 30
GGG AAG TTC C1'G AGA CTC TCC TGT GTA GCC TCT TTCAGT 259
GGA TTC ACC
Gly Lys Phe Leu Arg Leu Ser Cys Val Ala Ser PheSer
Gly Phe Thr
35 40 . 45
AGC TAC TGA ATG AGC TGG GTC AAT GAG ACT CTA CTGGAG 307
GGG AAG GGG
Ser Tyr Met Ser Trp Val~Asn Glu Thr Leu Gly LeuGlu
Lys Gly
50: 55 60
GGA GTA ATA GAT GTA AAA TAT GAT GGA AGT CAC GCAGAC 355
ATA TAC CAT
Gly Val Ile Asp Yal Lys Tyr Asp Gly Ser Gln AlaAsp
Ile Tyr His
65 70 75 80
TCT GTG AAG GGC AGA TTC ACC ATC TCC AAA GAC AACTCA 403
AAT GCT AAG
Ser Val Lys Gly Arg Phe Thr Ile Ser Lys Asp AsnSer
Asn Ala Lys
85 90 95
CCG TAT CTC CAA ACG AAC AGT CTG AGA GCT GAG ATGCAT
GAC ATG ACC 451
Pro Tyr Leu Gln Thr Asn Ser Leu Arg Ala Glu MetHis
Asp Met Thr
100 105 110
,_
GGC TGT ACA TAA GG ~TTCCAAGTGA GGAAA1~ CG.GTGTGAGTCC AGACCAAAAT 505
Gly Cys Thr
115
TTCCTGCAGG 515
SEQUENCE ID NO.: 6 4
SEQUENCE LENGTH . 6 4 9
SEQUENCE TYPE : nucleic acid
STRANDEDNESS : double
TOPOLOGY : 1 inear
MOLECULE TYPE : Genomic DNA
ORIGINAL SOURCE : Homo Sapiens
IMMEDIATE SOURCE: human lymphoblastoidline CGMI
cell
SEQUENCE DESCRIPTION
AGCT~CTGGGA GAGGAGCCCC CCCCCTGGGA TTTTCATTTGGTGATCAGCA60
TTCCCAGGTG
CTGAACACAG AAGAGTC ATG ACG GAG TTT AGC TGG TTC CTT 110
GGG CTG GTT
Met Thr Glu Phe Gly Leu Ser Trp Phe Leu
Val
1 5 10
GTT GCT ATT TTT AAA G GTGATTCATG GATATTGAGTGTGAGTGGAC166
AGGAAATAGA
Val Ala Ile Phe Lys '
15
ATGAGTGAGA GAAACAGTGG ATTTGTGTGG CCTTGGTGTCTCTGTGTTTG226
CAGTTTCTGA
CAG -GT GTC CAG TGT GAG GTG CAG TCT GGG GGC TTG 273
CTG GTG GAG GGA
G1y Va1 Gln Cys Glu Val Gln Leu Ser Gly Gly Leu
Val Glu Gly
20 25 30
GTC CAG CCT GGG GGG TCC CTG AGA GCA GCC GGA TTC 321
CTC TCC TGT TCT
Val Gln Pro Gly Gly Ser Leu Arg Ala Ala Gly Phe
Leu Ser Cys Ser
35 ~ 40 45
ACC TTC AGT AGC TAT GCT ATG CAC CAG GCT GGG AAG 369
TGG GTC CGC CCA
-129-
Thr Phe Ser Ser.Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys
55 60 65
GGA CTG GAA TAT GTT TCA GCT ATT AGT AGT AAT GGG GGT AGC ACA TAT 417
Gly Leu Glu Tyr Val Ser Ala Ile Ser Ser Asn Gly Gly Ser Thr Tyr
70 75 80
TAT GCA AAC TCT.GTG AAG GGC AGA TTC ACC ATC TCC AGA GAC AAT TCC 465
Tyr Ala Asn Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser
85 90 95 100
AAG AAC ACG CTG TAT CTT CAA ATG GGC AGC CTG AGA GCT GAG GAC ATG 513
Lys Asn Thr Leu Tyr Leu Gln Met Gly Ser Leu Arg Ala Glu Asp Met
105 110 115
GCT GTG TAT TAC TGT GCG AGA GA CACAGTGAGG AGAAGTTAAT GTGGGACCAT 566
Ala Val Tyr Tyr Cys Ala Arg
120
GCAGAAACCT CCCTGCGGGA ACGCTGGGGA AAGTCATCTG CAGGGGGCGC TCAGGAGCCA 626
CTGATCAGCG TCAACCGCAG GGG
