Human immunoglobulin VH gene segments and DNA fragments containing the same

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No:

6936705 -

Application no:

09515697 -

Filed date:

2000-02-29 -

Issue date:

2005-08-30

Kind:

B1

Claims:

14

Drawing sheets:

4

Abstract:

Novel human immunoglobulin VH segments and DNA fragments containing the same are disclosed. The DNA fragment according to the present invention is the fragment having a size of about 800 kbp which is shown in FIG. 1. The human immunoglobulln VH segments according to the present invention are contained in the fragment of this DNA fragment of about 800 kbp, and there are 50 novel segments. The base sequences of these segments are shown in the Sequence Listing. The present invention also provides DNA fragments which contain two or more of these VH segments.

US Classes:

Inventors:

Agents:

Assignees:

Claims:

What is claimed is:

1. An isolated polynucleotide consisting of a nucleic acid sequence, wherein said nucleic acid sequence is that of the insert of a clone selected from the group consisting of: (a) a yeast artificial chromosome clone that is isolable from a transformant identified by international deposit number FERM BP-4271; (b) a yeast artificial chromosome clone that is isolable from a transformant identified by international deposit number FERM BP-4274; (c) a yeast artificial chromosome clone that is isolable from a transformant identified by international deposit number FERM BP-4273; (d) a cosmid vector clone that is isolable from a transformant identified by international deposit number FERM BP-4278; (e) a cosmid vector clone that is isolable from a transformant identified by international deposit number FERM BP-4277; (f) a cosmid vector clone that is isolable from a transformant, identified by international deposit number FERM BP-4279; and (g) a cosmid vector clone that is isolable from a transformant identified by international deposit number FERM BP-4276.

2. The polynucleotide of claim 1, where in the clone is a yeast artificial chromosome clone that is isolable from a transformant identified by international deposit number FERM BP-4271.

3. The polynucleotide of claim 1, wherein the clone is a yeast artificial chromosome clone that is isolable from a transformant identified by international deposit number FERM BP-4273.

4. The polynucleotide of claim 1, wherein the clone is a cosmid vector clone that is isolable from a transformant identified by international deposit number FERM BP-4278.

5. The polynucleotide of claim 1, wherein the clone is a cosmid vector clone that is isolable from a transformant identified by international deposit number FERM BP-4277.

6. The polynucleotide of claim 1, wherein the clone is a cosmid vector clone that is isolable from a transformant identified by international deposit number FERM BP-4279.

7. The polynucleotide of claim 1, wherein the clone is a cosmid vector clone that is isolable from a transformant identified by international deposit number FERM BP-4276.

8. A yeast artificial chromosome comprising a nucleic acid sequence insert, wherein said nucleic acid sequence insert consists of a sequence that is that of the insert of a clone selected from the group consisting of: (a) a yeast artificial chromosome clone that is isolable from a transformant identified by international deposit number FERM BP-4271; (b) a yeast artificial chromosome clone that is isolable from a transformant identified by international deposit number FERM BP-4274; and (c) a yeast artificial chromosome clone that is isolable from a transformant identified by international deposit number FERM BP-4273.

9. The yeast artificial chromosome of claim 8, wherein the yeast artificial chromosome is a clone selected from the group consisting of: (a) a yeast artificial chromosome clone that is isolable from a transfonnant identified by international deposit number FERM BP-4271; (b) a yeast artificial chromosome clone that is isolable from a transformant identified by international deposit number FERM BP-4274; and (c) a yeast artificial chromosome clone that is isolable from a transformant identified by international deposit number FERM BP-4273.

10. A cosmid vector comprising a nucleic acid sequence insert, wherein said nucleic acid sequence insert consists of a sequence that is that of the insert of a clone selected from the group consisting of: (a) a cosmid vector clone that is isolable from a transfornant identified by international deposit number FERM BP-4278; (b) a cosmid vector clone that is isolable from a transformant identified by international deposit number FERM BP-4277; (c) a cosmid vector clone that is isolable from a transformant identified by international deposit number FERM BP-4279; and (d) a cosmid vector clone that is isolable from a transformant identified by international deposit number FERM BP-4276.

11. The cosmid vector of claim 10, wherein the cosmid vector is a clone selected from the group consisting of: (a) a cosmid vector clone that is isolable from a transformant identified by international deposit number FERM BP-4278; (b) a cosmid vector clone that is isolable from a transformant identified by international deposit number FERM BP-4277; (c) a cosmid vector clone that is isolable from a transformant identified by international deposit number FERM BP-4279; and (d) a cosmid vector clone that is isolable from a transformant identified by international deposit number FERM BP-4276.

12. An isolated cell transformed by a nucleic acid sequence, wherein said nucleic acid sequence is that of the insert of a clone selected from the group consisting of: (a) a yeast artificial chromosome clone that is isolable from a transformant identified by international deposit number FERM BP-4271; (b) a yeast artificial chromosome clone that is isolable from a transformant identified by international deposit number FERM BP-4274; (c) a yeast artificial chromosome clone that is isolable from a transformant identified by international deposit number FERM BP4273; (d) a cosmid vector clone that is isolable from a transformant identified by international deposit number FERM BP-4278; (e) a cosmid vector clone that is isolable from a transformant identified by international deposit number FERM BP-4277; (f) a cosmid vector clone that is isolable from a transfornant identified by international deposit number FERM BP-4279; and (g) a cosmid vector clone that is isolable from a transfonnant identified by international deposit number FERM BP-4276.

13. An isolated cell transformed by a clone selected from the group consisting of: (a) a yeast artificial chromosome clone that is isolable from a transformant identified by international deposit number FERM BP-4271; (b) a yeast artificial chromosome clone that is isolable from a transformant identified by international deposit number FERM BP-4274; (c) a yeast artificial chromosome clone that is isolable from a transformant identified by international deposit number FERM BP-4273; (d) a cosmid vector clone that is isolable from a transformant identified by international deposit number FERM BP4278; (e) a cosmid vector clone that is isolable from a transforinant identified by international deposit number FERM BP-4277; (f) a cosmid vector clone that is isolable from a transformant identified by international deposit number FERM BP-4279; and (g) a cosmid vector clone that is isolable from a transformant identified by international deposit number FERM BP-4276.

14. The isolated cell of claim 12 wherein the cell is a transformant selected from the group consisting of: (a) a transformant identified by international deposit number FERM BP-4271; (b) a transformant identified by international deposit number FERM BP-4273; (c) a transformant identified by international deposit number FERM BP4274; (d) a transformant identified by international deposit number FERM BP-4276; (e) a transformant identified by international deposit number FERM BP4277; (f) a transformant identified by international deposit number FERM BP-4278; and (g) a transformant identified by international deposit number FERM BP-4279.

Text:

TECHNICAL FIELD

This invention relates to novel human immunoglobulin V.sub.H 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 region) 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 "V.sub.H "). 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 immunoglobulin V regions are provided.

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 immunoglobulins 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 9, 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 V.sub.H segments provided for the genetic recombination is very small, so that the diversity of the expressed human immunoglobulins is limited. Even if only one V.sub.H segment is recombined, the diversity of the immunoglobulin is assured to some degree 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 V.sub.H 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 in important for therapies and diagnoses to recombine V.sub.H 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 V.sub.H segments. Another object of the present invention is to provide a novel human immunoglobulin V.sub.H segments.

The present inventors intensively studied to 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 V.sub.H 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 structure shown in FIG. 1. It should be noted that in FIG. 1, the 64 human V.sub.H segments are those having DNA sequences shown in Sequence ID Nos. 1, 2, . . . 63, and 64, respectively, in the order from downstream (i.e., from the side near the J.sub.H gone).

The present invention also provides DNA fragments containing at least two consecutive functional human V.sub.H 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 V.sub.H 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 V.sub.H segments having DNA sequences shown in Sequence ID Nos. 6, 7, 8, 9, 10, 11, 12, 13, 14, 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 hu,an immunoglobulin V.sub.H 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 V.sub.H 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 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 V.sub.H gene region having a size of about 600 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, J.sub.H genes and D genes in the order mentioned from the 3' end. Subsequent to the D genes, there are 64 V.sub.H segments. The DNA sequences of all of these 64 V.sub.H segments have been determined as described in the examples below, and Sequence ID Nos. 1, 2, . . . 63, 64 were assigned to the 64 V.sub.H segments in the order from downstream. Among these V.sub.H segments, the functional V.sub.H 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 V.sub.H segments but do not presently encode polypeptides because of the termination codons contained therein, that is, pseudo V.sub.H segments are indicated by hollow rectangles. Immediately below the genetic map, restriction maps by Eco RI and gd III are shown. The restriction sites are indicated by short perpendicular lines. The short lines to which ends circles are 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 Nlu 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.593-591.

Among the DNA fragments inserted in the clones shown in FIG. 1, the yeasts each of which contains YAC clode Y20, Y103, Y21, Y6 and Y24 respectively have been deposited with the International Patent Organism Depository (IPOD), Agency of Industrial Science and Technology (AIST), Tsukuba Central 6 at 1-1, Higashi 1-chome, Tsukuba-shi, Ibaraki-Ken 305-8566, Japan, which is an International Depository Authonity (IDA) listed in MPEP .sctn. 2405 as being recognked under the Budapest Treaty, on April 22, 1993 under accession numbers FERM BP-4272, FERbM BP-4275, FERM BP-4273. FERM BP-4271 and FERM BP-4274, respoctively. The E.coli ceuls each of which contains cosmid clone M131, M118, M84 and 3-31, respectively have been deposited with the IPOD, AIST Tsukuba Central 6 at 1-1, Higashi l-chome, Tsuba-shi, Ibaraki-Ken 305-8566, Japan, which is an IDA listed in MPEP .sctn. 2405 as being recognized under the Budapest Treaty, on Apr. 22, 1993 under accession numbers FERM BP4279, FERM BP-4278, FERM BP4277 and FERM BP4276 respectively.

The DNA fragment having a size of about 800 kbp shown in FIG. 1 can be prepared by linking these 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 (Kohyo) 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.313S-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 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 III 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 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 V.sub.H segments as many as possible. However, if the fragment contains at least two human V.sub.H 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 V.sub.H segments, which region is contained in the DNA of about 800 kb shown in FIG. 1 can be employed and are useful. The number of the functional V.sub.H segments contained in such DNA fragments is at least two, and is preferably not less than 6. The more the number of the functional V.sub.H segments, the higher the diversity of the human immunoglobulin produced, so that the more preferred. Thus, the preferableness is increased when the number of the functional V.sub.H segments in 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 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 V.sub.H 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 V.sub.H segments using not less than two probes each of which hybridizes with one of the not less than two desired functional V.sub.H 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 V.sub.H 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 V.sub.H segments which are ligated in optional orders. That is, by ligating a plurality of the DNA fragments each containing not less than two functional V.sub.H segments, the number of V.sub.H segments in the DNA fragment can be increased when compared with the case where only one such DNA fragment containing not less than two V.sub.H 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 V.sub.H segments are recovered by the method of Hermanson et al (1991) (Nucleic Acids. Res.,19; 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 KIN are linearized and then introduced into yeast cells containing YAC by a conventional method. The plasmids 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 in 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 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 V.sub.H segments can be prepared.

By the present invention, the DNA sequences of the 64 V.sub.H 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 V.sub.H segments are novel segments which have DNA sequences that have not hitherto been known. These novel human immunoglobulin V.sub.H 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 human immunoglobulin V.sub.H 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 (Kohyo) No. 4-504365.

EXAMPLES

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 800 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 and G. R. Fink, eds), p.253, Academic Press, Orlando, 1991), and introduced into AB1380 yeast host strain (D. Burke and H. 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 (IgH) locus was first checked by Southern hybridization using the human D and J.sub.H probes. The result showed that an allele kept germine configuration while the other was VDJ rearranged.

(2) Primers Used for PCR-based Screening

For PCR-based screening of human V.sub.H YAC clones, oligonucleotide primers for V.sub.H-III and V.sub.H-I families, the first and the second largest V.sub.H families, were synthesized. V.sub.H region segments of immunoglobulins contain two hypervariable regions (CDR1 and CDR2) and three framework regions (FR1, FR2 and FR3) (E.A. Tabat at 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 PR1, FR2 and FR3 regions in all the known VU 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 V.sub.H-I and V.sub.H-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 V.sub.H 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 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 .mu.l) 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.degree. C., 56.degree. C., 60.degree. C. and 62.degree. C.) and cycles (25, 30, and 35 cycles). As a result, it was found that the reaction under high annealing temperature, namely 94.degree. C., 1 minute--62.degree. C., 2 minutes--72.degree. 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.times.96-well) as described (E. D. Green and M. V. Olson, Proc. Natl. Acad. Sci. USA, 87, 1213-1217 (1990)). Positive multi-filter pools were divided into five pools each of which consists of 384 colonies (4.times.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 V.sub.HMV (M. Kodaira et al., J. Mol. Biol., 19D, 529-541(1986)) were used for probes representative for human V.sub.H-I and V.sub.H-III families, respectively. These probes were labeled (5.times.10.sup.5 cpm) with .sup.32 P-dCTP using oligolabeling Kit (Pharmacia) and subjected to colony hybridization according to standard procedure (D. Burke, et al., supra). After the hybridization for 12 hours at 65.degree. C., filters were washed twice with 2.times.SSC (1.times.SSC is 0.15 M NaCl-15 mM sodium citrate) for 10 minutes at room temperature, then twice with 0.2.times.SSC-0.1% SDS for 30 minutes at 65.degree. 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 X. V. Olson, Proc. Natl. Acad. Sci. USA, 87, 1213-1217 (1990)). That is, the positive yeast clones were streaked onto AHC plates and grown. Four each of single colonies from each clone were transferred by toothpick into 5 .mu.l 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 V.sub.H locus contains a number of homologous DNA fragments consisting of V.sub.H 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 V.sub.H -positive single colonies checked by PCR were selected from 17 colonies originating from a single well, and miniprepared from 5 ml culture in ARC medium to give low-gelling temperature agarose blocks by a known method (D. Burke et al., supra). Appropriate sized piece of agarose block was used for sizing the YACs by PFGE with a Pulsaphor (Pharmacia) ora 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. All 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 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 V.sub.H -carrying YAC clones including the analyzed V.sub.H displayed instability of human inserts. Subsequent analysis revealed that such recombination took place regardless of the number of V.sub.H 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 V.sub.H, 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) V.sub.H -carrying YAC clones can be arrayed with several other information such as comparison of the size or the pattern of the fragments hybridized with V.sub.H probes or non-repetitive probes isolated from V.sub.H -carrying cosmid clones, 2) it is necessary to subclone the YACs into cosmids for 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 PPGE 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 stummed 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 Pvu 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 V.sub.H family-specific probes for the presence of V.sub.H segments in digested DNA fragments. Origin of V.sub.H family-specific probes for V.sub.H-II, V.sub.H-IV, V.sub.H-V and V.sub.H-VI families, respectively, are; V.sub.CE-1 (N. Takahashi et al., Proc. Natl. Acad. Sci. USA, 81, 5194-5198 (1984)), V.sub.71-2 (K. H. Lee et al., J. Mol. Biol., 195, 761-768 (1987)), 5-IRI (J. E. Bermanet al., EMBO J. 7, 727-1051 (1988) and 6-IRI (J. E. Berman et. al., EMBO J. 7, 727-1051 (1988)).

In order to array Mot 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 blocks (about 50 .mu.l each volume containing about 1 .mu.g of DNA, stored in 0.5 M EDTA (pH 8.0)) for 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.degree. C. for 30 minutes. 3. Transfer each block to 25-.mu.l reaction mixture containing 1 unit each of restriction enzyme in 1.times. digestion buffer. 4. Incubate all three tubes for 10 minutes, 30 minutes and 1 hour at 37.degree. C. 5. Stop the reaction by adding 100 .mu.l of 0.5 M EDTA (pH 8.0). 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 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 Hd III--Sal I fragment of pBR322 DNA (Tet.sup.R) which specifically hybridizes with insert-vector boundary sequence of pYAC4 vector. The DNA fractions of interest were recovered from the gel using DE81 paper and ligated to either EMEL4 or pUC19 vector depending on the insert size. Isolated fragments with EMBL4 vector were subcloned into pUC19 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 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-DRA 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-.mu.l reactions according to a known method (H. S. Kim and O. Smithies, Nucleic Acids Res., 16, 8870-8903 (1988)). 200 ng each of DNA was used for the reaction. Incubations containing DNAs from GM10479, CGM1 and Rag, respectively were subjected to 35 to 40 cycles at 95.degree. C., 1 minute--55 to 62.degree. C., 2 minutes 72.degree. 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 V.sub.H 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 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 V.sub.H segments of a large DNA fragment containing V.sub.H 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 thist: 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.times.10.sup.4 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 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 .mu.g 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).

1 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 digestion than gel block DNA. With a simple and rapid (6 hours for total procedure) method described below, about 50 .mu.g of large size DNA (>200 kb) can be routinely purified from 100-ml yeast culture.

(i) Spin down yeast calls and wash them with TE (10 mM, Tris HCl (pH 8.0)--1 mM EDTA) twice.

(ii) Resuspend the cells in 20 ml 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 37.degree. C. for 1 hour to form spheroplasts.

(iii) Spin down the spheroplasts and resuspend in 9 ml of 0.1 M Tris HCl (pH 7.5), 50 mM EDTA (pH 7.5).

(iv) Add 1 ml (1/10 final volume) of 108 SDS and mix gently. Incubate at 60.degree. 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 2000.times.g 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 2000.times.g for 30 minutes and discard supernatant. Dissolve the pellet 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 ethanol precipitation at room temperature for 10 to 20 minutes .

(ix) Centrifuge at 2000.times.g for 30 minutes. Rinae the pellet with 70% ethanol and dry up the pellet.

(x) Dissolve with 1 ml of TE.

2 Vector DNA Preparation

Lorist 2 DNA was linearized by digestion with Hind III or Bam HI. Linearized DNA was dephosphorylated by treatment with bacterial alkaline phosphatase. Small aliquots of DNA before and after phosphatase treatment were used for test ligation for phouphatase treatment according to a known method (J. Sambrook et al., supra).

3 Insert DNA Preparation

Analytical experiment of partial digestion of yeast DNA was performed according to standard procedure (J. Sambrook et al., supra) to determine the optimal enzyme concentration and reaction time. Preparation of size-fractionated DNA from the gel was achieved with LGT agarose and a agarase r. This very gentle method resulted in high recovery (>90%) of fractionated DNA without degradation. Scaled up cleavage reaction was done using 5 .mu.g 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-kb bands were also loaded as size markers. After visualizing the 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 p 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 10.times. .beta. agarase I buffer.

(iii) Melt the gel at 68.degree. C. for 10 minutes. Cool to 40.degree. C. and incubate the molten agarose at 40.degree. C. for 1 hour with optimal number of units of .beta. agarase I.

(iv) Adjust the salt concentration of the solution to 0.5 M NaCl for ethanol precipitation. Chill on ice for 10 minutes.

3 (v) Centrifuge at 15,000.times.g 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.degree. C. for 10 minutes.

(vii) Centrifuge at 15,000.times.g 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.

4 Ligation, in vitro Packaging and Infection to E. coli

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.

5 Screening of Commid Libraries

Initial screening was carried out using Lind III-partial cosmid libraries. About 10,000 colonies (500 colonies per .phi.10 cm plate.times.20) were plated on LB plates containing 50 .mu.g/ml of kanamycin so that single colonies can be picked up after first screening. Colonies were then lifted from the plates with .phi.8.2 cm detergent-free nitrocellulose membranes (Advantec Toyo Membrane) and subjected to colony hybridization. Three different kinds of probes were used for screening, nasely mixture of six V.sub.H -family specific probes to isolate V.sub.H -containing cosmid clones, YAC vector probes (Tet.sup.R 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.

6 Construction of Cosmid Contigs

DNA from cosmid clones was isolated by the alkaline lysis method by a conventional method (J. Sambrook et al., supra). Purified cosmid DNAs were digested with Eco RI or Hind III and subjected to agarose gel electrophoresis for restriction mapping. Overlaps between clones were easily found by comparing restriction patterns among cosmid clones. Ordered cosmid clones were then cleaved with Eco RI or Hd III and loaded in a 0.7% agarose gel. Southern filter were hybridized with six V.sub.H -family specific probes for identification of location and number of V.sub.H segments in cosmid clones. Filters were washed three times for 30 minutes under standard conditions (at 50.degree. C. in 1.times.SSC, 0.1% SDS) followed by stringent conditions (at 65.degree. C. in 0.1.times.SSC, 0.1% SDS). Location of V.sub.H 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 sites within the YAC insert. The presence of some classes of sequences such as palindromic 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 J.sub.H of each V.sub.H 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 Taq I and the resultant was subjected to electrophoresis on 0.5% agarose gel. The 35-45-kb bands were recovered by using DEAE 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 8 cell line FLEB14-14, the vector and the host E. coli used were Lorist 2 and ED8767, respectively, the 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. Xaniatis, 1989, Molecular cloning; a Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.).

Example 3

Sequencing Analysis of V.sub.H Segments

Instead of sequencing subcloned V.sub.H -containing DNA fragments using vector primers, V.sub.H family-specific oligonucleotide primers were synthesized. As mentioned above, nucleotide sequences of FR regions of V.sub.H 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 V.sub.H -specific primers could be directly used without fluorescence-label.

(1) Subcloning of V.sub.H -containing Restriction Fragments

In order to use V.sub.H -family specific primers for sequencing, it is essential to subclone V.sub.H -containing DNA fragments so that each plasmid contains only one V.sub.H segment. Several other 6 bp-site enzymes than Eco RI and Hind III were used to isolate single V.sub.H -carrying DNA fragments. Plasmid DNA of the subcloned fragments wan isolated by alkaline lysis method followed by ultracentrifugation twice to obtain high quality DNA samples for accurate sequences.

(2) Oligonucleotide Synthesis for Sequencing

To select consensus sequences for V.sub.H family-specific oligonucleotide primer synthesis, nucleotide sequences of framework regions and exon-intron boundaries of the known V.sub.H 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/invariant amino acid residues. Nineteen additional primers were designed for five V.sub.H 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 V.sub.H Family-specific Primers

The primers F-univ and I-R were first chosen to sequence V.sub.H-I segments. An shown in Table 2, they annealed 11 of 12 V.sub.H-I segments analyzed. It is to be noted that all of 6 functional V.sub.H-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 V.sub.H segments to verify their sequences obtained by first two primers (Table 2).

Eight primers were designed and used for sequencing V.sub.H-III family segments. The first sequencing reaction of each V.sub.H segment was performed with F-univ and III-R primers. They annealed more-than 80% of the V.sub.H-III segments analyzed (25/30 for F-univ and 24/30 for III-R)(Table 2). Importantly, again, all the functional V.sub.H-III segments with one exception could be sequenced with this combination of primers, suggesting that they would be good for most of V.sub.H-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' flanking 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 V.sub.H segments. Sequences of V3-25P, V3-44P and V3-63P were determined using M13 vector primers from their internal restriction sites.

Five each of synthesized primers were used to determine the sequences of V.sub.H segments belonging to V.sub.H-II, V.sub.H-IV and V.sub.H-V families. Since V.sub.H 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 V.sub.H segments belonging to these smaller V.sub.H families. In fact, all four V.sub.H-II family-specific primers annealed three V.sub.H-II segments (V2-5, V2-10P and V2-26). In brief, in total 11 primers (F-univ and I-R for V.sub.H-I ; II-R1, Ir-F2 and II-R2 for V.sub.H-II ; F-univ and III-R for V.sub.H-III ; IV-R1, IV-F2 and IV-R2 for V.sub.H-IV ; V-R2 and V-R3 for V.sub.H-V) would be sufficient for sequencing most of the V.sub.H segments belonging to five V.sub.H families. The I-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 V.sub.H segments were determined and they are shown in Sequence ID Noe. 1-64 as mentioned above. The distance of each V.sub.H segment from J.sub.H and the sizes of Eco RI and Hind III fragments are summarized in Table 3.

(5) Transcriptional Polarities of V.sub.H Segments

The strategy for sequencing V.sub.H segments with family-specific primers was not suitable for determination of transcriptional polarities of the V.sub.H segments because it did not require restriction map of single V.sub.H -containing subcloned fragments. The present inventors could not determine orientations of all the V.sub.H segments within this region for that reason. The present inventors found, however, that 8 regions containing 21 V.sub.H segments were already isolated in cosmid or phage clones since sequences between corresponding V.sub.H segments as well as their restriction maps were identical with each other. As the relative orders of these 21 V.sub.H segments within these clones are identical to those in the 0.8-mb region, it was concluded that the orientation of these 21 V.sub.H segments are the same as those of the J.sub.H segments.

TABLE 1 VH family-specific primers used for screening and sequencing FAMILY NAME SEQUENCE (5' to 3') *LOCATION DIRECTION SEQ ID NOS I, III, V F -- univ AGGTGCAGCTGGTGCAGTCTG 1-8 forward 65 I I -- R CCAGGGGCCTGTCGCACCCA 36-42 reverse 66 I -- N F 1 TGGGGCCTCAGTGAAGGTCTCCTG 14-22 forward 67 I -- N R 1 GATCC(A/G)TCCCATCCACTCAAG 45-51 reverse 68/69 II II -- F 1 TGTCTTCTCCACAGGGGTCTT intron-(-2) forward 70 II -- F 2 GGGAAGGCCCTGGAGTGGCT 42-48 forward 71 II -- R 1 GTGCAGGTCAGCGTGAGGGT 17-23 reverse 72 II -- R 2 TGGTTTTTGGAGGTGTCCTTGG 70-77 reverse 73 III III -- R CACTCCAGCCCCTTCCCTGGAGC 40-47 reverse 74 III -- F 3 GTGAGGTTCAGCTGGTGGAGT (-I)-7 forward 75 III -- R 3 AGCTGAACCTCACACTGGAC (-3)-4 reverse 76 III -- F 4 AAGGGCCGATTCACCATCT 64-70 Forward 77 III -- R 4 TTGTCTCTGGAGATGGTGAA 68-73 reverse 78 III -- N F 1 TGAGACTCTCCTGTGCAGCCTCTG 18-26 forward 79 III -- N F 2 TCT(T/C)TGTGTTTGCAGGTGT intron-(-3) forward 80/81 IV IV -- F 1 TCTGTTCACAGGGGTCCTGTC intron-(-I) forward 82 IV -- F 2 TCCGGCAGCCCCCAGGGAA 37-43 forward 83 IV -- R 1 GCAGGTGAGGGACAGGGT 17-22 reverse 84 IV -- R 2 CAGGGAGAACTGGTTCTTGGA 74-80 reverse 85 V V -- R 1 CCCGGGCATCTGGCGCACCCA 36-42 reverse 86 V -- R 2 GCTGCTCCACTGCAGGTAGGC 78-82R reverse 87 V -- R 3 CTTCAGGCTGCTCCACTGCAG 74-83 reverse 88 *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.

TABLE 2 List of useful primers for sequencing V.sub.H clones V.sub.H-I primers V.sub.H-III primers V.sub.H-IV primers V.sub.H segments univ R NF1 NR1 univ R F3 R3 F4 R4 NF1 NF2 F1 R1 F2 R2 V.sub.H I 1-2 + + 1-3 + + 1-8 + + 1-12P + + 1-14P - + + 1-17P + + + + 1-18 + + + 1-24P + + + + 1-27P + - + + 1-40P + + 1-45 + + 1-46 + + V.sub.H III 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 + + V.sub.H IV 4-4 + + + + 4-31 + + - + 4-34 + + + + 4-39 + + 4-55P + +

TABLE 3 kb from Fragment size (kb) V.sub.H J.sub.H EcoRI Hind III 6-1 75 0.9 25 1-2 125 7.2 12.5 1-3 150 3.4 1.7 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 2-10P 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 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 775 4.6 9.0 3-63P 780 8.9 6.2 3-64 790 4.4 >7.4

SEQUENCE LISTING (1) GENERAL INFORMATION: (iii) NUMBER OF SEQUENCES: 145 (2) INFORMATION FOR SEQ ID NO: 1: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1429 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 1 CTGATCTATG AATAAGGGTA TATAGACCAG TTTGGCCTGA TGTAGGGAAC GCCAAAGTGC 60 TGGAATTTCA GAGTCATCAC ACCCAGGGGC CCTGCCTCTG AGCTCCTCTT TGCATCCAAT 120 CTGCTGAAGA ACATGGCTCT AGGGAAACCC AGTTGTAGAC CTGAGGGCCC CGGCTCTTCA 180 ATGAGCCATC TCCGTCCCGG GGCCTTATAT CAGCAAGTGA CGCACACAGG CAAATGCCAG 240 GGTGTGGTTT CCTGTTTAAA TGTAGCCTCC CCCGCTGCAG AACTGCAGAG CCTGCTGAAT 300 TCTGGCTGAC CAGGGCAGTC ACCAGAGCTC CAGACAATGT CTGTCTCCTT CCTCATCTTC 360 CTGCCCGTGC TGGGCCTCCC ATGGGGTCAG TGTCAGGGAG ATGCCGTATT CACAGCAGCA 420 TTCACAGACT GAGGGGTGTT TCACTTTGCT GTTTCCTTTT GTCTCCAGGT GTCCTGTCAC 480 AGGTACAGCT GCAGCAGTCA GGTCCAGGAC TGGTGAAGCC CTCGCAGACC CTCTCACTCA 540 CCTGTGCCAT CTCCGGGGAC AGTGTCTCTA GCAACAGTGC TGCTTGGAAC TGGATCAGGC 600 AGTCCCCATC GAGAGGCCTT GAGTGGCTGG GAAGGACATA CTACAGGTCC AAGTGGTATA 660 ATGATTATGC AGTATCTGTG AAAAGTCGAA TAACCATCAA CCCAGACACA TCCAAGAACC 720 AGTTCTCCCT GCAGCTGAAC TCTGTGACTC CCGAGGACAC GGCTGTGTAT TACTGTGCAA 780 GAGACACAGT GAGGGGAAGT CAGTGTGAGC CCAGACACAA ACCTCCCTGC AGGGATGCTC 840 AGGACCCCAG AAGGCACCCA GCACTACCAG CGCAGGGCCC AGACCAGGAG CAGGTGTGGA 900 GTTAAGCCAA AATGGAACTT CTTGCTGTGT CTTAAACTGT TGTTGTTTTT TTTTTTTTTT 960 TGGCTCAGCA ACAGAGATCA TAGAAAACCC TTTTTCATAT TTTTCAAATC TGTTCTTAGT 1020 CTAATGGAGA TTCTCTAATA TGTGACATTG TTTTTCTCTT GCTTGTTTTT GGAATTCTTT 1080 GTCTTTGACT TTTGACAACT TGACTTTTGA CAGTGTGCCT CAAAGAAGTT CTATTTTGGG 1140 TTCTGTGAAC CTCCTGGATC TGGGAAGTTT TCAGCTATGA TTTCATTAAA CGTGTTTTCT 1200 ACACCATTTC CCTACTTCTT TCCAATACCC ATAATGCAAA TATTTGTTCA CTTAATTGTG 1260 TCCCATAAAT GCCTGGGGAT TTTCTTCATT CCTTTTTACT CTTTTTTTCT TTTTATTCAT 1320 CTGCCTGAAT TATTTCAAAA GATCTGTCTT CAACTTCAGA AACTCTTTGG CTTGGCCTAG 1380 TCTAATCTTG AAGGTCTCAA TTGTACTTTT AATTTCATTC ATTGAATTC 1429 (2) INFORMATION FOR SEQ ID NO: 2: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 512 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 2 TGAGAGCTCC GTTCCTCACC ATGGACTGGA CCTGGAGGAT CCTCTTCTTG GTGGCAGCAG 60 CCACAGGTAA GAGGCTCCCT AGTCCCAGTG ATGAGAAAGA GATTGAGTCC AGTCCAGGGA 120 GATCTCATCC ACTTCTGTGT TCTCTCCACA GGAGCCCACT CCCAGGTGCA GCTGGTGCAG 180 TCTGGGGCTG AGGTGAAGAA GCCTGGGGCC TCAGTGAAGG TCTCCTGCAA GGCTTCTGGA 240 TACACCTTCA CCGGCTACTA TATGCACTGG GTGCGACAGG CCCCTGGACA AGGGCTTGAG 300 TGGATGGGAT GGATCAACCC TAACAGTGGT GGCACAAACT ATGCACAGAA GTTTCAGGGC 360 AGGGTCACCA TGACCAGGGA CACGTCCATC AGCACAGCCT ACATGGAGCT GAGCAGGCTG 420 AGATCTGACG ACACGGCCGT GTATTACTGT GCGAGAGACA CAGTGTGAAA ACCCACATCC 480 TGAGGGTGTC AGAAACCCAA GGGAGGAGGC AG 512 (2) INFORMATION FOR SEQ ID NO: 3: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 496 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 3 CACAACTCCT CACCATGGAC TGGACCTGGA GGATCCTCTT TTTGGTGGCA GCAGCCACAG 60 GTAAGGGGCT GCCAAATCCC AGTGAGGAGG AAGGGACTGA AGCCAGTCAA GGGGGCTTCC 120 ATCCACTCCT GTGTCTTCTC TACAGGTGTC CACTCCCAGG TTCAGCTGGT GCAGTCTGGG 180 GCTGAGGTGA AGAAGCCTGG GGCCTCAGTG AAGGTTTCCT GCAAGGCTTC TGGATACACC 240 TTCACTAGCT ATGCTATGCA TTGGGTGCGC CAGGCCCCCG GACAAAGGCT TGAGTGGATG 300 GGATGGAGCA ACGCTGGCAA TGGTAACACA AAATATTCAC AGGAGTTCCA GGGCAGAGTC 360 ACCATTACCA GGGACACATC CGCGAGCACA GCCTACATGG AGCTGAGCAG CCTGAGATCT 420 GAGGACATGG CTGTGTATTA CTGTGCGAGA GACACAGTGT GAAAACCCAC ATCCTGAGAG 480 TGTCAGAAAC CCCAGG 496 (2) INFORMATION FOR SEQ ID NO: 4: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 650 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 4 CACAGGAAAC CACCACACAT TTCCTTAAAT TCAGGGTCCA GCTCACATGG GAAATACTTT 60 CTGAGACTCA TGGACCTCCT GCACAAGAAC ATGAAACACC TGTGGTTCTT CCTCCTGCTG 120 GTGGCAGCTC CCAGATGTGA GTGTCTCAAG GCTGCAGACA TGGGATATGG GAGGTGCCTC 180 TGATCCCAGG GCTCACTGTG GGTCTCTCTG TTCACAGGGG TCCTGTCCCA GGTGCAGCTG 240 CAGGAGTCGG GCCCAGGACT GGTGAAGCCT TCGGAGACCC TGTCCCTCAC CTGCACTGTC 300 TCTGGTGGCT CCATCAGTAG TTACTACTGG AGCTGGATCC GGCAGCCCGC CGGGAAGGGA 360 CTGGAGTGGA TTGGGCGTAT CTATACCAGT GGGAGCACCA ACTACAACCC CTCCCTCAAG 420 AGTCGAGTCA CCATGTCAGT AGACACGTCC AAGAACCAGT TCTCCCTGAA GCTGAGCTCT 480 GTGACCGCCG CGGACACGGC CGTGTATTAC TGTGCGAGAG ACACAGTGAG GGGAGGTGAG 540 TGTGAGCCCA GACACAAACC TCCCTGCAGG GAGGCGGAGG GGACCGGCGC AGGTGCTGCT 600 CAAGACCAGC AGGGGGCGCG CGGGGCCCAC AGAGCAAGAG GCCGGGTCAG 650 (2) INFORMATION FOR SEQ ID NO: 5: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 613 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 5 CCAGCTCCAC CCTCCTCTGG GTTGAAAAAG CCGAGCACAG GTACCAGCTC AGTGACTCCT 60 GTGCACCACC ATGGACACAC TTTGCTCCAC GCTCCTGCTG CTGACCATCC CTTCATGTGA 120 GTGCTGTGGT CAGGGACTCC TTCACGGGTG AAACATCAGT TTTCTTGTTT GTGGGCTTCA 180 TCTTCTTATG CTTTCTCCAC AGGGGTCTTG TCCCAGATCA CCTTGAAGGA GTCTGGTCCT 240 ACGCTGGTGA AACCCACACA GACCCTCACG CTGACCTGCA CCTTCTCTGG GTTCTCACTC 300 AGCACTAGTG GAGTGGGTGT GGGCTGGATC CGTCAGCCCC CAGGAAAGGC CCTGGAGTGG 360 CTTGCACTCA TTTATTGGAA TGATGATAAG CGCTACAGCC CATCTCTGAA GAGCAGGCTC 420 ACCATCACCA AGGACACCTC CAAAAACCAG GTGGTCCTTA CAATGACCAA CATGGACCCT 480 GTGGACACAG CCACATATTA CTGTGCACAC AGACCACAAA GACACAGCCC AGGGCACCTC 540 CTGTACAAAA ACCCAGGCTG CTTCTCATTG GTGCTCCCTC CCCACCTCTG CAGAACAGGA 600 AAGTCTGTCT GCT 613 (2) INFORMATION FOR SEQ ID NO: 6: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 594 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 6 ACAGGATTCA CCATGGAGTT GGGGCTGAGG TGGGTTTTCC TTGCTGCTAT TTTAAAAGGT 60 GATTTATGGT TAACTAGAGC TATTGAGTGT GAATGGACAT AAGTGAGCGA AACAGTGGAT 120 ATGTGTGGCA GTTTCTTACC AGGATGTCTC TGTGTTTGCA GGTGTCCAGT GTGAGATGCA 180 GCTGGTAGAG TCTGGAGCAA ACTTGACAAA GCCTGGGTGT CCCTGAGACT CTCCTGTGCA 240 GCCTCTGGAT TCACCTTCAG TAGCCATAGC ACGCACTGGG TCCCCCAGGC TCCAGGGAAG 300 GGTCTGCAGT GGGTCCCAGT TATTAGTGGT AGTGGTAGTA CCATGTACTA CGCAGACTCT 360 GTGAAGGGCC GATTCACCAT TTCCAGAGAC AATACCAAAA ACTCACTGTA TCTGCAAATG 420 AACAGACTGA GGGCAGAGGA TGCAGCTGCA TATGACTCTG TGAGAGATAC GGTAAGGAGA 480 AGTCAGTGTG AGCCCAGACA CAAACCTCCC TTCAGGGTAC CTGGGACAAC CAGGGAAAGC 540 CTGGGACACT GTGCACTGTG CTGACCCCAG GGGCAAGTGC AGGTGCTACA AGGG 594 (2) INFORMATION FOR SEQ ID NO: 7: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 877 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 7 ACAGCCTATT CCTCCAGCAT CCCACTAGAG CTTCTTATAT AGTAGGAGAC ATGCAAATAG 60 GGCCCTCCCT CTACTGATGA AAACCAACCC AACCCTGACC CTGCAGGTCT CAGAGAGGAG 120 CCTTAGCCCT GGACTCCAAG GCCTTTCCAC TTGGTGATCA GCACTGAGCA CAGAGGACTC 180 ACCATGGAAT TGGGGCTGAG CTGGGTTTTC CTTGTTGCTA TTTTAGAAGG TGATTCATGG 240 AAAACTAGGA AGATTGAGTG TGTGTGGATA TGAGTGTGAG AAACAGTGGA TTTGTGTGGC 300 AGTTTCTGAC CTTGGTGTCT CTTTGTTTGC AGGTGTCCAG TGTGAGGTGC AGCTGGTGGA 360 GTCTGGGGGA GGCTTGGTCC AGCCTGGGGG GTCCCTGAGA CTCTCCTGTG CAGCCTCTGG 420 ATTCACCTTT AGTAGCTATT GGATGAGCTG GGTCCGCCAG GCTCCAGGGA AGGGGCTGGA 480 GTGGGTGGCC AACATAAAGC AAGATGGAAG TGAGAAATAC TATGTGGACT CTGTGAAGGG 540 CCGATTCACC ATCTCCAGAG ACAACGCCAA GAACTCACTG TATCTGCAAA TGAACAGCCT 600 GAGAGCCGAG GACACGGCTG TGTATTACTG TGCGAGAGAC ACAGTGAGGG GAAGTCAGTG 660 TGAGCCCAGA CACAAACCTC CCTGCAGGGG TCCCTTGGGA CCACCAGGGG GCGACAGGGC 720 ATTGAGCACT GGGCTGTCTC CAGGGCAGGT GCAGGTGCTG CTGAGGGCTG GCTTCCTGTC 780 GCGGTCTGGG GCTGCCTCGT CGTCAAATTT CCCCAGGAAC TTCTCCAGAT TTACAATTCT 840 GTACTGACAT TTCATGTCTC TAAATGCAAT ACTTTTT 877 (2) INFORMATION FOR SEQ ID NO: 8: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 564 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 8 CACTCCACCA ACCACATCTG TCCTCTAGAG AAAACCCTGT GAGCACACCT CCTCACCATG 60 GACTGGACCT GGAGGATCCT CTTCTTGGTG GCAGCAGCTA CAAGTAAGGG GCTTCCTAGT 120 CTCAAAGCTG AGGAACGGAT CCTGGTTCAG TCAAAGAGGA TTTTATTCTC TCCTGTGTTC 180 TCTCCACAGG TGCCCACTCC CAGGTGCAGC TGGTGCAGTC TGGGGCTGAG GTGAAGAAGC 240 CTGGGGCCTC AGTGAAGGTC TCCTGCAAGG CTTCTGGATA CACCTTCACC AGTTATGATA 300 TCAACTGGGT GCGACAGGCC ACTGGACAAG GGCTTGAGTG GATGGGATGG ATGAACCCTA 360 ACAGTGGTAA CACAGGCTAT GCACAGAAGT TCCAGGGCAG AGTCACCATG ACCAGGAACA 420 CCTCCATAAG CACAGCCTAC ATGGAGCTGA GCAGCCTGAG ATCTGAGGAC ACGGCCGTGT 480 ATTACTGTGC GAGAGGCACA GTGTGAAAAA CCACATCCTC AGAGAGTCAG AAACCCCTAG 540 GGGAGAAGGC AGCTTCTGCT GGGC 564 (2) INFORMATION FOR SEQ ID NO: 9: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 640 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 9 CAAATAGGGC CCTCCCTCTG CTGATGAAAA CCAGCCCAGC CCTGACCCTG CAGCTCTGGG 60 AGAGGAGCCC CAGCCCTGAG ATTCCCAGGT GTTTCCATTC AGTGATCAGC ACTGAACACA 120 GAGGACTCAC CATGGAGTTG GGACTGAGCT GGATTTTCCT TTTGGCTATT TTAAAAGGTG 180 ATTCATGGAG AAATAGAGAG ATTGAGTGTG AGTGGACATG AGTGGATTTG TGTGGCAGTT 240 TCTGACCTTG GTGTCTCTGT GTTTGCAGGT GTCCAGTGTG AAGTGCAGCT GGTGGAGTCT 300 GGGGGAGGCT TGGTACAGCC TGGCAGGTCC CTGAGACTCT CCTGTGCAGC CTCTGGATTC 360 ACCTTTGATG ATTATGCCAT GCACTGGGTC CGGCAAGCTC CAGGGAAGGG CCTGGAGTGG 420 GTCTCAGGTA TTAGTTGGAA TAGTGGTAGC ATAGGCTATG CGGACTCTGT GAAGGGCCGA 480 TTCACCATCT CCAGAGACAA CGCCAAGAAC TCCCTGTATC TGCAAATGAA CAGTCTGAGA 540 GCTGAGGACA CGGCCTTGTA TTACTGTGCA AAAGATACAC AGTGAGGGGA AGTCAGCGAG 600 AGCCCAGACA AAAACCTCCT GCAGGAAGAC AGGAGGGGCC 640 (2) INFORMATION FOR SEQ ID NO: 10: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 630 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 10 AGCTCCACCC TTCTCTGTGT TGAAAAGCCG AGCATGGGGA CCTAGTTCAG TGACTCCTGC 60 GCCCCACCAC ATGGAGCTTT ACTCCACGCT TCTCCTGCTG ACTGTCCCTT CCTGTGAGTT 120 CAGTGGTCAG GGAATCCTTC AGGGGTGAAA CACCTGTTCT TTTCTTTGTG GGCTTCATCT 180 TCTTATGCTT TCTCCACAGG GGTCTTATCC CAGGTCACCT TGAAGGAGTC TGGTCCTGCA 240 CTGGTGAAAC CCACACAGAC CCTCATGCTG ACCTGCACCT TCTCTGGGTT CTCACTCAGC 300 ACTTCTGGAA TGGGTGTGGG TTAGATCTGT CAGCCCTCAG CAAAGGCCCT GGAGTGGCTT 360 GCACACATTT ATTAGAATGA TAATAAATAC TACAGCCCAT CTCTGAAGAG TAGGCTCATT 420 ATCTCCAAGG ACACCTCCAA GAATGAAGTG GTTCTAACAG TGATCAACAT GGACATTGTG 480 GACACAGCCA CACATTACTG TGCAAGGAGA CCACAGAGAC AGAGCCCAGG GTGCCTCTTG 540 TACAAGACCC AGGCTGCTTC TCAGTGGCGC TCCCTCCCCA CCTCTGCAGA ACAGGAAAGT 600 GTGGCTGAGA TGCCATTTCC TGTCAGGGTC 630 (2) INFORMATION FOR SEQ ID NO: 11: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 715 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA

(vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 11 CACCCCAGGC TTTACACTTT ATGCTTCCGG CTCGTATGTT GTGTGGAATT GTGAGCGGAT 60 AACAATTTCA CACAGGAAAC AGCTATGACC ATGATTACGC CAAGCTTGCA TGCCTGCAGG 120 TCGACTCTAG AGGATCCCCG GGTACCGAGC TCGAATTCCC AGGAGTTTCC ATTCGGTGAT 180 CAGCACTGAA CACAGAGGAC TCACCATGGA GTTTGGGCTG AGCTGGGTTT TCCTTGTTGC 240 TATAATAAAA GGTGATTTAT GGAGAACTAG AGACATTGAG TGGACGTGAG TGAGATAAGC 300 AGTGAATATA TGTGGCAGTT TCTGACTAGG TTGTCTCTGT GTTTGCAGGT GTCCAGTGTC 360 AGGTGCAGCT GGTGGAGTCT GGGGGAGGCT TGGTCAAGCC TGGAGGGTCC CTGAGACTCT 420 CCTGTGCAGC CTCTGGATTC ACCTTCAGTG ACTACTACAT GAGCTGGATC CGCCAGGCTC 480 CAGGGAAGGG GCTGGAGTGG GTTTCATACA TTAGTAGTAG TGGTAGTACC ATATACTACG 540 CAGACTCTGT GAAGGGCCGA TTCACCATCT CCAGGGACAA CGCCAAGAAC TCACTGTATC 600 TGCAAATGAA CAGCCTGAGA GCCGAGGACA CGGCCGTGTA TTACTGTGCG AGAGACACAG 660 TGAGGGGAAG TCAGTGTGAG CCCAGACACA AACCTCCCTG CAGGGGGTCC CTTGG 715 (2) INFORMATION FOR SEQ ID NO: 12: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 660 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 12 GGATTGGGCT TTGAGCTAAG GANAGGCTTT GTCNNATGAA TATNCGAATA TACTGATATC 60 CACTGAGNTG AATATGTTCT GTNCCCTGAG AGAATCACCT GAGAGAATCC CCTGAGAGCA 120 CATCTCCTCA TGGNCTGGAC CTACAAGATC CTCTTCTTGG TGGCAGCAGC CACAGGTAAG 180 CAGTTCCCAG GTCCAAGTAA TGAGGAGGGG ATTGAGTCCA GTCAAGGGGG CTTTCATCCA 240 CTCCTGTGTC CTCCCCACAG GTGCCCACTC CCAGGTGCAG CTGGTGCAAT CTGGGGCTGA 300 GGTGAAGAAG CCTGGGGCCT CAGTGAAGGT CTCCTGCAAG GCTTCTGGAT ACACCTTCAC 360 CTACTGCTAC TTGCACTGGG TATGACAGGC CCCTGGACAA GGGCTTGAAT GGACAGGATT 420 TTAGTTATTT GAGAGATTTT TCATACAACA TTTATTCTGT AAGCAAATTT CAGGGATTGT 480 AGAATGAATC ATATTAACAA ATCTGACACA GAACTTCCTC TGAATCAATC TTTGTAAACA 540 TCAATTTCTG AATCAATGTT GTNAATATTT CAGAACACAA GCACAANTTC ACATTTNAAC 600 TCTACTTTNA TCTCTATTTA AAANATATCA AAAANTCTCA TCNNGTGCAT GTAACGTTTG 660 (2) INFORMATION FOR SEQ ID NO: 13: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 819 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 13 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 TCACCATGGA GTTGGGGCTG AGCTGGGTTT TCCTTGTTGC TATATTAGAA GGTGATTCAT 360 GGAGAACTAG AGATATTGAG TGTGAATGGG CATGAATGAG AGAAACAGTG GGTATGTGTG 420 GCAATTTCTG ACTTTTGTGT CTCTGTGCCT TGCAGGTGTC CAGTGTGAGG TGCATCTGGT 480 GGAGTCTGGG GGAGGCTTGG TACAGCCTGG GGGGGCCCTG AGACTCTCCT GTGCAGCCTC 540 TGGATTCACC TTCAGTAACT ACGACATGCA CTGGGTCCGC CAAGCTACAG GAAAAGGTCT 600 GGAGTGGGTC TCAGCCAATG GTACTGCTGG TGACACATAC TATCCAGGCT CCGTGAAGGG 660 GCGATTCACC ATCTCCAGAG AAAATGCCAA GAACTCCTTG TATCTTCAAA TGAACAGCCT 720 GAGAGCCGGG GACACGGCTG TGTATTACTG TGCAAGAGAC ACAGTGAGGG GAAGTCAGTA 780 TGAGCCCAGA CACAAACCTC CCTGCAGAAT GCCTGGGGG 819 (2) INFORMATION FOR SEQ ID NO: 14: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 816 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 14 AGNGANGAAG GNAGTGATCA CTGTGATCTT TTCNCCAAGT TCACCATTTC NCTGAAGGTG 60 AGCACAGGTC CTCCTGCATG TGTTCAAACA AAAGNNNNAG AGACTACCTG GTAAGTGAGG 120 TGCTCACCTG GTTCTGGATG TTTGGTCTGT CTCCTCCCCT CTGTTGCCCC ACACAAGGTC 180 AGCCCACTCT TTCCAGGTCC GAAGAAGAGA GCACAGGTTT GTCCTGATTA TATGACTCAC 240 CCAGCTTCTG ATGACTCTCC 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 GNTTCGCCTG AGNATA 816 (2) INFORMATION FOR SEQ ID NO: 15: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 535 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 15 CACAGAGGAC TCACCATGGA GTTTGGGCTG AGCTGGATTT TCCTTCCTGC TATTTTAAAA 60 GGTGATTTAT GGAGAACTAG AGAGATTAAG TGTGAGTGGA CGTGAGTGAG AGAAACAGTG 120 GATATGTGTG GCAGTTTCTG ATCTTAGTGT CTCTGTGTTT GCAGGTGTCC AGTGTGAGGT 180 GCAGCTGGTG GAGTCTGGGG GAGCCTTGGT AAAGCCTGGG GGGTCCCTTA GACTCTCCTG 240 TGCAGCCTCT GGATTCACTT TCAGTAACGC CTGGATGAGC TGGGTCCGCC AGGCTCCAGG 300 GAAGGGGCTG GAGTGGGTTG GCCGTATTAA AAGCAAAACT GATGGTGGGA CAACAGACTA 360 CGCTGCACCC GTGAAAGGCA GATTCACCAT CTCAAGAGAT GATTCAAAAA ACACGCTGTA 420 TCTGCAAATG AACAGCCTGA AAACCGAGGA CACAGCCGTG TATTACTGTA CCACAGACAC 480 AGTGAGGGGA GGTCAGTGTG AGCCCGGACA CAAACCTCCC TGCAGGGGCG CGCGG 535 (2) INFORMATION FOR SEQ ID NO: 16: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 542 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 16 ATTGGGTCAA CAGCAATAAA CAAATTACCA TGGAATTTGG GCTGAGCTGG GTTTTTCTTG 60 CTGGTATTTT AAAAGGTGAT TCATGGAGAA CTAAGGATAT TGAGTGAGTG GACATGAGTG 120 AGAGAAACAG TGGATATGTG TGGCAGTTTC TGACCAGGGT GTCTCTGTGT TTGCAGGTGT 180 CCAGTGTGAG GTACAACTGG TGGAGTCTGG GGGAGGCTTG GTACAGCCTG GGGGGTCCCT 240 GAGACTCTCC TGTGCAGCCT CTGGATTCAC CTTCAGTAAC AGTGACATGA ACTGGGCCCG 300 CAAGGCTCCA GGAAAGGGGC TGGAGTGGGT ATCGGGTGTT AGTTGGAATG GCAGTAGGAC 360 GCACTATGTG GACTCCGTGA AGCGCCGATT CATCATCTCC AGAGACAATT CCAGGAACTC 420 CCTGTATCTG CAAAAGAACA GACGGAGAGC CGAGGACATG GCTGTGTATT ACTGTGTGAG 480 AAATCCTGTG AGGGGACACA AGTGCGAGCC CAGACACAAA CCTCCTGCAG GAACACTGGG 540 CG 542 (2) INFORMATION FOR SEQ ID NO: 17: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 591 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 17 ACATCCCTCC TCTATAGAAG CCCCTGAGAG CACAGCTCCT CACCATGGAC TGTACCTGGG 60 GGATCCTCTT CTTGGTGGCA TCTNCCACAG GTAAGGGGCT CCCAAGTCCT AGTGATGAGG 120 AGGGGATTGA GTCCAGTCAA GGGGGCTTTT ATCATCTCCT CCCTTCTCCT CACAGATGTC 180 CATTCCCAGG TTCAGCTGTT GCAGCCTGGG GCTGAGGTGA AGAAGCCTGC GTCCTCAGTG 240 AAGGTCTCCT GGCCAGGCTT CCAGATACAC CTTCACCAAA TACTTTACAC AGTGGGTGCG 300 ACAGGGCCCT GGACAAGGGC ATAGTGGTTG GGATGCATCA ACCCTTACAA TGATAACACA 360 CACTACGCAC AGAAGTTCCG GGGCAGAGTC ACCATTACCA GTGACAGGTC CGTGAGCACA 420 GCCTACATGG AGCTGAGCAG TCTGAGATCT GAAGACATGG TCGTGTATTC CTGTGTGAGA 480 GACACAGTGC GAAAACCCAC ATCCTGAGAG TGTCAGAAAC CCCAGGAAGG AGGCACCTGT 540 GCTGACACAG AGGGAGATGA CAAAGATTAT TAGATTAACG ATTTTCTTAG A 591 (2) INFORMATION FOR SEQ ID NO: 18: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 539 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 18 CAAACACCCC TCCTTGGGAG AATCCCCTAG ATCACAGCTC CTCACCATGG ACTGGACCTG 60 GAGCATCCTT TTCTTGGTGG CAGCACCAAC AGGTAACGGA CTCCCCAGTC CCAGGGCTGA 120 GAGAGAAACC AGGCCAGTCA TGTGAGACTT CACCCACTCC TGTGTCCTCT CCACAGGTGC 180 CCACTCCCAG GTTCAGCTGG TGCAGTCTGG AGCTGAGGTG AAGAAGCCTG GGGCCTCAGT 240 GAAGGTCTCC TGCAAGGCTT CTGGTTACAC CTTTACCAGC TATGGTATCA GCTGGGTGCG 300 ACAGGCCCCT GGACAAGGGC TTGAGTGGAT GGGATGGATC AGCGCTTACA ATGGTAACAC 360 AAACTATGCA CAGAAGCTCC AGGGCAGAGT CACCATGACC ACAGACACAT CCACGAGCAC 420 AGCCTACATG GAGCTGAGGA GCCTGAGATC TGACGACACG GCCGTGTATT ACTGTGCGAG 480 AGACACAGTG TGAAAACCCA CATCCTGAGG GTTTCAGAAA CCCCAGGGAG GAGGCAGCT 539 (2) INFORMATION FOR SEQ ID NO: 19: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 727 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 19 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 ACTATGCAGA 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 (2) INFORMATION FOR SEQ ID NO: 20: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 514 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 20 GGACTCGCCA TGGAGTTTGG GCTGAGCTGG GTTTTCCTTG TTGCTATTTT AAAAGGTGAT 60 TCATGGATCA ATAGAGATGT TGAGTGTGAG TGAACACGAG TGAGAGAAAC AGTGGATTTG 120 TGTGGCAGTT TCTGACCAGG GTGTCTCTGT GTTTGCAGGT GTCCAGTGTG AGGTGCAGCT 180 GGTGGAGTCT GGGGGAGGTG TGGTACGGCC TGGGGGGTCC CTGAGACTCT CCTGTGCAGC 240 CTCTGGATTC ACCTTTGATG ATTATGGCAT GAGCTGGGTC CGCCAAGCTC CAGGGAAGGG 300 GCTGGAGTGG GTCTCTGGTA TTAATTGGAA TGGTGGTAGC ACAGGTTATG CAGACTCTGT 360 GAAGGGCCGA TTCACCATCT CCAGAGACAA CGCCAAGAAC TCCCTGTATC TGCAAATGAA 420 CAGTCTGAGA GCCGAGGACA CGGCCTTGTA TCACTGTGCG AGAGACACAG TGAGGGGAAG 480 CCAGTGAGAG CCCAGACACA AACGTCCCTG CAGG 514 (2) INFORMATION FOR SEQ ID NO: 21: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 519 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 21 AGGATTCACC ATGGAACTGG GGCTCCGCTG GGTTTTCCTT GTTGCTATTT TAGAAGGTGA 60 ATCATGGAAA AGTAGAGAGA TTTAGTGTGT GTGGATATGA GTGAGAGAAA CGGTGGATGT 120 GTGTGACAGT TTCTGACCAA TGTCTCTCTG TTTGCAGGTG TCCAGTGTGA GGTGCAACTG 180 GTGGAGTCTG GGGGAGGCCT GGTCAAGCCT GGGGGGTCCC TGAGACTCTC CTGTGCAGCC 240 TCTGGATTCA CCTTCAGTAG CTATAGCATG AACTGGGTCC GCCAGGCTCC AGGGAAGGGG 300 CTGGAGTGGG TCTCATCCAT TAGTAGTAGT AGTAGTTACA TATACTACGC AGACTCAGTG 360 AAGGGCCGAT TCACCATCTC CAGAGACAAC GCCAAGAACT CACTGTATCT GCAAATGAAC 420 AGCCTGAGAG CCGAGGACAC GGCTGTGTAT TACTGTGCGA GAGACACAGT GAGGGGAAGT 480 CAGTGTGAGC CCAGACACAA ACCTCCCTGC AGGGGTCCC 519 (2) INFORMATION FOR SEQ ID NO: 22: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 606 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear

(ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 22 CTACAGCTCT GGGAGAGGAC CCCCAGCCCT GGGATTTTCA GATGTTTTCA TTTGGTGATC 60 AGGACTGAAC ACAGAGGACT CACCATGGAG TCATGGCTGA GCTGGGTTTT TCTTGCCGCT 120 ATTTTAAAAG GTAATTCATT GAGAACTATT GAAATTGAGT GTGAGCGGAT AAGAGTGAGA 180 GAAACAGTGG ATACGTGTGG CAGTTTCTGA CCAGGGTTTC TTTTTGTTTG CAGGTGTCCA 240 GTGTGAGGTG CATCTGGTGG AGTCTGGGGG AGCCTTGGTA CAGCCTGGGG GGTCCCTGAG 300 ACTCTCCTGT GCAGCCTCTG GATTCACCTT CAGTTACTAC TACATGAGCG GGGTCCGCCA 360 GGCTCCCGGG AAGGGGCTGG AATGGGTAGG TTTCATTAGA AACAAAGCTA ATGGTGGGAC 420 AACAGAATAG ACCACGTCTG TGAAAGGCAG ATTCACAATC TCAAGAGATG ATTCCAAAAG 480 CATCACCTAT CTGCAAATGA AGAGCCTGAA AACCGAGGAC ACGGCCGTGT ATTACTGTTC 540 CAGAGACACA GTGAGGGGAG GTCAGTGTGA GCCCGGACAC AAACCTCCCT GCAGGGGCGC 600 GCGGGG 606 (2) INFORMATION FOR SEQ ID NO: 23: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 514 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 23 GAACTCACCA TGGAGTTTGG GCTGAGCTGG CTTTTTCTTG TGGCTAAAAT AAAAGGTAAT 60 TCATGGAGAA ATAGAAAAAT TGAGTGTGAA TGGATAAGAG TGAGAGAAAC AGTGGATACG 120 TGTGGCAGTT TCTGACCAGG GTTTCTTTTT GTTTGCAGGT GTCCAGTGTG AGGTGCAGCT 180 GTTGGAGTCT GGGGGAGGCT TGGTACAGCC TGGGGGGTCC CTGAGACTCT CCTGTGCAGC 240 CTCTGGATTC ACCTTTAGCA GCTATGCCAT GAGCTGGGTC CGCCAGGCTC CAGGGAAGGG 300 GCTGGAGTGG GTCTCAGCTA TTAGTGGTAG TGGTGGTAGC ACATACTACG CAGACTCCGT 360 GAAGGGCCGG TTCACCATCT CCAGAGACAA TTCCAAGAAC ACGCTGTATC TGCAAATGAA 420 CAGCCTGAGA GCCGAGGACA CGGCCGTATA TTACTGTGCG AAAGACACAG TGAGGGGAAG 480 TCATTGTGAG CCCAGACACA AACCTCCCTG CAGG 514 (2) INFORMATION FOR SEQ ID NO: 24: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 600 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 24 CCCAGAGACC ATCACACAAC AGCCACATCC CTCCCCTACA GAAGCCCCCA GAGCGCAGCA 60 CCTCACCATG GACTGCACCT GGAGGATCCT CTTCTTGGTG GCAGCAGCTA CAGGCAAGAG 120 AATCCTGAGT TCCAGGTCTG ATGAGGGGAC TGGGTCCAGT TAAGTGGTGT CTCATCCACT 180 CCTCTGTCCT CTCCACAGGC ACCCACGCCC AGGTCCAGCT GGTACAGTCT GGGGCTGAGG 240 TGAAGAAGCC TGGGGCCTCA GTGAAGGTCT CCTGCAAGGT TTCCGGATAC ACCCTCACTG 300 AATTATCCAT GCACTGGGTG CGACAGGCTC CTGGAAAAGG GCTTGAGTGG ATGGGAGGTT 360 TTGATCCTGA AGATGGTGAA ACAATCTACG CACAGAAGTT CCAGGGCAGA GTCACCATGA 420 CCGAGGACAC ATCTACAGAC ACAGCCTACA TGGAGCTGAG CAGCCTGAGA TCTGAGGACA 480 CGGCCGTGTA TTACTGTGCA ACAGACACAG TGTGAAAACC CACATCCTGA GAGCGTCAGA 540 AACCCTGAGG AATGAGGCAG CTGTGCTGAG GCTGAGGAGA TGACAGGATT TATGAAGTTT 600 (2) INFORMATION FOR SEQ ID NO: 25: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 655 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 25 ATTCACGTTT TCGAGCTCGG TACCCGGGGG ATCCTCTAGA GTCGACCTGC AGCTCTGGGA 60 GAGGAGCCCA GCCCCCGAAT TCCCAGGTGT TTTCATCTGG TGATCAGCAC CGAACACAGA 120 GGACTCACCA TGGAGTTTGT GCTGAGCTGG GTTTTCCTTG TTGCTATTTT AAAACGTGAT 180 CTATAGAGAA CTAGAGATAT TGAGTATGAA TGGATATGAG TGAGAAACAG TGGATACGTG 240 TGGCAGTTTC TGACCGGGGT GTCTCTGTGT TTGCAGGTAT CCAGTGTGAG ATGCAGCTGG 300 TGGAGTCTGG GGGAGGCTTG CAAAAGCCTG CGTGGTCCCC GAGACTCTCC TGTGCAGCCT 360 CTCAATTCAC CTTCAGTAGC TACTACATGA ACTGTGTCCG CCAGGCTCCA GGGAATGGGC 420 TGGAGTTGGT TTGACAAGTT AATCCTAATG GGGGTAGCAC ATACCTCATA GACTCCGGTA 480 AGGACCGATT CAATACCTCC AGAGATAACG CCAAGAACAC ACTTCATCTG CAAATGAACA 540 GCCTGAAAAC CGAGGACACG GCCCTCTATT AGTGTACCAG AGACACAGTG AGGGGAGGTC 600 AGTGTGAGCC CAGACACAAA CCTCCCTGCA GGCATGCAAG CTTGGCACTG ACCGT 655 (2) INFORMATION FOR SEQ ID NO: 26: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 546 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 26 AGTGACTCCT GTGCCCCACC ATGGACACAC TTTGCTACAC ACTCCTGCTG CTGACCACCC 60 CTTCCTGTGA GTGCTGTGGT CAGGGACTTC CTCAGAAGTG AAACATCAGT TGTCTCCTTT 120 GTGGGCTTCA TCTTCTTATG TCTTCTCCAC AGGGGTCTTG TCCCAGGTCA CCTTGAAGGA 180 GTCTGGTCCT GTGCTGGTGA AACCCACAGA GACCCTCACG CTGACCTGCA CCGTCTCTGG 240 GTTCTCACTC AGCAATGCTA GAATGGGTGT GAGCTGGATC CGTCAGCCCC CAGGGAAGGC 300 CCTGGAGTGG CTTGCACACA TTTTTTCGAA TGACGAAAAA TCCTACAGCA CATCTCTGAA 360 GAGCAGGCTC ACCATCTCCA AGGACACCTC CAAAAGCCAG GTGGTCCTTA CCATGACCAA 420 CATGGACCCT GTGGACACAG CCACATATTA CTGTGCACGG ATACCACAGA GACACAGCCC 480 AGGATGCCTC CTGTACAAGA ACCTAGCTGC ATCTCAGTGG TGCTCCCTCC CTACCTCTGC 540 AGAACA 546 (2) INFORMATION FOR SEQ ID NO: 27: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 587 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 27 TGAGAGCATC ATCCAACAAC CACAACTCTC CTCAGAAGAA GCCCCTAGAC CACAGCACCT 60 CAACATGTAC TGGACCTGGA GGATCCTCTT CTTGGTGGCA GCAGCAACAG GTAAGGGACC 120 TCCCAGTCAC CGGGCTGAGA GAGAAACCAG GCCAGTCAAG TGAGACTTCA CGCACTCCTG 180 TCTCCTCTCC ACAGGTGTCC ACTCACAGGT GCAGCTGGTG CAGTCTGGGC CTGAGGTGAA 240 GAAGCCTGGA GCCTCATTGA AGGTTTCCTG CAAGGCTTCT GGATACACCT TCACAAGCTA 300 TGCTATCAGC TGGGTATGAC AGGCCCATGG ACAAGGGCTT GAGGAAATGG GATGGATCAA 360 CACCAACACT GGGAACCTAA CGTATGCCCA GGGCTTCACA GGACGGTTTG TCTTCTCCAT 420 GGACACCTCC GTCAGCATGG CATATCTTCA TATCAGCAGC CTAAAGGCTG AGGACACGTG 480 CAAGAGGCAC AGTGTGGAAA CCCACATCCT GAGAGAACCA GAAATCCTGA GGGAGGAGGC 540 AGCTGTGCTG AGCTGAGGCA GTGACAGGGA CAACGTGGCT GCACCCT 587 (2) INFORMATION FOR SEQ ID NO: 28: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 624 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 28 CATCCCTTTT CACCTCTCCA TACAGAGGCA CCACCCACAT GCAAATCTCA CTTAGGCACC 60 CAAGGGAAAC CATCACACAT TTCCTTAAAT TCAGGGTCCT GCTCACATGG GAAATACTTT 120 CTGAGAGCTC TGGACCTCCT GTGCAAGAAC ATGAAACACC TGTGGTTCTT CCTCCTGCTG 180 GTGGCAGCTC CCAGATGTGA GTGTCTCAAG GCTGCAGACA TGGAGATATG GGAGGTGCCT 240 CTGAGCCCAG GGCTCACTGT GGGTCTCTCT GTTCACAGGG GTCCTGTCCC AGGTGCAGCT 300 GCAGGAGTCG GGCCCAGGAC TGGTGAAGCC TTCGGACACC CTGTCCCTCA CCTGCGCTGT 360 CTCTGGTTAC TCCATCAGCA GTAGTAACTG GTGGGGCTGG ATCCGGCAGC CCCCAGGGAA 420 GGGACTGGAG TGGATTGGGT ACATCTATTA TAGTGGGAGC ACCTACTACA ACCCGTCCCT 480 CAAGAGTCGA GTCACCATGT CAGTAGACAC GTCCAAGAAC CAGTTCTCCC TGAAGCTGAG 540 CTCTGTGACC GCCGTGGACA CGGCCGTGTA TTACTGTGCG AGAAACACAG TGAGGGGAGG 600 TGAGTGTGAG CCCAGACACA AACC 624 (2) INFORMATION FOR SEQ ID NO: 29: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 304 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 29 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 (2) INFORMATION FOR SEQ ID NO: 30: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 512 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 30 GGACTCACCA TGGAGTTTGG GCTGAGCTGG GTTTTCCTCG TTGCTCTTTT AAGAGGTGAT 60 TCATGGAGAA ATAGAGAGAC TGAGTGTGAG TGAACATGAG TGAGAAAAAC TGGATTTGTG 120 TGGCATTTTC TGATAACGGT GTCCTTCTGT TTGCAGGTGT CCAGTGTCAG GTGCAGCTGG 180 TGGAGTCTGG GGGAGGCGTG GTCCAGCCTG GGAGGTCCCT GAGACTCTCC TGTGCAGCCT 240 CTGGATTCAC CTTCAGTAGC TATGGCATGC ACTGGGTCCG CCAGGCTCCA GGCAAGGGGC 300 TGGAGTGGGT GGCAGTTATA TCATATGATG GAAGTAATAA ATACTATGCA GACTCCGTGA 360 AGGGCCGATT CACCATCTCC AGAGACAATT CCAAGAACAC GCTGTATCTG CAAATGAACA 420 GCCTGAGAGC TGAGGACACG GCTGTGTATT ACTGTGCGAG AGACACAGTG AGGGGAAGTC 480 ATTGTGCGCC CAGACACAAA CCTCCCTGCA GG 512 (2) INFORMATION FOR SEQ ID NO: 31: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 631 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 31 CATCCCTTTT CACCTGTCCA TAGAGAGGCA CCAGCCACAT GCAAATCTCA CTTAGGCACC 60 CACAGAAAAC CGCCACACAT TTCCTTAAAA TCAGGGTCCT GCTCACATGG GAAATACTTT 120 CTGAGAGTCC TGGACCTCCT GTGCGAGAAC ATGAAACACC TGTGGTTCTT CCTCCTGCTG 180 GTGGCAGCTC CCAGATGTGA GTGTCTCAAG GCTGCAGACA TGGAGATATG GGAGGTGCCT 240 CTGATCCCAG GGCTCACTGT GTGTCTCTCT GTTCACAGGG GTCCTGCCCC AGGTGCAGCT 300 GCAGGAGTCG GGCCCAGGAC TGGTGAAGCC TTCACAGACC CTGTCCCTCA CCTGTACTGT 360 CTCTGGTGGC TCCATCAGCA GTGGTGGTTA CTACTGGAGC TGGATCCGCC AGCACCCAGG 420 GAAGGGCCTG GAGTGGATTG GGTACATCTA TTACAGTGGG AGCACCTACT ACAACCCGTC 480 CCTCAAGAGT CGAGTTACCA TATCAGTAGA CACGTCTAAG AACCAGTTCT CCCTGAAGCT 540 GAGCTCTGTG ACTGCCGCGG ACACGGCCGT GTATTACTGT GCGAGAGACA CAGTGAGGGG 600 AGGTGAGTGT GAGCCCAGAC ACAAACCTCC C 631 (2) INFORMATION FOR SEQ ID NO: 32: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 341 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 32 ACCAGTCTCC AGGCAAGGGG CTGGAGTGAG TAATAGATAT AAAAGATGAT GGAAGTCAGA 60 TACACCATGC AGACTCTGTG AAGGGCAGAT TCTCCATCTC CAAAGACAAT GCTAAGAACT 120 CTCTGTATCT GCAAATGAAC ACTCAGAGAG CTGAGGACGT GGCCGTGTAT GGCTATACAT 180 AAGGTCCCAA GTGAGGAAAT ATCGGTGTGA GTCCAGACAC AACATTTCCT GCAAAAAGAA 240 GAAAGGAGTC TGGGCCGAAG GGGACACTCA GCACTCACAA AACAGGTGCA GCCCCACGGC 300 AGGTGCAGAT GGAGGGAGGG TAAGGGCTGC TTTTCCTTCA G 341 (2) INFORMATION FOR SEQ ID NO: 33: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 583 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 33 TGAACACAGA GGACTCACCA TGGAGTTTGG GCTGAGCTGG GTTTTCCTCG TTGCTCTTTT 60 AAGAGGTGAT TCATTGGAGA AATAGAGAGA CTGAGTGTGA GTGAACATGA GTGAGAAAAA 120 CTGGATTTGT GTGGCATTTT CTGATAACGG TGTCCTTCTG TTTGCAGGTG TCCAGTGTCA 180 GGTACAGCTG GTGGAGTCTG GGGGAGGCGT GGTCCAGCCT GGGAGGTCCC TGAGACTCTC 240 CTGTGCAGCG TCTGGATTCA CCTTCAGTAG CTATGGCATG CACTGGGTCC GCCAGGCTCC 300 AGGCAAGGGG CTGGAGTGGG TGGCAGTTAT ATGGTATGAT GGAAGTAATA AATACTATGC 360 AGACTCCGCG AAGGGCCGAT TCACCATCTC CAGAGACAAT TCCACGAACA CGCTGTTTCT 420 GCAAATGAAC AGCCTGAGAG CCGAGGACAC GGCTGTGTAT TACTGTGCGA GAGACACAGT 480 GAGGGGAGGT CATTGTGCGC CCAGACACAA ACCTCCCTGC AGGAACGCTG GCGGGAAATC 540

AGCTGCAGGG GGGGCTCAGG AGCCACTGAT CAGAGTCAGC CCT 583 (2) INFORMATION FOR SEQ ID NO: 34: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 687 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 34 AAAAGACTGG GCCCTCCCTC ATCCCTTTTT ACCTATCCAT ACAAAGGCAC CACCCACATG 60 CAAATCCTCA CTTAGGCACC CACAGGAAAT GACTACACAT TTCCTTAAAT TCAGGGTCCA 120 GCTCACATGG GAAGTGCTTT CTGAGAGTCA TGGACCTCCT GCACAAGAAC ATGAAACACC 180 TGTGGTTCTT CCTCCTCCTG GTGGCAGCTC CCAGATGTGA GTGTCTCAGG AATGCGGATA 240 TGAAGATATG AGATGCTGCC TCTGATCCCA GGGCTCACTG TGGGTTTCTC TGTTCACAGG 300 GGTCCTGTCC CAGGTGCAGC TACAACAGTG GGGCGCAGGA CTGTTGAAGC CTTCGGAGAC 360 CCTGTCCCTC ACCTGCGCTG TCTATGGTGG GTCCTTCAGT GGTTACTACT GGAGCTGGAT 420 CCGCCAGCCC CCAGGGAAGG GGCTGGAGTG GATTGGGGAA ATCAATCATA GTGGAAGCAC 480 CAACTACAAC CCGTCCCTCA AGAGTCGAGT CACCATATCA GTAGACACGT CCAAGAACCA 540 GTTCTCCCTG AAGCTGAGCT CTGTGACCGC CGCGGACACG GCTGTGTATT ACTGTGCGAG 600 AGGCACAGTG AGGGGAGGTG AGTGTGAGCC CAGACAAAAA CCTCCCTGCA GGTAGGCAGA 660 GGGGGCGGGC GCAGGTACTG CTCAAGA 687 (2) INFORMATION FOR SEQ ID NO: 35: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 700 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 35 AAATAGGAGA CATNCAAATA GGCCCCCCCC TTTCCTGATA AAAAGCAGCC CAGTCCTGAC 60 CCTGCAGCCC TGGGAGAGAA GCACCAGCCC TGGGATTCTC AGGTGTTTCC ACTTTGTCAT 120 CAGCAACAAA CAAATTACCA TGGAATTTGG CCTGAGCTGG GTTTTCCTTG CTGCTATTTT 180 AAAAGGTGAT TCATGAAGAA CTAAGGATAT TGAGTGAGTG GACATGAGTG AGAGAAACAG 240 TGGATTTGTG TGGCAGTTTC TGACCAGGGT GTCTCTGTGT TTGCAGGTGT CCAGTGTGAG 300 GTGCAGCTGG TGGAGTCTGG GGGAGGCTTG GTACAGCCTG GGGGATCCCT GAGACTCTCC 360 TGTGCAGCCT CTGGATTCAC CTTCAGTAAC AGTGACATGA ACTGGGTCCA TCAGGCTCCA 420 GGAAAGGGGC TGGAGTGGGT ATCGGGTGTT AGTTGGAATG GCAGTAGGAC GCACTATGCA 480 GACTCTGTGA AGGGCCGATT CATCATCTCC AGAGACAATT CCAGGAACAC CCTGTATCTG 540 CAAACGAATA GCCTGAGGGC CGAGGACACG GCTGTGTATT ACTGTGTGAG AAACACTGTG 600 AGAGGTCGGA AGTGTGAGCC CAGACACAAA CCTCCTGCAG GAACGTTGGG GGAAATCAGC 660 TGCAGGGGGC GCTCAGGACC CACTCATCAG AGTCAACCCC 700 (2) INFORMATION FOR SEQ ID NO: 36: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 806 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 36 TGACACTAAC TCCCCCAGGA TCTCACATCT GCTCTGGANA CGGCTCTCCT GTTGTCCCTA 60 CCCCAGAGCT TGCTATAGAG GAGGAGACAT CCACATAGGG CCCTCNCTTG TCCTGATGAA 120 AACCAGCCTT GCCTGCGTCT ACGGGAGAAG AGCCCCAGTC CAGAAGTACC AGGGGTTTCC 180 ATTTGGTGGT CAGGTCTCTG AACACAGAGG ACTCACTATG GAGTTTGGGC TGAGCTGGGG 240 TTTCCATGTT GCTAATGTAA AAGGTGACTC ATGGAGAACT AGAGATATTG AGTGTGAGTG 300 GACACAAGTG AGAGAAACAG TGGATATGTG TGGCAGGTTC TGACCAGGGT GTCTGTGTGT 360 GTTTGCAGGT GTCCAGTGTG AGGTGCACCT GGTGGAGTCT TTGGGAGGCT TGTTATAGCC 420 TGGGGGTCCC TGAGACTTTC TTTTGCAGCC TCTGGATTCA CCTTTAGTAC CTTTATTAGG 480 TACTGGATGA GCTGGGTCCA TCAGGCTCCT GGGAAAGGGC TGGAGTAGGT CTCATTTATG 540 AGTTGTTGTG TAGGTAGCAC AAGCTATGCA GACTCTGTGA AGGGTCGATT CACCCTCTCC 600 AGAGATGATG CCAAGAAATC ACTGTATCTG CAAATGAACA GCGTCAGAGC CGAGGATAGG 660 TCTGTGTATT ACTGTGGTGG CATTGTGTGC ATCCCTTGTT TAGGTACATG CAGAGATGCT 720 GCTTTGGTGT GTTCAGGGGC TCCTGTTTTG GGGACACCAA TTTTGGAGTT TGCAGTATCC 780 TTGAGTCCAG TACGTTCATG GTGGCA 806 (2) INFORMATION FOR SEQ ID NO: 37: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 500 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 37 GGAATCACCA TGTTGTTTGG ACTGAGCTGG CCGTTCCGAT TTACTATTTT AAGGGGTGAC 60 ACGTGAAGCA CTACAGATAT TGCTCGTGAG TGGATATTAG AGAAACAGTG GATATGTGTG 120 GCAGTTTCTG ACCAGGATGT CTCTGTGTTT ACAGGTGTGC AGTATGAGGT GCAGCTGGTA 180 GAGTCTGGGG GAGACTTGGT ACAGCTGTGG TGGGTCCTGA GACTCTCATG TGCAGCCTGT 240 GGATTCATCT TGAGAAGCAA CTGGTCCCAC CGGGCTTCAC GAAAGGGGCT GGCATGGAAT 300 GACATGGTCT CATACATTAG TGCTAGTGGT GGTAGTCTAT ACTATGCAGA CACTGAAGGG 360 TAGATTCACC ATCTCTAGAG ACAATGGCAA GAACATGCTG TTCTTGCAAA TGAACAGTCT 420 GAGAGATGAG GACTCGGTTG TGTTGAGAGA CATGGTGAGG GGAAAATCAG TATGAGCCCA 480 GCCAGAACTC TCCCTGCAGG 500 (2) INFORMATION FOR SEQ ID NO: 38: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 507 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 38 CAACTCATCA TGCAGTTTGT GCTGAGCTGG GTTTTCCTTG TTGGTATTTT AAAAGGTGAT 60 TCATGGAGAA CTACAGATGT TGAGTGTGAG TGGACATGAG TGAGCCAAAC AGTGGGTTTG 120 TGTGGCAGTT TCTGACCTGG TGTCTCTGTG TTTACAGGTG TCCAGTGTGA GGTGCAGCTG 180 GTGGAGTCTG GGGGAGGCTT GGTACAGCCT AGGGGGTCCC TGAGACTCTC CTGTGCAGCC 240 TCTGGATTCA CCGTCAGTAG CAATGAGATG AGCTGGATCC GCCAGGCTCC AGGGAAGGGG 300 CTGGAGTGGG TCTCATCCAT TAGTGGTGGT AGCACATACT ACGCAGACTC CAGGAAGGGC 360 AGATTCACCA TCTCCAGAGA CAATTCCAAG AACACGCTGT ATCTTCAAAT GAACAACCTG 420 AGAGCTGAGG GCACGGCCGC GTATTACTGT GCCAGATATA CACAGAGGGG AAGTCATTGT 480 GCGCCCAGAC ACAAACCTCC CTGTAGG 507 (2) INFORMATION FOR SEQ ID NO: 39: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 800 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 39 AGAAGAGGAC TCTGGGCTTG GAGAGGGGAG CCCCCCAAGA AGAGAAACTT GATTCTCCAA 60 AGGGCACAGC CAGCATTCTC CTCCCAGGGT GAGCTCCAAA AGACTGGCGC CTCTCTCATC 120 CCTTTTCACT GCTCCGTACA AACGCACNCA CCCCCATGCA AATCCTCACT TAGGCGCCCA 180 CAGGAAGCCA CCACACATTT CCTTAAATTC AGGTCCAACT CATAAGGGAA ATGCTTTCTG 240 AGAGTCATGG ATCTCATGTG CAAGAAAATG AAGCACCTGT GGTTCTTCCT CCTGCTGGTG 300 GCGGCTCCCA GATGTGAGTG TTTCTAGGAT GCAGACATGG AGATATGGGA GGCTGCCTCT 360 GATCCCAGGG CTCACTGTGG GTTTTTCTGT TCACAGGGGT CCTGTCCCAG CTGCAGCTGC 420 AGGAGTCGGG CCCAGGACTG GTGAAGCCTT CGGAGACCCT GTCCCTCACC TGCACTGTCT 480 CTGGTGGCTC CATCAGCAGT AGTAGTTACT ACTGGGGCTG GATCCGCCAG CCCCCAGGGA 540 AGGGGCTGGA GTGGATTGGG AGTATCTATT ATAGTGGGAG CACCTACTAC AACCCGTCCC 600 TCAAGAGTCG AGTCACCATA TCCGTAGACA CGTCCAAGAA CCAGTTCTCC CTGAAGCTGA 660 GCTCTGTGAC CGCCGCAGAC ACGGCTGTGT ATTACTGTGC GAGACACACA GTGAGGGGAG 720 GTGAGTGTGA GCCCAGACAA AAACCTCCCT GCAGGGAGGC TGAGGGGGCG GTCGCAGGTG 780 CAGCTCAGNG CCAGCAGGGG 800 (2) INFORMATION FOR SEQ ID NO: 40: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 970 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 40 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 CAGCAGCCTA 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 TTTGATGGGT 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 (2) INFORMATION FOR SEQ ID NO: 41: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 819 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 41 CCCCACTCTC TCCTCAGNCG TCCCATCCCA GAGCTTGGCA TTGTAGTAGG AGACATCCAA 60 ATAGAGCCCT CCCTCTGCTT ATGAAAACCA GCCCAGCCCT GACCCTGCAG CTGTGGGAGA 120 GGAGCCCCAG CCCTGGGATT TTCAGGTGCT TTCATTTTGT GATCAGGACT GAACACAGAG 180 GATTCACCAT GGAGTCATGG CTGAGCTGGG TTTTTCTTGC CGCTATTTTA AAAGGTAATT 240 CATTGAGAAC TATTGAAATT GAGTGTGAGT GGATAAGAGT GAGATAAACA GTGGATACGT 300 GTGGCAGTTT CTGACCAGGG TTTCTTTGTG TTTGCAGGTG TCCAGTGTGA GGTGCAGCTG 360 GTGGAGTCTG GGGGAGGCTT GGTCCAGCCT GGGGGGTCCC TGAGACTCTC CTGTGCAGCC 420 TCAGGATTCT CCTTTAGTAG CTATGGCATG AGCTGGGTCC GCCAGGCTCC AGGGAAGGGG 480 CTGGAGTGAG TGGCACATAT CTGGAATGAT GGAAGTCAGA AATACTATGC AGACTCTGTG 540 AAGGGCCGAT TCACAATCTC CGAGACAATT CTAAGAGCAT GCTCTATCTG CAAATGGACA 600 GTCTGAAAGC TAAGGACACG GCCATGTATT ACTGTACCAG ACACAGTGAG AGGAAGTCCG 660 TGTGAGCCCA GACACAAACC TCCCTGCAGG GGCACGCGGG GCCACCAGAG GGTGCCCAGG 720 ATCCCCTGAA GACAGGGACA GNCCAAAGGC AGGTGCAGAT GGNTGTCAAG AGGGTCTTGT 780 GGCTTCGTCT ACATCTAACT GGTTTCCTGG GTGAGCCTC 819 (2) INFORMATION FOR SEQ ID NO: 42: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 471 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 42 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 (2) INFORMATION FOR SEQ ID NO: 43: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 870 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 43 CATCTGTTAC AGAACTCATT ATATAGTAGG AGACATCCAA ATNGGGTCCC TCCCTCTGCT 60 GATGAAAACC AGCCCAGCCC TGACCCTGCA GCTCTGGGAG AGGAGCCCCA GCCCTGAGAT 120 TCCCAGGTGT TTCCATTCGG TGATCAGCAC TGAACACAGA GAACGCACCA TGGAGTTTGG 180 ACTGAGCTGG GTTTTCCTTG TTGCTATTTT AAAAGGTGAT TCATGGATAA ATAGAGATGT 240 TGAGTGTGAG TGAACATGAG TGAGAGAAAC AGTGGATATG TGTGGCAGTG TCTGACCAGG 300 GTGTCTCTGT GTTTGCAGGT GTCCAGTGTG AAGTGCAGCT GGTGGAGTCT GGGGGAGTCG 360 TGGTACAGCC TGGGGGGTCC CTGAGACTCT CCTGTGCAGC CTCTGGATTC ACCTTTGATG 420 ATTATACCAT GCACTGGGTC CGTCAAGCTC CGGGGAAGGG TCTGGAGTGG GTCTCTCTTA 480 TTAGTTGGGA TGGTGGTAGC ACATACTATG CAGACTCTGT GAAGGGCCGA TTCACCATCT 540 CCAGAGACAA CAGCAAAAAC TCCCTGTATC TGCAAATGAA CAGTCTGAGA ACTGAGGACA 600 CCGCCTTGTA TTACTGTGCA AAAGATACAC AGTGAGGGGA AGTCAGCGAG AGCCCAGACA 660 AAAACCTCGC TGCAGGAAGA CAGGAGGGGC CTGGGCTGCA GAGGCCACTC AAGACACACT 720 GAGCATAGGG TTAACTCTGG GACAAGTTGC TCAGGAAGGT TAAGAGCTGG TTTCCTTTCA 780 GAGTCTTCAC AAATTTCTCC ATCTAACAGT TTCCCCAGGA ACCNGTCTAG ATCTGTGATC 840 TTGGATCTGC TGAAACTGCC TGTGTCACCT 870 (2) INFORMATION FOR SEQ ID NO: 44: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 529 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear

(ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 44 TCCCCGGGTA CCGAGCTCAA GTGCCAGGAT TCCCAGGTGT TTTCACTTGG TGATCAGAAC 60 TTAACACAGA GGACTCACCA TGTTGTTTGG GCTGAGCTGG GCTTTCCTTG TTACTATTTT 120 AAGAGGTGAT TCATGAAGAA CTACAGATAT TGTTTGTGAG TGGATATTAG AGAAACAGTG 180 GATATGTGTG GCAGTTGCTG ACCAGGATTT CTCTGTGTTT GCAGGTGTGC AGTATGAGGT 240 GCAGCTGGTA GAGTCTTTTT TTTTTTTTTT TTTTCACTTT TTAGCGAACA TCCATGGGTT 300 ACAAAATAAT GGGTTGGCTT TTCTTCCAAC ACTTTACAGA CACCATCAAT TTTCCCCTTG 360 CTTATAAGGT TTTTAACCAG AAGAATGCTG TCATCATCTT TCCTGTTCTT TTAGGAAGAA 420 TGCCCCCTCA ACTCATCTCC ACTTGTCTGC ATGTATTTCT ATTTGTCTTG GACGTTCCCA 480 ACAGCCTCNC GAACACTCAC CTCACCCTAC AATGCTGCTC GAGGGGGTC 529 (2) INFORMATION FOR SEQ ID NO: 45: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 748 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 45 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 CCATGGACTG 240 GACCTGGAGA ATCCTCTTCT TGGTGGCAGC AGCCACAGGT AAGGGGCTCC CAAGTCCCAG 300 TGATGAGGAG GGGATTGAGT CCAGTCAAGG TGGCTTTTAT CCACTCCTGT GTCCCCTCCA 360 CAGATGCCTA CTCCCAGATG CAGCTGGTGC AGTCTGGGGC TGAGGTGAAG AAGACTGGGT 420 CCTCAGTGAA GGTTTCCTGC AAGGCTTCCG GATACACCTT CACCTACCGC TACCTGCACT 480 GGGTGCGACA GGCCCCCGGA CAAGCGCTTG AGTGGATGGG ATGGATCACA CCTTTCAATG 540 GTAACACCAA CTACGCACAG AAATTCCAGG ACAGAGTCAC CATTACCAGG GACAGGTCTA 600 TGAGCACAGC CTACATGGAG CTGAGCAGCC TGAGATCTGA GGACACAGCC ATGTATTACT 660 GTGCAAGATA CACAGTGTGA AAACCCACAT CCTGAGACCG TCAGAAACCC CAAGGAGGAG 720 GCAGCTTCAC TGAATGAGGA GGTTACAG 748 (2) INFORMATION FOR SEQ ID NO: 46: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 799 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 46 CATTTCTTCA AAGCAGGATT AGGGCTTGGA CCATCAGCAT CCCACTCCTG TGTGGCAGAT 60 GGGACATCTA TCTTCTTTCT CCAACCTCGA TCAGGCTTTT GAGGTATGAA ATAATCTGTC 120 TCATGAATAT GCAAATAACC TTAGATCTAC TGAGGTAAAT ATGGATACAT CTGGGCCCTG 180 AAAGCATCAT CCAACAACCA CATCCCTTCT CTACAGAAGC CTCTGAGAGG AAAGTTCTTC 240 ACCATGGACT GGACCTGGAG GGTCTTCTGC TTGCTGGCTG TAGCTCCAGG TAAAGGGCCA 300 ACTGGTTCCA GGGCTGAGGA AGGGATTTTT TCCAGTTTAG AGGACTGTCA TTCTCTACTG 360 TGTCCTCTCC GCAGGTGCTC ACTCCCAGGT GCAGCTGGTG CAGTCTGGGG CTGAGGTGAA 420 GAAGCCTGGG GCCTCAGTGA AGGTTTCCTG CAAGGCATCT GGATACACCT TCACCAGCTA 480 CTATATGCAC TGGGTGCGAC AGGCCCCTGG ACAAGGGCTT GAGTGGATGG GAATAATCAA 540 CCCTAGTGGT GGTAGCACAA GCTACGCACA GAAGTTCCAG GGCAGAGTCA CCATGACCAG 600 GGACACGTCC ACGAGCACAG TCTACATGGA GCTGAGCAGC CTGAGATCTG AGGACACGGC 660 CGTGTATTAC TGTGCGAGAG ACACAGTGTG AGAAACCACA TCCTCAGAGT GTCAGAAACC 720 CTGAGGGAGG AGTCAGCTGT GCTGAGCTGA GAAAATGACA GGGGTTATTC AGTTTAAGAC 780 TGTTTAGAAA ACGGGTTAT 799 (2) INFORMATION FOR SEQ ID NO: 47: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 627 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 47 CCAAATAAAC ACATTAAATG TCAAGATACG CCCAAAAACT TATCTGCCTG ACCCCCTAGT 60 TGTCTCCGTA ATTTTTGGAT GAAAACCAGC CCACCCCTGA CCCTGCTGCT CTGGGAGAGG 120 AGCCCCAGCC TTGGGATTCC CAAGTGTTTG CATTCAGTGA TCAGGACTGA ACACACAGGA 180 CTCACCAGGG AGTTTGTGCT AAGCTGGGTT TTCCTTGTTG CTATATTAAA ATGTGATTCA 240 TGGAGAACTA GAGAGATTGA GTGTGAGTTA CATGAGTGAG AGAAACAGTG GATATGTTTG 300 GCAATTTCTG ACTTTTGTGT CTCTGTGTTT GCAGGTGTCC AGTGTGAGGA TCAGCTGGTG 360 GAGTCTGGGG GAGGCTTGGT ACAGCCTGGG GGGTCCCTGA GACCCTCCTG TGCAGCCTCT 420 GGATTCGCCT TCAGTAGCTA TGTTCTGCAC TGGGTTCGCC GGGCTCCAGG GAAGGGTCCG 480 GAGTGGGTAT CAGCTATTGG TACTGGTGGT GATACATACT ATGCAGACTC CGTGATGGGC 540 CGATTCACCA TCTCCAGAGA CAACGCCAAG AAGTCCTTGT ATCTCAAATG AACAGCCTGA 600 TAGCTGAGGA CATGGCTGTG TATTATG 627 (2) INFORMATION FOR SEQ ID NO: 48: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 743 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 48 AAGGGTCCCC ACCCTAGAGC TTGCTATATA GTAGGAGATA TCCAAATAGG NCCCTCCCTC 60 TACTGATGAA AACCCAACCC AACCCTGACC CTGCAGCTCT CAGAGAGGTG CCTTAGCCCT 120 GGATTCCAAG GCATTTCCAC TTGGTGATCA GCACTGAACA CAGAGGACTC ACCATGGAGT 180 TGGGGCTGTG CTGGGTTTTC CTTGTTGCTA TTTTAGAAGG TGATTCATGG AAAACTAGAG 240 AGATTTAGTG TGTGTGGATA TGAGTGAGAG AAACAGTGGA TATGTGTGGC AGTTTCTGAC 300 CTTGGTGTCT CTTTGTTTGC AGGTGTCCAG TGTGAGGTGC AGCTGGTGGA GTCTGGGGGA 360 GGCTTGGTAC AGCCTGGGGG GTCCCTGAGA CTCTCCTGTG CAGCCTCTGG ATTCACCTTC 420 AGTAGCTATA GCATGAACTG GGTCCGCCAG GCTCCAGGGA AGGGGCTGGA GTGGGTTTCA 480 TACATTAGTA GTAGTAGTAG TACCATATAC TACGCAGACT CTGTGAAGGG CCGATTCACC 540 ATCTCCAGAG ACAATGCCAA GAACTCACTG TATCTGCAAA TGAACAGCCT GAGAGCCGAG 600 GACACGGCTG TGTATTACTG TGCGAGAGAC ACAGTGAGGG GAGGTCAGTG TGACACCAGA 660 CACAAACCTC CCTGCAGGGG TCCGCAGGAC CACCAGGGGG CGACAGGACA CTGAGCACGG 720 GGCTGTCTCC AGGGCAGGTG CAG 743 (2) INFORMATION FOR SEQ ID NO: 49: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 763 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 49 TCACCCAACT CCTCCAGGCA CAGTCATCTT ATCTGGCCCC GTCCTCTCCT CAGNTGTCCC 60 ACCCCAGAGC TTGGTATATA GTAGGAGACA TNCAAATAAG GCCCTCCCTC TGCTGATGAA 120 AATGAGCCCA GCCCTGACCC TGCAGCTCTG GGAGAGGAGC CCCANCCGTG AGATTCCCAG 180 GAGTTTCCAC TTGGTGATCA GCACTGAACA CAGACCACCA ACCATGGAGT TTGGGCTTAG 240 CTGGGTTTTC CTTGTTGCTA TTTTAAAAGG TAATTCATGG TGTACTAGAG ATACTGAGTG 300 TGAGGGGACA TGAGTGGTAG AAACAGTGGA TATGTGTGGC AGTTTCTGAC CTTGGTGTTT 360 CTGTGTTTGC AGGTGTCCAA TGTGAGGTGC AGCTGGTGGA GTCTGGGGGA GGCTTGGTAC 420 AGCCAGGGCG GTCCCTGAGA CTCTCCTGTA CAGCTTCTGG ATTCACCTTT GGTGATTATG 480 CTATGAGCTG GTTCCGCCAG GCTCCAGGGA AGGGGCTGGA GTGGGTAGGT TTCATTAGAA 540 GCAAAGCTTA TGGTGGGACA ACAGAATACA CCGCGTCTGT GAAAGGCAGA TTCACCATCT 600 CAAGAGATGG TTCCAAAAGC ATCGCCTATC TGCAAATGAA CAGCCTGAAA ACCGAGGACA 660 CAGCCGTGTA TTACTGTACT AGAGACACAG TGNGGGGAGG TCAATGTGAG CCCAGACACA 720 GACCTCCCTG CAGGCCCGCA CAGAGCCACC AGGGGGCGCT AGG 763 (2) INFORMATION FOR SEQ ID NO: 50: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 283 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 50 TGGCTCACCA TGGAGTTAGG GCTGAGCTGG GTTTCCCTTG TCATTATATT AAAAGGCGAA 60 TAATGGAGAA CTTGAGATAT GGAGTGTGAG TGGATATGAG TGAAGAAACA GTGATTCTGT 120 GTGGCAGGTT CTGACTCAGA TGTCCTCTGT GCTTGTAGGT GTCTAGTGTG GGGTGCAGAT 180 GGTGGAGTCT TGGGGAGAGT TGGCACAANC TGAATGTGCC TGAGACTCTG CCGTGCATCC 240 TCTGAATCCA CCTTCTGTAG CTACTAGATC AGCTGAATCT GCC 283 (2) INFORMATION FOR SEQ ID NO: 51: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 700 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 51 AGGTTCTGGG TTATAAACNC TGTAGACTCC TCCCTTCAGG GCAGGNTGAC CAACTATGCA 60 AATGCAAGTG GGGGCCTCCC CACTTAAACC CAGGGCTCCC CTCCACAGTG AGTCTCCCTC 120 ACTGCCCAGC TGGGATCTCA GGGCTTCATT TTCTGTCCTC CACCATCATG GGGTCAACCG 180 CCATCCTCGC CCTCCTCCTG GCTGTTCTCC AAGGTCAGTC CTGCCGAGGG CTTGAGGTCA 240 CAGAGGAGAA CGGGTGGAAA GGAGCCCCTG ATTCAAATTT TGTGTCTCCC CCACAGGAGT 300 CTGTTCCGAG GTGCAGCTGG TGCAGTCTGG AGCAGAGGTG AAAAAGCCCG GGGAGTCTCT 360 GAAGATCTCC TGTAAGGGTT CTGGATACAG CTTTACCAGC TACTGGATCG GCTGGGTGCG 420 CCAGATGCCC GGGAAAGGCC TGGAGTGGAT GGGGATCATC TATCCTGGTG ACTCTGATAC 480 CAGATACAGC CCGTCCTTCC AAGGCCAGGT CACCATCTCA GCCGACAAGT CCATCAGCAC 540 CGCCTACCTG CAGTGGAGCA GCCTGAAGGC CTCGGACACC GCCATGTATT ACTGTGCGAG 600 ACACACAGTG AGAGAAACCA GCCCCGAGCC CGTCTAAAAC CCTCCACACC GCAGGTGCAG 660 AATGAGCTGC TAGAGACTCA CTCCCCAGGG GCCTCTCTAT 700 (2) INFORMATION FOR SEQ ID NO: 52: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 767 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 52 ACACTCACCT GCTCTGGGCT CCTCCAAACT CTCCTCAGGA TTCCCCACCC CAGAGCTTGC 60 TATATAGTAG GAGACATCCA AACAAGAGCC NAAACCTCTG CTGATGAAAA GCAGCCCAGC 120 CCTGACCCTG CAGCTCTGGG AGAGGAGCCC CAGCTCCAGG ATTCCCAGGT CTTTCCATTT 180 AGTCTTCAGG GCTGAGCACA GAGGACTCAC CATGGAGTCT GGGCTGAGCT GGGTTTTCCT 240 TGTTGCTATT TTGAAAGGTG ATTCATGGGG AATGAGTTGA ATGTAAGTGA ATATGAGTGA 300 GAGAAACAGT GGATGTGTGC GGCAGTTTCT GACCAGGGTG TCTCTGTGTT TGCAGGTGTC 360 CAGTGTGAGG TGCAGCTGGT GGAGTCTGGG TGAGGCTTGG TACAGCCTGG AGGGTCCCTG 420 AGACTCTCCT GTGCAGCCTC TGGATTCACC TTCAGTAGCT CCTGGATGCA CTGGGTCTGC 480 CAGGCTCCGG AGAAGGGGCT GGAGTGGGTG GCCGACATAA AGTGTGACGG AAGTGAGAAA 540 TACTATGTAG ACTCTGTGAA GGGCCGATTG ACCATCTCCA GAGACAATGC CAAGAACTCC 600 CTCTATCTGC AAGTGAACAG CCTGAGAGCT GAGGACATGA CCGTGTATTA CTGTGTGAGA 660 GGCACAGTGA GGGGAGGTCA GTGTGAGCCC AGACACAAAC CTCCTGCAGG GGCATCTGGA 720 GCCACAAGGG GGCGCTCAGG ATACACAGAG GGACAGGGGC AGCCCCA 767 (2) INFORMATION FOR SEQ ID NO: 53: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 724 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 53 CCATTCGGTG ATCAGCACTG AACACAGAGG ACTCACCATG GAGTTTTGGC TGAGCTGGGT 60 TTTCCTTGTT GCTATTTTAA AAGGTGATTC ATGGAGAACT AGAGATATTG AGTGTGAGTG 120 AACACGAGTG AGAGAAACAG TGGATATGTG TGGCAGTTTC TAACCAATGT CTCTGTGTTT 180 GCAGGTGTCC AGTGTGAGGT GCAGCTGGTG GAGTCTGGAG GAGGCTTGAT CCAGCCTGGG 240 GGGTCCCTGA GACTCTCCTG TGCAGCCTCT GGGTTCACCG TCAGTAGCAA CTACATGAGC 300 TGGGTCCGCC AGGCTCCAGG GAAGGGGCTG GAGTGGGTCT CAGTTATTTA TAGCGGTGGT 360 AGCACATACT ACGCAGACTC CGTGAAGGGC CGATTCACCA TCTCCAGAGA CAATTCCAAG 420 AACACGCTGT ATCTTCAAAT GAACAGCCTG AGAGCCGAGG ACACGGCCGT GTATTACTGT 480 GCGAGAGACA CAGTGAGGGG AAGTCATTGT GCGCCCAGAC ACAAACCTCC CTGCAGGAAC 540 GCTGGGGGGA AATCAGCGGN AGGGGGCGCT CAGGAGCCAC TGATCAGAGT CAGCCCCGGA 600 GGCAGGTGCA GATGGAGGCT GATTTCCTTG TCAGGATGTG GGGACTTTTG TCTTCTTCTG 660 ACGGGTTCCC CAGGGGAACC TCTCTAAGTT TAGCATTCTG TGCCTATGAA CGTCTTCTCT 720 AAGT 724 (2) INFORMATION FOR SEQ ID NO: 54: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 706 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 54 CTTGCTATAC AGTAGGAGAC ATGCNAATAG GTTTCTCCCT CTGCTGATGA CCAGTCCTGA 60 CCCCATAGCT CTGGGAGAGA AGCGCCAGCC CTGGGATTCC CAGGGGTTTC CATTTGGTGA 120 TCAGGACTAA AGACAGAGGA CCCACCATGG AGCTTGGGCT GAGCTGGGTT TTCACTGTTA 180 CTGTTTTAAA AGGTGAACTA GAGAGATTGA GTGTGAATGG ATACACTTGA GAGAAACAGT 240 GGATATGTCT GGAACTTTCT GACCAGGACA CCTACAAGTT TGCAGGTGTC CAGTGTGAGG 300 TACAGCTGGT GGAGTCTGAA GAAAACCAAA GACAACTTGG GGGATCCCTG AGACTCTCCT 360 GTGCAGACTC TGGATTAACC TTCAGTAGCT ACTGAATGAG CTCAGATTCC CAAGCTCCAG 420 GGAAGGGGCT GGAGTGAGTA GTAGATATAT AGTAGGATAG AAGTCAGCTA TGTTATGCAC 480 AATCTGTGAA GAGCAGATTC ACCATCTCCA AAGAAAATGC CAAGAACTCA CTCTGTTTGC 540

AAATGAACAG TCTGAGAGCA GAGGGCACGG CCGTGTATTA CTGTATGTGA GTCACCAGGT 600 AAGAAGACAT CAGTGTGATC ACAGACACAG AATTTCCTGA AATAAGGGAG GAGTCTGGGC 660 TAAAAGGGCA CTCAGGACCC ACAGAAAACA GCGGAAGCTC TAGGGC 706 (2) INFORMATION FOR SEQ ID NO: 55: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 800 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 55 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 CACAAGAACA TGAAACACCT 240 GTGGTTCTTC CTCCTGCTGG TGGCAGCTCC CAGATGTGAG TGCCTCAGGG ATCCAGACCT 300 GAAGATATGA GATGCTGCCT CTCATCCCAG GGCTCACCGT GGTTCTCTCT GTTCACAGGG 360 GTCCTGTCCC AGGTGCAGCT GCAGGAGTCG GGCCCAGGAC TGGTGAAGCC TTCGGAGACC 420 CTGTCCCTCA TCTGCGCTGT CTCTGGTGAC TCCATCAGCA GTGGTAACTG GTGAATCTGG 480 GTCCGCCAGC CCCCAGGGAA GGGGCTGGAG TGGATTGGGG AAATCCATCA TAGTGGGAGC 540 ACCTACTACA ACCCGTCCCT CAAGAGTCGA ATCACCATGT CCGTAGACAC GTCCAAGAAC 600 CAGTTCTACC TGAAGCTGAG CTCTGTGACC GCCGCGGACA CGGCCGTGTA TTACTGTGCG 660 AGATACACAG TGAGGGGAGG TGAGTGTGAG CCCAGACACA AACCTCCCTA CAGATAGGCA 720 GAGGGGGNGG GCACAGGTGC TGCTCAGGAN CAACAGGGGG CGCGCGANGN CACAGAGCCC 780 GAGGNCCGGG TCANGAGCAG 800 (2) INFORMATION FOR SEQ ID NO: 56: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 429 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 56 AGGAATTGGG CTATTCAATG CATCCTTCGT GAATATGCAA ATCACTAAGG TTAATACAGA 60 TATCTCTGTG CCGTGAGAGC ATCACCCAAC AACCACACCC CTCCTTGGAG AATCCCTAGA 120 TCACAGCTCC TCACCATGGA CTGGACCTGG AGCATCCTCT TCTTGGTGGC AGCAGCAACA 180 GGTAAGGACT CCCCAGTCCC AGGGCTGAGG GAGAAACCAG GCCAGTCATG TGAGACTTCA 240 CCCACTGCTG TCTCCTCTCC ACAGGTGCCC ACTCCCGAGT GCAGCTGGTG CAGTCTGGGC 300 CTGAGGTGAA GCAGCCTGGG GCCTCGGCGA AGGTCTCCTG CAAGGTGTCT GGTTAAACTG 360 TCATCACCTA TGGTATGAAT TGGATACGAC AGACCCCAGG ACAGGGGCTT GAGTGGATGG 420 GATGGATCC 429 (2) INFORMATION FOR SEQ ID NO: 57: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 462 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 57 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 (2) INFORMATION FOR SEQ ID NO: 58: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 629 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 58 AGGGTCTTCA GCTATGAAAT GCTCTGACTC ATGAATATGC AAATAACCTG AGATGCACTG 60 AGGTAAATAT GGATATTTGT CAGCCCTGAG AGCATCATCC AGAAACCACA TCCCTCCGCT 120 AGAGAAGCCC TGACGGCACA GTTCCTCACT ATGGACTGGA TTTGGAGGAT CCTCTTCTTG 180 GTGGGAGCAG CGACAGGCAA GGAGATGCCA AGTCCCAGTG ATGAGGAGGG GATTGAGTCC 240 AGTCAAGGTG GCTTTCATCC ACTCCTGTGT TCTCTCCACA GGTGCCCACT CCCAAATGCA 300 GCTGGTGCAG TCTGGGCCTG AGGTGAAGAA GCCTGGGACC TCAGTGAAGG TCTCCTGCAA 360 GGCTTCTGGA TTCACCTTTA CTAGCTCTGC TGTGCAGTGG GTGCGACAGG CTCGTGGACA 420 ACGCCTTGAG TGGATAGGAT GGATCGTCGT TGGCAGTGGT AACACAAACT ACGCACAGAA 480 GTTCCAGGAA AGAGTCACCA TTACCAGGGA CATGTCCACA AGCACAGCCT ACATGGAGCT 540 GAGCAGCCTG AGATCCGAGG ACACGGCCGT GTATTACTGT GCGGCAGACA CAGTGTGAAA 600 ACCCACATCC TGAGAGTGTC AGAAACGCC 629 (2) INFORMATION FOR SEQ ID NO: 59: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 622 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 59 CCTCCTTTTT CACCTCTCCA TACAAAGGCA CCACCCACAT GCAAATCCTC ACTTAAGCAC 60 CCACAGGAAA CCACCACACA TTTCCTTAAA TTCAGGTTCC AGCTCACATG GGAAATACTT 120 TCTGAGAGCT CTGGACCTCC TGTGCAAGAA CATGAAACAT CTGTGGTTCT TCCTTCTCCT 180 GGTGGCAGCT CCCAGATGTG AGTATCTCAG GGATCCAGAC ATGGGGATAT GGGAGGTGCC 240 TCTGATCCCA GGGCTCACTG TGGGTCTCTC TGTTCACAGG GGTCCTGTCC CAGGTGCAGC 300 TGCAGGAGTC GGGCCCAGGA CTGGTGAAGC CTTCGGAGAC CCTGTCCCTC ACCTGCACTG 360 TCTCTGGTGG CTCCGTCAGT AGTTACTACT GGAGCTGGAT CCGGCAGCCC CCAGGGAAGG 420 GACTGGAGTG GATTGGGTAT ATCTATTACA GTGGGAGCAC CAACTACAAC CCCTCCCTCA 480 AGAGTCGAGT CACCATATCA GTAGACACGT CCAAGAACCA GTTCTCCCTG AAGCTGAGCT 540 CTGTGACCGC TGCGGACACG GCCGTGTATT ACTGTGCGAG AGACACAGTG AGGGGAGGTG 600 AGTGTGAGCC CAGACAAAAA CC 622 (2) INFORMATION FOR SEQ ID NO: 60: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 588 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 60 CCCGGGATTC CCAGCTGTCT CCACTTGGTC ATGAACACTG AACACAGAAG ACACACCATG 60 GAGTCTGGGC TGAGCTGGAT TTTCCTTGTT GCAGTTTTAA AAGGTGATTT ATGGAGAATA 120 GACACACTGA GTGTGACTGG ACATAAGTGA GAGAAACAGT GGATTTGTGT GGCAGTTTCT 180 GACCAGGGTG TCTCCGTGTT TGCAGGTGTC CAGTGTGAGG TGCAGCTGGT GGAGTCTGGG 240 GGAGGCTTAG TAAAGACTGG GGGGTCTCTG AGACTCTCCT GTGCAGCCTC TGGATTCACC 300 TTCAGTAGCT CTGCTATGCA CTGGGTCCAC CAGGCTCCAG GAAAGGGTTT GGAGTGGGTC 360 TCAGTTATTA GTACAAGTGG TGATACCGTA CTCTACACAG ACTCTGTGAA GGGCTGATTC 420 ACCATCTCTA GAGACAATGC CCAGAATTCA CTGTATCTGC AAATGAACAG CCTGAGAGCC 480 GACGACATGG CTGTGTATTA CTGTGTGAAA GACGCAGTGA GAAGTCAGTG TGAGCCCAGA 540 CACAAACCTC CTGCAGGGTA CCTGGGACAA CCAGGGAAAG CCTGGGAC 588 (2) INFORMATION FOR SEQ ID NO: 61: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1212 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 61 CCTCCTTTTT CACCTCTCCG TACAAAGGCA CCACCCACAT GCAAATCCTT ACTTAAGCAC 60 CCACAGGAAA CCACCACACA TTTCCTTAAA TTCAGGTTCC AGCTCACATG GGAAATACTT 120 TCTGAGAGCC TGGACCTCCT GTGCAAGAAC ATGAAACACC TGTGGTTCTT CCTCCTCCTG 180 GTGGCAGCTC CCAGATGTGA GTGTCTCAGG GATCCAGACA TGGGGGTATG GGAGGTGCCT 240 CTGATCCCAG GGCTCACTGT GGGTCTCTCT GTTCACAGGG GTCCTGTCCC AGGTGCAGCT 300 GCAGGAGTCG GGCCCAGGAC TGGTGAAGCC TTCGGAGACC CTGTCCCTCA CCTGCACTGT 360 CTCTGGTGGC TCCGTCAGCA GTGGTAGTTA CTACTGGAGC TGGATCCGGC AGCCCCCAGG 420 GAAGGGACTG GAGTGGATTG GGTATATCTA TTACAGTGGG AGCACCAACT ACAACCCCTC 480 CCTCAAGAGT CGAGTCACCA TATCAGTAGA CACGTCCAAG AACCAGTTCT CCCTGAAGCT 540 GAGCTCTGTG ACCGCTGCGG ACACGGCCGT GTATTACTGT GCGAGAGACA CAGTGAGGGG 600 AGGTGAGTGT GAGCCCAGGA CACAAACCTC CCTCATGGAC GCGGAGGGGA CCGGCGCAGG 660 TGCTGCTCAG GACCAGCAGG TGGCGCGCGG GGCCCCCAGA GCATGAGGCC GGGTCAGGAC 720 AGGTGCAGGG AGGGCTTCCT CATCTGCTCA CTGGTCTCCG TCCTCGCCAG CACCTCGCTG 780 TCACCAGGGC TCCTCTTTCT TTATTATCTG TGGTTCTGCT TCCTCACATT CTTGTGCCAG 840 GAAAGAAACG AGGAAGACGG GTTTTCGTCT ATAGTTGAAG CTTTTACTAG GATCTTGCCT 900 ACAAGTTCCT GCATGACCCA TTATAACTTA TCGATTAAAA AATATATATT CTAATGCTTC 960 TCACCATCTC TTGATTTGTA TCATCAACTG AATTGTACCC TCTTTGAAAT TCATATGATG 1020 AAACCTTAAA TTCAATGGAT CTATATTGGA ATTTTAATGA AATAATTAAG GTTAAATGTG 1080 GTCATAATTG TAAGACCCTA ATGCAATAGA CGTGTTGTCT TTATAAGAAG AGGAAGAGAC 1140 ACCAGAGACC TCTCACTTTT CACGTGCAGG CAGAGAAGAG GCCATGTGGA GACATAGTGC 1200 ACTAGAAGGT GG 1212 (2) INFORMATION FOR SEQ ID NO: 62: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 560 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 62 GATCAGCACT GAACACAGAG GACTCACCAT GGAGTTTGGG CTGAGCTGGG TTTTCCTTGT 60 TGCTAATTTA AGAGGTGATT CATAGATAAA TAGAGATGTT GAGTGGGAGT GGACATGAGT 120 GAGAGAAACA GTGGATGTGT GTGGCAGTTT CTGACCTTGG TGTCTTTGTG TTTGCAGGTG 180 TCCAGTGTGA GGTGCAGCTG GTGGAGTCTG GGGAAGGCTT GGTCCAGCCT GGGGGGTCCC 240 TGAGACTCTC CTGTGCAGCC TCTGGATTCA CCTTCAGTAG CTCTGCTATG CACTGGGTCC 300 GCCAGGCTCC AAGAAAGGGT TTGTAGTGGG TCTCAGTTAT TAGTACAAGT GGTGATACCG 360 TACTCTACAC AGACTCTGTG AAGGGCCGAT TCACCATCTC CAGAGACAAT GCCCAGAATT 420 CACTGTCTCT GCAAATGAAC AGCCTGAGAG CCGAGGGCAC AGTTGTGTAC TACTGTGTGA 480 AAGACGCAGT GAGAAGTCAG TGTGAGCCCA GACACAAACC TCCTGCAGGG TACCTGGGAC 540 AATCAGGGAA AGCCTGGGAC 560 (2) INFORMATION FOR SEQ ID NO: 63: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 515 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 63 GAGCTCACTA TGGGGTTTGA GCTAACCAGA ATTTTTCTTG TTGCTATTTT AAAAGGTGAC 60 TCATAGAGAA ATAGAGTGAG TGAGAGTGAG TGGATATAAG TGAGAAAAAC AGTAGATGTG 120 TTTGGCAGTT TCTGACCAGG ACGTTTGTGT ATTTTCAGGT GTTCAGTGTG AGGTGGAGCT 180 GATAGAGTCC ATAGAGGGCC TGAGACAACT TGGGAAGTTC CTGAGACTCT CCTGTGTAGC 240 CTCTGGATTC ACCTTCAGTA GCTACTGAAT GAGCTGGGTC AATGAGACTC TAGGGAAGGG 300 GCTGGAGGGA GTAATAGATG TAAAATATGA TGGAAGTCAG ATATACCATG CAGACTCTGT 360 GAAGGGCAGA TTCACCATCT CCAAAGACAA TGCTAAGAAC TCACCGTATC TCCAAACGAA 420 CAGTCTGAGA GCTGAGGACA TGACCATGCA TGGCTGTACA TAAGGTTCCA AGTGAGGAAA 480 CATCGGTGTG AGTCCAGACC AAAATTTCCT GCAGG 515 (2) INFORMATION FOR SEQ ID NO: 64: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 649 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (G) CELL TYPE: human lymphoblast (H) CELL LINE: CGM1 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 64 AGCTCTGGGA GAGGAGCCCC CCCCCTGGGA TTCCCAGGTG TTTTCATTTG GTGATCAGCA 60 CTGAACACAG AAGAGTCATG ACGGAGTTTG GGCTGAGCTG GGTTTTCCTT GTTGCTATTT 120 TTAAAGGTGA TTCATGAGGA AATAGAGATA TTGAGTGTGA GTGGACATGA GTGAGAGAAA 180 CAGTGGATTT GTGTGGCAGT TTCTGACCTT GGTGTCTCTG TGTTTGCAGG TGTCCAGTGT 240 GAGGTGCAGC TGGTGGAGTC TGGGGGAGGC TTGGTCCAGC CTGGGGGGTC CCTGAGACTC 300 TCCTGTGCAG CCTCTGGATT CACCTTCAGT AGCTATGCTA TGCACTGGGT CCGCCAGGCT 360 CCAGGGAAGG GACTGGAATA TGTTTCAGCT ATTAGTAGTA ATGGGGGTAG CACATATTAT 420 GCAAACTCTG TGAAGGGCAG ATTCACCATC TCCAGAGACA ATTCCAAGAA CACGCTGTAT 480 CTTCAAATGG GCAGCCTGAG AGCTGAGGAC ATGGCTGTGT ATTACTGTGC GAGAGACACA 540 GTGAGGAGAA GTTAATGTGG GACCATGCAG AAACCTCCCT GCGGGAACGC TGGGGAAAGT 600 CATCTGCAGG GGGCGCTCAG GAGCCACTGA TCAGCGTCAA CCGCAGCGG 649 (2) INFORMATION FOR SEQ ID NO: 65: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 21 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 65 AGGTGCAGCT GGTGCAGTCT G 21 (2) INFORMATION FOR SEQ ID NO: 66: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 20 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear

(ii) MOLECULE TYPE: Genomic DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 66 CCAGGGGCCT GTCGCACCCA 20 (2) INFORMATION FOR SEQ ID NO: 67: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 24 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 67 TGGGGCCTCA GTGAAGGTCT CCTG 24 (2) INFORMATION FOR SEQ ID NO: 68: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 21 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 68 GATCCATCCC ATCCACTCAA G 21 (2) INFORMATION FOR SEQ ID NO: 69: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 21 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 69 GATCCGTCCC ATCCACTCAA G 21 (2) INFORMATION FOR SEQ ID NO: 70: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 21 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 70 TGTCTTCTCC ACAGGGGTCT T 21 (2) INFORMATION FOR SEQ ID NO: 71: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 20 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 71 GGGAAGGCCC TGGAGTGGCT 20 (2) INFORMATION FOR SEQ ID NO: 72: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 20 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 72 GTGCAGGTCA GCGTGAGGGT 20 (2) INFORMATION FOR SEQ ID NO: 73: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 22 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 73 TGGTTTTTGG AGGTGTCCTT GG 22 (2) INFORMATION FOR SEQ ID NO: 74: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 23 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 74 CACTCCAGCC CCTTCCCTGG AGC 23 (2) INFORMATION FOR SEQ ID NO: 75: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 21 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 75 GTGAGGTTCA GCTGGTGGAG T 21 (2) INFORMATION FOR SEQ ID NO: 76: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 20 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 76 AGCTGAACCT CACACTGGAC 20 (2) INFORMATION FOR SEQ ID NO: 77: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 19 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 77 AAGGGCCGAT TCACCATCT 19 (2) INFORMATION FOR SEQ ID NO: 78: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 20 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 78 TTGTCTCTGG AGATGGTGAA 20 (2) INFORMATION FOR SEQ ID NO: 79: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 24 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 79 TGAGACTCTC CTGTGCAGCC TCTG 24 (2) INFORMATION FOR SEQ ID NO: 80: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 19 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 80 TCTTTGTGTT TGCAGGTGT 19 (2) INFORMATION FOR SEQ ID NO: 81: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 19 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 81 TCTCTGTGTT TGCAGGTGT 19 (2) INFORMATION FOR SEQ ID NO: 82: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 21 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 82 TCTGTTCACA GGGGTCCTGT C 21 (2) INFORMATION FOR SEQ ID NO: 83: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 19 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 83 TCCGGCAGCC CCCAGGGAA 19 (2) INFORMATION FOR SEQ ID NO: 84: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 18 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 84 GCAGGTGAGG GACAGGGT 18 (2) INFORMATION FOR SEQ ID NO: 85: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 21 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 85 CAGGGAGAAC TGGTTCTTGG A 21 (2) INFORMATION FOR SEQ ID NO: 86: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 21 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 86 CCCGGGCATC TGGCGCACCC A 21 (2) INFORMATION FOR SEQ ID NO: 87: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 21 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 87 GCTGCTCCAC TGCAGGTAGG C 21 (2) INFORMATION FOR SEQ ID NO: 88: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 21 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 88 CTTCAGGCTG CTCCACTGCA G 21 (2) INFORMATION FOR SEQ ID NO: 89: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 121 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 89 Met Ser Val Ser Phe Leu Ile Phe Leu Pro Val Leu Gly Leu Pro Trp 1 5 10 15 Gly Val Leu Ser Gln Val Gln Leu Gln Gln Ser Gly Pro Gly Leu Val 20 25 30 Lys Pro Ser Gln Thr Leu Ser Leu Thr Cys Ala Ile Ser Gly Asp Ser 35 40 45 Val Ser Ser Asn Ser Ala Ala Trp Asn Trp Ile Arg Gln Ser Pro Ser 50 55 60 Arg Gly Leu Glu Trp Leu Gly Arg Thr Tyr Tyr Arg Ser Lys Trp Tyr 65 70 75 80 Asn Asp Tyr Ala Val Ser Val Lys Ser Arg Ile Thr Ile Asn Pro Asp 85 90 95 Thr Ser Lys Asn Gln Phe Ser Leu Gln Leu Asn Ser Val Thr Pro Glu 100 105 110 Asp Thr Ala Val Tyr Tyr Cys Ala Arg 115 120 (2) INFORMATION FOR SEQ ID NO: 90: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 117 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 90 Met Asp Trp Thr Trp Arg Ile Leu Phe Leu Val Ala Ala Ala Thr Gly 1 5 10 15 Ala His Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys 20 25 30 Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe 35 40 45 Thr Gly Tyr Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu 50 55 60 Glu Trp Met Gly Trp Ile Asn Pro Asn Ser Gly Gly Thr Asn Tyr Ala 65 70 75 80 Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser 85 90 95 Thr Ala Tyr Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val 100 105 110 Tyr Tyr Cys Ala Arg 115 (2) INFORMATION FOR SEQ ID NO: 91: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 117 amino acids (B) TYPE: amino acid

(D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 91 Met Asp Trp Thr Trp Arg Ile Leu Phe Leu Val Ala Ala Ala Thr Gly 1 5 10 15 Val His Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys 20 25 30 Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe 35 40 45 Thr Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Gln Arg Leu 50 55 60 Glu Trp Met Gly Trp Ser Asn Ala Gly Asn Gly Asn Thr Lys Tyr Ser 65 70 75 80 Gln Glu Phe Gln Gly Arg Val Thr Ile Thr Arg Asp Thr Ser Ala Ser 85 90 95 Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Met Ala Val 100 105 110 Tyr Tyr Cys Ala Arg 115 (2) INFORMATION FOR SEQ ID NO: 92: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 116 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 92 Met Lys His Leu Trp Phe Phe Leu Leu Leu Val Ala Ala Pro Arg Trp 1 5 10 15 Val Leu Ser Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys 20 25 30 Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile 35 40 45 Ser Ser Tyr Tyr Trp Ser Trp Ile Arg Gln Pro Ala Gly Lys Gly Leu 50 55 60 Glu Trp Ile Gly Arg Ile Tyr Thr Ser Gly Ser Thr Asn Tyr Asn Pro 65 70 75 80 Ser Leu Lys Ser Arg Val Thr Met Ser Val Asp Thr Ser Lys Asn Gln 85 90 95 Phe Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr 100 105 110 Tyr Cys Ala Arg 115 (2) INFORMATION FOR SEQ ID NO: 93: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 119 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 93 Met Asp Thr Leu Cys Ser Thr Leu Leu Leu Leu Thr Ile Pro Ser Trp 1 5 10 15 Val Leu Ser Gln Ile Thr Leu Lys Glu Ser Gly Pro Thr Leu Val Lys 20 25 30 Pro Thr Gln Thr Leu Thr Leu Thr Cys Thr Phe Ser Gly Phe Ser Leu 35 40 45 Ser Thr Ser Gly Val Gly Val Gly Trp Ile Arg Gln Pro Pro Gly Lys 50 55 60 Ala Leu Glu Trp Leu Ala Leu Ile Tyr Trp Asn Asp Asp Lys Arg Tyr 65 70 75 80 Ser Pro Ser Leu Lys Ser Arg Leu Thr Ile Thr Lys Asp Thr Ser Lys 85 90 95 Asn Gln Val Val Leu Thr Met Thr Asn Met Asp Pro Val Asp Thr Ala 100 105 110 Thr Tyr Tyr Cys Ala His Arg 115 (2) INFORMATION FOR SEQ ID NO: 94: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 112 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 94 Met Glu Leu Gly Leu Arg Trp Val Phe Leu Ala Ala Ile Leu Lys Gly 1 5 10 15 Val Gln Cys Glu Met Gln Leu Val Glu Ser Gly Ala Asn Leu Thr Lys 20 25 30 Pro Gly Cys Pro Asp Ser Pro Val Gln Pro Leu Asp Ser Pro Ser Val 35 40 45 Ala Ile Ala Arg Thr Gly Ser Pro Arg Leu Gln Gly Arg Val Cys Ser 50 55 60 Gly Ser Gln Leu Leu Val Val Val Val Val Pro Cys Thr Thr Gln Thr 65 70 75 80 Leu Arg Ala Asp Ser Pro Phe Pro Glu Thr Ile Pro Lys Thr His Cys 85 90 95 Ile Cys Lys Thr Asp Gly Gln Arg Met Gln Leu His Met Thr Leu Glu 100 105 110 (2) INFORMATION FOR SEQ ID NO: 95: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 117 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 95 Met Glu Leu Gly Leu Ser Trp Val Phe Leu Val Ala Ile Leu Glu Gly 1 5 10 15 Val Gln Cys Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln 20 25 30 Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe 35 40 45 Ser Ser Tyr Trp Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu 50 55 60 Glu Trp Val Ala Asn Ile Lys Gln Asp Gly Ser Glu Lys Tyr Tyr Val 65 70 75 80 Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn 85 90 95 Ser Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val 100 105 110 Tyr Tyr Cys Ala Arg 115 (2) INFORMATION FOR SEQ ID NO: 96: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 117 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 96 Met Asp Trp Thr Trp Arg Ile Leu Phe Leu Val Ala Ala Ala Thr Ser 1 5 10 15 Ala His Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys 20 25 30 Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe 35 40 45 Thr Ser Tyr Asp Ile Asn Trp Val Arg Gln Ala Thr Gly Gln Gly Leu 50 55 60 Glu Trp Met Gly Trp Met Asn Pro Asn Ser Gly Asn Thr Gly Tyr Ala 65 70 75 80 Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asn Thr Ser Ile Ser 85 90 95 Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val 100 105 110 Tyr Tyr Cys Ala Arg 115 (2) INFORMATION FOR SEQ ID NO: 97: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 118 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 97 Met Glu Leu Gly Leu Ser Trp Ile Phe Leu Leu Ala Ile Leu Lys Gly 1 5 10 15 Val Gln Cys Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln 20 25 30 Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe 35 40 45 Asp Asp Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu 50 55 60 Glu Trp Val Ser Gly Ile Ser Trp Asn Ser Gly Ser Ile Gly Tyr Ala 65 70 75 80 Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn 85 90 95 Ser Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu 100 105 110 Tyr Tyr Cys Ala Lys Asp 115 (2) INFORMATION FOR SEQ ID NO: 98: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 111 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 98 Met Glu Leu Tyr Ser Thr Leu Leu Leu Leu Thr Val Pro Ser Trp Val 1 5 10 15 Leu Ser Gln Val Thr Leu Lys Glu Ser Gly Pro Ala Leu Val Lys Pro 20 25 30 Thr Gln Thr Leu Met Leu Thr Cys Thr Phe Ser Gly Phe Ser Leu Ser 35 40 45 Thr Ser Gly Met Gly Val Gly Ile Cys Gln Pro Ser Ala Lys Ala Leu 50 55 60 Glu Trp Leu Ala His Ile Tyr Asn Asp Asn Lys Tyr Tyr Ser Pro Ser 65 70 75 80 Leu Lys Ser Arg Leu Ile Ile Ser Lys Asp Thr Ser Lys Asn Glu Val 85 90 95 Val Leu Thr Val Ile Asn Met Asp Ile Val Asp Thr Ala Thr His 100 105 110 (2) INFORMATION FOR SEQ ID NO: 99: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 117 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 99 Met Glu Phe Gly Leu Ser Trp Val Phe Leu Val Ala Ile Ile Lys Gly 1 5 10 15 Val Gln Cys Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Lys 20 25 30 Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe 35 40 45 Ser Asp Tyr Tyr Met Ser Trp Ile Arg Gln Ala Pro Gly Lys Gly Leu 50 55 60 Glu Trp Val Ser Tyr Ile Ser Ser Ser Gly Ser Thr Ile Tyr Tyr Ala 65 70 75 80 Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn 85 90 95 Ser Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val 100 105 110 Tyr Tyr Cys Ala Arg 115 (2) INFORMATION FOR SEQ ID NO: 100: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 144 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 100 Met Xaa Trp Thr Tyr Lys Ile Leu Phe Leu Val Ala Ala Ala Thr Gly 1 5 10 15 Ala His Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys 20 25 30 Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe 35 40 45 Thr Tyr Cys Tyr Leu His Trp Val Gln Ala Pro Gly Gln Gly Leu Glu 50 55 60 Trp Thr Gly Phe Leu Phe Glu Arg Phe Phe Ile Gln His Leu Phe Cys 65 70 75 80 Lys Gln Ile Ser Gly Ile Val Glu Ile Ile Leu Thr Asn Leu Thr Gln 85 90 95 Asn Phe Leu Ile Asn Leu Cys Lys His Gln Phe Leu Asn Gln Cys Cys 100 105 110 Xaa Tyr Phe Arg Thr Gln Ala Gln Xaa His Ile Xaa Thr Leu Leu Xaa 115 120 125 Ser Leu Phe Lys Xaa Tyr Gln Lys Xaa Ser Ser Xaa Ala Cys Asn Val 130 135 140 (2) INFORMATION FOR SEQ ID NO: 101: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 116 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 101 Met Glu Leu Gly Leu Ser Trp Val Phe Leu Val Ala Ile Leu Glu Gly 1 5 10 15 Val Gln Cys Glu Val His Leu Val Glu Ser Gly Gly Gly Leu Val Gln 20 25 30 Pro Gly Gly Ala Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe 35 40 45 Ser Asn Tyr Asp Met His Trp Val Arg Gln Ala Thr Gly Lys Gly Leu 50 55 60 Glu Trp Val Ser Ala Asn Gly Thr Ala Gly Asp Thr Tyr Tyr Pro Gly 65 70 75 80 Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Glu Asn Ala Lys Asn Ser 85 90 95 Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Gly Asp Thr Ala Val Tyr 100 105 110 Tyr Cys Ala Arg 115 (2) INFORMATION FOR SEQ ID NO: 102: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 119 amino acids (B) TYPE: amino acid

(D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 102 Met Glu Phe Gly Leu Ser Trp Ile Phe Leu Pro Ala Ile Leu Lys Gly 1 5 10 15 Val Gln Cys Glu Val Gln Leu Val Glu Ser Gly Gly Ala Leu Val Lys 20 25 30 Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe 35 40 45 Ser Asn Ala Trp Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu 50 55 60 Glu Trp Val Gly Arg Ile Lys Ser Lys Thr Asp Gly Gly Thr Thr Asp 65 70 75 80 Tyr Ala Ala Pro Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser 85 90 95 Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Lys Thr Glu Asp Thr 100 105 110 Ala Val Tyr Tyr Cys Thr Thr 115 (2) INFORMATION FOR SEQ ID NO: 103: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 117 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 103 Met Glu Phe Gly Leu Ser Trp Val Phe Leu Ala Gly Ile Leu Lys Gly 1 5 10 15 Val Gln Cys Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln 20 25 30 Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe 35 40 45 Ser Asn Ser Asp Met Asn Trp Ala Arg Lys Ala Pro Gly Lys Gly Leu 50 55 60 Glu Trp Val Ser Gly Val Ser Trp Asn Gly Ser Arg Thr His Tyr Val 65 70 75 80 Asp Ser Val Lys Arg Arg Phe Ile Ile Ser Arg Asp Asn Ser Arg Asn 85 90 95 Ser Leu Tyr Leu Gln Lys Asn Arg Arg Arg Ala Glu Asp Met Ala Val 100 105 110 Tyr Tyr Cys Val Arg 115 (2) INFORMATION FOR SEQ ID NO: 104: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 116 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 104 Met Asp Cys Thr Trp Gly Ile Leu Phe Leu Val Ala Ser Xaa Thr Asp 1 5 10 15 Val His Ser Gln Val Gln Leu Leu Gln Pro Gly Ala Glu Val Lys Lys 20 25 30 Pro Ala Ser Ser Val Lys Val Ser Trp Pro Gly Phe Gln Ile His Leu 35 40 45 His Gln Ile Leu Tyr Thr Val Gly Ala Thr Gly Pro Trp Thr Arg Ala 50 55 60 Trp Leu Gly Cys Ile Asn Pro Tyr Asn Asp Asn Thr His Tyr Ala Gln 65 70 75 80 Lys Phe Arg Gly Arg Val Thr Ile Thr Ser Asp Arg Ser Val Ser Thr 85 90 95 Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Met Val Val Tyr 100 105 110 Ser Cys Val Arg 115 (2) INFORMATION FOR SEQ ID NO: 105: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 117 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 105 Met Asp Trp Thr Trp Ser Ile Leu Phe Leu Val Ala Ala Pro Thr Gly 1 5 10 15 Ala His Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys 20 25 30 Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe 35 40 45 Thr Ser Tyr Gly Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu 50 55 60 Glu Trp Met Gly Trp Ile Ser Ala Tyr Asn Gly Asn Thr Asn Tyr Ala 65 70 75 80 Gln Lys Leu Gln Gly Arg Val Thr Met Thr Thr Asp Thr Ser Thr Ser 85 90 95 Thr Ala Tyr Met Glu Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val 100 105 110 Tyr Tyr Cys Ala Arg 115 (2) INFORMATION FOR SEQ ID NO: 106: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 117 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 106 Met Glu Phe Gly Leu Ser Trp Val Phe Leu Val Ala Ile Leu Lys Gly 1 5 10 15 Val Gln Cys Glu Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Arg 20 25 30 Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe 35 40 45 Asp Asp Tyr Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu 50 55 60 Glu Trp Val Ser Gly Ile Asn Trp Asn Gly Gly Ser Thr Gly Tyr Ala 65 70 75 80 Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn 85 90 95 Ser Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu 100 105 110 Tyr His Cys Ala Arg 115 (2) INFORMATION FOR SEQ ID NO: 107: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 117 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 107 Met Glu Leu Gly Leu Arg Trp Val Phe Leu Val Ala Ile Leu Glu Gly 1 5 10 15 Val Gln Cys Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Lys 20 25 30 Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe 35 40 45 Ser Ser Tyr Ser Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu 50 55 60 Glu Trp Val Ser Ser Ile Ser Ser Ser Ser Ser Tyr Ile Tyr Tyr Ala 65 70 75 80 Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn 85 90 95 Ser Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val 100 105 110 Tyr Tyr Cys Ala Arg 115 (2) INFORMATION FOR SEQ ID NO: 108: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 118 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 108 Met Glu Ser Trp Leu Ser Trp Val Phe Leu Ala Ala Ile Leu Lys Gly 1 5 10 15 Val Gln Cys Glu Val His Leu Val Glu Ser Gly Gly Ala Leu Val Gln 20 25 30 Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe 35 40 45 Ser Tyr Tyr Tyr Met Ser Gly Val Arg Gln Ala Pro Gly Lys Gly Leu 50 55 60 Glu Trp Val Gly Phe Ile Arg Asn Lys Ala Asn Gly Gly Thr Thr Glu 65 70 75 80 Thr Thr Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys 85 90 95 Ser Ile Thr Tyr Leu Gln Met Lys Ser Leu Lys Thr Glu Asp Thr Ala 100 105 110 Val Tyr Tyr Cys Ser Arg 115 (2) INFORMATION FOR SEQ ID NO: 109: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 117 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 109 Met Glu Phe Gly Leu Ser Trp Leu Phe Leu Val Ala Lys Ile Lys Gly 1 5 10 15 Val Gln Cys Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln 20 25 30 Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe 35 40 45 Ser Ser Tyr Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu 50 55 60 Glu Trp Val Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala 65 70 75 80 Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn 85 90 95 Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val 100 105 110 Tyr Tyr Cys Ala Lys 115 (2) INFORMATION FOR SEQ ID NO: 110: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 117 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 110 Met Asp Cys Thr Trp Arg Ile Leu Phe Leu Val Ala Ala Ala Thr Gly 1 5 10 15 Thr His Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys 20 25 30 Pro Gly Ala Ser Val Lys Val Ser Cys Lys Val Ser Gly Tyr Thr Leu 35 40 45 Thr Glu Leu Ser Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu 50 55 60 Glu Trp Met Gly Gly Phe Asp Pro Glu Asp Gly Glu Thr Ile Tyr Ala 65 70 75 80 Gln Lys Phe Gln Gly Arg Val Thr Met Thr Glu Asp Thr Ser Thr Asp 85 90 95 Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val 100 105 110 Tyr Tyr Cys Ala Thr 115 (2) INFORMATION FOR SEQ ID NO: 111: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 111 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 111 Trp Ser Leu Cys Ala Gly Phe Ser Leu Leu Leu Phe Asn Val Ser Ser 1 5 10 15 Val Arg Cys Ser Trp Trp Ser Leu Gly Glu Ala Cys Lys Ser Leu Arg 20 25 30 Gly Pro Arg Asp Ser Pro Val Gln Pro Leu Asn Ser Pro Ser Val Ala 35 40 45 Thr Thr Thr Val Ser Ala Arg Leu Gln Gly Met Gly Trp Ser Trp Phe 50 55 60 Asp Lys Leu Ile Leu Met Gly Val Ala His Thr Ser Thr Pro Val Arg 65 70 75 80 Thr Asp Ser Ile Pro Pro Glu Ile Thr Pro Arg Thr His Phe Ile Cys 85 90 95 Lys Thr Ala Lys Pro Arg Thr Arg Pro Ser Ile Ser Val Pro Glu 100 105 110 (2) INFORMATION FOR SEQ ID NO: 112: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 119 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 112 Met Asp Thr Leu Cys Tyr Thr Leu Leu Leu Leu Thr Thr Pro Ser Trp 1 5 10 15 Val Leu Ser Gln Val Thr Leu Lys Glu Ser Gly Pro Val Leu Val Lys 20 25 30 Pro Thr Glu Thr Leu Thr Leu Thr Cys Thr Val Ser Gly Phe Ser Leu 35 40 45 Ser Asn Ala Arg Met Gly Val Ser Trp Ile Arg Gln Pro Pro Gly Lys 50 55 60 Ala Leu Glu Trp Leu Ala His Ile Phe Ser Asn Asp Glu Lys Ser Tyr 65 70 75 80 Ser Thr Ser Leu Lys Ser Arg Leu Thr Ile Ser Lys Asp Thr Ser Lys 85 90 95 Ser Gln Val Val Leu Thr Met Thr Asn Met Asp Pro Val Asp Thr Ala 100 105 110 Thr Tyr Tyr Cys Ala Arg Ile 115 (2) INFORMATION FOR SEQ ID NO: 113: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 112 amino acids (B) TYPE: amino acid

(D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 113 Met Tyr Trp Thr Trp Arg Ile Leu Phe Leu Val Ala Ala Ala Thr Gly 1 5 10 15 Val His Ser Gln Val Gln Leu Val Gln Ser Gly Pro Glu Val Lys Lys 20 25 30 Pro Gly Ala Ser Leu Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe 35 40 45 Thr Ser Tyr Ala Ile Ser Trp Val Gln Ala His Gly Gln Gly Leu Glu 50 55 60 Glu Met Gly Trp Ile Asn Thr Asn Thr Gly Asn Leu Thr Tyr Ala Gln 65 70 75 80 Gly Phe Thr Gly Arg Phe Val Phe Ser Met Asp Thr Ser Val Ser Met 85 90 95 Ala Tyr Leu His Ile Ser Ser Leu Lys Ala Glu Asp Thr Cys Lys Arg 100 105 110 (2) INFORMATION FOR SEQ ID NO: 114: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 117 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 114 Met Lys His Leu Trp Phe Phe Leu Leu Leu Val Ala Ala Pro Arg Trp 1 5 10 15 Val Leu Ser Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys 20 25 30 Pro Ser Asp Thr Leu Ser Leu Thr Cys Ala Val Ser Gly Tyr Ser Ile 35 40 45 Ser Ser Ser Asn Trp Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly 50 55 60 Leu Glu Trp Ile Gly Tyr Ile Tyr Tyr Ser Gly Ser Thr Tyr Tyr Asn 65 70 75 80 Pro Ser Leu Lys Ser Arg Val Thr Met Ser Val Asp Thr Ser Lys Asn 85 90 95 Gln Phe Ser Leu Lys Leu Ser Ser Val Thr Ala Val Asp Thr Ala Val 100 105 110 Tyr Tyr Cys Ala Arg 115 (2) INFORMATION FOR SEQ ID NO: 115: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 117 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 115 Met Glu Phe Gly Leu Ser Trp Val Phe Leu Val Ala Leu Leu Arg Gly 1 5 10 15 Val Gln Cys Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln 20 25 30 Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe 35 40 45 Ser Ser Tyr Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu 50 55 60 Glu Trp Val Ala Val Ile Ser Tyr Asp Gly Ser Asn Lys Tyr Tyr Ala 65 70 75 80 Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn 85 90 95 Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val 100 105 110 Tyr Tyr Cys Ala Arg 115 (2) INFORMATION FOR SEQ ID NO: 116: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 118 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 116 Met Lys His Leu Trp Phe Phe Leu Leu Leu Val Ala Ala Pro Arg Trp 1 5 10 15 Val Leu Pro Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys 20 25 30 Pro Ser Gln Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile 35 40 45 Ser Ser Gly Gly Tyr Tyr Trp Ser Trp Ile Arg Gln His Pro Gly Lys 50 55 60 Gly Leu Glu Trp Ile Gly Tyr Ile Tyr Tyr Ser Gly Ser Thr Tyr Tyr 65 70 75 80 Asn Pro Ser Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys 85 90 95 Asn Gln Phe Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala 100 105 110 Val Tyr Tyr Cys Ala Arg 115 (2) INFORMATION FOR SEQ ID NO: 117: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 117 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 117 Met Glu Phe Gly Leu Ser Trp Val Phe Leu Val Ala Leu Leu Arg Gly 1 5 10 15 Val Gln Cys Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln 20 25 30 Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe 35 40 45 Ser Ser Tyr Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu 50 55 60 Glu Trp Val Ala Val Ile Trp Tyr Asp Gly Ser Asn Lys Tyr Tyr Ala 65 70 75 80 Asp Ser Ala Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Thr Asn 85 90 95 Thr Leu Phe Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val 100 105 110 Tyr Tyr Cys Ala Arg 115 (2) INFORMATION FOR SEQ ID NO: 118: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 116 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 118 Met Lys His Leu Trp Phe Phe Leu Leu Leu Val Ala Ala Pro Arg Trp 1 5 10 15 Val Leu Ser Gln Val Gln Leu Gln Gln Trp Gly Ala Gly Leu Leu Lys 20 25 30 Pro Ser Glu Thr Leu Ser Leu Thr Cys Ala Val Tyr Gly Gly Ser Phe 35 40 45 Ser Gly Tyr Tyr Trp Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu 50 55 60 Glu Trp Ile Gly Glu Ile Asn His Ser Gly Ser Thr Asn Tyr Asn Pro 65 70 75 80 Ser Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln 85 90 95 Phe Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr 100 105 110 Tyr Cys Ala Arg 115 (2) INFORMATION FOR SEQ ID NO: 119: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 117 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 119 Met Glu Phe Gly Leu Ser Trp Val Phe Leu Ala Ala Ile Leu Lys Gly 1 5 10 15 Val Gln Cys Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln 20 25 30 Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe 35 40 45 Ser Asn Ser Asp Met Asn Trp Val His Gln Ala Pro Gly Lys Gly Leu 50 55 60 Glu Trp Val Ser Gly Val Ser Trp Asn Gly Ser Arg Thr His Tyr Ala 65 70 75 80 Asp Ser Val Lys Gly Arg Phe Ile Ile Ser Arg Asp Asn Ser Arg Asn 85 90 95 Thr Leu Tyr Leu Gln Thr Asn Ser Leu Arg Ala Glu Asp Thr Ala Val 100 105 110 Tyr Tyr Cys Val Arg 115 (2) INFORMATION FOR SEQ ID NO: 120: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 112 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 120 Met Glu Phe Gly Leu Ser Trp Gly Phe His Val Ala Asn Val Lys Gly 1 5 10 15 Val Gln Cys Glu Val His Leu Val Glu Ser Leu Gly Gly Leu Leu Pro 20 25 30 Gly Gly Pro Asp Phe Leu Leu Gln Pro Leu Asp Ser Pro Leu Val Pro 35 40 45 Leu Leu Gly Thr Gly Ala Gly Ser Ile Arg Leu Leu Gly Lys Gly Trp 50 55 60 Ser Arg Ser His Leu Val Val Val Val Ala Gln Ala Met Gln Thr Leu 65 70 75 80 Arg Val Asp Ser Pro Ser Pro Glu Met Met Pro Arg Asn His Cys Ile 85 90 95 Cys Lys Thr Ala Ser Glu Pro Arg Ile Gly Leu Cys Ile Thr Val Val 100 105 110 (2) INFORMATION FOR SEQ ID NO: 121: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 111 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 121 Met Leu Phe Gly Leu Ser Trp Pro Phe Arg Phe Thr Ile Leu Arg Gly 1 5 10 15 Val Gln Tyr Glu Val Gln Leu Val Glu Ser Gly Gly Asp Leu Val Gln 20 25 30 Leu Trp Trp Val Leu Arg Leu Ser Cys Ala Ala Cys Gly Phe Ile Leu 35 40 45 Arg Ser Asn Trp Ser His Arg Ala Ser Arg Lys Gly Leu Ala Trp Asn 50 55 60 Asp Met Val Ser Tyr Ile Ser Ala Ser Gly Gly Ser Leu Tyr Tyr Ala 65 70 75 80 Asp Thr Glu Gly Ile His His Leu Arg Gln Trp Gln Glu His Ala Val 85 90 95 Leu Ala Asn Glu Gln Ser Glu Arg Gly Leu Gly Cys Val Glu Arg 100 105 110 (2) INFORMATION FOR SEQ ID NO: 122: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 115 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 122 Met Gln Phe Val Leu Ser Trp Val Phe Leu Val Gly Ile Leu Lys Gly 1 5 10 15 Val Gln Cys Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln 20 25 30 Pro Arg Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Val 35 40 45 Ser Ser Asn Glu Met Ser Trp Ile Arg Gln Ala Pro Gly Lys Gly Leu 50 55 60 Glu Trp Val Ser Ser Ile Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser 65 70 75 80 Arg Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu 85 90 95 Tyr Leu Gln Met Asn Asn Leu Arg Ala Glu Gly Thr Ala Ala Tyr Tyr 100 105 110 Cys Ala Arg 115 (2) INFORMATION FOR SEQ ID NO: 123: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 118 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 123 Met Lys His Leu Trp Phe Phe Leu Leu Leu Val Ala Ala Pro Arg Trp 1 5 10 15 Val Leu Ser Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys 20 25 30 Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile 35 40 45 Ser Ser Ser Ser Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys 50 55 60 Gly Leu Glu Trp Ile Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr Tyr 65 70 75 80 Asn Pro Ser Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys 85 90 95 Asn Gln Phe Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala 100 105 110 Val Tyr Tyr Cys Ala Arg 115 (2) INFORMATION FOR SEQ ID NO: 124: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 114 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 124 Met Glu Ser Trp Leu Ser Trp Val Phe Leu Ala Ala Ile Leu Lys Gly

1 5 10 15 Val Gln Cys Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln 20 25 30 Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Phe 35 40 45 Ser Ser Tyr Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu 50 55 60 Glu Val Ala His Ile Trp Asn Asp Gly Ser Gln Lys Tyr Tyr Ala Asp 65 70 75 80 Ser Val Lys Gly Arg Phe Thr Ile Ser Glu Thr Ile Leu Arg Ala Cys 85 90 95 Ser Ile Cys Lys Trp Thr Val Lys Leu Arg Thr Arg Pro Cys Ile Thr 100 105 110 Val Pro (2) INFORMATION FOR SEQ ID NO: 125: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 118 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 125 Met Glu Phe Gly Leu Ser Trp Val Phe Leu Val Ala Ile Leu Lys Gly 1 5 10 15 Val Gln Cys Glu Val Gln Leu Val Glu Ser Gly Gly Val Val Val Gln 20 25 30 Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe 35 40 45 Asp Asp Tyr Thr Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu 50 55 60 Glu Trp Val Ser Leu Ile Ser Trp Asp Gly Gly Ser Thr Tyr Tyr Ala 65 70 75 80 Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn 85 90 95 Ser Leu Tyr Leu Gln Met Asn Ser Leu Arg Thr Glu Asp Thr Ala Leu 100 105 110 Tyr Tyr Cys Ala Lys Asp 115 (2) INFORMATION FOR SEQ ID NO: 126: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 115 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 126 Met Leu Phe Gly Leu Ser Trp Ala Phe Leu Val Thr Ile Leu Arg Gly 1 5 10 15 Val Gln Tyr Glu Val Gln Leu Val Glu Ser Phe Phe Phe Phe Phe Phe 20 25 30 His Phe Leu Ala Asn Ile His Gly Leu Gln Asn Asn Gly Leu Ala Phe 35 40 45 Leu Pro Thr Leu Tyr Arg His His Gln Phe Ser Pro Cys Leu Gly Phe 50 55 60 Pro Glu Glu Cys Cys His His Leu Ser Cys Ser Phe Arg Lys Asn Ala 65 70 75 80 Pro Ser Thr His Leu His Leu Ser Ala Cys Ile Ser Ile Cys Leu Gly 85 90 95 Arg Ser Gln Gln Pro Xaa Glu His Ser Pro His Pro Thr Met Leu Leu 100 105 110 Glu Gly Val 115 (2) INFORMATION FOR SEQ ID NO: 127: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 117 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 127 Met Asp Trp Thr Trp Arg Ile Leu Phe Leu Val Ala Ala Ala Thr Asp 1 5 10 15 Ala Tyr Ser Gln Met Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys 20 25 30 Thr Gly Ser Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe 35 40 45 Thr Tyr Arg Tyr Leu His Trp Val Arg Gln Ala Pro Gly Gln Ala Leu 50 55 60 Glu Trp Met Gly Trp Ile Thr Pro Phe Asn Gly Asn Thr Asn Tyr Ala 65 70 75 80 Gln Lys Phe Gln Asp Arg Val Thr Ile Thr Arg Asp Arg Ser Met Ser 85 90 95 Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Met 100 105 110 Tyr Tyr Cys Ala Arg 115 (2) INFORMATION FOR SEQ ID NO: 128: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 117 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 128 Met Asp Trp Thr Trp Arg Val Phe Cys Leu Leu Ala Val Ala Pro Gly 1 5 10 15 Ala His Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys 20 25 30 Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe 35 40 45 Thr Ser Tyr Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu 50 55 60 Glu Trp Met Gly Ile Ile Asn Pro Ser Gly Gly Ser Thr Ser Tyr Ala 65 70 75 80 Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser 85 90 95 Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val 100 105 110 Tyr Tyr Cys Ala Arg 115 (2) INFORMATION FOR SEQ ID NO: 129: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 110 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 129 Arg Glu Phe Val Leu Ser Trp Val Phe Leu Val Ala Ile Leu Lys Cys 1 5 10 15 Val Gln Cys Glu Asp Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln 20 25 30 Pro Gly Gly Ser Leu Arg Pro Ser Cys Ala Ala Ser Gly Phe Ala Phe 35 40 45 Ser Ser Tyr Val Leu His Trp Val Arg Arg Ala Pro Gly Lys Gly Pro 50 55 60 Glu Trp Val Ser Ala Ile Gly Thr Gly Gly Asp Thr Tyr Tyr Ala Asp 65 70 75 80 Ser Val Met Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Lys Ser 85 90 95 Leu Tyr Leu Lys Thr Ala Leu Arg Thr Trp Leu Cys Ile Met 100 105 110 (2) INFORMATION FOR SEQ ID NO: 130: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 117 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 130 Met Glu Leu Gly Leu Cys Trp Val Phe Leu Val Ala Ile Leu Glu Gly 1 5 10 15 Val Gln Cys Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln 20 25 30 Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe 35 40 45 Ser Ser Tyr Ser Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu 50 55 60 Glu Trp Val Ser Tyr Ile Ser Ser Ser Ser Ser Thr Ile Tyr Tyr Ala 65 70 75 80 Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn 85 90 95 Ser Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val 100 105 110 Tyr Tyr Cys Ala Arg 115 (2) INFORMATION FOR SEQ ID NO: 131: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 119 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 131 Met Glu Phe Gly Leu Ser Trp Val Phe Leu Val Ala Ile Leu Lys Gly 1 5 10 15 Val Gln Cys Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln 20 25 30 Pro Gly Arg Ser Leu Arg Leu Ser Cys Thr Ala Ser Gly Phe Thr Phe 35 40 45 Gly Asp Tyr Ala Met Ser Trp Phe Arg Gln Ala Pro Gly Lys Gly Leu 50 55 60 Glu Trp Val Gly Phe Ile Arg Ser Lys Ala Tyr Gly Gly Thr Thr Glu 65 70 75 80 Tyr Thr Ala Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Gly Ser 85 90 95 Lys Ser Ile Ala Tyr Leu Gln Met Asn Ser Leu Lys Thr Glu Asp Thr 100 105 110 Ala Val Tyr Tyr Cys Thr Arg 115 (2) INFORMATION FOR SEQ ID NO: 132: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 55 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 132 Met Glu Leu Gly Leu Ser Trp Val Ser Leu Val Ile Ile Leu Lys Gly 1 5 10 15 Val Cys Gly Val Gln Met Val Glu Ser Trp Gly Glu Leu Ala Gln Xaa 20 25 30 Glu Cys Ala Asp Ser Ala Val His Pro Leu Asn Pro Pro Ser Val Ala 35 40 45 Thr Arg Ser Ala Glu Ser Ala 50 55 (2) INFORMATION FOR SEQ ID NO: 133: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 117 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 133 Met Gly Ser Thr Ala Ile Leu Ala Leu Leu Leu Ala Val Leu Gln Gly 1 5 10 15 Val Cys Ser Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys 20 25 30 Pro Gly Glu Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe 35 40 45 Thr Ser Tyr Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu 50 55 60 Glu Trp Met Gly Ile Ile Tyr Pro Gly Asp Ser Asp Thr Arg Tyr Ser 65 70 75 80 Pro Ser Phe Gln Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Ser 85 90 95 Thr Ala Tyr Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met 100 105 110 Tyr Tyr Cys Ala Arg 115 (2) INFORMATION FOR SEQ ID NO: 134: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 116 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 134 Met Glu Ser Gly Leu Ser Trp Val Phe Leu Val Ala Ile Leu Lys Gly 1 5 10 15 Val Gln Cys Glu Val Gln Leu Val Glu Ser Gly Gly Leu Val Gln Pro 20 25 30 Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser 35 40 45 Ser Ser Trp Met His Trp Val Cys Gln Ala Pro Glu Lys Gly Leu Glu 50 55 60 Trp Val Ala Asp Ile Lys Cys Asp Gly Ser Glu Lys Tyr Tyr Val Asp 65 70 75 80 Ser Val Lys Gly Arg Leu Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser 85 90 95 Leu Tyr Leu Gln Val Asn Ser Leu Arg Ala Glu Asp Met Thr Val Tyr 100 105 110 Tyr Cys Val Arg 115 (2) INFORMATION FOR SEQ ID NO: 135: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 116 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 135 Met Glu Phe Trp Leu Ser Trp Val Phe Leu Val Ala Ile Leu Lys Gly 1 5 10 15 Val Gln Cys Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Ile Gln 20 25 30 Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Val 35 40 45 Ser Ser Asn Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu 50 55 60 Glu Trp Val Ser Val Ile Tyr Ser Gly Gly Ser Thr Tyr Tyr Ala Asp 65 70 75 80

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr 85 90 95 Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 100 105 110 Tyr Cys Ala Arg 115 (2) INFORMATION FOR SEQ ID NO: 136: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 112 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 136 Met Glu Leu Gly Leu Ser Trp Val Phe Thr Val Thr Val Leu Lys Gly 1 5 10 15 Val Gln Cys Glu Val Gln Leu Val Glu Ser Glu Glu Asn Gln Arg Gln 20 25 30 Leu Gly Gly Ser Leu Arg Leu Ser Cys Ala Asp Ser Gly Leu Thr Phe 35 40 45 Ser Ser Tyr Met Ser Ser Asp Ser Gln Ala Pro Gly Lys Gly Leu Glu 50 55 60 Val Val Asp Ile Asp Arg Ser Gln Leu Cys Tyr Ala Gln Ser Val Lys 65 70 75 80 Ser Arg Phe Thr Ile Ser Lys Glu Asn Ala Lys Asn Ser Leu Cys Leu 85 90 95 Gln Met Asn Ser Leu Arg Ala Glu Gly Thr Ala Val Tyr Tyr Cys Met 100 105 110 (2) INFORMATION FOR SEQ ID NO: 137: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 120 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 137 Met Lys His Leu Trp Phe Phe Leu Leu Leu Val Ala Ala Pro Arg Trp 1 5 10 15 Val Leu Ser Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys 20 25 30 Pro Ser Glu Thr Leu Ser Leu Ile Cys Ala Val Ser Gly Asp Ser Ile 35 40 45 Ser Ser Gly Asn Trp Ile Trp Val Arg Gln Pro Pro Gly Lys Gly Leu 50 55 60 Glu Trp Ile Gly Glu Ile His His Ser Gly Ser Thr Tyr Tyr Asn Pro 65 70 75 80 Ser Leu Lys Ser Arg Ile Thr Met Ser Val Asp Thr Ser Lys Asn Gln 85 90 95 Phe Tyr Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr 100 105 110 Tyr Cys Ala Arg Tyr Thr Val Arg 115 120 (2) INFORMATION FOR SEQ ID NO: 138: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 69 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 138 Met Asp Trp Thr Trp Ser Ile Leu Phe Leu Val Ala Ala Ala Thr Gly 1 5 10 15 Ala His Ser Arg Val Gln Leu Val Gln Ser Gly Pro Glu Val Lys Gln 20 25 30 Pro Gly Ala Ser Ala Lys Val Ser Cys Lys Val Ser Gly Thr Val Ile 35 40 45 Thr Tyr Gly Met Asn Trp Ile Arg Gln Thr Pro Gly Gln Gly Leu Glu 50 55 60 Trp Met Gly Trp Ile 65 (2) INFORMATION FOR SEQ ID NO: 139: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 117 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 139 Met Asp Trp Ile Trp Arg Ile Leu Phe Leu Val Gly Ala Ala Ile Gly 1 5 10 15 Ala His Ser Gln Met Gln Leu Val Gln Ser Gly Pro Glu Val Lys Lys 20 25 30 Pro Gly Thr Ser Val Lys Val Ser Cys Lys Ala Ser Gly Phe Thr Phe 35 40 45 Thr Ser Ser Ala Val Gln Trp Val Arg Gln Ala Arg Gly Gln Arg Leu 50 55 60 Glu Trp Ile Gly Trp Ile Val Val Gly Ser Gly Asn Thr Asn Tyr Ala 65 70 75 80 Gln Lys Phe Gln Glu Arg Val Thr Ile Thr Arg Asp Met Ser Thr Ser 85 90 95 Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val 100 105 110 Tyr Tyr Cys Ala Ala 115 (2) INFORMATION FOR SEQ ID NO: 140: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 116 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 140 Met Lys His Leu Trp Phe Phe Leu Leu Leu Val Ala Ala Pro Arg Trp 1 5 10 15 Val Leu Ser Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys 20 25 30 Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Val 35 40 45 Ser Ser Tyr Tyr Trp Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu 50 55 60 Glu Trp Ile Gly Tyr Ile Tyr Tyr Ser Gly Ser Thr Asn Tyr Asn Pro 65 70 75 80 Ser Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln 85 90 95 Phe Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr 100 105 110 Tyr Cys Ala Arg 115 (2) INFORMATION FOR SEQ ID NO: 141: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 113 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 141 Met Glu Ser Gly Leu Ser Trp Ile Phe Leu Val Ala Val Leu Lys Gly 1 5 10 15 Cys Pro Val Gly Ala Ala Gly Gly Val Trp Gly Arg Leu Ser Lys Asp 20 25 30 Trp Gly Val Ser Glu Thr Leu Leu Cys Ser Leu Trp Ile His Leu Gln 35 40 45 Leu Cys Tyr Ala Leu Gly Pro Pro Gly Ser Arg Lys Gly Phe Gly Val 50 55 60 Gly Leu Ser Tyr Tyr Lys Trp Tyr Arg Thr Leu His Arg Leu Cys Glu 65 70 75 80 Gly Leu Ile His His Leu Arg Gln Cys Pro Glu Phe Thr Val Ser Ala 85 90 95 Asn Glu Gln Pro Glu Ser Arg Arg His Gly Cys Val Leu Leu Cys Glu 100 105 110 Arg (2) INFORMATION FOR SEQ ID NO: 142: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 118 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 142 Met Lys His Leu Trp Phe Phe Leu Leu Leu Val Ala Ala Pro Arg Trp 1 5 10 15 Val Leu Ser Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys 20 25 30 Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Val 35 40 45 Ser Ser Gly Ser Tyr Tyr Trp Ser Trp Ile Arg Gln Pro Pro Gly Lys 50 55 60 Gly Leu Glu Trp Ile Gly Tyr Ile Tyr Tyr Ser Gly Ser Thr Asn Tyr 65 70 75 80 Asn Pro Ser Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys 85 90 95 Asn Gln Phe Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala 100 105 110 Val Tyr Tyr Cys Ala Arg 115 (2) INFORMATION FOR SEQ ID NO: 143: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 116 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 143 Met Glu Phe Gly Leu Ser Trp Val Phe Leu Val Ala Asn Leu Arg Gly 1 5 10 15 Val Gln Cys Glu Val Gln Leu Val Glu Ser Gly Glu Gly Leu Val Gln 20 25 30 Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe 35 40 45 Ser Ser Ser Ala Met His Trp Val Arg Gln Ala Pro Arg Lys Gly Leu 50 55 60 Trp Val Ser Val Ile Ser Thr Ser Gly Asp Thr Val Leu Tyr Thr Asp 65 70 75 80 Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Gln Asn Ser 85 90 95 Leu Ser Leu Gln Met Asn Ser Leu Arg Ala Glu Gly Thr Val Val Tyr 100 105 110 Tyr Cys Val Lys 115 (2) INFORMATION FOR SEQ ID NO: 144: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 115 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 144 Met Gly Phe Glu Leu Thr Arg Ile Phe Leu Val Ala Ile Leu Lys Gly 1 5 10 15 Val Gln Cys Glu Val Glu Leu Ile Glu Ser Ile Glu Gly Leu Arg Gln 20 25 30 Leu Gly Lys Phe Leu Arg Leu Ser Cys Val Ala Ser Gly Phe Thr Phe 35 40 45 Ser Ser Tyr Met Ser Trp Val Asn Glu Thr Leu Gly Lys Gly Leu Glu 50 55 60 Gly Val Ile Asp Val Lys Tyr Asp Gly Ser Gln Ile Tyr His Ala Asp 65 70 75 80 Ser Val Lys Gly Arg Phe Thr Ile Ser Lys Asp Asn Ala Lys Asn Ser 85 90 95 Pro Tyr Leu Gln Thr Asn Ser Leu Arg Ala Glu Asp Met Thr Met His 100 105 110 Gly Cys Thr 115 (2) INFORMATION FOR SEQ ID NO: 145: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 118 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 145 Met Thr Glu Phe Gly Leu Ser Trp Val Phe Leu Val Ala Ile Phe Lys 1 5 10 15 Gly Val Gln Cys Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val 20 25 30 Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr 35 40 45 Phe Ser Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly 50 55 60 Leu Glu Tyr Val Ser Ala Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr 65 70 75 80 Ala Asn Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys 85 90 95 Asn Thr Leu Tyr Leu Gln Met Gly Ser Leu Arg Ala Glu Asp Met Ala 100 105 110 Val Tyr Tyr Cys Ala Arg 115

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