Human RAD50 gene and methods of use thereof

FIELD OF THE INVENTION
The present invention relates to human RAD50 gene and protein compositions and to diagnostic and therapeutic methods of use thereof.
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BACKGROUND OF THE INVENTION
A common genetic abnormality associated with malignant myeloid neoplasms in humans is the loss of whole chromosome 5 or 7 or a deletion of the long arm 5q or 7q of one of these chromosomes. In one reported study of 129 patients with therapy-related myelodisplastic syndrome (t-MDS) or therapy-related acute myeloid leukemia (t-AML), 75% of the patients had a loss or deletion of chromosome 5 or 7 (LeBeau). In addition, a deletion in 5q has also been observed in 10% of patients with AML arising de novo, and in 15% of patients who have MDS arising de novo (Nimer).
The 5q human chromosome region is known to contain a number of genes encoding growth factors, hormone receptors, and proteins involved in signal transduction or transcriptional regulation, and several of these genes are good candidates for tumor suppressor genes. The LeBeau study cited above investigated the possibility that deletion of a particular one or more of these genes, including the hematopoietic growth factors CSF2, IL3, IL4, IL5, and IL9, as well as EGR1, might be responsible for the predisposition to malignant myeloid neoplasms. The study was unsuccessful in identifying such a gene.
It has now been discovered, in accordance with the present invention, that at least one of the genes whose deletion in the 5q chromosome region correlates strongly with leukemia is a gene which is herein identified as a human RAD50 (hRAD50) gene, analogous to RAD50 gene in the yeast Saccharomyces cerevisiae (Sc).
In yeast, RAD50 is one of an epistatic group of genes whose products have been implicated in the recombinational repair of double-strand breaks (DSB's). The group of yeast genes include RAD50-57, MRE2, MRE11, XRS2, and RFA1 (Hays). Studies to date suggest that several genes in the group form a multi-protein complex (or complexes) that function in DSB repair, and participate in meiotic recombinational events (Firmenich, Hays).
Sc RAD50 itself appears to be required for recombinational repair of many types of DSB's (Tran), possibly in a complex with MRE11 (Johzuka, Ivanov). RAD50 functions in Sc is required during vegetative growth for recombinational repair of DSB, and during meiosis, for initiation of meiotic recombination (Raymond, 1993a). In light of the key role played by the protein, and the fact that the protein is known to bind to DNA in the presence of ATP (Raymond, 1993b), it has been proposed that the protein functions in chromosomal homology searching between interacting DNA molecules (Alani, 1989; 1990).
SUMMARY OF THE INVENTION
The invention includes, in one aspect, an isolated or substantially-isolated hRAD50 DNA composition capable of selectively hybridizing to a polynucleotide fragment having a sequence or the reverse complement of one or more of the DNA sequences identified by SEQ ID NO:55-115. The composition is at least 20, preferably at least 30 nucleotides in length.
In a general embodiment, the hRAD50 DNA composition is capable of selectively hybridizing under stringent conditions to a polynucleotide fragment having a sequence or the reverse complement of one or more of the DNA sequences identified by SEQ ID NO:55-115.
In one embodiment, the composition is capable of selectively hybridizing to a polynucleotide fragment (e.g., a fragment derived from a genomic library) corresponding to a hRAD50 exon and identified by one of the sequences SEQ ID NO:55, 56, 58, 61, 64, 66, 69, 71, 73, 75, 77, 79, 82, 84, 87, 89, 92, 95, 97, 99, 102, 104, 107, 110, 112, or 114.
In another embodiment, the composition is capable of selectively hybridizing to a polynucleotide corresponding to a hRAD50 intron and identified by one of the sequences SEQ ID NO:57, 59, 60, 62, 63, 65, 67, 68, 70, 72, 74, 76, 78, 80, 81, 83, 85, 86, 88, 90, 91, 93, 94, 96, 98, 100, 101, 103, 105, 106, 108, 109, 111, or 113.
In yet another embodiment, the composition is capable of selectively hybridizing to a polynucleotide derived from a cDNA library and identified by one of the sequences SEQ ID NO:44, 45 and 46.
In a related aspect, the invention includes a nucleic acid probe, at least 30 nucleotides in length, capable of selectively hybridizing under stringent conditions to a polynucleotide fragment having a sequence selected from the group consisting of SEQ ID NO:55-114. The probe has a sequence such that under typical hybridization conditions (see example provided in "definitions"), it does not hybridize to corresponding yeast RAD50 sequences, but does hybridize to the corresponding human RAD50 sequences. In a general embodiment, the probe is capable of selectively hybridizing to a polynucleotide fragment corresponding to a hRAD50 exon, such as a fragment having a sequence selected from the group consisting of SEQ ID NO:55, 56, 58, 61, 64, 66, 69, 71, 73, 75, 77, 79, 82, 84, 87, 89, 92, 95, 97, 99, 102, 104, 107, 110, 112, or 114.
DNA compositions and nucleic acid probes such as described above are useful in a number of screening applications, including but not limited to fluorescent in situ hybridization (FISH), Northern and Southern blot analyses, dot blot and slot blot analyses and the like.
The invention also includes a pair of single-stranded DNA primers useful for DNA amplification of a fragment of the human RAD50 (hRAD50) gene, wherein each primer of said pair is at least 15 nucleotides in length, and use of said pair in a polymerase chain reaction containing either human genomic DNA or suitable human cDNA target results in synthesis of a DNA fragment containing all or preferably part of the sequence of a human RAD50 gene. The primer pair is preferably capable of amplifying at least one exon of hRAD50 (or portion thereof), such as an exon having a sequence selected from the group consisting of SEQ ID NO:55, 56, 58, 61, 64, 66, 69, 71, 73, 75, 77, 79, 82, 84, 87, 89, 92, 95, 97, 99, 102, 104, 107, 110, 112, or 114. For example, the primers of the pair can have sequences derived from a sequence selected from the group consisting of SEQ ID NO:55-114, or SEQ ID NO:116-163.
Exemplary applications of such primer pairs include amplification of DNA fragments for use in single-strand conformational polymorphism (SSCP), denaturing gel electrophoresis (DGGE), or heteroduplex analyses (HA) of hRAD50 for the presence of mutations.
Also forming parts of the invention are (i) a method for screening an individual for predisposition to cancer, and (ii) a method for screening an individual for predisposition to hypersensitivity to electromagnetic (EM) radiation (e.g., X-rays, ultraviolet (UV) light). The methods include isolating genomic or cDNA fragments from the individual, testing the isolated fragments for an alteration in the polynucleotide sequence of the individual's hRAD50 gene relative to the polynucleotide sequence of a normal hRAD50 gene, and identifying the test individual as being predisposed to cancer or hypersensitivity to EM radiation if (i) an alteration is identified and (ii) the alteration results in a change in the amino acid sequence of the individual's hRAD50 protein relative to the amino acid sequence of a normal hRAD50 protein, or loss of the protein.
The predisposition to cancer screen may be applied, for example for screening for a predisposition to acute myeloid leukemia (AML), therapy-related acute myeloid leukemia (t-AML), therapy-related myelodysplastic syndrome, (t-MDS), and refractory anemia with excess blasts in transformation (RAEB-T).
The alteration in DNA sequence may be detected, for example, using hybridization analysis, such as in situ (e.g., fluorescent) hybridization, Northern and Southern blot analyses, dot blot or slot blot analyses. The alteration in DNA sequence may also be detected, for example, using single-strand conformational polymorphism (SSCP) analysis, denaturing gel electrophoresis (DGGE), or heteroduplex analysis (HA)
The invention also includes kits for detection of an alteration in the polynucleotide sequence of the individual's RAD50 gene. Hybridization kits include hRad50 hybridization probes, such as the probes identified above (e.g., probes suitable for Southern hybridization, dot blots, slot blots or FISH analysis), and may include other reagents as well as instructions for use. Polymerase chain reaction (PCR) amplification kits include primer pairs such as those described above, and may include additional reagents, such as Taq polymerase, amplification buffer and the like. Specific embodiments of the PCR amplification kits can include additional reagents specific for SSCP analysis, DGGE analysis or HA analysis.
In yet another aspect, the invention includes a gene therapy vector effective to transform human bone marrow cells. The vector includes an expression cassette containing an hRAD50 cDNA coding sequence identified by SEQ ID NO:44 or SEQ ID NO:45, under control of suitable control elements.
Also forming part of the invention is a method of decreasing the risk of a cancer in an individual having a defective hRAD50 gene, including the steps of: (a) isolating bone marrow stem cells from said individual, (b) transfecting cells of the individual with a gene therapy vector encoding a wild-type hRAD50 protein, and (c) introducing the transfected cells back into the individual, with the transfected cells now expressing wild-type hRAD50 protein.
In another aspect, the invention includes a substantially purified or substantially isolated hRAD50 polypeptide containing at least 11 consecutive residues in common with SEQ ID NO:51. The polypeptide may be produced by the protein expression vector constructed in accordance with another aspect of the invention, and containing, as a heterologous gene under the control of suitable control elements, an hRAD50 cDNA coding sequence portion effective to hybridize, under stringent hybridization conditions, with an hRAD50 cDNA having a sequence identified by SEQ ID NO:44.
hRAD50 polypeptides can be used, for example, to generate antibodies useful in assaying the presence of a hRAD50 protein in a sample, e.g., in a Western blot format. Such an analysis may be employed, for example, in a method of diagnosing an individual as being at increased risk for a cancer, described below.
The invention further includes an antibody (monoclonal or polyclonal) which is immunoreactive with hRAD50 protein identified by SEQ ID NO:51. The antibody is useful in methods of screening an individual for (i) predisposition to cancer, and (ii) predisposition to hypersensitivity to EM radiation. The methods include (a) obtaining from the individual, blood cells which in normal individuals contain hRAD50 as a soluble nuclear protein, (b) contacting soluble nuclear proteins from the cells obtained with an antibody which is immunoreactive with hRAD50 protein identified by SEQ ID NO:51, and (c) identifying the test individual as being predisposed to cancer or hypersensitivity to EM radiation if no normal immunocomplex between the cytosol proteins and the antibody is produced. A "normal" immunocomplex is defined as an association of the antibody with an antigen on a hRad50 polypeptide having the molecular weight of a wild-type hRad50 polypeptide (about 153 kD). The formation such an immunocomplex is described in Example 8 and shown in FIG. 7.
In another aspect, the invention includes a therapeutic method of decreasing risk of a cancer in an individual having a defective RAD50 gene. The method includes transfecting cells of the individual with an expression vector encoding a wild-type RAD50 protein, and expressing the protein in the cells. Exemplary cells amenable to such treatment include bone marrow stem cells. The cells can be transfected by a number of methods, including liposome-mediated transfection, CaPO.sub.4 mediated transfection and electroporation. In one embodiment, the transfecting is done ex vivo or extracorporeally, by isolating selected cells (e.g., bone marrow stem cells or peripheral blood mononuclear cells (PBMC)), transfecting the cells ex vivo, and introducing the transfected cells back into the individual.
In a general embodiment, the expression vector used in the method is a viral vector, such as a retroviral vector, adenoviral vector or herpesviral vector. In another general embodiment, the vector is a mammalian expression vector.
The method is particularly amenable to decreasing risk for the following cancers: acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), therapy-related myelodysplastic syndrome, (t-MDS), therapy-related acute myeloid leukemia (t-AML), refractory anemia (RA), and refractory anemia with excess blasts (RAEB).
An exemplary wild-type hRad50 protein suitable for use with the above-described method has the sequence represented as SEQ ID NO:51.
In still another aspect, the invention includes a human cell or cell line having a defective hRAD50 gene. The cell or cell line is useful in screening agents for the ability to promote DNA breaks in human cells. The screening is carried out by (a) exposing a human cell or cell line that is deficient for the wild-type hRAD50 gene to the test compound, (b) observing the morphology of the exposed cells, and (c) identifying a test agent as having the capability to promote DNA breaks if the observed morphology of the exposed cells differs from that of the same cells, but in the absence of exposure to the agent.
The invention further includes a transgenic mouse having a defective or missing RAD50 gene. The mouse is preferably homozygous for the defective or missing gene.
These and other objects and features of the invention will be more fully appreciated when the following detailed description of the invention is read in conjunction with the accompanying drawings.

BRIEF DESCRIPTION OF THE FIGURES
FIGS. 1A-1C are comparisons of the amino acid sequences of human Rad50 (hRad5O) with S. cerevisiae Rad50 (ScRad50).
FIG. 2A shows the % similarity and % identity in a pairwise comparison of hRad50 and ScRad50.
FIGS. 2B-2C shows the probability of coil formation as a function of amino acid position based on the amino acid sequences of hRad50 and ScRad50.
FIG. 3 shows the position of hRAD5O and selected cosmid clones with respect to other loci in the 5q23-31 region.
FIG. 4 shows the results of a PCR using primers directed to the 5' untranslated region of hRAD50.
FIGS. 5A, 5B and 5C show DNA fragments used for primer design for determining the genomic sequence of RAD50. The sequences of these fragments are provided herein as SEQ ID NO:52, SEQ ID NO:53 and SEQ ID NO:54, respectively.
FIG. 6 shows a Northern blot of hRAD50 expression.
FIG. 7 shows immunoblots of immunoprecipitated material stained with hRad50 antiserum or hMrell antiserum.
FIG. 8 shows immunoblots of immunoprecipitations carried out at NaCl concentrations ranging from 300 mM to 1000 mM, stained with hRad50 antiserum or hMrell antiserum.

DETAILED DESCRIPTION OF THE INVENTION
I. Definitions
"Substantially isolated" when used with respect to polynucleotide or polypeptides refers to the at least partial purification of such polynucleotides or polypeptides away from unrelated or contaminating components (e.g., cellular components other than the specified polynucleotide or polypeptide, and polypeptides or polynucleotides having a sequence different from that of the selected polypeptide or polynucleotide. Methods and procedures for the isolation or purification of compounds or components of interest are described below (e.g., recombinant production of polypeptides having immunomodulatory activity).
A nucleic acid fragment is considered to be "selectively hybridizable" to hRAD50 sequences if it is capable of specifically hybridizing to hRAD50 sequences but not to yeast RAD50 sequences (i) under typical hybridization and wash conditions, as described, for example, in Maniatis, et al., pages 320-328, and 382-389, or (ii) using reduced stringency wash conditions that allow at most about 25-30% basepair mismatches, for example: 2.times.SSC, 0.1 SDS, room temperature twice, 30 minutes each; then 2.times.SSC, 0.1% SDS, 37.degree. C. once, 30 minutes; then 2.times.SSC room temperature twice, 10 minutes each.
"Stringent hybridization conditions" refer to hybridization under typical hybridization conditions as above, followed by stringent wash conditions, e.g., three washes in 0.1.times.SSC, 0.1% SDS at 65.degree. C., 15 min each. "Stringent hybridization conditions" typically allow at most about 10-20% basepair mismatches.
A polynucleotide sequence or fragment is "derived from" another polynucleotide sequence or fragment when it contains the same sequence of nucleotides as are present in the sequence or fragment from which it is derived. For example, a bacterial plasmid contains an insert "derived from" a selected human gene if the sequence of the polynucleotides in the insert is the same as the sequence of the polynucleotides in the selected human gene. A polynucleotide sequence or fragment is also "derived from" another polynucleotide sequence or fragment if its sequence is the complement or reverse complement of the sequence from which it is derived (applicable, e.g., in the case or PCR primers "derived" from a target sequence, where the downstream primer is the reverse complement of the corresponding region in the target sequence).
Similarly, a polypeptide sequence or fragment is "derived from" another polypeptide sequence or fragment when it contains the same sequence of amino acids as are present in the sequence or fragment from which it is derived.
Percent (%) identity, with respect to two amino acid sequences, refers to the % of residues that are identical in the two sequences when the sequences are optimally aligned and no penalty is assigned to "gaps". In other words, if a gap needs to be inserted into a first sequence to optimally align it with a second sequence, the % identity is calculated using only the residues that are paired with a corresponding amino acid residue (i.e., the calculation does not consider residues in the second sequences that are in the "gap" of the first sequence). Optimal alignment is defined as the alignment giving the highest % identity score. Such alignments can be preformed using the "GENEWORKS" program. Alternatively, alignments may be performed using the local alignment program LALIGN with a ktup of 1, default parameters and the default PAM.
When a first polynucleotide fragment or polypeptide fragment is said to "correspond to" a second polynucleotide fragment or polypeptide fragment, respectively, it means that the fragments are essentially co-extensive with one another when the sequences representing the fragments (or complements or reverse complements thereof) are aligned using a sequence alignment program, such as "MACVECTOR" (IBI, New Haven, Conn.). "Corresponding" polynucleotide or polypeptide fragments typically contain a similar, if not identical, number of residues. It will be understood, however, that corresponding fragments may contain insertions or deletions of residues with respect to one another, as well as some differences in their sequences.
A cell or a cell line is "selectively deficient" for a copy of a selected gene, such as a wild-type copy of the hRAD50 gene, if (i) the cell or cell line contains no normal or wild-type functional copies of the selected gene, and (ii) the chromosome region in which the selected gene is normally contained is, in both chromosomes, substantially normal or wild-type with respect to all genes in that region with the exception of the selected gene. For example, a cell containing a large deletion on chromosome 5 encompassing hRAD50 as well as other genes is not selectively-deficient for hRAD50, whereas a cell containing a deletion of a portion of the hRAD50 gene is selectively-deficient for hRAD50 if the deletion prevents expression of functional protein and if the cell has no other functional copies of hRAD50.
A "defective" gene, such as a defective hRAD50 gene, is a gene that cannot cause expression of a functional gene product, i.e., a gene product having the biological activity associated with a gene product expressed by a normal, wild-type copy of the gene.
II. Direct Selection and Analysis of Chromosome 5-Specific cDNA Sequences
Experiments performed in support of the present invention detail the generation of cDNA samples enriched for sequences from the 5q23-31 region of human chromosome 5. This region has been identified as containing a tumor suppressor, which may be involved in the development of certain cancers and immunodeficiencies (LeBeau). The cDNA samples were derived from a variety of tissues, including human fetal brain and liver, adult bone marrow, leukemias, lymphomas, activated lymphocytes and cytokine-producing clones, as detailed in Example 1A. The samples were assayed for the presence of known cytokines as detailed in Example 1B using primers shown in Table 1. Results of these assays are shown in Table 2. Those samples showing increased expression of cytokines were combined to create "cDNA pools". The composition of the different pools is detailed in Example 1.
Pools containing relatively high levels of cDNAs encoding different cytokines (see Example 1, Table 2) were further processed using genomic "direct selection", as detailed in Examples 2 and 3. Here, yeast artificial chromosome (YAC) clones containing the 5q23-31 region of chromosome 5 were used to select cDNA that hybridized to sequences in that region. Analysis of approximately 3,000 cDNAs selected with the genomic region spanning 1.3 Mb of 5q23-31 revealed several hundred cDNA clones ranging from about 500 to about 800 bp in length. The sequences were further analyzed by mapping them to YAC clones containing fragments of the 5q23-31 region. About 79% of these clones were mapped to human chromosome 5 and starting YACs either by RT-PCR or Southern blot hybridization.
The data obtained from the physical mapping of the cDNAs to the starting YACs and chromosome 5-specific cosmids were used to group the cDNAs according to their location and partial overlap with one another, resulting in over 50 groups, or "bins", of cDNAs comprised of overlapping clones. Some of the selected cDNAs were also sequenced as described in Example 4 to facilitate placement into the bins.
The consensus cDNA sequences from one of these "bins" were homologous to the yeast RAD50 gene (he results of a "BLASTX" homology search against a protein sequence database (PIR +SWISS-PROT) showed that the human RAD50 homologue had a .about.35% overall homology to S. cerevisiae Rad50: Score=390, P=3.8e-89.). Accordingly, the human gene from which these consensus sequences were derived was termed hRAD50 (human RAD50).
Three alternatively-spliced hRAD50 cDNA sequences were identified--SEQ ID NO:44, SEQ ID NO:45 and SEQ ID NO:46. SEQ ID NO:44 is a full-length cDNA sequence of hRAD50, and is about ten times more abundant than either of G18 (SEQ ID NO:45) or G102 (SEQ ID NO:46)
The hRAD50 consensus sequence (SEQ ID NO:44) was arrived at by analysis of a number of overlapping clones. In some cases, the clones overlapped only near their ends and the sequence between the overlaps was derived from a single cDNA. In such cases and some others, the consensus sequence may contain alternatively-spliced sequences from the same gene. It will be noted that two different alternatively-spliced transcripts G102 (SEQ ID NO:46) and G18 (SEQ ID NO:45), derived from the same region of the gene, were detected. G102 (SEQ ID NO:46) corresponds to sequences within the first intron (SEQ ID NO:57), while G18 corresponds to sequences in exon 11 (SEQ ID NO:79) and intron 11 (SEQ ID NO:80, 81). A proposed hRad5O alternatively-spliced isoform amino acid sequence encoded in part by G18 (SEQ ID NO:45) sequences is presented as SEQ ID NO:47. The first 597 amino acids of SEQ ID NO:47 are the same as the first 597 amino acids of SEQ ID NO:51 and the remaining amino acids of SEQ ID NO:47 are encoded in part by DNA sequences in G18 (SEQ ID NO:45). It is contemplated that G18 and/or G102 are fragments of cDNAs which encode truncated, alternatively-spliced forms of the hRad50 molecule.
Additional RAD50 sequences (e.g., other alternatively-spliced forms) may be obtained by one of skill in the art using the sequence information and teachings contained in the present specification combined with standard molecular techniques. For example, the cDNA clones described herein, or fragments thereof, may be used to screen a cDNA library constructed from, e.g., human T-cells using standard methods (e.g., Ausubel, et al., 1988). Such libraries are commercially available, for example, from Clontech (Palo Alto, Calif.). Full length clones may also be obtained by similar screening of cDNA pools generated as described herein.
III. Characterization of RAD50 cDNA
The expression pattern of hRAD50 cDNA was determined using RT-PCR with primers specific for the consensus sequence (SEQ ID NO:44). The details of the experimental methods are presented in Example 6B. Primers specific for the sequences to be amplified were constructed using standard methods. The primers were selected such that the expected amplification products were typically between 200 and 1000 bp in length. The following tissues were used for the RT-PCR reactions: total embryo (6, 8, 12 weeks of gestation), fetal liver, fetal brain, fetal muscle, placenta, adult heart, adult muscle, adult liver, adult brain, adult pancreas, adult kidney, adult aorta, adult spleen, adult testis, adult bone marrow, JY B-cell line, resting T-cells and activated T-cells.
Expression of hRAD50 sequences was also assessed using Northern blot analyses, as detailed in Example 6A. The Northern analyses were performed using probes derived from sequences SEQ ID NO:44 and SEQ ID NO:45. A non-coding 3'-flanking fragment of the gene corresponding to nucleotides 4333-5567 of SEQ ID NO:44 was used to probe a Northern Blot containing RNA derived from the same set of adult tissues as described above. mRNA species of 1.9 and 0.85 kb were detected in all tissues tested, with the strongest expression in testis, ovary and small intestine. Uniformity of RNA loading was confirmed using a beta-actin probe.
Similar experiments employing a probe corresponding to nucleotides 417-4353 of SEQ ID NO:44 revealed two mRNA species. A stronger signal was observed at about 5.8 kb and much lower signal was detected at about 6.5 kb in all tissues, with strongest expression in testis. The results of RT-PCR and Northern blot analyses taken together confirmed expression of the human RAD50 gene in activated T-cells, B-cells, placenta and multiple fetal tissues, including fetal liver. Genomic equivalent of this gene is about 100 kb.
In yeast, RAD50 encodes major and minor transcripts of 4.2 and 4.6 kb in length, respectively (Raymond and Kleckner, 1993a). Steady-state levels of both transcripts increase during meiosis, reaching maximal levels midway during meiotic prophase. Yeast RAD50 appears to be involved in DNA repair. It is required during vegetative growth for recombinational repair of double strand breaks and for efficient mating type switching, a direct recombination event promoted by a site-specific double strand break. Most S. cerevisiae mutants of Rad50 are deficient in repair of damage induced by X rays and in meiotic recombination.
The polypeptide predicted for S. cerevisiae Rad50 protein is 153 kDa (1312 aa) (Alani, et al., 1989). The protein contains an amino-terminal ATP-binding domain. Inactivation of this site by point mutations results in a null phenotype, and primary defects in meiosis. The remainder of the protein includes two long segments of heptad repeat sequence diagnostic of regions capable of forming alpha-helical coiled coils, one of which is similar to the S-2 domain of the myosin heavy chain. Since some mutations in the protein affect meiotic recombination but not the repair, it is likely that the protein has domains with different roles.
In accord with the present invention, human RAD50 is also involved in DNA repair. It will be appreciated that failure to express functional gene products of genes involved in DNA repair may be associated with cancer. In particular, an unrepaired double-strand (dbs) break of DNA can lead to a breakup of genomic DNA and culminate in any of a variety of cellular dysfunctions, including high sensitivity to ionizing radiation and impaired recombination. Defective recombination events (e.g., ones involving little or no sequence homology) have been implicated in carcinogenesis and severe immunodeficiencies.
Loss of human chromosome 5 as well as deletions of 5q have been associated with development of therapy-related acute non-lymphocytic leukemia (ANLL) or myeloid disorders (MDS). High resolution fluorescent in situ hybridization (FISH) has identified 5q31 as the most common cytogenetically deleted segment in t-MDS or t-ANLL (LeBeau, et al., 1993). Experiments performed in support of the present invention strongly suggest that hRAD50 is one of the genes involved in suppressing such disorders.
In particular, it is contemplated that hRAD50 has tumor suppression activity, i.e., that hRAD50 is a tumor suppression (TS) gene. Tumor suppressors (see review by Weinberg) are normal cellular genes that function by constraining the growth of cells. A number of tumor suppressor genes have been identified, including neurofibromatosis type I (NF-1), Wilms tumor (WT), the retinoblastoma susceptibility (RB) gene, the deleted in colon carcinoma (DCC) gene, the erbA gene and the p53 gene (Weinberg). According to the present invention, genes that when absent or when encoding nonfunctional gene product, predispose a cell toward neoplastic transformation, can also be considered tumor suppressor genes.
Genetic lesions that inactivate tumor suppressors liberate the cell from such constraints and lead to or predispose a cell to unregulated cellular proliferation, i.e., tumors. In other words, tumor suppressor genes contribute to oncogenicity through their loss rather than their activation. Accordingly, mutations in tumor suppressor genes are typically recessive with respect to precipitating the growth of a tumor--both copies of the gene must be inactivated for tumor formation to occur.
However, although both copies of a TS gene must typically be inactivated for tumor growth, individuals having one mutant or inactivated allele and one wild type allele of a particular TS gene are nevertheless at a significantly increased risk for developing a cancer precipitated by loss of that TS gene. This is due not only to the loss of the "backup" capability against deleterious effects of somatic mutations that two normal alleles provide for all non sex-linked genes, but also to the fact that evolving tumor cells employ genetic mechanisms to actively eliminate genes that interfere with their growth. In particular, when one allele of a TS gene is inactivated (e.g., by a germline mutation), the chromosomal region carrying the surviving wild-type allele may be replaced by a duplicated copy of the homologous chromosome region that carries the mutant allele. This replacement may be accomplished by, e.g., chromosomal nondisjunction, mitotic recombination, or gene conversion. These events typically occur with a frequency of as high as 10.sup.-3 to 10.sup.-4 per cell generations--a much higher rate than independent knockouts of the second copy, which occur on the order of 10.sup.-6 per generation.
Accordingly, in view of the above and the teachings of the present invention, deletion or inactivation of a single allele of the RAD50 gene has the effect of increasing the likelihood of cancer in a subject having such a deletion or inactivation. Such a deletion or inactivation also has the effect of increasing the likelihood that an individual will develop a hypersensitivity to electromagnetic (EM) radiation (e.g., X-rays, ultraviolet (UV) light), as discussed below.
The types of cancers and/or tumors which may be diagnosed and/or treated, or the risk of which may be assessed, using the methods and compositions of the present invention include hematological conditions (e.g., leukemias and lymphomas). In particular, the present inventions is particularly useful with respect to refractory anemias, acute nonlymphocytic leukemia, treatment-induced leukemias, lymphoproliferative disorders, and chronic myeloproliferative disorders. Specific examples of such hematological conditions which are manifested as cancers per se include but are not limited to acute myeloid leukemia (AML), therapy-related acute myeloid leukemia (t-AML), and therapy-related myelodysplastic syndrome (t-MDS). Specific examples of hematological conditions manifested as precancerous conditions include but are not limited to primary myelodysplastic syndrome (MDS), refractory anemia (RA), and refractory anemia with excess blasts (RAEB).
The sections below describe certain diagnostic and therapeutic methods enabled by the discoveries disclosed herein.
IV. hRAD50 Diagnostic Methods
In one aspect, the invention includes a method for diagnosing an individual as being predisposed to, or at increased risk for, cancer. The method includes detecting an alteration in the polynucleotide sequence of the individual's RAD50 gene relative to the polynucleotide sequence of a normal hRAD50 gene (e.g., SEQ ID NO:44), wherein the alteration results in a change in the amino acid sequence of the individual's Rad50 protein relative to the amino acid sequence of a normal hRad50 protein.
According to the present invention, an individual is at an increased risk for cancer, particularly a hematological cancer such as a leukemia or a lymphoma, if the individual contains at least one chromosome 5 with a defective or inactive or missing copy of hRAD50. For example, as illustrated in Example 9 and Table 4, individuals having deletions in the region of 5q23-q31 on one of their chromosomes have a hematological cancer (e.g., acute myeloid leukemia (AML), therapy-related acute myeloid leukemia (t-AML), and therapy-related myelodysplastic syndrome, (t-MDS)) or a precancerous condition (e.g., primary myelodysplastic syndrome (MDS), refractory anemia (RA), or refractory anemia with excess blasts (RAEB).
Several methods may be used to detect an alteration in the polynucleotide sequence of a RAD50 gene. Alterations as small as point mutations (i.e., single base-pair substitutions, insertions or deletions) can be detected using a number of different methods. A traditional approach to the detection of such alteration has been restriction fragment length polymorphism (RFLP) analysis, where the genomic DNA of a test individual is digested with different restriction endonucleases, probed with a fragment corresponding to the gene of interest, and the pattern of fragments analyzed.
Another exemplary method suitable for detection of point mutations is single-strand conformational (SSC) polymorphism (SSCP) analysis, as detailed in Grompe. SSCP is a conventional mutation screening technique where primer pairs are used to PCR amplify genomic DNA from a test subject, and the amplification products are resolved on a non-denaturing (e.g., glycerol-containing) polyacrylamide gel. The two single-stranded DNA molecules from each denatured PCR product assume a three-dimensional conformation dependent on the primary sequence. A difference in sequence between two such single-stranded molecules typically results in the molecules having different three-dimensional conformations, detectable as different bands on an SSCP non-denaturing gel. SSCP analysis typically detects 70-95% of mutations in PCR products that are 200 bp or shorter in length (Michaud, et al., Sheffield, et al.).
Subtle alterations in sequence (e.g., point mutations) may also be detected using denaturing gel electrophoresis (DGGE). This technique also uses differential electrophoretic migration of wild-type and mutant DNA to detect mutations. Double-stranded DNA (dsDNA) amplified by PCR is electrophoresed through a gradient of increasing concentration of a denaturant (e.g., urea and formamide). As they migrate through the gradient, the strands progressively dissociate in a sequence-dependent manner. Such partial melting of the duplex results in a marked decrease in mobility, allowing fragments differing in sequence by as little as one base-pair to be resolved (Myers, et al.). Accordingly, hRAD50 DNA from individuals with one normal and one mutant copy of hRAD50 would form normal/mutant heteroduplexes in the region of the alteration giving rise to the mutation. Such heteroduplexes can be resolved from the normal/normal and mutant/mutant homoduplexes using DGGE, and used to identify an individual as potentially at increased risk for cancer.
Heteroduplex analysis (HA) can also be used to detect mutations as subtle as single base-pair alterations. HA analysis typically employs PCR to generate amplification fragments corresponding to the region of a gene (e.g., hRAD50) being assayed. As described above for DGGE, when the target DNA contains two different sequences (e.g., one from a normal chromosome and one from a chromosome containing a mutant hRAD50 having an altered sequence with respect to wild-type hRAD50), and the sequences are similar enough to dimerize (i.e., the differences between the sequences are point mutations or small insertions/deletions), the amplification products will contain (i) homodimers consisting of either two strands having the wild-type sequence or two strands having the mutant sequence, and (ii) heterodimers consisting of one mutant strand and one wild-type strand. HA analyses are based on the observation that some such heteroduplexes have a different mobility than corresponding homoduplexes, even in regular polyacrylamide gels (Nagamine, C. M., et al.). HA analysis is facilitated, however, by use of specialized matrices, including "HYDROLINK" and "MDE", available from AT Biochem.
Other methods which may be used to detect heteroduplexes include RNase A cleavage (see, e.g., Ausubel, et al., Chapter 4) and chemical mismatch cleavage (Cotton, et al.).
Primer pairs used for SSCP, DGGE or HA analyses are typically designed based on sequences within introns adjacent splice junctions. Such primer pairs are then used to PCR amplify exons from target DNA (e.g., genomic DNA isolated from a subject in need of a diagnosis). The primers are preferably selected to generate amplification products in the range of 200-400 base pairs (bp). Exemplary primers suitable for SSCP, DGGE or HA analyses of the RAD50 gene include primers having sequences represented as SEQ ID NO:116 through SEQ ID NO:163. These primers correspond to the introns in vicinity of exon/intron splice junctions and are designed to amplify exon sequences from RAD50 genomic sequences. They are arranged in pairs corresponding to upstream and downstream primers. For example, primers r1 (SEQ ID NO:116) and r2 (SEQ ID NO:117) together constitute a primer pair effective to amplify a selected exon of the hRAD50 gene.
The selection of regions of a sequence suitable for serving as templates for PCR primer design is well known in the art (e.g., Innis, et al., 1990). In fact computer programs designed specifically for this purpose are commercially-available (e.g., "OLIGO" primer analysis software, NCBI, Inc., Plymouth, Minn.).
The methods described above can be used to detect several different types of mutations, including deletion mutations, insertion mutations and point mutations.
Deletion and insertion mutations may also be detected using hybridization methods, such as Southern blot hybridization, dot-blot hybridization, in situ hybridization (including fluorescent in situ hybridization (FISH)) and Northern blot hybridization. For example, extremely large (>1 megabase (Mb)) deletions and insertions can be detected by high resolution cytogenetics (Rooney, et al.) using FISH (Zhang, et al.), as described in Example 9. Smaller insertions and deletions, as well as some point mutations (e.g., point mutations that alter a relevant endonuclease restriction site) can be detected by Southern blot. Such hybridization analyses are also amenable to multiplex approaches, e.g., where probes to different portions of a gene are labelled with different dyes and used to probe a blot simultaneously.
An exemplary hybridization probe is a nucleic acid probe capable of selectively hybridizing to a polynucleotide fragment having a sequence selected from the group consisting of SEQ ID NO:55-114, wherein the probe is at least 30 nucleotides in length. Preferably, the probe is capable of selectively hybridizing to a polynucleotide fragment having a sequence selected from the group consisting of SEQ ID NO:55, 56, 58, 61, 64, 66, 69, 71, 73, 75, 77, 79, 82, 84, 87, 89, 92, 95, 97, 99, 102, 104, 107, 110, 112, or 114.
Deletion and insertion mutations may also be detected using a "multiplex" PCR approach, where a family of primer sets is designed to amplify a series of fragments (e.g., 200-400 bp fragments) having different lengths which together span substantially all of the cDNA encoding a selected gene (e.g., hRAD50). The fragments are then resolved on a gel, and insertions/deletions are detected by a change in the size of one or more fragments relative to fragments amplified using wild-type or normal hRAD50 as target.
hRAD50 DNA fragments having heterologous sequences (identified using, e.g., SSCP, DGGE or HA) are typically analyzed further using sequence analysis to determine if the nucleotide sequence alteration results in an alteration in the amino acid sequence. According to the present invention, hRad50 amino acid sequence alterations which predispose an individual to cancer or a precancerous condition are preferably ones that result in a substantial alteration in the activity of hRad50; i.e., alterations which represent mutations and not merely sequence polymorphisms among various individuals. For example, a missense point mutation resulting in conservative amino substitutions might not affect the biological activity of hRad50, and would be characterized as a sequence polymorphism rather than a mutation that is deleterious to the function of the protein. Examples of mutations having such a deleterious effect include point mutations that introduce a frame shift or a stop codon in the coding sequence of the cDNA.
DNA alterations having a substantial effect on the amino acid sequence can also be identified by analyzing the hRAD50 polypeptide itself, using, e.g., a Western immunoblot: Rad50 is a soluble protein confined to nucleus. A sample (e.g., a nuclear-enriched sample) from cells that in normal individuals express Rad50 (e.g., activated lymphocytes) can be used as a source for partially-purified Rad50 polypeptide, which can then be resolved on a polyacrylamide gel, the gel blotted and probed with anti-Rad50 antibodies, and the molecular weight and antibody-binding properties of the protein determined.
According to the present invention, alterations or mutations in the gene sequences of RAD50 which result in a functional change (e.g., non-conservative substitution, frame-shift, truncation or deletion) in the amino acid sequence of the Rad50 protein are indicative of the individual being at an increased risk for developing a precancerous condition or a cancer, particularly a hematological cancer such as a lymphoma or leukemia.
Lymphomas are neoplastic transformations of cells that reside primarily in lymphoid tissues. The two major forms of malignant lymphoma are Hodgkin's disease and non-Hodgkin's lymphoma (Nadler). Leukemias are a diverse group of neoplasms arising from the malignant transformation of hematopoietic cells. The transformed cells initially proliferate mainly in bone marrow and lymphoid tissues, where they interfere with immune function and hematopoiesis. Eventually, the leukemic cells migrate into the peripheral blood and infiltrate other tissues. Leukemias can be classified according to the affected cell types (myeloid or lymphoid) and as acute or chronic, depending on the history of the disease (Champlin and Golde).
Methods and compositions are particularly suitable for assessing the propensity or risk for contracting therapy-related malignant myeloid disorders. Specific examples of cancers amenable to analysis as described herein include acute nonlymphocytic leukemia (ANLL), which can include acute myeloid leukemia (AML), therapy-related acute myeloid leukemia (t-AML), and therapy-related myelodysplastic syndrome, (t-MDS).
Primary myelodysplastic syndrome (MDS) is a precancerous condition and includes a heterogeneous group of progressive, irreversible, multipotent stem cell disorders, including refractory anemia (RA), RA with ring sideroblasts (RARS), RA with excess blasts (RAEB), RAEB in transformation (RAEB-T) and chronic myelogenous leukemia (CMML). RA is not a cancer per se, unless it gains excessive blasts and becomes a RAEB-T, t-MDS or ANLL.
5q.sup.- syndrome is a distinct hematological disorder, occurring principally in elderly females. Its classical features includes macrocytic anaemia and mild infrequent progression to leukemias. Both t-MDS and 5q.sup.- syndromes are possible undesirable consequences of successful chemotherapy following treatment of a previously-diagnosed malignant disease or non-neoplastic disorder. Their incidence varies with the different causative agents. For instance, 5q.sup.- syndrome has been frequently reported in Hodgkin's disease patients treated with MOPP chemotherapy and radiotherapy and in myeloma patients treated with alkylating agents.
The above analysis can also be used in a method for diagnosing an individual as being predisposed to, or at increased risk for, hypersensitivity to electromagnetic (EM) radiation (e.g., X-rays, ultraviolet (UV) light), i.e., increased propensity for radiation-induced DNA damage. It is known, for example, that ultraviolet (UV) light and X-rays can cause DNA damage. According to the present invention, individuals who do not have two normal or wild-type copies of hRAD50 are at increased risk for suffering such damage. If diagnosed as being at increased risk, the individuals may take special precautions to minimize their exposure to potentially-risky radiation, such as avoiding certain routine X-rays and wearing extra protective clothing and UV-blocking sunscreen when outside in the sun.
The steps in the method are essentially the same as the steps of the method of diagnosing an individual for increased propensity for cancer.
V. hRAD50 Therapeutic Methods
In another aspect, the invention includes a method of decreasing risk of a cancer in an individual having a defective Rad50 gene, a method of treating a condition characterized by increased risk for developing a cancer in an individual, and a method of treating a cancer or cancerous condition in an individual.
According to the teachings herein, an individual suffering from a myeloid malignancy, where the transformed cells have no wild-type copies of hRAD50, can be treated using a gene therapy. Untransformed bone marrow stem cells are isolated from the individual and transfected with a gene therapy vector encoding wild-type hRad50. The individuals cancerous cells are then destroyed, and the transfected cells are infused or transplanted back into the individual, where they differentiate into cells expressing hRad50.
Exemplary gene therapy vectors of the present invention are effective to transform human bone marrow cells, and include an expression cassette containing an hRAD50 cDNA coding sequence identified by SEQ ID NO:44 or SEQ ID NO:45, under control of suitable control elements.
Any of a variety of gene therapy approaches may be used. One suitable approach is virally-mediated gene transfer, where host cells are transfected with chimeric genes or constructs of the present invention by infection with mature virions containing hybrid vectors (the chimeric genes along with selected viral sequences). The virions used to transfect host cells are preferably replication-defective, such that the virus is not able to replicate in the host cells.
The virions may be produced by co-infection of cultured host cells with a helper virus. Following coinfection, the virions are isolated (e.g., by cesium chloride centrifugation) and any remaining helper virus is inactivated (e.g., by heating). The resulting mature virions contain a chimeric gene of the present invention and may be used to infect host cells in the absence of helper virus. Alternatively, high titers of replication-defective recombinant virus, free of helper virus, may be produced in packaging cell lines containing those components for which the virus is defective (Miller).
Several types of viruses may be amenable for use as vectors with chimeric gene constructs of the present invention. Each type of virus has specific advantages and disadvantages, which are appreciated by those of skill in the art. Methods for manipulating viral vectors are also known in the art (e.g., Grunhaus and Horowitz; Hertz and Gerard; and Rosenfeld, et al.). Retroviruses may be particularly advantageous for use with the present invention--they are highly efficient at transfection (some vectors can stably transduce close to 100% of target cells), they stably integrate their DNA into the chromosomal DNA of the target cell and are suitable for use with proliferating cells, since they typically require replication of the target cells in order for proviral integration to occur.
The bone marrow are isolated using standard methods and transfected using a transfection system suitable for the vector. For example, transfection with certain viral constructs can be accomplished by simply incubating the construct or vector with the cells to be transfected. Other gene therapy vectors can be transfected into cells using liposome-mediated transfection, CaPO.sub.4 mediated transfection or electroporation. The above-described methods can also be applied to treatment of other cells, such as peripheral blood mononuclear cells (PBMC) In addition to the diagnostic and therapeutic methods described above, the present invention enables the production of recombinant hRad5O, antibodies specifically immunoreactive with hRad5O, diagnostic methods using such antibodies and the construction of cell lines and transgenic animals defective for the RAD50 gene, as described below.
VI. hRAD50 Expression Vectors, Polypeptides and Antibodies
The present invention includes a recombinant expression vector capable of expressing hRAD50 sequences. Such a vector can then be used to express recombinant polypeptides in selected host cells, such as E. coli. Expression vectors such as described above typically contain control sequences, such as sequences containing promoter regions, enhancer elements, and the like, which are compatible with the selected host cell. These control sequences are operably linked to the insert sequence such that the insert sequence can be expressed in the selected host cell.
One example of an expression vector for recombinant production of hRad50 polypeptides is the plasmid PGEX (Smith and Johnson, 1988, Smith, 1993) and its derivatives (e.g., the pGEX series from Pharmacia Biotech, Piscataway, N.J.). These vectors express the polypeptide sequences of a cloned insert fused in-frame with glutathione-S-transferase. Recombinant PGEX plasmids can be transformed into appropriate strains of E. coli and fusion protein production can be induced by the addition of IPTG (isopropyl-thio galactopyranoside). Solubilized recombinant fusion protein can then be purified from cell lysates of the induced cultures using glutathione agarose affinity chromatography according to standard methods (Ausubel, et al., 1988).
Alternatively, affinity chromatography may also be employed for isolating .beta.-galactosidase fusion proteins, such as those produced by cloning hRad50 polypeptide sequences in lambda gt11. The fused protein is isolated by passing cell lysis material over a solid support having surface-bound anti-.beta.-galactosidase antibody.
Other suitable expression systems include a number of bacterial expression vectors, such as lambda gt11 (Promega, Madison Wis.), pGEX (Smith and Johnson, 1988), and pBS (Stratagene, La Jolla Calif.) vectors; yeast expression systems, such as the Pichia expression kit from Invitrogen (San Diego, Calif.); baculovirus expression systems (Reilly, et al.; Beames, et al.; Clontech, Palo Alto Calif.); and mammalian cell expression systems (Clontech, Palo Alto Calif.; Gibco-BRL, Gaithersburg Md.).
A number of features can be engineered into the expression vectors, such as leader sequences which promote the secretion of the expressed sequences into culture medium. The recombinantly produced polypeptides are typically isolated from lysed cells or culture media.
Isolated recombinant polypeptides produced as described above may be purified by standard protein purification procedures, including differential precipitation, molecular sieve chromatography, ion-exchange chromatography, isoelectric focusing, gel electrophoresis and affinity chromatography. Protein preparations can also be concentrated by, for example, filtration (Amicon, Danvers, Mass.).
In addition to recombinant methods, Rad50 proteins or polypeptides may be chemically synthesized using methods known to those skilled in the art.
hRad50 polypeptides, or immunogenic portions thereof, can be used as antigens in the generation of anti-sera or antibody preparations, as described in the Materials and Methods, herein. Typically, to prepare antibodies, a host animal, such as a rabbit, is immunized with the purified antigen or fused protein antigen. The host serum or plasma is collected following an appropriate time interval, and this serum is tested for antibodies specific against the antigen.
The gamma globulin fraction or the IgG antibodies of immunized animals can be obtained, for example, by use of saturated ammonium sulfate or DEAE Sephadex, or other techniques known to those skilled in the art for producing polyclonal antibodies.
Alternatively, a purified hRad5O antigen or fused antigen protein may be used for producing monoclonal antibodies. Here the spleen or lymphocytes from an immunized animal are removed and immortalized or used to prepare hybridomas by methods known to those skilled in the art (e.g., Harlow, et al.).
Antibodies secreted by the immortalized cells are screened to determine the clones that secrete antibodies of the desired specificity, for example, using Western blot (immunoblot) analysis. Example 8 describes the use of rabbit serum antibodies which are specific against hRad50 polypeptides in immunoprecipitation and immunoblot analyses.
Antibodies such as described above are useful in a method of screening an individual for predisposition to cancer. Blood cells, e.g., peripheral blood mononuclear cells (PBMC) are obtained from the individual using standard methods. These cells, in normal individuals, typically contain hRAD50 as a soluble nuclear protein. A protein fraction containing hRadSO is isolated from the cells, e.g., as described in the Materials and Methods under "Immunoprecipitation" and the soluble proteins in the fraction are contacted with an antibody which is immunoreactive with hRAD50 protein identified by SEQ ID NO:51. A polyclonal serum containing such an antibody was generated for used with experiments performed in support of the present invention as described in the Materials and Methods section.
The individual is identified as being predisposed to cancer if no normal immunocomplex between the cytosol proteins and the antibody is produced. A "normal" immunocomplex is defined as an association of the antibody with an antigen on a hRad50 polypeptide having the molecular weight of a wild-type hRad50 polypeptide (about 153 kD). Examples of such normal complexes are shown in FIG. 7 with reference to FIG. 8.
VII. hRAD50-Deficient Cell Lines and Transgenic Mice
Also included in the invention are human cells, cell lines and transgenic animals selectively deficient for hRAD50 function. A convenient method for generating such "knockout" compositions (both cells and animals) is through the use of embryonic stem (ES) cell technology. ES cells are the derivatives of the inner cell mass of the blastocyst. ES cells are totipotent, nontransformed, primitive ectoderm-like cells that can be maintained in culture for many passages in an undifferentiated state. The cells have two advantageous characteristics with respect to the present invention: (ii) if ES cells are allowed to reach a high density in monolayers or to form aggregates in suspension, they will spontaneously differentiate to various cell types, and (ii) they can be reintroduced back into a 3.5 day blastocyst which, when placed into a suitable host (e.g., foster mother mouse) can colonize all tissues of the developing embryo, giving rise to a chimeric animal.
ES cells have many features in common with embryonal carcinoma (EC) cell lines: both are indistinguishable in their morphology and growth requirements, and their differentiation in vitro results in the formation of similar cell types (Martin, et al.). For example, it has been reported that ES cells can differentiate into parietal and visceral endoderm, cardiac muscle, as well as other cell types (Doetschman, et al., 1987).
As described in Example 10, the present invention enables the construction of cells, particularly human cells, that are null for the RAD50 gene. Such cells can be in the form of an immortalized cell line, or differentiated ES cells which can be passaged for several generation. hRAD50.sup.- cells have a number of uses. For example, in view of RAD50's role in DNA repair, cells defective for RAD50 gene expression may be used to screen for carcinogenic compounds. In accordance with the invention, such cells are more sensitive to carcinogenic agents that cause DNA breaks or that render the DNA more prone to breakage by other causes (e.g., agents which increase the photosensitivity of the DNA), and may therefore be used to screen test compounds for the ability to promote DNA breaks.
In one embodiment, test compounds may be screened by exposing such a hRAD50.sup.- cell (one that is deficient for the wild-type hRAD50 gene) to the test compound in a suitable carrier, and observing the morphology of the exposed cells. Controls preferably include (i) hRAD50.sup.- cells exposed only to the carrier, and (ii) hRAD50.sup.+ cells identical to the hRAD50.sup.- cells in all respects except for hRAD50 expression. The test compound can be left on the cells for an extended duration (e.g., for days), or may be used to briefly "pulse" the cells (e.g., for hours). The cells are allowed to grow for a selected period (e.g., 1-4 days) and are assayed for effects of the test compound.
Compounds which selectively induce changes in the morphology of the treated hRAD50.sup.- cells, but not in the hRAD5.sup.+ control cells, are identified as having the capability to promote DNA breaks, i.e., as compounds which increase the rate of or cause DNA breaks, or which render the cells hypersensitive to other factors (e.g., UV light) which can cause DNA breaks.
The change in morphology that is typically associated with DNA breaks is apoptosis/cell death. Accordingly, in a preferred embodiment, viable cells in compound-exposed and control cultures are counted during the test phase, and compounds which cause an increase in cell death in hRAD50.sup.- cells relative to hRAD50.sup.+ and unexposed control samples are identified as having the capability to promote DNA breaks. Other changes in morphology may also be indicative of DNA breaks. For example, exposure of cells to low doses of DNA-damaging carcinogens can transform cultured cells, and rapidly growing foci could be observed among untransformed cells.
Compounds which promote DNA breaks may affect cells in many ways, including cell-growth control, cell morphology, cell-to-cell interactions, membrane properties, cytoskeletal structure, protein secretion, gene expression, and cell mortality. As a consequence of such changes, cells may acquire different "transformed" phenotypes (e.g., rounded blast-like shapes) which depend on the dose and the exposure times of the reagents.
The above-described method may be applied to the screening of, e.g., chemotherapeutic drugs, and to test the carcinogenicity or mutagenicity of compounds or substances for which such carcinogenicity or mutagenicity data are needed.
Transfected ES may also be directly injected into the blastocoel of a host blastocyst or incubated in association with a zona-free morula, as described in Example 10, to generate a transgenic mouse. The host embryos are transferred into intermediate hosts or surrogate females for continued development. Using such an approach, it is possible to produce chimeric or transgenic mice with 30% of the live-borne stock containing tissue derived from the injected stem cells.
Other methods may be used to generate transgenic mice that are deficient for either one or both copies of the RAD50 gene. Such methods are described, for example, in the following U.S. Patents, all of which are incorporated herein by reference: (i) Ser. No. 5,491,283 ('283), issued Feb. 13, 1996, (ii) Ser. No. 5,487,992 ('992), issued Jan. 30, 1996 and (iii) Ser. No. 5,416,260 ('260), issued May 16, 1996. The '260 patent in particular discusses the modification of embryonic stem cells by homologous recombination to inactivate endogenous genes, and the use of such modified stem cells to produce a transgenic mouse.
It is contemplated that transgenic animals generated, e.g., as described above, can be used as models for human cancers associated with defective RAD50 function. For example, such animals may be useful in screens to identify therapeutic compounds effective to treat cancers such as acute myeloid leukemia (AML), therapy-related acute myeloid leukemia (t-AML), therapy-related myelodysplastic syndrome, (t-MDS), and refractory anemia with excess blasts in transformation (RAEB-T). Further, such animals may be useful in screens for or evaluation of compounds with the capability to promote DNA breaks, i.e., as compounds which increase the rate of or cause DNA breaks. Such screens may be useful, for example, in evaluating known compounds for their carcinogenicity.
The following examples illustrate but in no way are intended to limit the present invention.
MATERIALS AND METHODS
Unless otherwise indicated, restriction enzymes and DNA modifying enzymes were obtained from New England Biolabs (Beverly, Mass.) or Boehringer Mannheim (Indianapolis, Ind.). Nitrocellulose paper was obtained from Schleicher and Schuell (Keene, N.H.). Materials for SDS-polyacrylamide gel electrophoresis (SDS-PAGE) were obtained from Bio-Rad Laboratories (Hercules, Calif.). Other chemicals were purchased from Sigma (St. Louis, Mo.) or United States Biochemical (Cleveland, Ohio).
A. Buffers and Media
Phosphate-buffered saline (PBS)
10.times.stock solution, 1 liter:
80 g NaCl
2 g KCl
11.5 g Na.sub.2 HPO4--7H.sub.2 O
2 g KH.sub.2 PO.sub.4
Working solution, pH 7.3:
137 mM NaCl
2.7 mM KCl
4.3 mM Na.sub.2 HPO.sub.4 --7H.sub.2 O
1.4 mM KH.sub.2 PO.sub.4
SSC (sodium chloride/sodium citrate), 20.times.
3 M NaCl (175 g/liter)
0.3 M Na.sub.3 citrate-2H.sub.2 O (88 g/liter)
Adjust pH to 7.0 with 1 M HCl
SSPE (sodium chloride/sodium phosphate/edta), 20.times.
3.0 M NaCl
0.20 M NaH.sub.2 PO.sub.4
20 mM EDTA, pH 7.4
Tris/EDTA Buffer (THE)
10 mM Tris-Cl, pH as indicated
1 mM EDTA, pH 8.0
AHC Medium and Plates (ura.sup.-, trp.sup.-)
1.7 g yeast nitrogen base without amino acids and without ammonium sulfate (Difco Laboratories, Detroit, Mich.).
5 g ammonium sulfate.
10 g casein hydrolysate-acid, salt-free and vitamin-free (United States Biochemical, Cat. #12852, Cleveland, Ohio).
50 ml (for medium) or 10 ml (for plates) of 2 mg/ml adenine hemisulfate (Sigma Chemical, Cat. #A-9126, St. Louis, Mo.).
Dissolve in a final volume of 900 ml H.sub.2 O, adjust pH to 5.8.
Autoclave 30 min, then add 100 ml sterile 20% (w/v) glucose. For AHC plates, add 20 g agar prior to autoclaving. Store at 4.degree. C. for .ltoreq.6 weeks.
Denhardt solution, 100.times.
10 g Ficoll 400
10 g polyvinylpyrrolidone
10 g bovine serum albumin (Pentex Fraction V, Miles Laboratories, Kankakee, Ill.)
H.sub.2 O to 500 ml
Filter sterilize and store at -20.degree. C. in 25-ml aliquots
High Salt Buffer
500 mM NaCl
10 mM Tris, pH 7.5
10 mM EDTA
0.5% NP-40
0.2 mg/ml PMSF
Standard Lysis Buffer
100 mM NaCl
50 mM Tris, pH 7.4
5 mM EDTA
0.5% NP40
Strip Buffer
62.5 mM Tris-HCl, pH 6.8
100 mM p-mercaptoethanol
2% SDS
B. Cell Lines
IMR90 primary fibroblasts were maintained in DMEM/10% FCS/1% Pen-Strep/2 mM L-Glutamine, and serially passed 1:3 from passage 8. Experiments utilizing IMR90 cells were performed using cells from passages 12-16. TK6 lymphoblastoid and K562 CML cells were grown in RPMI-1640/10% NBCS/1% Pen-Strep/2 mM L-Glutamine. All cells were grown at 37.degree. C. in 5% CO2. IMR90 and TK6 cells were obtained from the American Type Culture Collection (ATCC; Rockville, Md.).
C. Irradiation
Cells were irradiated in a Mark I .sup.137 Cs source at a rate of approximately 200 cGy/min.
D. Immunoblots
hRad50 and hMre11 antisera were raised in New Zealand White rabbits using bacterially produced histidine-tagged (hMre11) or GST (hRad50) fusion proteins using standard methods (Harlow, et al., Smith and Johnson, 1988, Smith, 1993). The resulting reagents were: preimmune serum 204pre and immune serum 204/6 (.alpha.hMre11); preimmune serum 84pre and immune serum 84 (.alpha.hRad50).
For Western blotting, 0.5-2.times.10.sup.6 cells were lysed in SDS lysis buffer containing p-mercaptoethanol, aspirated through a 25 gauge needle to shear the genomic DNA and boiled before fractionation on SDS-PAGE gels. Immunoblot analyses were carried out with the indicated antisera at dilutions of 1:400 to 1:1000 using standard procedures (Harlow and Lane, 1988). Chemiluminescent detection of filter-bound antigen/antibody complexes was done with horseradish peroxidase-conjugated G+A protein in conjunction with Luminol reagent (Pierce, Rockford, Ill.). Where indicated, blots were stripped at 50.degree. C. for 30 minutes in Strip Buffer and retreated with primary and secondary immunoblot reagents as described.
E. Immunoprecipitation
2.5.times.10.sup.6 TK6 cells were lysed on ice for 30 minutes in High Salt Buffer. Lysates were then diluted 1:2 with Standard Lysis Buffer or with Lysis Buffer containing increased NaCl concentrations, and precleared for 1 hour at 4.degree. C. with Protein A-Sepharose beads (Pharmacia, Piscataway, N.J.). Cleared lysates (final NaCl concentration 300 mM to 1000 mM) were incubated on ice for 1 hour with hMrell serum 204/3p (affinity purified .alpha.hMrell), 204pre, hRad50 serum 84, or 84pre. Immune complexes were precipitated for 1 hour by rolling at 4.degree. C. with Protein A-Sepharose beads. Bead-bound immunoprecipitates were washed 4 times with Standard Lysis Buffer, boiled in SDS sample buffer, and loaded on 8.5% polyacrylamide/SDS gels. Proteins were analyzed by immunoblotting using standard methods (Harlow and Lane, 1988) and detected as above.
F. Metabolic Labeling
5.times.10.sup.6 K562 cells were removed from normal media, washed once with PBS, and resuspended in methionine- and phosphate-free RPMI1640 supplemented with 2% dialyzed NBCS, 8 mg/ml Na.sub.2 HPO.sub.4, 85 .mu.Ci/ml [.sup.35 S]methionine (10 .mu.Ci/.mu.l). Cells were incubated for 6 hours prior to harvesting for immunoprecipitation. Immunoprecipitates were fractionated on 8.5% SDS-PAGE gels. Gels were fixed for 30 minutes in 30% methanol/10% acetic acid, washed in ddH.sub.2 O, and incubated in 1 M sodium salicylate for 30 minutes prior to drying and autoradiography. Protein bands were readily visible within 7 hours.
EXAMPLE 1
Construction of cDNA Pools for Use in Direct Selection
Complementary DNA (cDNA) was prepared using standard methods from tissues and cell lines that expressed or were likely to express sufficient amounts of messenger RNA (mRNA) encoding proteins of interest. cDNA samples from several sources were sometimes grouped into "cDNA pools". For example, ionomycin-stimulated T cells, T cell clones, and T-lineage lymphomas were found be the best mRNA source for construction of a polymerase chain reaction (PCR) -amplifiable cDNA pool for direct selection due to high levels of corresponding cytokines expressed (first eight samples in Table 2, below). Similarly, a hybrid cDNA pool, termed pool #1, was constructed using mRNA isolated from a mixture of several activated T-cell clones and lymphomas (obtained from David Lewis, University of Washington, Seattle; Lewis, et al., 1988).
A complex primary cDNA pool, termed pool #2, was constructed from human fetal and adult tissues, including fetal brain and liver, adult bone marrow, and activated lymphocytes, as well as the following cytokine-producing cell lines, which, unless otherwise indicated, were obtained from the American Type Culture Collection (ATCC), Rockville Md.: A-10 cells (T cell clone), Jurkat cells (ATCC TIB-152), CEM cells (ATCC CCL-119), HUT-78 cells (ATCC TIB-161), JM cells (ATCC CRL-8294), Molt-4 cells (ATCC accession number CRL1582) and NG-1 cells.
Prior to isolating MRNA from "activated" T-cell samples, the cells were grown at 5.times.10.sup.6 cells/ml in RPMI medium (GIBCO/BRL Life Technologies) supplemented with 5% human AB serum as previously described (Georgopoulos, et al., 1990) and activated using 50 ng/ml phorbol myristate acetate (PMA; Sigma, St. Louis, Mo.) in combination with either 25 .mu.g/ml concanavalin A (Con A) (Pharmacia, Piscataway, N.J.) or 0.5 .mu.M ionomycin (Calbiochem-Behring, San Diego, Calif.).
A. Cell Isolation and Synthesis of cDNA
1. Isolation of Primary T Cells and Thymocytes. Circulating adult T cells and thymocytes were isolated as previously described (Georgopoulos, et al., 1990) by Ficoll-Hypaque density gradient centrifugation and treated with CD4 Lymphokwik (One Lambda, Los Angeles, Calif.), a mixture of complement and monoclonal antibodies (mAb) directed against non-T-lineage markers and the CD8 surface antigen, following the manufacturer's instructions. The final purity of each T-lineage cell population was consistently >95% based on flow cytometric analysis after staining with appropriate mAbs.
2. Cell Activation. Cells were activated at 5.times.10.sup.6 /ml in RPMI medium supplemented with 5% human AB serum as previously described (Georgopoulos, et al., 1990) using 50 ng/ml phorbol myristate acetate (PMA; Sigma, St. Louis, Mo.) in combination with either 25 .mu.g/ml concanavalin A (ConA) (Pharmacia, Piscataway, N.J.), 0.5 AM ionomycin (Calbiochem-Behring, San Diego, Calif,), or 2.5 .mu.g/ml PHA (Sigma, St. Louis, Mo.).
3. RNA Isolation. Cell or tissue homogenates were prepared using a Polytron homogenizer as described (Chomczynski and Sacchi, 1987). Total RNA was isolated by the guanidinium isothiocyanate/CsCl method (Glizin, et al., 1974) or by the acid guanidinium isothiocyanate-phenol-chloroform extraction method (Chomczynski and Sacchi, 1987) using a commercial kit ("TRIZOL", Life Technologies, Inc., Gaithersburg, Md.). mRNA was isolated from the total RNA using oligo(dT).sub.25 "DYNABEADS" (Dynal Inc., Lake Success, N.Y.) following manufacturer's instructions ("mRNA Isolation Using "DYNABEADS" OLIGO(dT).sub.25 ", pp 35-60 in BIOMAGNETIC TECHNIQUES IN MOLECULAR BIOLOGY--TECHNICAL HANDBOOK, Second Edition, Dynal, A. S. (Oslo, Norway) (1995). Briefly, Poly-A.sup.+ mRNA was selected using "MAGNETIC DYNABEADS OLIGO (dT).sub.25 " (Dyndal A. S., Oslo, Norway) according to protocol 2.3.1 (Jakobsen, et al., 1990, 1994) as recommended by the manufacturer.
4. cDNA Synthesis. Cell or tissue Double-stranded (ds) cDNA was synthesized using the "SUPERSCRIPT" "CHOICE SYSTEM" kit for cDNA synthesis (GIBCO/BRL Life Technologies, Gaithersburg, Md.) according to the manufacturer's instructions, except that custom adapters (Adapter #3 and adapter #5, described below) were used in place of the EcoR1 adapters supplied with the kit. Approximately 5 .mu.g of poly(A.sup.+) mRNA were used with oligo dT15 or random hexamers to synthesize ds cDNA. The cDNA was purified from the primers and the low molecular weight products (<250 bp) on "WIZARD" PCR Preps DNA Purification System columns (Promega, Madison, Wis.) according to the manufacturer's protocol, and ligated to dephosphorylated adapters #3 (SEQ ID NO:1, SEQ ID NO:2) or #5 (SEQ ID NO:3, SEQ ID NO:4) using standard methods (Sambrook, et al., 1989). Typically, cDNA pools designed for direct selection contained adapter #3 at their ends to allow single primer PCR amplification (e.g., using primer #A3-2 (SEQ ID NO:5) or primer #AD3-CUA (SEQ ID NO:6; see below).
The adapters were made by combining oligonucleotides #4665 (SEQ ID NO:1) and #4666 (SEQ ID NO:2) (Adapter #3), or oligonucleotides #A5-1 (SEQ ID NO:3) and #A5-2 (SEQ ID NO:4) (Adapter #5), heating the mixtures to 95.degree. C. for 5 minutes, and allowing the mixtures to gradually cool to room temperature over about 30 minutes. This caused the oligonucleotides in the mixtures to hybridize and form double stranded adapters with 3' overhangs as illustrated below. The adapters were then dephosphorylated with calf intestine phosphatase (CIP) using a standard protocol (Ausubel, et al., 1988), and the phosphatase inactivated by incubating at 70.degree. C. for 10 min.
5'-biotinylated primer #A5-2b (SEQ ID NO:7) was designed to synthesize biotinylated subtraction probes (e.g., ribosomal, mitochondrial, Alu-, etc.) from cDNA fragments containing Adapter #5 using PCR. Primer #A3-2 (SEQ ID NO:5) was designed to synthesize similar probes from cDNA fragments containing Adapter #3. CUA-containing primer #AD3-CUA (SEQ ID NO:6) was designed to PCR amplify cDNAs that subcloned into the pAMP10 vector (GIBCO/BRL Life Technologies, Inc).
B. Screening of cDNA Samples with Cytokine PCR Primers
The presence of specific cytokine cDNAs in the different cDNA samples/pools was determined using PCR to provide an estimate of the degree to which such cytokine transcripts were present, i.e., to "validate" the cDNA samples/pools as sources for cytokine cDNAs. The PCR reactions were carried out using standard methods (Mullis, 1987; Mullis, et al., 1987) with the primer pairs presented in Table 1, below.
TABLE 1______________________________________ SEQ ID ProductPrimers NO: T.sub.ann Sequence Size______________________________________GM-CSF-2 8 60.degree. C. CCTTGACCATGATGGCC- 187 bp AGCCGM-CSF-1 9 CCCGGCTTGGCCAGCCT- CATCIL3-1 10 55.degree. C. CTCTGTGGTGAGAAGGC- 287 bp CCAIL3-2 11 CTTCGAAGGCCAAACCT- GGAIL4-3 12 55.degree. C. GGTTTCCTTCTCAGTTG- 210 bp TGTTIL4-4 13 CTCACCTCCCAACTGCT- TCCCIL5-1 14 55.degree. C. CACCAACTGTGCACTGA- 213 bp AGAAATCIL4-2 15 CCACTCGGTGTTCATTAC- ACCIL9-1 16 60.degree. C. AGCTTCTGGCCATGGTC- 360 bp CTTACIL9-6 17 TCAGCGCGTTGCCTGCC- GTGGTIL13-1 18 55.degree. C. ATGGCGCTTTTGTTGACC- 1013 bp ACIL13-5 19 CCTGCCTCGGATGAGGC- TCCIRF1-7 20 55.degree. C. GAAGGCCAACTTTCGCT- 367 bp GTGIRF1-8 21 CACTGGGATGTGCCAGT- CGGTCF7-3 22 55.degree. C. CCGTTCCTTCCGATGACA- 898 bp GTGCTTCF7-4 23 GACATCAGCCAGAAGCA- AGTEGRI1-6 24 60.degree. C. CCACCTCCTCTCTCTCTT- 750 bp CCTAEGRI1-7 25 TCCATGGCACAGATGCT- GTACCD14-5 26 65.degree. C. CCGCTGGTGCACGTCTCT- 1022 bp GCGACCCD14-6 27 CACGCCGGAGTTCATTG- AGCCCDC25-3 28 65.degree. C. GAGAGGAAGGAAGCTCT- 282 bp GGCTCCDC25-5 29 GTCCTGAAGAATCCAGG- TGACC______________________________________
All cDNA samples and cDNA pools #1 and #2 were screened using PCR with the above primers, and the relative amount of specific amplification product determined. Prior to amplification, the samples were diluted such that the concentration of cDNA was the same in each sample (about 200 .mu.g/ml). The results for individual cDNA samples are presented in the Table 2, below. Three pluses (+++) indicate a relatively high level of expression, (++) an intermediate level, (+) a relatively low level, (.+-.) a very low but consistent level, (.-+.) a very low and inconsistent level, and (-) no detectable expression.
TABLE 2__________________________________________________________________________cDNA IL13 IL4 IRF1 IL5 IL3 GM-CSF TCF7 IL9 EGR1 CD14 CDC25__________________________________________________________________________T-cells ++ +++ +++ +++ +++ ++++ +++ +++ - .+-. -A-10 +++ ++++ +++ ++++ +++ ++++ .+-. +++ ++ .+-. .-+.Jurkat + + +++ - +++ +++ +++ - - .+-. +CEM ++ ++ +++ .-+. +++ +++ +++ - ++ .+-. ++HUT78 ++ ++ +++ + +++ ++++ +++ - +++ .+-. ++JM + - +++ .-+. +++ ++++ +++ - - .+-. +++Molt4 + ++ +++ - - - +++ - - .+-. ++HNG-1 ++ - ++= - - ++++ +++ - +++ .+-. ++Daudi - - + - - - .+-. - - .-+. +816 - +++ +++ .+-. - - .+-. +++ - - .-+.Mono - - +++ - - +++ - - - +++ -__________________________________________________________________________ Daudi Blineage cell lymphoma (Daudi); Monocytes stimulated with LPS for 6 hrs (Mono); Adult T cells stimulated with Con A and PMA for 6 hrs (Tcells); EBVtransformed Bcell line 816 (816); HNG1 Tcell lineage lymphom (HNG1); Molt4 Tcell lineage lymphoma (Molt4); JM Tcell lineage lymphoma (JM); HUT78 Tcell lineage lymphoma (HUT78); CEM Tcell lineage lymphoma stimulated with ionomycin and PMA for 6 hrs (CEM); Jurkat Tcell lineage lymphoma (Jurkat); and Clone A10 of Tcell origin, #producing high levels of IL4 and IL5 and stimulated with Con A for 6 hrs (A10).
The data in Table 2, above, suggest that a cDNA pool formed of cDNA samples in the first 6 rows of the table, along with the monocyte cDNA, may be particularly effective as a source of cytokine cDNAs. Accordingly, cDNA pool #3 was formed by combining equal fractions of these seven cDNA samples. cDNA pool #4 was formed by combining equal fractions of all eleven cDNA samples listed in Table 2, above, along with cDNA from adult bone marrow.
Eight additional cDNA pools, termed cDNA pools #5-12, were constructed by combining, at a 1:1 vol/vol ratio, cDNA pool #3 with cDNA samples of similar concentrations isolated from human tissues, including total embryo (6, 8, 12 weeks of gestation; pools #5, 6 and 7, respectively), fetal liver (pool #8), fetal brain (pool #9), adult bone marrow (pool #10), adult thymus (pool #11), and adult spleen (pool #12).
EXAMPLE 2
Preparation of Genomic DNA for Direct Selection
A. Mapping of Genomic Clones used for Direct Selection
Yeast artificial chromosome (YAC) clones containing sequences from the cytokine gene cluster area of chromosome 5 (5q23-31) were isolated and physically mapped to provide a template for the direct selection of the cDNA samples and pools described in Example 1. YAC clone A94G6 (.about.425 kb) was obtained from the YAC Washington University library (St. Louis, Mo.) (Burke, et al., 1987; Morgan, et al., 1992). Clones 259E7 (.about.490 kb) and 854G6 (.about.1.3 mb) were isolated from CEPH (Centre d' Etude du Polymorphisme Humain, France) regular and mega YAC libraries (Bellanne-Chantelot, et al., 1992).
To construct a physical map of the YAC clones, the clones were digested with NotI and run on a clamped homogeneous electrical fields (CHEF) mapper system ("CHEF-DR III" Variable Angle Pulsed Field Electrophoresis System, Bio-Rad Laboratories, Hercules, Calif.). The yeast clones were grown in liquid AHC medium (Bellanne-Chantelot, et al., 1992) for 48 hrs at 30.degree. C. Cells were harvested, washed and embedded in 0.5% low melting temperature agarose (LMT) as described (Chumakov, et al., 1992). After the zymolase treatment and lysis, YACs were separated in 1% LMT agarose pulsed field gels in 0.5.times.TBE at 14.degree. C. as described below.
All the separations were carried out in "CHEF-DR III" pulsed-field electrophoresis system (Bio-Rad) with following parameters: 1) small YACs (400-500 kb)--power OG V/cm; run time 24 hrs 4 min; initial switch time 21.41; final switch time 39.48; 2) mega YACs (1-1.5 mb)--power 0.6V/cm; run time.sup.1 22 hrs 30 min; switch time.sup.1 60.00; run time.sup.2 12 hrs 30 min; switch time.sup.2 90.00.
The CHEF gels were blotted and hybridized by standard Southern hybridization (Sambrook, et al., 1989) to probes for IL13, IL4, IL5, IRF1, IL3, GM-CSF, all of which are located in 5q23-31. The hybridization conditions, unless specified, were: 5.times.SSPE, 0.1% SDS, 5.times.Denhardt's, .sup.32 P-labelled probe, 65.degree. C. overnight. The blots were washed first with 1.times.SSC+0.1% SDS at room temperature, and then with 0.1.times.SSC+0.1% SDS at 65.degree. C. several times, 15 min each.
The results from the hybridizations were used to construct a physical map of the 1.3 megabase (Mb) region encompassed by YACs A94G6, 259E7 and 854G6. This map was confirmed and further refined by physically mapping a panel of chromosome 5-specific cosmids, as described in Example 5, below.
B. Direct Selection Protocol
DNA from the genomic clones was isolated as described in part C, below. The isolated DNA was labeled with biotin either by PCR using biotinylated primers SEQ ID NO:34 and SEQ ID NO:35, or by conventional labelling technique. For PCR labelling 5'-biotinylated primers were used that had been synthesized at Genosys Biotechnologies, Inc. (Woodlands, Tex.). For conventional labelling either photo-activatable biotin (PAB) or Biotin-21-dUTP nick translation labelling kits from Clontech (Palo Alto, Calif.) were used.
Biotinylated genomic DNA was hybridized in solution with complex representative cDNA pools #4-12. In selection with YACs A94G6 and 259E7, cDNA pool #4 was used. In selection with the mega YAC 854G6, a mixture of equal amounts of cDNA pools #4-12 was used. Hybridization was done at 65.degree. C. in 20 .mu.l of 5.times.SSPE, 1.times.Denhardt, 0.1% SDS to Cot=500. cDNAs that was close to saturation was efficiently-captured under these conditions. Specifically-bound cDNAs were captured with Dynal streptavidin beads and washed with 400 .mu.l of 2.times.SSC, 0.5% SDS twice at RT, 10 min each and 4 times with 400 .mu.l of 0.2.times.SSC+0.1% SDS at 65.degree. C., 5 min each time.
Biotinylated genomic DNA-cDNA hybrids and free YAC DNA fragments were captured with streptavidin coated magnetic beads (Dynal A. S., Oslo, Norway) for 30 min at RT with occasional tapping. Two hundred .mu.g of the beads (40 .mu.l, 5 .mu.g/.mu.l) were added per each 5 pMoles of biotinylated PCR product (up to 4 kb in length). About 4 .mu.g of the biotinylated PCR products within the range of 1-4 kb could be captured by this amount of beads. Dynabeads were washed twice with buffer containing 1M NaCl in preblocking buffer (THE pH 7.5+200 .mu.g/ml Herring sperm DNA+0.1% BSA) and resuspended to 5 .mu.g/.mu.l in the same buffer without DNA or RNA. The suspension was incubated at room temperature (RT) for 30 min, and the beads were captured and isolated with the aid of a magnet. The isolated beads were then washed with 400 .mu.l of 2.times.SSC, 0.5% SDS twice at RT, 10 min each and 4 times with 400 .mu.l of 0.2.times.SSC+0.1% SDS at 65.degree. C., 5 min each time.
After washing, specifically bound cDNAs were eluted from the hybrids of the biotinylated DNA-cDNA either by incubating the beads with 40 .mu.l of 2.5 mM EDTA at 80.degree. C. or with 100 mM NaOH at RT. The latter was followed by neutralization with 20 .mu.l of 0.2 M HCl and 10 .mu.l of 1M Tris-HCl pH 8.0.
Eluted cDNAs were PCR amplified by single primer amplification (SISPA) using either primer #AD3-2 (SEQ ID NO:5) or #AD3-CUA (SEQ ID NO:6). Primer #AD3-CUA was used when PCR products were to be cloned in pAMP10. This cloning system substantially reduced the background of "0"-insert and chimeric clones.
A second round of direct selection was usually performed following completion of the first round. The first round typically resulted in a several hundred to a thousand fold enrichment. The second round of selection enabled enrichment up to about a hundred-thousand-fold (Morgan, et al., 1992).
To determine whether a second round of selection was necessary, cDNA aliquots were SISPA-propagated the #AD3-2 primer (SEQ ID NO:5), cleaned up by "WIZARD" PCR column chromatography, quantitated, and run a on 1% agarose gel (about 1 .mu.g/lane) both before and after selection. The gels were visualized, blotted, and hybridized with the probes known to reside within given genomic DNA. Alternatively, PCR was used to assess the enrichment by direct selection (Morgan, et al., 1992). If the degree of enrichment was less than about ten thousand-fold, a second round was performed.
C. Preparation of YAC DNA for Direct Selection
YAC clones A94G6, 259E7 and 854G6 were grown overnight in AHC medium at 30.degree. C. Agarose blocks were prepared according to the protocol of LePaslier (Chumakov, et al., 1992). Briefly, yeast cells harboring the YACs were harvested, washed, counted and embedded in 0.5% Sea-Plaque GTG agarose (FMC, Rockland, Me.) as described in CHEF-DR.sup.R III instruction manual and application guide. YAC DNAs or their restriction fragments were separated in 1% LMT agarose (FMC) pulsed field gels in 0.5.times.TBE at 14.degree. C. according to the Bio-Rad protocols. For smaller YACs (400-500 kb), the following parameters were applied: power 0.6 V/cm; run time 24 hrs 4 min; initial switch time 21.41; final switch time 39.48. For mega YACs (1-1.5 mb), the following parameters were applied: power 0.6V/cm; run time.sup.1 22 hrs 30 min; switch time.sup.1 60.00; run time.sup.2 12 hrs 30 min; switch time.sup.2 90.00.
YAC DNA-containing bands (containing .about.250 ng DNA) were excised, placed into tubes with 2 vol of 1.times.Sau3AI buffer (New England Biolabs (NEB), Beverly, Mass.), and treated with 12 U of Sau3AI (NEB) at 37.degree. C. for 5 hrs.
The agarose containing the digested YAC DNA was then melted in 1 volume of THE at 68.degree. C., and the DNA isolated using the "WIZARD" PCR Preps DNA Purification System (Promega, Madison, Wis.) at 37.degree. C. following the manufacturer's instructions. DNA was eluted with THE (pH 8.0).
Due to steric hindrance of the incorporated biotin, one of the following adapters was ligated to the eluted YAC DNA to allow more efficient SISPA amplification and PCR controlled labelling with biotin: (i) Sau3A1 semiadapter #1, made of primers having sequences SEQ ID NO:42 and SEQ ID NO:43, (ii) Sau3A1 semiadapter #2, made of primers having sequences SEQ ID NO:30 and SEQ ID NO:31, or (iii) Sau3Al adapter #S-1/S-2, made of primers having sequences SEQ ID NO:32 and SEQ ID NO:33. Sau3A1 semiadapter #2 provided better yields and specificity in ligations and subsequent PCRs.
Ligation of the linkers was typically carried overnight at +14.degree. C. in 20 .mu.l of the reaction mix, containing 100 ng of Sau3AI-digested YAC DNA, 100 pmoles of adapter, and 6 U of T4 DNA Ligase (New England Biolabs).
EXAMPLE 3
Direct cDNA Selection with the Genomic DNA Fragments Encompassing Cytokine Gene Cluster in 5q23-31
YAC clone DNA was PCR-amplified for 30 cycles using biotinylated primers SEQ ID NO:34 and SEQ ID NO:35. The amplified YAC DNA was then preblocked with Cot1 DNA (GIBCO/BRL Life Technologies, Inc.) and used for direct selection with cDNA samples as follows.
One hundred ng of the amplified biotinylated YAC DNA were mixed with either 5 .mu.g Cot1 DNA and 5 .mu.pg yeast host strain AB1380, or 10 .mu.g Cot1 DNA, in 8 .mu.l of water and denatured for 15 min under mineral oil at 98.degree. C. in a heating block. The mixture was then supplemented with 2 .mu.l of 25.times.SSPE+5.times.Denhardt+0.5% SDS to a final concentration of 5.times.SSPE, 1.times.Denhardt solution and 0.1% sodium dodecyl sulfate (SDS) in 10 .mu.l, and hybridized for 2.0 hrs at 60.degree. C. to Cot=20. In parallel, 10 .mu.g of cDNAs were denatured in 8 .mu.l of water for 15 min under mineral oil and treated as described above.
Ten .mu.g of cDNAs from selected samples were denatured in 8 .mu.l of water for 15 min under mineral oil as described above and supplemented to a final concentration of 5.times.SSPE, 1.times.Denhardt and 0.1% SDS. Direct selection was initiated by mixing 10 .mu.l of the amplified cDNAs with 10 .mu.l of the amplified and preblocked biotinylated YAC DNA (100 ng), and hybridization was conducted to a Cot=500 (about 4 hrs) at 65.degree. C. under mineral oil. A Cot value of 1 is equivalent to 83 .mu.g/ml of DNA.times.1 hour at 60.degree. C. in 5.times.SSPE.
A. Isolation of cDNA/DNA Hybrids with Magnetic Beads
The hybridization mixture was then incubated with streptavidin coated magnetic beads (Dynal, Inc., Lake Success, N.Y.) in a buffer containing 1M NaCl in THE pH 7.5+0.1% BSA for 30 min at room temperature with occasional tapping to immobilize the biotinylated genomic DNA fragments, some of which contained hybridized cDNA species. Two hundred .mu.g of the beads (40 .mu.l, 5 .mu.g/.mu.l), effective to capture about 4 .mu.g of the biotinylated PCR products (1-4 kb), were added per each 5 pMoles of biotinylated YAC DNA PCR product.
Following the incubation, the "DYNABEADS" were collected using a magnetic stand (Dynal, Inc.). The beads were then washed with 400 .mu.l of 2.times.SSC, 0.5% SDS twice at RT, 10 min each, and 4 times with 400 .mu.l of 0.2.times.SSC+0.1% SDS at 65.degree. C., 5 min each. Specifically bound biotinylated DNA-cDNAs were incubated either with 40 .mu.l of 2.5 mM EDTA at 80.degree. C., or with 100 mM NaOH at RT with occasional tapping of the tube, eluted and neutralized with 20 .mu.l of 0.2 M HCl and 10 .mu.l of 1M Tris-HCl pH 8.0.
Specifically bound biotinylated DNA-cDNAs were eluted either with 40 .mu.l of 2.5 mM EDTA at 80.degree. C. or with 100 mM NaOH at RT with occasional tapping of the tube. In cases where NaOH was used, the eluted beads were neutralized with 20 .mu.l of 0.2 M HCl and 10 .mu.l of 1M Tris-HCl pH 8.0.
B. Subcloning of Selected cDNAs
The eluted material (.about.2 .mu.l) was PCR-amplified for approximately 30 cycles in 100 .mu.l tubes using approximately 50 pmoles each of primers SEQ ID NO:5 and SEQ ID NO:6, typically for 30 cycles using 2 .mu.l of the eluate per 100 .mu.l reaction. Primer SEQ ID NO:6 was used only when the PCR products were to be subcloned into the pAM10 vector. The PCR cycle parameters were as follows: 30 sec at 94.degree. C., 30 sec at T.sub.ann -5.degree. C., and 2 min at 72.degree. C. After the last cycle, the reactions were incubated for 7 min at 72.degree. C., and then kept at 4.degree. C. until further processing.
The PCR-amplified material was typically used for a second round of direct selection as described above, selected products were PCR amplified with primer SEQ ID NO:6, and .about.1-5 .mu.g of the selected cDNAs were subcloned into plasmid pCRTMII (Invitrogen Corporation, San Diego, Calif.) or the pAMP10 vector ("CLONEAMP" directional PCR cloning system, GIBCO/BRL Life Technologies, Inc). The pAMP10 vector is adapted for uracil DNA glycosilase (UDG) cloning. This approach does not require restriction endonuclease digestion, end-polishing, purification or ligation. With this system, PCR products should contain specified 12-base 5' sequence that contains dUMP residues instead of dTMP.
Treatment with UDG renders dUMP residues abasic, disrupting base-pairing which results in 3'-protruding termini. pAMP10 plasmid contains a modified multiple cloning site and 3' ends that are complementary to the 3' protruding termini of the UDG-treated PCR amplification products obtained with the primer SEQ ID NO:6. Linear vector and UDG both go to the selected amplified cDNAs, without ligase, and are complete in less than 30 min, producing recombinant molecules ready for transformation.
1 .mu.l of 20 .mu.l UDG-reaction mixture was typically used to electroporate 50 .mu.l of electrocompetent JS5 E.coli cells (Bio-Rad) according to manufacture's protocol in a "GENE PULSER" apparatus (Bio-Rad), in 0.1 cm electrode gap cuvettes. After 1 hr incubation of electroporated cells in 1 ml of Luria Broth (LB), 100 .mu.l of the culture was plated onto LB plates containing 100 .mu.g/ml Ampicillin.
The quality of a direct selection was monitored by Southern blot hybridization using a probe known to reside on the YAC, when similar quantities of the PCR amplified cDNA were loaded on the gel before and after the selection. Usually up to 100,000-fold enrichment was observed in two rounds of selection. Before and after the selection cDNA aliquots were SISPA-propagated with the primer SEQ ID NO:5, cleaned up by Wizard PCR column chromatography, quantitated, and run in 1% agarose gel (about 1 .mu.g/lane). The gels were visualized, blotted, and hybridized with the probes known to reside within given genomic DNA. Alternatively, quantitative PCR was used to assess the enrichment by direct selection. The enrichment ratios of direct selection were also monitored by plating cDNA aliquots before and after the selection, and counting the ratio of several marker clones to overall colonies. For example, if there was one IL3 positive clone in 10.sup.6 colonies before and one in 10 after the selection, the enrichment was considered to be around 10.sup.5 fold on this step. The selection process was controlled such that there was at least a 10 thousand-fold enrichment for at least one marker. Alternatively, negative selection was controlled for the markers known not to be on the YACs. In this case, the data were examined for a decrease in the ratio of this gene during selection.
EXAMPLE 4
Hybridization and Sequence Analysis of the Arrayed Region-Specific cDNAs
A. Analysis and Subcloning of the PCR Products
Individual colonies of PCR pAMP10 clones generated as described above were used to inoculate wells containing LB broth in 96-well plates. The cultures were incubated overnight at 37.degree. C. and an aliquot from each well was transferred to an Immobilon-N membrane (Millipore, Bedford, Mass.), forming a grid corresponding to the locations of the samples in the plate.
The DNA was immobilized on the membranes using UV-crosslinking, and the membranes were then screened with .sup.32 P-labelled YAC, Cot1, mitochondrial, ribosomal and single copy probes known to reside on a starting genomic clone, in order to eliminate nonspecific or already known cDNAs from further analysis, as follows.
Membranes with the arrayed cDNAs were hybridized with different .sup.32 P-labelled probes: highly repetitive, high molecular weight human COT1 DNA (Life Technologies, Inc.), human mitochondrial and ribosomal probes, starting YAC probe, single copy marker genes, known to reside within the genomic region in question. Because starting total cellular RNA contained certain amount of heteronuclear, ribosomal and mitochondrial species, final cDNA pools still contained these species, and it was much easier to prescreen the arrayed libraries for them rather than to introduce additional steps into the selection protocol.
About 55% of the clones in arrayed selected cDNA libraries were eliminated in such a prescreening procedure. Single copy known genes from the genomic region in question were monitored as well, and were used to evaluate the quality of the selected material and the depth of the libraries. These statistics also aided in determining how many novel cDNAs might be expected. For instance, 18% of the clones in the A94G6 YAC selection library belonged to IRF1, IL13, IL3 and IL5.
Negative clones were subject to sequencing. Sequencing data confirmed that there were at least 7 novel gene candidates, one of which was assembled into a full-length clone of a human homolog of S.cerevisiae RAD50. After computer analysis of the sequencing data, PCR primers were designed for prospective novel gene cDNAs and were used both to evaluate the tissue-specificity of expression of the gene candidates and for physical mapping of cDNAs to human chromosome 5 and the starting YAC, as described below.
B. Sequence Analysis
Unique and presumably novel cDNA clones were sequenced and screened for similarity of their nucleotide and amino acid sequences using Fasta, BlastN, BlastX, tBlastN programs in known protein and nucleic acid databases. For efficient and quick identification of non-overlapping cDNAs, redundant cDNAs were eliminated by subsequent hybridization of the arrayed libraries with already identified individual cDNAs as probes and unique sequences were further analyzed as described below.
After two rounds of selection, .about.66% of all clones mapped back to the starting genomic region, i.e., YAC or any other genomic DNA used to select these particular cDNAs. Each cDNA species comprised >1% of the selected material. The complexity of the selected cDNAs (i.e., the number of distinct species of DNAs) was dependent on the gene density in the region with respect to which the cDNAs were selected, and on the complexity of the starting cDNA sources.
EXAMPLE 5
Mapping Selected Clones to Chromosome 5: Physical Mapping of cDNAs to Cosmids
A human chromosome 5-specific cosmid library was obtained from L. Deaven (Los Alamos National laboratories, N. Mex.) as arrayed individual clones in 96 well-plates that represented 8 x genome equivalents subcloned in the sCos1 vector (Longmire, et al., 1993). The E. coli DHS clones contained about 81% human inserts, 8% rodent inserts and 3% nonrecombinants. About 25,000 individual cosmid clones were microgridded onto "HYBOND-N" nylon membrane (Amersham Life Sciences, UK) using a "BIOMEK 1" (Beckman, Palo Alto, Calif.) robotic station. The filters with spotted clones were grown overnight on 96-well plate lids (Cat.#76-205-05, ICN Flow, Costa Mesa, Calif.) filled with 1.5% LB SeaKem GTG agarose (FMC Bioproducts, Rockland, Me.) supplemented with 20 .mu.g/ml kanamycin (Sigma).
After treating the filters on Whatman 3mm paper saturated with 2.times.SSC/0.5% SDS for 2 min, the filters were microwaved for 2.5 min at .about.750 W until dry. Then they were submerged in a buffer containing 50 mM Tris-HCl pH 8.0, 50 mM EDTA, 100 mM NaCl, 1% Na-lauryl-sarcosine, and 250 mg/ml Proteinase K (Boehringer). After incubation for 20 min at 37.degree. C. the filters were UV-crosslinked on Fotodyne crosslinker for 35 sec. After washing, the microgrids were hybridized with different .sup.32 P-oligolabelled YAC, cDNA or terminal cosmid walking probes as described below. Many cDNAs selected with the above specified YACs were mapped to the clones on the microgrids. Other libraries may be similarly used for mapping purposes, including YAC, BAC, and P1 genomic libraries.
EXAMPLE 6
Determining Tissue Specific Expression
Tissue specificity of expression was performed using Northern blot analyses and PCR detection.
A. Northern Blot Analyses
Total RNA was isolated by the guanidinium isothiocyanate/CsCl method (Glisin, et al., 1974) or by the acid guanidinium isothiocyanate- phenol-chloroform extraction method using a commercial kit (Tri-reagent, Molecular Research Center, Cincinnati, Ohio), and was resolved on formaldehyde gels using standard methods (Sambrook, et al., 1989). The gels were blotted onto "HYBOND N" membranes (Amersham Life Sciences, UK), fixed by UV-crosslinking, and the membranes probed with radiolabeled probes corresponding to the clones. Conditions: Hybridization buffer, containing 5.times.SSPE, 2.times.Denhardt, 100 .mu.g/ml sonicated salmon sperm DNA, 0.5% SDS; Hybridization temperature=65.degree. C.
All probes consisted of DNA labeled by the random hexamer priming method using a commercial kit (Pharmacia, Piscataway, N.J.), with the exception of the IL4 probe, for which a single-stranded RNA probe was employed.
B. RT-PCR Analysis
About 1 .mu.g of total RNA from different sources was reverse transcribed (RT) by random priming with "SUPERSCRIPT II" (GIBCO/BRL Life Technologies, Gaithersburg, Md.) in 20 .mu.l of reaction mix as specified by the manufacturer. After heat inactivation, 1 .mu.l of the RT-reaction was used in a 30 .mu.l PCR of 30 cycles of conventional PCR with the primers and T.sub.ann specified below. Each PCR reaction contained 20 mM Tris-HCl pH 8.9 (at 25.degree. C.), 16.7 mM (NH.sub.4).sub.2 SO.sub.4, 1.5 mM MgCl.sub.2, 200 AM dNTPs, 1 .mu.M primers, and 0.8 U AmpliTaq (Cetus).
PCR-based detection of tissue-specific expression was performed using the following PCR-amplifiable primary cDNA pools: Total Embryo (6, 8, 12 weeks of gestation), Fetal Liver, Fetal Brain, Fetal Muscle, Placenta, Adult Heart, Adult Muscle, Adult Liver, Adult Brain, Adult Pancreas, Adult Kidney, Adult Aorta, Adult Spleen, Adult Testis, Adult Bone Marrow, JY B-cell line, Resting T-cells and Activated T-cells.
These cDNAs were either used directly as targets or PCR amplified for 30 cycles using primer SEQ ID NO:5. Amplified cDNAs were purified on a "WIZARD-PCR" column (Promega, Madison, Wis.), quantitated, and used in PCR reactions. Each PCR reaction contained 50 ng of one cDNA sample or pool (amplified or unamplified) as the target. After 30 cycles of PCR the products were separated on agarose gels and the intensity of the signals recorded.
EXAMPLE 7
hRAD50--Human Homolog of the Yeast Gene RAD50
A. Isolation of hRAD50
Three cDNA clones A106, G157, G170, selected with the YACs A94G6 and 854G6 as described in Example 3, were mapped to chromosome 5-specific cosmid 256E1 about 10 kb upstream of the IL13 gene.
A full-length cDNA, termed G10 (also referred to as "RAD50.seq"; SEQ ID NO:44), was obtained using marathon RACE (rapid amplification of cDNA ends; Chenchik, et al., 1995) techniques with activated T-cell and testis cDNA marathon pools. A marathon cDNA pool, in contrast to a regular cDNA pool, has a special adapter at the ends of cDNAs. Such cDNAs can not be SISPA amplified, because the adapter design suppresses PCR with a single adapter-specific primer (Siebert, et al., 1995). Exponential PCR is observed only if a gene-specific primer is employed along with the adapter-specific primer. Such cDNA pools allow both 5'- and 3'-RACE amplifications, and finally isolation of intact genes via combination PCR (Chenchik, et al., 1995).
B. cDNA Sequence Analysis
cDNA clone G10 is about 5,800 bp long and encodes a protein of 1312 aa (SEQ ID NO:51) with two highly-conserved domains with respect yeast RAD50 (>50% identity): an N-terminal ATP-binding domain and a conserved C-terminal domain. The locus corresponding to G10 was accordingly termed human RAD50 (hRAD50). FIGS. 1A-1C show an alignment of hRad50 and ScRad50. Identical amino acid residues are identified by solid-line boxes, and similar residues (as defined in the following paragraph) are identified by dashed boxes. Potential nuclear localization signals are indicated by hatched boxes over the hRad50 sequence. Two of these are bipartite (Robbins, et al., 1991) with a dashed line connecting the two segments. The Walker "A" and "B" NTP binding domains are overlined.
The two sequences were also compared pairwise in 130 amino acid segments using the Lipman-Pearson algorithm (Lipman and Pearson, 1985). The results are shown in FIG. 2A. Identical residues are indicated by solid white regions and similarities, with residues weighted according to the PAM250 matrix (Dayhoff, 1978), are indicated by filled boxes. The following amino acids were considered similar: {D, E, N, Q} {F, W, Y} {K, R} {A, G} {I, V} {L, M} {S, T} {C} {H} {P}.
hRad50 contains three potential nuclear localization signals (FIGS. 1A and 1B). The conserved N terminal domain includes the Walker A-type ATP binding signature (Alani, et al., 1989; Gorbalenya and Koonin, 1990), whereas the Walker B-type "DA" box is encoded by the C terminal conserved region (Gorbalenya and Koonin, 1990; Hirano, et al., 1995). The DA box-containing region of hRad5O is the most conserved region of the protein, exhibiting 68% identity over the C terminal 270 amino acids (FIGS. 1A, 1B and 2A).
The internal portion of ScRad50 is conserved to a much lesser extent. This region encodes the heptad repeat regions of the protein from amino acids 177-421 and amino acids 743-995 (Dayhoff, 1978). The heptad repeat motif in ScRad50 is likely to be significant for the assembly of ScRad50-containing protein complexes (Alani, et al., 1989; Raymond and Kleckner, 1993b).
The COILS program (Lupas, et al., 1991; available over the World Wide Web (WWW) from Uniform Resource Locator (URL) http://ulrec3.unil.ch/software/COILS.sub.-- form.html), which calculates the probability that a given segment of a protein will adopt a coiled coil conformation, was used to compare the predicted secondary structures of the two Rad50 homologues (Lupas, et al., 1991). Shown is the data at window width 28. The probabilities determined by the COILS program (Lupas, et al., 1991) (FIGS. 2B-2C). In spite of the relatively divergent primary sequence of the heptad repeat domains, these regions in hRad5O and ScRad50 are predicted to adopt very similar coiled coil structures.
C. Chromosomal Localization of the hRAD50 locus
The chromosomal position of the RAD50 locus was determined using Southern blot analysis. The results are summarized in FIG. 3, which shows a physical map of the human RAD50 gene within the cytokine gene cluster in 5q23-q31. The genes depicted above map to a 320 kb NotI restriction fragment at 5q31. The distance between the IL4 and IL5 genes is about 150 kb. Because of the gaps in the chromosome 5-specific cosmid contig, represented by a double broken line, accurate estimation of the distance between the RAD50 and the IL5 genes, as well as of the size of the genomic RAD50 was not feasible. Some of the hRAD50 cosmid clones described herein are depicted below the map. Direction of gene transcription is indicated by the arrows. Cosmids 256E1, 113E9, and 58D6 placed the RAD50 locus approximately 14.0 kb upstream of the IL13 gene. Full-length hRAD50 cDNA was also used as a probe in Southern blot hybridization analysis of the YACs A94G6 and 854G6. This analysis confirmed that hRAD50 maps to the same 320 kb NotI restriction fragment as the IL4, IL13 and IL5 genes.
Additional confirmation of this localization was established by PCR of DNA prepared from YACs A94G6 and 854G6, as well as from the chromosome 5-containing human/hamster hybrid cell line HHW105 with primers based on the 5' hRAD50 noncoding region. The data are presented in FIG. 4, which shows the results of PCR using primers G10-2 (SEQ ID NO:169) and G10-14 (SEQ ID NO:170), based on the 5' untranslated region of hRAD50. Template DNAs were as follows: Lane 1, No DNA control; Lane 2, Human genomic DNA; Lane 3, YAC 854G6; Lane 4, HHW105 human/hamster hybrid cell line DNA; Lane 5, CHO genomic DNA; Lane 6, YAC A94G6. L, 1 kb ladder. The hRAD50 primers amplified the expected products in the YAC clones derived from 5q31 and the human/hamster hybrid cell, whereas PCR with these primers on hamster genomic DNA failed to give any amplification products.
Four additional cosmid clones 54A2, 98F5, 192E2, and 32H4 were obtained by further screening of the chromosome 5-specific cosmid library with additional hRAD50 cDNA segments. By mapping various portions of the hRAD50 coding sequence to hRAD50-containing cosmids and YAC clones, the hRAD50 gene was estimated to span about 90-100 kb.
D. Genomic Sequence Analysis
All 25 exons, splice junctions, and portions of all 24 introns of the hRAD50 locus were sequenced. Primers for the genomic sequencing were designed from the cDNA sequence. The fragments used for primer design are presented in FIGS. 5A, 5B and 5C. The sequences of these fragments are provided herein as SEQ ID NO:52, SEQ ID NO:53 and SEQ ID NO:54, respectively. The regions used for design of upstream (5') primers are indicated in bold; regions used for design of downstream (3') primers are underlined.
The genomic sequence data are presented herein as SEQ ID NO:55-SEQ ID NO:114. Different SEQ ID NOs were assigned to each exon and each intron. Some introns were only sequenced at their ends, resulting in a "gap" in the central portion. These "gap-containing" introns are each represented by two SEQ ID NOs--one for the sequence at the 5' end and one for the sequence at the 3' end. The 5' and 3' ends of the genomic sequence were are presented herein as SEQ ID NO:55 and SEQ ID NO:114, respectively. The relationship of the SEQ ID NOs to the genomic structure is summarized in Table 3, below.
TABLE 3______________________________________Genomic Organization RAD50Exon # SEQ ID # #b.p. Intron # SEQ ID NOS. #b.p.______________________________________1 55, 56 >516 1 57 1,8292 58 84 2 59, 60 18,4073 61 152 3 52, 63 >1,8004 64 186 4 65 3595 66 205 5 67, 68 >6,9006 69 129 6 70 2337 71 166 7 72 5978 73 194 8 79 7509 75 207 9 76 1,38610 77 183 10 78 47011 79 158 11 80, 81 >2,40012 82 176 12 83 53513 84 238 13 85, 86 >58014 87 190 14 88 43015 89 121 15 90, 91 74116 92 194 16 93, 94 3,61617 95 111 17 96 39118 97 93 18 98 7319 99 114 19 109, 101 6,60620 102 128 20 103 1,93921 104 225 21 105, 106 18,81522 107 86 22 108, 109 88023 110 143 23 111 2,44824 112 134 24 113 1,37125 114, 115 1,730______________________________________
E. hRAD50 expression
hRAD50 expression was assessed by Northern blotting of mRNA prepared from various human tissues using A1 .sup.32 P-labelled probe, generated by PCR with the primers G10-N (SEQ ID NO:171)/G10-C1 (SEQ ID NO:172) on the G10 hRAD50 cDNA as a template (SEQ ID NO:44). A Northern blot filter was prepared with 1.5 .mu.g of polyA+ RNA from various human tissues (Clontech, Palo Alto, Calif.). The results are shown in FIG. 6. The positions of RNA size standards are indicated. .beta.-actin hybridization was included to control for mRNA abundance Lanes: 1, spleen; 2, thymus; 3, prostate; 4, testis; 5, ovary; 6, small intestine; 7, colon; 8, peripheral blood leukocytes.
The 5.5 kb hRAD50 transcript is seen in the testis, but is barely detectable in the other tissues examined. A faintly hybridizing band is also seen at 7 kb. The origin of this signal has not been established. Since a single protein species is observed with hRad50 antiserum (FIG. 6), the 7 kb band most likely corresponds to alternative 3' end processing of the hRAD50 transcript. Support for this explanation comes from the structure of the A106 cDNA which contains evidence of alternative 3' end processing. Increased expression of hRAD50 in the testis is reminiscent of the hMRE11 expression pattern, as well as that of another mammalian RAD52 epistasis group member, RAD51 (Petrini, et al., 1995; Shinohara, et al., 1993). hRAD50 transcripts were also detected in fetal liver and in activated T- and B-cells by RT-PCR.
A non-coding 3'-flanking portion of the gene, when used as a probe, detected mRNA species of 1.9 and 0.85 kb in multiple tissues. This may indicate either unusual alternative splicing of the RAD50 gene or an overlap with another gene.
The above results confirm that hRAD50 is expressed in activated T-cells, B-cells, total embryo, fetal muscle, fetal liver, placenta, adult heart, and adult bone marrow.
EXAMPLE 8
Association of hRad50 with hMre11--Immunoprecipitation Analyses
It is recognized that S. cerevisiae Mre11 interacts with both ScRad50 and ScXrs2 in a two hybrid system (Johzhuka and ogawa, 1995). Experiments were performed to determine whether an analogous complex involving hMrell and hRad50 exists in human cells. hMrell antiserum or hRad50 antiserum was used to immunoprecipitate whole cell extracts of the human lymphoblastoid cell line, TK6 (Liber and Thilly, 1982). Since nuclear staining was observed with hMre11 and hRad50 antisera, whole cell extracts were prepared in high salt (500 mM NaCl) to increase the yield of chromatin-associated nuclear proteins (Boubnov, et al., 1995). The extracts were then diluted to 300 mM NaCl for immunoprecipitation as described in Materials and Methods.
TK6 cells (2.5.times.10.sup.6 /lane) were lysed in High Salt buffer and diluted 1:2 in Standard Lysis Buffer. Following incubation with the indicated antisera, immunoprecipitation was carried out with Protein A-Sepharose beads and immunoprecipitated material was analyzed by immunoblotting with hRad50 antiserum or hMre11 antiserum as described above. The filters were then stripped and retreated with the converse antiserum--hMre11 (following hRad50) or hRad50 (following hMre11).
The results are shown in FIG. 7. The positions of protein molecular weight standards are indicated. Lanes 1/2 and 3/4 are the same filter; lanes 5/6 and 7/8 are the same filter. Immunoprecipitation with 204pre (lanes 1 and 3) or .alpha.hMre11 204/6 (lanes 2 and 4) was followed by immunodetection with .alpha.hmre11 204/6 (Lanes 1 and 2) or .alpha.hRad50 84 (Lanes 3 and 4). Immunoprecipitation with 84pre (lanes 6 and 8) or .alpha.hRad50 84 (lanes 5 and 7) was followed by immunodetection with ahRad50 84 (lanes 5 and 6) or .alpha.hMre11 204/6 (lanes 7 and 8).
A single 153 kD band, corresponding to the predicted size of the hRad50 protein was precipitated by the hRad50 antiserum but not by the pre-immune serum (FIG. 7, lanes 5 and 6). The hRad50 antiserum also recognized an identical 153 kD band in the material immunoprecipitated by hMre11 antiserum (FIG. 7, lane 4). Conversely, a single 81 kD band corresponding to the hMre11 protein 3 was precipitated by the hMre11 antiserum as well as the hRad50 antiserum (FIG. 7, lanes 2 and 7). Immunoblotting the precipitated material with pre-immune serum produced neither the 81 kD nor the 153 kD signals observed with the specific antisera.
Association of these proteins in 300 mM NaCl demonstrates that hRad50 and hMre11 are in stable association. To assess the stability of this complex in more detail, immunoprecipitations were carried out at NaCl concentrations ranging from 300 mM to 1000 mM, followed by immunoblotting with hMre11 and hRad50 antisera as above.
The results are shown in FIG. 8. K562 cells (2.5.times.10.sup.6 /lane) were lysed in High Salt Buffer as above and diluted 1:2 in Lysis Buffer with increasing NaCl. Following incubation with 204/3p antiserum (affinity purified .alpha.hMre11 serum), immunoprecipitation was carried out with Protein A-Sepharose beads and immunoprecipitated material was analyzed by immunoblotting with 204/3p. Filters were then stripped and retreated with 84 (a hRad50 serum). From left to right, NaCl concentrations were: 300 mM, 500 mM, 750 mM, 850 mM, and 1000 mM.
As can be appreciated from the figure, the amount of hMre11 protein immunoprecipitated at increasing salt concentrations was unchanged. Similarly, the relative abundance of coimmunoprecipitated hRad50 remained essentially constant until the NaCl concentration exceeded 750 mM, and was still detectable at 1000 mM NaCl. These data demonstrate that hRad50 and hMre11 are tightly associated in cultured cells.
In S. cerevisiae, ScMre11 is associated with ScRad50 as well as the 96 kD protein, ScXrs2 (Johzhuka and Ogawa, 1995). Having demonstrated the association of hRad50 and hMre11, immunoprecipitation experiments were carried out using metabolically-labeled cells to determine whether the hRad50/hMre11 complex was associated with a protein corresponding to hXrs2.
K562 cells (5.times.10.sup.6 /lane) were grown in the presence of [.sup.35 S]Methionine for 6 hours and lysed in High Salt Buffer. Immunoprecipitation was carried out as described in the Materials and Methods using 204/3p (affinity purified .alpha.hMre11 sera) or 204pre antiserum. Immunoprecipitated material was analyzed by SDS-PAGE on 8.5% gels. The gels were then dried and autoradiographed for 13 hours. As expected, bands of 81 kD and 153 kD, corresponding to hMre11 and hRad50, were immunoprecipitated by the hNre11 antiserum. However, three additional bands (95 kD, 210 kD and .about.350 kD) were also present in the immunoprecipitated material. These three proteins were not present in the control immunoprecipitation reaction, suggesting that hRad50 and three proteins of 95, 210, and 350 kD physically associate with hMre11. The detection of a 95 kD species in the immunoprecipitated material suggests that the human hRad50/hMre11 complex contains the human Xrs2 homologue.
EXAMPLE 9
Genetic Evidence for the Association of the hRAD50 with Myelogenous Leukemias
A. FISH Analysis
Fluorescence In Situ Hybridization (FISH) was performed as described by Rowley, et al., (1990), using an hRAD50 mixed probe, consisting of the cosmids 98F5, 192E2, and 256E1 (LANL chromosome 5-specific cosmid library) which span 80 kb of the C-terminal part of the gene, on chromosomes isolated from bone marrow cells, biopsy specimens or peripheral blood cells of patients who had previously been diagnosed with AML, MDS, t-MDS, t-AML, RA, or RAEB. These diagnoses were based on morphological and cytochemical studies of peripheral blood smears, bone marrow aspirates and biopsy specimens. The patients had also been previously characterized as having specific chromosome 5 deletions. The extent of the deletions, sex and ages of the patients, as well as the results of the FISH analyses are summarized in Table 4, below.
TABLE 4______________________________________Fluorescence In Situ Hybridization Analysisof Malignant Myeloid DisordersCharacterized by a del (5q) RAD50 Signal Age/ Chromosome Normal 5Pt. Sex DX Deletion Homolog del (5q)______________________________________1 53/F AML-M2 del (5) (q13q33) + -2 44/M t-MDS del (5) (q15q33) + -3 67/F MDS del (5) (q15q33) + -4 86/F MDS del (5) (q22q34) + -5 41/M t-MDS del (5) (q14q33) + -6 68/F t-AML del (5) (q23q33) + -7 45/M t-AML del (5) (q11q34) + -8 64/M RAEB del (5) (q15q33) + -9 79/M RA del (5) (q13q33or34) + -10 64/F RAEB del (5) (q13q33) + -______________________________________
The results demonstrate that individuals heterozygous for the indicated deletions were also heterozygous for the RAD50 signal, i.e., they were missing sequences capable of hybridizing to the RAD50 probe on the chromosome containing the indicated deletion. The results support the role of RAD50 as a tumor suppressor gene which can be used (i) to diagnose an individual as being at increased for a cancer, and (ii) to decrease the risk of cancer in an individual having insufficient normal RAD50 function.
B. DGGE Analyses
Denaturing gel electrophoresis (DGGE) analyses using primers capable of amplifying hRAD50 exons are performed on genomic DNA samples from the patients listed above. The analyses are performed using primer pairs selected from primers having SEQ ID NO:116-163, where each two consecutive primers in the series form a primer pair. For example, primers r1 (SEQ ID NO:116) and r2 (SEQ ID NO:117) are used as one primer pair. The amplification products are resolved on a "D GENE" denaturing gel electrophoresis system (BioRad) as described by Guldberg, et al.
Amplification products containing heteroduplexes are sequenced to determine the nature of the mismatch.
EXAMPLE 10
Generation of Human Cell Lines and Transgenic Mice Deficient for Wild-Type hRad50
Am hRAD50 construct suitable for generation of transformed embryonic stem (ES) cells is designed using the method of Ramirez-Solis, et al. A positive-negative selection strategy (Mansour, et al., 1988) in combination with the PPNT vector (Tybulewicz, et al., 1991), containing PGKneo and PGKtk, is used to obtain targeted disruption of RAD50 gene. Both genes in this vector are under the control of the housekeeping mouse phosphoglycerate kinase-1 promoter. This strategy enriches for homologous recombination events by simultaneously selecting for a neo gene within the homologous DNA and against an HSV-tk gene placed at the end of the targeting vector.
A. Isolation of N-terminal Fragment of hRad50
PCR is carried out in 100 .mu.l as described above, using hot start with "KLENTAQ1" (Ab Peptides, Inc., St. Louis, Mo.) and 50 ng of 854G6 YAC DNA as a template. The reaction is run on 1% agarose gel and a product of about 2.7 kb is excised from the gel, digested with NotI and XhoI, and ligated into NotI-XhoI linearized vector pPNT. Ligations and in vitro manipulations to generate PRAD50 are carried out according to Sambrook, et al.
A PCR fragment, generated with primers S1 (SEQ ID NO:174) and S2 (SEQ ID NO:175), encompasses 2.7 kb of the N-terminal region of the human RAD50 gene including the first and the second exons. This fragment is subcloned into the NotI and XhoI sites of PPNT.
A second C-terminal hRAD50 BamHI-EcoRI fragment (2.8 kb) of the cosmid 256E1 encompasses exon 24 and part of exon 25. This fragment is subcloned into BamHI-EcoRI sites of PPNT. The resulting plasmid (pRAD50-2) is linearized with restriction endonuclease NotI and used to electroporate ES cells as described below.
B. Transformation of Murine ES Cells
Linearized vector pRAD50-2 is used to electroporate the CCE line of ES cells (Robertson, et al., 1986) at passages 11-13, grown on STO feeder cells in Dulbecco's modified Eagle's medium supplemented with 10% fetal calf serum. To prepare cells for electroporation, confluent plates of ES cells are harvested by trypsinization, washed and resuspended in a buffer containing 20 mM HEPES (pH 7.0), 137 mM NaCl, 5 mM KCl, 0.7 mM Na.sub.2 HPO.sub.4, 6 mM dextrose, and 0.1 mM 2-mercaptoethanol at 10.sup.7 cells per ml. Twenty five .mu.g of the linearized pRAD50-2 plasmid are added to 0.9 ml of ES cell suspension, and the mixture is electroporated using the Bio-Rad Gene Pulser electroporator (Bio-Rad Laboratories, Hercules, Calif.) with a single discharge of 400 V at 25 .mu.F.
After electroporation the cells are incubated for 5 min at room temperature and plated on 10-cm tissue culture plate with feeder cells. G418 (neomycin, 300 .mu.g/ml) and gancyclovir (2 .mu.M) are applied 48 hr after the electroporation. The cells are re-fed when the media starts turning yellow, typically daily for first 5 days. In ten days after electroporation, individual colonies are typically ready to be selected. Selected clones are propagated and assayed by PCR and Southern blot analysis to determine whether homologous recombination took place.
C. Blastocyst Injection of Transformed ES Cells
ES cells from selected clones testing positive for homologous recombination are used for blastocyst injection. Ten to fifteen disintegrated ES cells from a selected clone are collected with a microinjection needle and injected into intercellular space of a C57bl/6J blastocysts at 3 days postcoitum as described in Hogan, et al., (1994).
Chimeras are typically born 17 days after transferring 5-10 recombinant blastocysts back into one uterine horn of a single foster mother. Remaining manipulations to generate chimeric mice and test the breeding, as well as genomic analyses are performed according to Ramirez-Solis, et al., (1993) and Hogan, et al., (1994).
D. In Vitro Differentiation of Transformed ES Cells
ES cell lines can differentiate in vitro to form a variety of cell types in a sequence that recapitulates the first stages of mouse embryogenesis. Upon withdrawal of leukemia inhibitory factor (LIF) from the media and stromal contact, ES cells form embryoid bodies (Ebs)--spherical aggregates of differentiated cell types which appear in a well-defined temporal pattern. Hematopoiesis within Ebs has been well documented, as well as vasculogenesis, myogenesis, and development of neuronal-like cells (Bain, et al., 1995; see review by Weiss and Orkin, 1996).
Gearing ES cells development into blood cells is facilitated by a "two-step" replating assay in which Ebs are disaggregated into single cells and replated into methylcellulose cultures containing various cytokines. Following this protocol, precursor cells give rise to pure hematopoietic colonies that can be enumerated and analyzed (Keller, et al., 1993). A similar approach can be undertaken to gear the ES differentiation into, e.g., myocytes or fibroblasts.
Both alleles of a single copy gene (e.g., RAD50) can be inactivated in ES cells using, e.g., the method of Mortensen, et al. In vitro differentiation of resultant homozygous mutant ES cells can complement and extend gene knockout experiments in animals. In vitro differentiation of murine ES cells generates relatively large numbers of early embryonic specific type cells and their immediate precursors which can be isolated and used for further study. For example, ES cells lacking any functional copies of RAD50 can be used in a method of screening agents for the ability to promote DNA breaks in a human cell line.
While the invention has been described with reference to specific methods and embodiments, it is appreciated that various modifications and changes may be made without departing from the invention.
__________________________________________________________________________# SEQUENCE LISTING- (1) GENERAL INFORMATION:- (iii) NUMBER OF SEQUENCES: 175- (2) INFORMATION FOR SEQ ID NO:1:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 22 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#oligonucleotide #4665 for adapter #3- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:1:# 22GAG TT- (2) INFORMATION FOR SEQ ID NO:2:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#oligonucleotide #4666 for adapter #3- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:2:# 20 GCTC- (2) INFORMATION FOR SEQ ID NO:3:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 23 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#oligonucleotide #A5-1 for adapter #5- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:3:# 23TGTG GTT- (2) INFORMATION FOR SEQ ID NO:4:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#oligonucleotide #A5-2 for adapter #5- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:4:#21 ACAC C- (2) INFORMATION FOR SEQ ID NO:5:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#oligo #AD3-2 for PCR amp of cDNAs- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:5:#21 TCCT C- (2) INFORMATION FOR SEQ ID NO:6:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 33 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#oligo #AD3-CUA for PCR amp of cDNAs- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:6:# 33 GAGA ATTCTGGATC CTC- (2) INFORMATION FOR SEQ ID NO:7:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#oligo #A5-2b for PCR amp of cDNAs- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:7:#21 ATCC A- (2) INFORMATION FOR SEQ ID NO:8:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#Primer GM-CSF-2DIVIDUAL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:8:#21 CAGC C- (2) INFORMATION FOR SEQ ID NO:9:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#Primer GM-CSF-1DIVIDUAL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:9:#21 TCAT C- (2) INFORMATION FOR SEQ ID NO:10:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#Primer IL3-1 INDIVIDUAL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:10:# 20 CCCA- (2) INFORMATION FOR SEQ ID NO:11:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#Primer IL3-2 INDIVIDUAL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:11:# 20 TGGA- (2) INFORMATION FOR SEQ ID NO:12:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 23 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#Primer IL4-3 INDIVIDUAL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:12:# 23GTGT TCT- (2) INFORMATION FOR SEQ ID NO:13:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#Primer IL4-4 INDIVIDUAL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:13:#21 TTCC C- (2) INFORMATION FOR SEQ ID NO:14:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 24 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#Primer IL5-1 INDIVIDUAL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:14:# 24AAGA AATC- (2) INFORMATION FOR SEQ ID NO:15:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#Primer IL4-2 INDIVIDUAL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:15:#21 ACAC C- (2) INFORMATION FOR SEQ ID NO:16:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 22 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#Primer IL9-1 INDIVIDUAL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:16:# 22CTT AC- (2) INFORMATION FOR SEQ ID NO:17:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 22 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#Primer IL9-6 INDIVIDUAL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:17:# 22GTG GT- (2) INFORMATION FOR SEQ ID NO:18:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#Primer IL13-1INDIVIDUAL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:18:# 20 CCAC- (2) INFORMATION FOR SEQ ID NO:19:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#Primer IL13-5INDIVIDUAL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:19:# 20 CTCC- (2) INFORMATION FOR SEQ ID NO:20:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#Primer IRF1-7INDIVIDUAL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:20:# 20 TGTG- (2) INFORMATION FOR SEQ ID NO:21:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#Primer IRF1-8INDIVIDUAL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:21:# 20 TCGG- (2) INFORMATION FOR SEQ ID NO:22:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 23 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#Primer TCF7-3INDIVIDUAL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:22:# 23CAGT GCT- (2) INFORMATION FOR SEQ ID NO:23:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#Primer TCF7-4INDIVIDUAL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:23:# 20 AAGT- (2) INFORMATION FOR SEQ ID NO:24:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 22 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#Primer EGRI1-6NDIVIDUAL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:24:# 22TCC TA- (2) INFORMATION FOR SEQ ID NO:25:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#Primer EGRI1-7NDIVIDUAL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:25:#21 TGTA C- (2) INFORMATION FOR SEQ ID NO:26:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 24 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#Primer CD14-5INDIVIDUAL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:26:# 24CTGC GACC- (2) INFORMATION FOR SEQ ID NO:27:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#Primer CD14-6INDIVIDUAL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:27:#21 GAGC C- (2) INFORMATION FOR SEQ ID NO:28:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 22 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#Primer CDC25-3NDIVIDUAL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:28:# 22GGC TC- (2) INFORMATION FOR SEQ ID NO:29:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 22 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#Primer CDC25-5NDIVIDUAL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:29:# 22TGA CC- (2) INFORMATION FOR SEQ ID NO:30:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 25 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#Primer Sau3AI-2 for semiadapter #2- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:30:# 25 GAGC TCGCT- (2) INFORMATION FOR SEQ ID NO:31:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#Primer Sau3AI-3DIVIDUAL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:31:#21 CGAG C- (2) INFORMATION FOR SEQ ID NO:32:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 28 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#Primer Sau3AI S-1VIDUAL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:32:# 28 AGAG AGTAGTAG- (2) INFORMATION FOR SEQ ID NO:33:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 24 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#Primer Sau3AI S-2 for adapter #S-1/2- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:33:# 24TCAT CATC- (2) INFORMATION FOR SEQ ID NO:34:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 23 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#5'Biotin-YAC primer #1: PCR amp of YACs- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:34:# 23CGGC CGC- (2) INFORMATION FOR SEQ ID NO:35:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 26 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#5'Biotin-YAC primer #2: PCR amp of YACs- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:35:# 26 ATCC TCGAGA- (2) INFORMATION FOR SEQ ID NO:36:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#Primer A106-1 for RAD50 ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:36:# 20 GCTC- (2) INFORMATION FOR SEQ ID NO:37:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#Primer A106-2 for RAD50 ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:37:# 20 GCTC- (2) INFORMATION FOR SEQ ID NO:38:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 38 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#Primer G10-C for RAD50L ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:38:# 38 ATGA ACATTGAATC CCAGGGAG- (2) INFORMATION FOR SEQ ID NO:39:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 39 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#Primer G10-N for RAD50L ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:39:# 39 GACT CCAGGTCCCT GGTGAGATT- (2) INFORMATION FOR SEQ ID NO:40:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 23 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#Primer G18-1 INDIVIDUAL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:40:# 23ACTT GCC- (2) INFORMATION FOR SEQ ID NO:41:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 22 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#Primer G18-2 INDIVIDUAL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:41:# 22AAC TG- (2) INFORMATION FOR SEQ ID NO:42:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#oligonucleotide #4578AL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:42:# 20 AGCT- (2) INFORMATION FOR SEQ ID NO:43:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 24 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#oligonucleotide #4579AL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:43:# 24GAGG ATCC- (2) INFORMATION FOR SEQ ID NO:44:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 5893 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: unknown- (ii) MOLECULE TYPE: cDNA to mRNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#RAD50 cDNA SEQUENCE, CDS: 389 TO 4324- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:44:- CCAGGAGAGC GGCGTGGACG CGTGCGGGCC TAGAGGCCCA CGTGATCCGC AG - #GGCGGCCG 60- AGGCAGGAAG CTTGTGAGTG CGCGGTTGCG GGGTCGCATT GTGGCTACGG CT - #TTGCGTCC 120- CCGGCGGGCA GCCCCAGGCT GGTCCCCGCC TCCGCTCTCC CCACCGGCGG GG - #AAAGCAGC 180- TGGTGTGGGA GGAAAGGCTC CATCCCCCGC CCCCTCTCTC CCGCTGTTGG CT - #GGCAGGAT 240- CTTTTGGCAG TCCTGTGGCC TCGCTCCCCG CCCGGATCCT CCTGACCCTG AG - #ATTCGCGG 300- GTCTCACGTC CCGTGCACGC CTTGCTTCGG CCTCAGTTAA GCCTTTGTGG AC - #TCCAGGTC 360- CCTGGTGAGA TTAGAAACGT TTGCAAACAT GTCCCGGATC GAAAAGATGA GC - #ATTCTGGG 420- CGTGCGGAGT TTTGGAATAG AGGACAAAGA TAAGCAAATT ATCACTTTCT TC - #AGCCCCCT 480- TACAATTTTG GTTGGACCCA ATGGGGCGGG AAAGACGACC ATCATTGAAT GT - #CTAAAATA 540- TATTTGTACT GGAGATTTCC CTCCTGGAAC CAAAGGAAAT ACATTTGTAC AC - #GATCCCAA 600- GGTTGCTCAA GAAACAGATG TGAGAGCCCA GATTCGTCTG CAATTTCGTG AT - #GTCAATGG 660- AGAACTTATA GCTGTGCAAA GATCTATGGT GTGTACTCAG AAAAGCAAAA AG - #ACAGAATT 720- TAAAACTCTG GAAGGAGTCA TTACTAGAAC AAAGCATGGT GAAAAGGTCA GT - #CTGAGCTC 780- TAAGTGTGCA GAAATTGACC GAGAAATGAT CAGTTCTCTT GGGGTTTCCA AG - #GCTGTGCT 840- AAATAATGTC ATTTTCTGTC ATCAAGAAGA TTCTAATTGG CCTTTAAGTG AA - #GGAAAGGC 900- TTTGAAGCAA AAGTTTGATG AGATTTTTTC AGCAACAAGA TACATTAAAG CC - #TTAGAAAC 960- ACTTCGGCAG GTACGTCAGA CACAAGGTCA GAAAGTAAAA GAATATCAAA TG - #GAACTAAA1020- ATATCTGAAG CAATATAAGG AAAAAGCTTG TGAGATTCGT GATCAGATTA CA - #AGTAAGGA1080- AGCCCAGTTA ACATCTTCAA AGGAAATTGT CAAATCCTAT GAGAATGAAC TT - #GATCCATT1140- GAAGAATCGT CTAAAAGAAA TTGAACATAA TCTCTCTAAA ATAATGAAAC TT - #GACAATGA1200- AATTAAAGCC TTGGATAGCC GAAAGAAGCA AATGGAGAAA GATAATAGTG AA - #CTGGAAGA1260- GAAAATGGAA AAGGTTTTTC AAGGGACTGA TGAGCAACTA AATGACTTAT AT - #CACAATCA1320- CCAGAGAACA GTAAGGGAGA AAGAAAGGAA ATTGGTAGAC TGTCATCGTG AA - #CTGGAAAA1380- ACTAAATAAA GAATCTAGGC TTCTCAATCA GGAAAAATCA GAACTGCTTG TT - #GAACAGGG1440- TCGTCTACAG CTGCAAGCAG ATCGCCATCA AGAACATATC CGAGCTAGAG AT - #TCATTAAT1500- TCAGTCTTTG GCAACACAGC TAGAATTGGA TGGCTTTGAG CGTGGACCAT TC - #AGTGAAAG1560- ACAGATTAAA AATTTTCACA AACTTGTGAG AGAGAGACAA GAAGGGGAAG CA - #AAAACTGC1620- CAACCAACTG ATGAATGACT TTGCAGAAAA AGAGACTCTG AAACAAAAAC AG - #ATAGATGA1680- GATAAGAGAT AAGAAAACTG GACTGGGAAG AATAATTGAG TTAAAATCAG AA - #ATCCTAAG1740- TAAGAAGCAG AATGAGCTGA AAAATGTGAA GTATGAATTA CAGCAGTTGG AA - #GGATCTTC1800- AGACAGGATT CTTGAACTGG ACCAGGAGCT CATAAAAGCT GAACGTGAGT TA - #AGCAAGGC1860- TGAGAAAAAC AGCAATGTAG AAACCTTAAA AATGGAAGTA ATAAGTCTCC AA - #AATGAAAA1920- AGCAGACTTA GACAGGACCC TGCGTAAACT TGACCAGGAG ATGGAGCAGT TA - #AACCATCA1980- TACAACAACA CGTACCCAAA TGGAGATGCT GACCAAAGAC AAAGCTGACA AA - #GATGAACA2040- AATCAGAAAA ATAAAATCTA GGCACAGTGA TGAATTAACC TCACTGTTGG GA - #TATTTTCC2100- CAACAAAAAA CAGCTTGAAG ACTGGCTACA TAGTAAATCA AAAGAAATTA AT - #CAGACCAG2160- GGACAGACTT GCCAAATTGA ACAAGGAACT AGCTTCATCT GAGCAGAATA AA - #AATCATAT2220- AAATAATGAA CTAAAAAGAA AGGAAGAGCA GTTGTCCAGT TACGAAGACA AG - #CTGTTTGA2280- TGTTTGTGGT AGCCAGGATT TTGAAAGTGA TTTAGACAGG CTTAAAGAGG AA - #ATTGAAAA2340- ATCATCAAAA CAGCGAGCCA TGCTGGCTGG AGCCACAGCA GTTTACTCCC AG - #TTCATTAC2400- TCAGCTAACA GACGAAAACC AGTCATGTTG CCCCGTTTGT CAGAGAGTTT TT - #CAGACAGA2460- GGCTGAGTTA CAAGAAGTCA TCAGTGATTT GCAGTCTAAA CTGCGACTTG CT - #CCAGATAA2520- ACTCAAGTCA ACAGAATCAG AGCTAAAAAA AAAGGAAAAG CGGCGTGATG AA - #ATGCTGGG2580- ACTTGTGCCC ATGAGGCAAA GCATAATTGA TTTGAAGGAG AAGGAAATAC CA - #GAATTAAG2640- AAACAAACTG CAGAATGTCA ATAGAGACAT ACAGCGCCTA AAGAACGACA TA - #GAAGAACA2700- AGAAACACTC TTGGGTACAA TAATGCCTGA AGAAGAAAGT GCCAAAGTAT GC - #CTGACAGA2760- TGTTACAATT ATGGAGAGGT TCCAGATGGA ACTTAAAGAT GTTGAAAGAA AA - #ATTGCACA2820- ACAAGCAGCT AAGCTACAAG GAATAGACTT AGATCGAACT GTCCAACAAG TC - #AACCAGGA2880- GAAACAAGAG AAACAGCACA AGTTAGACAC AGTTTCTAGT AAGATTGAAT TG - #AATCGTAA2940- GCTTATACAG GACCAGCAGG AACAGATTCA ACATCTAAAA AGTACAACAA AT - #GAGCTAAA3000- ATCTGAGAAA CTTCAGATAT CCACTAATTT GCAACGTCGT CAGCAACTGG AG - #GAGCAGAC3060- TGTGGAATTA TCCACTGAAG TTCAGTCTTT GTACAGAGAG ATAAAGGATG CT - #AAAGAGCA3120- GGTAAGCCCT TTGGAAACAA CATTGGAAAA GTTCCAGCAA GAAAAAGAAG AA - #TTAATCAA3180- CAAAAAAAAT ACAAGCAACA AAATAGCACA GGATAAACTG AATGATATTA AA - #GAGAAGGT3240- TAAAAATATT CATGGCTATA TGAAAGACAT TGAGAATTAT ATTCAAGATG GG - #AAAGACGA3300- CTATAAGAAG CAAAAAGAAA CTGAACTTAA TAAAGTAATA GCTCAACTAA GT - #GAATGCGA3360- GAAACACAAA GAAAAGATAA ATGAAGATAT GAGACTCATG AGACAAGATA TT - #GATACACA3420- GAAGATACAA GAAAGGTGGC TACAAGATAA CCTTACTTTA AGAAAAAGAA AT - #GAGGAACT3480- AAAAGAAGTT GAAGAAGAAA GAAAACAACA TTTGAAGGAA ATGGGTCAAA TG - #CAGGTTTT3540- GCAAATGAAA AGTGAACATC AGAAGTTGGA AGAGAACATA GACAATATAA AA - #AGAAATCA3600- TAATTTGGCA TTAGGGCGAC AGAAAGGTTA TGAAGAAGAA ATTATTCATT TT - #AAGAAAGA3660- ACTTCGAGAA CCACAATTTC GGGATGCTGA GGAAAAGTAT AGAGAAATGA TG - #ATTGTTAT3720- GAGGACAACA GAACTTGTGA ACAAGGATCT GGATATTTAT TATAAGACTC TT - #GACCAAGC3780- AATAATGAAA TTTCACAGTA TGAAAATGGA AGAAATCAAT AAAATTATAC GT - #GACCTGTG3840- GCGAAGTACC TATCGTGGAC AAGATATTGA ATACATAGAA ATACGGTCTG AT - #GCCGATGA3900- AAATGTATCA GCTTCTGATA AAAGGCGGAA TTATAACTAC CGAGTGGTGA TG - #CTGAAGGG3960- AGACACAGCC TTGGATATGC GAGGACGATG CAGTGCTGGA CAAAAGGTAT TA - #GCCTCACT4020- CATCATTCGC CTGGCCCTGG CTGAAACGTT CTGCCTCAAC TGTGGCATCA TT - #GCCTTGGA4080- TGAGCCAACA ACAAATCTTG ACCGAGAAAA CATTGAATCT CTTGCACATG CT - #CTGGTTGA4140- GATAATAAAA AGTCGCTCAC AGCAGCGTAA CTTCCAGCTT CTGGTAATCA CT - #CATGATGA4200- AGATTTTGTG GAGCTTTTAG GACGTTCTGA ATATGTGGAG AAATTCTACA GG - #ATTAAAAA4260- GAACATCGAT CAGTGCTCAG AGATTGTGAA ATGCAGTGTT AGCTCCCTGG GA - #TTCAATGT4320- TCATTAAAAA TATCCAAGAT TTAAATGCCA TAGAAATGTA GGTCCTCAGA AA - #GTGTATAA4380- TAAGAAACTT ATTTCTCATA TCAACTTAGT CAATAAGAAA ATATATTCTT TC - #AAAGGAAC4440- ATTGTGTCTA GGATTTTGGA TGTTGAGAGG TTCTAAAATC ATGAAACTTG TT - #TCACTGAA4500- AATTGGACAG ATTGCCTGTT TCTGATTTGC TGCTCTTCAT CCCATTCCAG GC - #AGCCTCTG4560- TCAGGCCTTC AGGGTTCAGC AGTACAGCCG AGACTCGACT CTGTGCCTCC CT - #CCCCAGTG4620- CAAATGCATG CTTCTTCTCA AAGCACTGTT GAGAAGGAGA TAATTACTGC CT - #TGAAAATT4680- TATGGTTTTG GTATTTTTTT AAATCATAGT TAAATGTTAC CTCTGAATTT AC - #TTCCTTGC4740- ATGTGGTTTG AAAAACTGAG TATTAATATC TGAGGATGAC CAGAAATGGT GA - #GATGTATG4800- TTTGGCTCTG CTTTTAACTT TATAAATCCA GTGACCTCTC TCTCTGGGAC TT - #GGTTTCCC4860- CAACTAAAAT TTGAAGTAGT TGAATGGGGT CTCAAAGTTT GACAGGAACC TT - #AAGTAATC4920- ATCTAAGTCA GTACCCACCA CCTTCTTCTC CTACATATCC CTTCCAGATG GT - #CATCCAGA4980- CTCAGAGCTC TCTCTACAGA GAGGAAATTC TCCACTGTGC ACACCCACCT TT - #GGAAAGCT5040- CTGACCACTT GAGGCCTGAT CTGCCCATCG TGAAGAAGCC TGTAACACTC CT - #CTGCGTCT5100- ATCCTGTGTA GCATACTGGC TTCACCATCA ATCCTGATTC CTCTCTAAGT GG - #GCATTGCC5160- ATGTGGAAGG CAAGCCAGGC TCACTCACAG AGTCAAGGCC TGCTCCCTGT AG - #GGTCCAAC5220- CAGACCTGGA AGAACAGGCC TCTCCATTTG CTCTTCAGAT GCCACTTCTA AG - #AAAAGCCT5280- AATCACAGTT TTTCCTGGAA TTGCCAGCTG ACATCTTGAA TCCTTCCATT CC - #ACACAGAA5340- TGCAACCAAG TCACACGCTT TTGAATTATG CTTTGTAGAG TTTTGTCATT CA - #GAGTCAGC5400- CAGGACCATA CCGGGTCTTG ATTCAGTCAC ATGGCATGGT TTTGTGCCAT CT - #GTAGCTAT5460- AATGAGCATG TTTGCCTAGA CAGCTTTTCT CAACTGGGTC CAGAAGAGAA TT - #AAGCCCTA5520- AGGTCCTAAG GCATCTATCT GTGCTAGGTT AAATGGTTGG CCCCCAAAGA TA - #GACAGGTC5580- CTGATTTCTA GAACCCGTGA CTGTTACTTT ATACAGCAAA GGAAACTTTG CA - #GATGTGAT5640- TAAAGCTAAG GACCTTAAGA CAGAGTATCC TGGGGGTGGT GGTGGGGTGG GG - #GGGGGTCC5700- TAAATGTAAT CACGAGTAAG ATTAAGAGCA AATCAATTCT AGTCATATAT TA - #AACATCCA5760- CAATAACCAA GATATTTTTA TCCCAAGAAT GCAAGATTTC AGAAAATGAA AA - #ATCTGTTG5820- ATAAATCCAT CACTATAATA AAACCGAAGG TGAAAAAAAT TCTGAAAAAA AA - #AAAAAAAA5880# 5893- (2) INFORMATION FOR SEQ ID NO:45:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 472 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: cDNA to mRNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#G18.seq (C) INDIVIDUAL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:45:- GTGGAAGAAT GGTGAAATCA TTGATACTTT ACAACAAGTT TATGAGATCA AT - #GCCCCAAA 60- CAAATCAGCA GTTTACAAAT GGATAACTCA GTTTAAGAAG GGATGAGACG AT - #ATTAAAGA 120- TGAAGCCCAC AGTGACAGAC TGTTCACATC AATTTGTGAG GAAAAAAATC AT - #CTTCTTCA 180- TGCCCTAACT GAAGAAGATC AATGATTAAC AGCAGAAACA ATAGCCAACA CC - #ATAGACAC 240- CTCAATTGAT TCAGGTTACA CAATTCTGAC TGAAAAATTA AAGTTGAGTA AA - #CGTTCTAC 300- TTGATGGATG CCCAAATCAC TGCTTCCAGA TCAGCTGCAG ACAACAGCAG AA - #CTTCCTCA 360- ATAAGTGGGA TCAAGTTCCT AAAGCATTTC TTCAAAGAAT TGTAACAGGA GG - #TGATGGAA 420- TGTGGCTTTA CCAGTACAAT CTTCAATTTG GCAAGTCTGT CCCTGGTCTG AT - # 472- (2) INFORMATION FOR SEQ ID NO:46:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 371 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: cDNA to mRNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#G102.seq (C) INDIVIDUAL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:46:- GGGGGATCCA GCTCAGAAGC AGAGTGTCCA CGCCAGGGAA TAGTGTGGGG AT - #TCAGAGCC 60- TGATAATGAT GAGAAGGGGA CCCACCTGAG GGTTAAGTCG GCTAGGGGGA AG - #TCAGATCA 120- TAGAGTAGAG ACGGCATTCT TGCGAGAAGC CACCTGGTAT AAAGTATCAG AC - #CGAGAAGA 180- GTGACCCTCT CAGTGACACA GATCTGGGGA GATTCAGGTC AGAGTACAGT GG - #GCATCCCT 240- GCAAGAGGCC ACCTGGTATC AGAGAAGGGC GGGGAATGAG GACATGATCT AG - #CACCAGAA 300- GTCAAAGTGT ATACAGAATG GAAAAGCATC CCATGAGGGA GTCGGAATGA AG - #AGTCAAGA 360# 371- (2) INFORMATION FOR SEQ ID NO:47:- (i) SEQUENCE CHARACTERISTICS:#acids (A) LENGTH: 645 amino (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: protein- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#G18.pep (C) INDIVIDUAL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:47:- Met Ser Arg Ile Glu Lys Met Ser Ile Leu Gl - #y Val Arg Ser Phe Gly# 15- Ile Glu Asp Lys Asp Lys Gln Ile Ile Thr Ph - #e Phe Ser Pro Leu Thr# 30- Ile Leu Val Gly Pro Asn Gly Ala Gly Lys Th - #r Thr Ile Ile Glu Cys# 45- Leu Lys Tyr Ile Cys Thr Gly Asp Phe Pro Pr - #o Gly Thr Lys Gly Asn# 60- Thr Phe Val Asn Asp Pro Lys Val Ala Gln Gl - #u Thr Asp Val Arg Ala#80- Gln Ile Arg Leu Gln Phe Arg Asp Val Asn Gl - #y Glu Leu Ile Ala Val# 95- Gln Arg Ser Met Val Cys Thr Gln Lys Ser Ly - #s Lys Thr Glu Phe Lys# 110- Thr Leu Glu Gly Val Ile Thr Arg Thr Lys Hi - #s Gly Glu Lys Val Ser# 125- Leu Ser Ser Lys Cys Ala Glu Ile Asp Arg Gl - #u Met Ile Ser Ser Leu# 140- Gly Val Ser Lys Ala Val Leu Asn Asn Val Il - #e Phe Cys His Gln Glu145 1 - #50 1 - #55 1 -#60- Asp Ser Asn Trp Pro Leu Ser Glu Gly Lys Al - #a Leu Lys Gln Lys Phe# 175- Asp Glu Ile Phe Ser Ala Thr Arg Tyr Ile Ly - #s Ala Leu Glu Thr Leu# 190- Arg Gln Val Arg Gln Thr Gln Gly Gln Lys Va - #l Lys Glu Tyr Gln Met# 205- Glu Leu Lys Tyr Leu Lys Gln Tyr Lys Glu Ly - #s Ala Cys Glu Ile Arg# 220- Asp Gln Ile Thr Ser Lys Glu Ala Gln Leu Th - #r Ser Ser Lys Glu Ile225 2 - #30 2 - #35 2 -#40- Val Lys Ser Tyr Glu Asn Glu Leu Asp Pro Le - #u Lys Asn Arg Leu Lys# 255- Glu Ile Glu His Asn Leu Ser Lys Ile Met Ly - #s Leu Asp Asn Glu Ile# 270- Lys Ala Leu Asp Ser Arg Lys Lys Gln Met Gl - #u Lys Asp Asn Ser Glu# 285- Leu Glu Glu Lys Met Glu Lys Val Phe Gln Gl - #y Thr Asp Glu Gln Leu# 300- Asn Asp Leu Tyr His Asn His Gln Arg Thr Va - #l Arg Glu Lys Glu Arg305 3 - #10 3 - #15 3 -#20- Lys Leu Val Asp Cys His Arg Glu Leu Glu Ly - #s Leu Asn Lys Glu Ser# 335- Arg Leu Leu Asn Gln Glu Lys Ser Glu Leu Le - #u Val Glu Gln Gly Arg# 350- Leu Gln Leu Gln Ala Asp Arg His Gln Glu Hi - #s Ile Arg Ala Arg Asp# 365- Ser Leu Ile Gln Ser Leu Ala Thr Gln Leu Gl - #u Leu Asp Gly Phe Glu# 380- Arg Gly Pro Phe Ser Glu Arg Gln Ile Lys As - #n Phe His Lys Leu Val385 3 - #90 3 - #95 4 -#00- Arg Glu Arg Gln Glu Gly Glu Ala Lys Thr Al - #a Asn Gln Leu Met Asn# 415- Asp Phe Ala Glu Lys Glu Thr Leu Lys Gln Ly - #s Gln Ile Asp Glu Ile# 430- Arg Asp Lys Lys Thr Gly Leu Gly Arg Ile Il - #e Glu Leu Lys Ser Glu# 445- Ile Leu Ser Lys Lys Gln Asn Glu Leu Lys As - #n Val Lys Tyr Glu Leu# 460- Gln Gln Leu Glu Gly Ser Ser Asp Arg Ile Le - #u Glu Leu Asp Gln Glu465 4 - #70 4 - #75 4 -#80- Leu Ile Lys Ala Glu Arg Glu Leu Ser Lys Al - #a Glu Lys Asn Ser Asn# 495- Val Glu Thr Leu Lys Met Glu Val Ile Ser Le - #u Gln Asn Glu Lys Ala# 510- Asp Leu Asp Arg Thr Leu Arg Lys Leu Asp Gl - #n Glu Met Glu Gln Leu# 525- Asn His His Thr Thr Thr Arg Thr Gln Met Gl - #u Met Leu Thr Lys Asp# 540- Lys Ala Asp Lys Asp Glu Gln Ile Arg Lys Il - #e Lys Ser Arg His Ser545 5 - #50 5 - #55 5 -#60- Asp Glu Leu Thr Ser Leu Leu Gly Tyr Phe Pr - #o Asn Lys Lys Gln Leu# 575- Glu Asp Trp Leu His Ser Lys Ser Lys Glu Il - #e Asn Gln Thr Arg Asp# 590- Arg Leu Ala Lys Leu Lys Ile Val Leu Val Ly - #s Pro His Ser Ile Thr# 605- Ser Cys Tyr Asn Ser Leu Lys Lys Cys Phe Ar - #g Asn Leu Ile Pro Leu# 620- Ile Glu Glu Val Leu Leu Leu Ser Ala Ala As - #p Leu Glu Ala Val Ile625 6 - #30 6 - #35 6 -#40- Trp Ala Ser Ile Lys 645- (2) INFORMATION FOR SEQ ID NO:48:- (i) SEQUENCE CHARACTERISTICS:#acids (A) LENGTH: 527 amino (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: protein- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#G65.pep (C) INDIVIDUAL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:48:- Met Lys Leu Trp Val Ser Ala Leu Leu Met Al - #a Trp Phe Gly Val Leu# 15- Ser Cys Val Gln Ala Glu Phe Phe Thr Ser Il - #e Gly His Met Thr Asp# 30- Leu Ile Tyr Ala Glu Lys Glu Leu Val Gln Se - #r Leu Lys Glu Tyr Ile# 45- Leu Val Glu Glu Ala Lys Leu Ser Lys Ile Ly - #s Ser Trp Ala Asn Lys# 60- Met Glu Ala Leu Thr Ser Lys Ser Ala Ala As - #p Ala Glu Gly Tyr Leu#80- Ala His Pro Val Asn Ala Tyr Lys Leu Val Ly - #s Arg Leu Asn Thr Asp# 95- Trp Pro Ala Leu Glu Asp Leu Val Leu Gln As - #p Ser Ala Ala Gly Phe# 110- Ile Ala Asn Leu Ser Val Gln Arg Gln Phe Ph - #e Pro Thr Asp Glu Asp# 125- Glu Ile Gly Ala Ala Lys Ala Leu Met Arg Le - #u Gln Asp Thr Tyr Arg# 140- Leu Asp Pro Gly Thr Ile Ser Arg Gly Glu Le - #u Pro Gly Thr Lys Tyr145 1 - #50 1 - #55 1 -#60- Gln Ala Met Leu Ser Val Asp Asp Cys Phe Gl - #y Met Gly Arg Ser Ala# 175- Tyr Asn Glu Gly Asp Tyr Tyr His Thr Val Le - #u Trp Met Glu Gln Val# 190- Leu Lys Gln Leu Asp Ala Gly Glu Glu Ala Th - #r Thr Thr Lys Ser Gln# 205- Val Leu Asp Tyr Leu Ser Tyr Ala Val Phe Gl - #n Leu Gly Asp Leu His# 220- Arg Ala Leu Glu Leu Thr Arg Arg Leu Leu Se - #r Leu Asp Pro Ser His225 2 - #30 2 - #35 2 -#40- Glu Arg Ala Gly Gly Asn Leu Arg Tyr Phe Gl - #u Gln Leu Leu Glu Glu# 255- Glu Arg Glu Lys Thr Leu Thr Asn Gln Thr Gl - #u Ala Glu Leu Ala Thr# 270- Pro Glu Gly Ile Tyr Glu Arg Pro Val Asp Ty - #r Leu Pro Glu Arg Asp# 285- Val Tyr Glu Ser Leu Cys Arg Gly Glu Gly Va - #l Lys Leu Thr Pro Arg# 300- Arg Gln Lys Arg Leu Phe Cys Arg Tyr His Hi - #s Gly Asn Arg Ala Pro305 3 - #10 3 - #15 3 -#20- Gln Leu Leu Ile Ala Pro Phe Lys Glu Glu As - #p Glu Trp Asp Ser Pro# 335- His Ile Val Arg Tyr Tyr Asp Val Met Ser As - #p Glu Glu Ile Glu Arg# 350- Ile Lys Glu Ile Ala Lys Pro Lys Leu Ala Ar - #g Ala Thr Val Arg Asp# 365- Pro Lys Thr Gly Val Leu Thr Val Ala Ser Ty - #r Arg Val Ser Lys Ser# 380- Ser Trp Leu Glu Glu Asp Asp Asp Pro Val Va - #l Ala Arg Val Asn Arg385 3 - #90 3 - #95 4 -#00- Arg Met Gln His Ile Thr Gly Leu Thr Val Ly - #s Thr Ala Glu Leu Leu# 415- Gln Val Ala Asn Tyr Gly Val Gly Gly Gln Ty - #r Glu Pro His Phe Asp# 430- Phe Ser Arg Arg Pro Phe Asp Ser Gly Leu Pr - #o Thr Leu Gly Gln Arg# 445- Gly Ile Val Leu Ala Thr Phe Leu Asn Tyr Me - #t Ser Asp Val Glu Ala# 460- Gly Gly Ala Thr Val Phe Pro Asp Leu Gly Al - #a Ala Ile Trp Pro Lys465 4 - #70 4 - #75 4 -#80- Lys Gly Thr Lys Leu Cys Ser Gly Thr Thr Se - #r Cys Gly Ala Gly Lys# 495- Val Thr Thr Glu Gln Asp Met Leu Pro Ala Le - #u Cys Leu Trp Ala Ala# 510- Ser Gly Ser Pro Ile Ser Gly Ser Met Asn Gl - #u Asp Arg Ser Ser# 525- (2) INFORMATION FOR SEQ ID NO:49:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 727 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: cDNA to mRNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE: N-terminal fragmentDUAL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:49:- GTTGGTGTCA GCGGGCAACA GCCCACAGGA GTGTGCACCT CCTAGGACAG AG - #TTTGTCCT 60- CTCACTTCTG GAGAAGATGC AGACACAGGA GATCCTGAGG ATACTGCGAC TG - #CCTGAGCT 120- AGGTGACTTG GGACAGTTTT TCCGCAGCCT CTCGGCCACC ACCCTCGTGA GT - #ATGGGTGC 180- CCTGGCTGCC ATCCTTGCCT ACTGGTTCAC TCACCGGCCA AAGGCCTTGC AG - #CCGCCATG 240- CAACCTCCTG ATGCAGTCAG AAGAAGTAGA GGACAGTGGC GGGGCACGGC GA - #TCTGTGAT 300- TGGGTCTGGC CCTCAGCTAC TTACCCACTA CTATGATGAT GCCCGGACCA TG - #TACCAGGT 360- GTTCCGCCGT GGGCTTAGCA TCTCAGGGAA TGGGCCCTGT CTTGGTTTCA GG - #AAGCCTAA 420- GCAGCCTTAC CAGTGGCTGT CCTACCAGGA GGTGGCCGAC AGGGCTGAAT TT - #CTGGGGTC 480- CGGACTTCTC CAGCACAATT GTAAAGCATG CACTGATCAG TTTATTGGTG TT - #TTTGCACA 540- AAATCGGCCA GAGTGGATCA TTGTGGAGCT GGCCTGCTAC ACATATTCCA TG - #GTGGTGGT 600- CCCGCTCTAT GACACCCTGG GCCCTGGGGC TATCCGCTAC ATCATCAATA CA - #GCGGACAT 660- CAGCACCGTG ATTGTGGACA AACCTCAGAA GGCTGTGCTT CTGCTAGAGC AT - #GTGGAGAG 720# 727- (2) INFORMATION FOR SEQ ID NO:50:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 874 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: cDNA to mRNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE: C-terminal fragmentDUAL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:50:- GTGTGAGAGG ACCAAATGTG TTCAAAGGCT ACTTGAAAGA TCCAGACAGG AC - #GAAGGAGG 60- CCCTGGACAG CGATGGCTGG CTTCACACTG GAGACATCGG AAAATGGCTG CC - #GGCAGGAA 120- CTCTTAAAAT TATTGATCGG AAAAAGCATA TATTTAAACT TGCTCAGGGA GA - #ATATGTTG 180- CACCCGAGAA GATTGAGAAC ATCTACATCC GGAGCCAACC TGTGGCGCAA AT - #CTATGTCC 240- ATGGGGACAG CTTAAAGGCC TTTTTGGTAG GCATTGTTGT GCCTGACCCT GA - #AGTTATGC 300- CCTCCTGGGC CCAGAAGAGA GGAATTGAAG GAACATATGC AGATCTCTGC AC - #AAATAAGG 360- ATCTGAAGAA AGCCATTTTG GAAGATATGG TGAGGTTAGG AAAAGAAAGT GG - #ACTCCATT 420- CTTTTGAGCA GGTTAAAGCC ATTCACATCC ATTCTGACAT GTTCTCAGTT CA - #AAATGGCT 480- TGCTGACACC AACACTAAAA GCTAAGAGAC CTGAGCTGAG AGAGTACTTC AA - #AAAACAAA 540- TAGAAGAGCT TTACTCAATC TCCATGTGAA GTTCAAGGAA AGTTCTTCTC AG - #TGTAATGA 600- ACTGTCTAGC AATATTATAG TTATTCTTGA AAGTAATGAG TCAAAATGAC AC - #AGCTGAAA 660- ATGAATAAGC ATCTGATTTT ATGACTGAGC CTTTTCCTGT CCCAAGAGGT CT - #TTAACAAT 720- ATTTTCTCTA TCATCAATGA GTATATTTTA TTTTTATTAT AAAAATGATA TT - #GTGGTGGA 780- CTGCTAAAAA TATCACAAAT GGCAATGTAA AAATCAAGAC ATTTTCTCAA GA - #ACTGTGTA 840# 874 ATTG TCAATGTTCA CAGG- (2) INFORMATION FOR SEQ ID NO:51:- (i) SEQUENCE CHARACTERISTICS:#acids (A) LENGTH: 1312 amino (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: protein- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#TRANS. OF RAD50 cDNA (SEQ. 54), NT.#4324 389 TO- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:51:- Met Ser Arg Ile Glu Lys Met Ser Ile Leu Gl - #y Val Arg Ser Phe Gly# 15- Ile Glu Asp Lys Asp Lys Gln Ile Ile Thr Ph - #e Phe Ser Pro Leu Thr# 30- Ile Leu Val Gly Pro Asn Gly Ala Gly Lys Th - #r Thr Ile Ile Glu Cys# 45- Leu Lys Tyr Ile Cys Thr Gly Asp Phe Pro Pr - #o Gly Thr Lys Gly Asn# 60- Thr Phe Val His Asp Pro Lys Val Ala Gln Gl - #u Thr Asp Val Arg Ala#80- Gln Ile Arg Leu Gln Phe Arg Asp Val Asn Gl - #y Glu Leu Ile Ala Val# 95- Gln Arg Ser Met Val Cys Thr Gln Lys Ser Ly - #s Lys Thr Glu Phe Lys# 110- Thr Leu Glu Gly Val Ile Thr Arg Thr Lys Hi - #s Gly Glu Lys Val Ser# 125- Leu Ser Ser Lys Cys Ala Glu Ile Asp Arg Gl - #u Met Ile Ser Ser Leu# 140- Gly Val Ser Lys Ala Val Leu Asn Asn Val Il - #e Phe Cys His Gln Glu145 1 - #50 1 - #55 1 -#60- Asp Ser Asn Trp Pro Leu Ser Glu Gly Lys Al - #a Leu Lys Gln Lys Phe# 175- Asp Glu Ile Phe Ser Ala Thr Arg Tyr Ile Ly - #s Ala Leu Glu Thr Leu# 190- Arg Gln Val Arg Gln Thr Gln Gly Gln Lys Va - #l Lys Glu Tyr Gln Met# 205- Glu Leu Lys Tyr Leu Lys Gln Tyr Lys Glu Ly - #s Ala Cys Glu Ile Arg# 220- Asp Gln Ile Thr Ser Lys Glu Ala Gln Leu Th - #r Ser Ser Lys Glu Ile225 2 - #30 2 - #35 2 -#40- Val Lys Ser Tyr Glu Asn Glu Leu Asp Pro Le - #u Lys Asn Arg Leu Lys# 255- Glu Ile Glu His Asn Leu Ser Lys Ile Met Ly - #s Leu Asp Asn Glu Ile# 270- Lys Ala Leu Asp Ser Arg Lys Lys Gln Met Gl - #u Lys Asp Asn Ser Glu# 285- Leu Glu Glu Lys Met Glu Lys Val Phe Gln Gl - #y Thr Asp Glu Gln Leu# 300- Asn Asp Leu Tyr His Asn His Gln Arg Thr Va - #l Arg Glu Lys Glu Arg305 3 - #10 3 - #15 3 -#20- Lys Leu Val Asp Cys His Arg Glu Leu Glu Ly - #s Leu Asn Lys Glu Ser# 335- Arg Leu Leu Asn Gln Glu Lys Ser Glu Leu Le - #u Val Glu Gln Gly Arg# 350- Leu Gln Leu Gln Ala Asp Arg His Gln Glu Hi - #s Ile Arg Ala Arg Asp# 365- Ser Leu Ile Gln Ser Leu Ala Thr Gln Leu Gl - #u Leu Asp Gly Phe Glu# 380- Arg Gly Pro Phe Ser Glu Arg Gln Ile Lys As - #n Phe His Lys Leu Val385 3 - #90 3 - #95 4 -#00- Arg Glu Arg Gln Glu Gly Glu Ala Lys Thr Al - #a Asn Gln Leu Met Asn# 415- Asp Phe Ala Glu Lys Glu Thr Leu Lys Gln Ly - #s Gln Ile Asp Glu Ile# 430- Arg Asp Lys Lys Thr Gly Leu Gly Arg Ile Il - #e Glu Leu Lys Ser Glu# 445- Ile Leu Ser Lys Lys Gln Asn Glu Leu Lys As - #n Val Lys Tyr Glu Leu# 460- Gln Gln Leu Glu Gly Ser Ser Asp Arg Ile Le - #u Glu Leu Asp Gln Glu465 4 - #70 4 - #75 4 -#80- Leu Ile Lys Ala Glu Arg Glu Leu Ser Lys Al - #a Glu Lys Asn Ser Asn# 495- Val Glu Thr Leu Lys Met Glu Val Ile Ser Le - #u Gln Asn Glu Lys Ala# 510- Asp Leu Asp Arg Thr Leu Arg Lys Leu Asp Gl - #n Glu Met Glu Gln Leu# 525- Asn His His Thr Thr Thr Arg Thr Gln Met Gl - #u Met Leu Thr Lys Asp# 540- Lys Ala Asp Lys Asp Glu Gln Ile Arg Lys Il - #e Lys Ser Arg His Ser545 5 - #50 5 - #55 5 -#60- Asp Glu Leu Thr Ser Leu Leu Gly Tyr Phe Pr - #o Asn Lys Lys Gln Leu# 575- Glu Asp Trp Leu His Ser Lys Ser Lys Glu Il - #e Asn Gln Thr Arg Asp# 590- Arg Leu Ala Lys Leu Asn Lys Glu Leu Ala Se - #r Ser Glu Gln Asn Lys# 605- Asn His Ile Asn Asn Glu Leu Lys Arg Lys Gl - #u Glu Gln Leu Ser Ser# 620- Tyr Glu Asp Lys Leu Phe Asp Val Cys Gly Se - #r Gln Asp Phe Glu Ser625 6 - #30 6 - #35 6 -#40- Asp Leu Asp Arg Leu Lys Glu Glu Ile Glu Ly - #s Ser Ser Lys Gln Arg# 655- Ala Met Leu Ala Gly Ala Thr Ala Val Tyr Se - #r Gln Phe Ile Thr Gln# 670- Leu Thr Asp Glu Asn Gln Ser Cys Cys Pro Va - #l Cys Gln Arg Val Phe# 685- Gln Thr Glu Ala Glu Leu Gln Glu Val Ile Se - #r Asp Leu Gln Ser Lys# 700- Leu Arg Leu Ala Pro Asp Lys Leu Lys Ser Th - #r Glu Ser Glu Leu Lys705 7 - #10 7 - #15 7 -#20- Lys Lys Glu Lys Arg Arg Asp Glu Met Leu Gl - #y Leu Val Pro Met Arg# 735- Gln Ser Ile Ile Asp Leu Lys Glu Lys Glu Il - #e Pro Glu Leu Arg Asn# 750- Lys Leu Gln Asn Val Asn Arg Asp Ile Gln Ar - #g Leu Lys Asn Asp Ile# 765- Glu Glu Gln Glu Thr Leu Leu Gly Thr Ile Me - #t Pro Glu Glu Glu Ser# 780- Ala Lys Val Cys Leu Thr Asp Val Thr Ile Me - #t Glu Arg Phe Gln Met785 7 - #90 7 - #95 8 -#00- Glu Leu Lys Asp Val Glu Arg Lys Ile Ala Gl - #n Gln Ala Ala Lys Leu# 815- Gln Gly Ile Asp Leu Asp Arg Thr Val Gln Gl - #n Val Asn Gln Glu Lys# 830- Gln Glu Lys Gln His Lys Leu Asp Thr Val Se - #r Ser Lys Ile Glu Leu# 845- Asn Arg Lys Leu Ile Gln Asp Gln Gln Glu Gl - #n Ile Gln His Leu Lys# 860- Ser Thr Thr Asn Glu Leu Lys Ser Glu Lys Le - #u Gln Ile Ser Thr Asn865 8 - #70 8 - #75 8 -#80- Leu Gln Arg Arg Gln Gln Leu Glu Glu Gln Th - #r Val Glu Leu Ser Thr# 895- Glu Val Gln Ser Leu Tyr Arg Glu Ile Lys As - #p Ala Lys Glu Gln Val# 910- Ser Pro Leu Glu Thr Thr Leu Glu Lys Phe Gl - #n Gln Glu Lys Glu Glu# 925- Leu Ile Asn Lys Lys Asn Thr Ser Asn Lys Il - #e Ala Gln Asp Lys Leu# 940- Asn Asp Ile Lys Glu Lys Val Lys Asn Ile Hi - #s Gly Tyr Met Lys Asp945 9 - #50 9 - #55 9 -#60- Ile Glu Asn Tyr Ile Gln Asp Gly Lys Asp As - #p Tyr Lys Lys Gln Lys# 975- Glu Thr Glu Leu Asn Lys Val Ile Ala Gln Le - #u Ser Glu Cys Glu Lys# 990- His Lys Glu Lys Ile Asn Glu Asp Met Arg Le - #u Met Arg Gln Asp Ile# 10050- Asp Thr Gln Lys Ile Gln Glu Arg Trp Leu Gl - #n Asp Asn Leu Thr Leu# 10205- Arg Lys Arg Asn Glu Glu Leu Lys Glu Val Gl - #u Glu Glu Arg Lys Gln# 10401030 - # 1035- His Leu Lys Glu Met Gly Gln Met Gln Val Le - #u Gln Met Lys Ser Glu# 10550- His Gln Lys Leu Glu Glu Asn Ile Asp Asn Il - #e Lys Arg Asn His Asn# 10705- Leu Ala Leu Gly Arg Gln Lys Gly Tyr Glu Gl - #u Glu Ile Ile His Phe# 10850- Lys Lys Glu Leu Arg Glu Pro Gln Phe Arg As - #p Ala Glu Glu Lys Tyr# 11005- Arg Glu Met Met Ile Val Met Arg Thr Thr Gl - #u Leu Val Asn Lys Asp# 11201110 - # 1115- Leu Asp Ile Tyr Tyr Lys Thr Leu Asp Gln Al - #a Ile Met Lys Phe His# 11350- Ser Met Lys Met Glu Glu Ile Asn Lys Ile Il - #e Arg Asp Leu Trp Arg# 11505- Ser Thr Tyr Arg Gly Gln Asp Ile Glu Tyr Il - #e Glu Ile Arg Ser Asp# 11650- Ala Asp Glu Asn Val Ser Ala Ser Asp Lys Ar - #g Arg Asn Tyr Asn Tyr# 11805- Arg Val Val Met Leu Lys Gly Asp Thr Ala Le - #u Asp Met Arg Gly Arg# 12001190 - # 1195- Cys Ser Ala Gly Gln Lys Val Leu Ala Ser Le - #u Ile Ile Arg Leu Ala# 12150- Leu Ala Glu Thr Phe Cys Leu Asn Cys Gly Il - #e Ile Ala Leu Asp Glu# 12305- Pro Thr Thr Asn Leu Asp Arg Glu Asn Ile Gl - #u Ser Leu Ala His Ala# 12450- Leu Val Glu Ile Ile Lys Ser Arg Ser Gln Gl - #n Arg Asn Phe Gln Leu# 12605- Leu Val Ile Thr His Asp Glu Asp Phe Val Gl - #u Leu Leu Gly Arg Ser# 12801270 - # 1275- Glu Tyr Val Glu Lys Phe Tyr Arg Ile Lys Ly - #s Asn Ile Asp Gln Cys# 12950- Ser Glu Ile Val Lys Cys Ser Val Ser Ser Le - #u Gly Phe Asn Val His# 13105- (2) INFORMATION FOR SEQ ID NO:52:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 86 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: cDNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#RAD50-2 (C) INDIVIDUAL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:52:- AGCAATAATG AAATTTCACA GTATGAAAAT GGAAGAAATC AATAAAATTA TA - #CGTGACCT 60# 86 CGTG GACAAG- (2) INFORMATION FOR SEQ ID NO:53:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 1243 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: cDNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#RAD50-4 (C) INDIVIDUAL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:53:- CAAGGAACTA GCTTCATCTG AGCAGAATAA AAATCATATA AATAATGAAC TA - #AAAAGAAG 60- GGAAGAGCAG TTGTCCAGTT ACGAAGACAA GCTGTTTGAT GTTTGTGGTA GC - #CAGGATTT 120- TGAAAGTGAT TTAGACAGGC TTAAAGAGGA AATTGAAAAA TCATCAAAAC AG - #CGAGCCAT 180- GCTGGCTGGA GCCACAGCAG TTTACTCCCA GTTCATTACT CAGCTAACAG AC - #GAAAACCA 240- GTCATGTTGC CCCGTTTGTC AGAGAGTTTT TCAGACAGAG GCTGAGTTAC AA - #GAAGTCAT 300- CAGTGATTTG CAGTCTAAAC TGCGACTTGC TCCAGATAAA CTCAAGTCAA CA - #GAATCAGA 360- GCTAAAAAAA AAGGAAAAGC GGCGTGATGA AATGCTGGGA CTTGTGCCCA TG - #AGGCAAAG 420- CATAATTGAT TTGAAGGAGA AGGAAATACC AGAATTAAGA AACAAACTGC AG - #AATGTCAA 480- TAGAGACATA CAGCGCCTAA AGAACGACAT AGAAGAACAA GAAACACTCT TG - #GGTACAAT 540- AATGCCTGAA GAAGAAAGTG CCAAAGTATG CCTGACAGAT GTTACAATTA TG - #GAGAGGTT 600- CCAGATGGAA CTTAAAGATG TTGAAAGAAA AATTGCACAA CAAGCAGCTA AG - #CTACAAGG 660- AATAGACTTA GATCGAACTG TCCAACAAGT CAACCAGGAG AAACAAGAGA AA - #CAGCACAA 720- GTTAGACACA GTTTCTAGTA AGATTGAATT GAATCGTAAG CTTATACAGG AC - #CAGCAGGA 780- ACAGATTCAA CATCTAAAAA GTACAACAAA TGAGCTAAAA TCTGAGAAAC TT - #CAGATATC 840- CACTAATTTG CAACGTCGTC AGCAACTGGA GGAGCAGACT GTGGAATTAT CC - #ACTGAAGT 900- TCAGTCTTTG TACAGAGAGA TAAAGGATGC TAAAGAGCAG GTAAGCCCTT TG - #GAAACAAC 960- ATTGGAAAAG TTCCAGCAAG AAAAAGAAGA ATTAATCAAC AAAAAAAATA CA - #AGCAACAA1020- AATAGCACAG GATAAACTGA ATGATATTAA AGAGAAGGTT AAAAATATTC AT - #GGCTATAT1080- GAAAGACATT GAGAATTATA TTCAAGATGG GAAAGACGAC TATAAGAAGC AA - #AAAGAAAC1140- TGAACTTAAT AAAGTAATAG CTCAACTAAG TGAATGCGAG AAACACAAAG AA - #AAGATAAA1200# 124 - #3CAAGATAT TGATACACAG AAG- (2) INFORMATION FOR SEQ ID NO:54:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 543 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: cDNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#RAD50-3 (C) INDIVIDUAL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:54:- GTTGCTCAAG AAACAGATGT GAGAGCCCAG ATTCGTCTGC AATTTCGTGA TG - #TCAATGGA 60- GAACTTATAG CTGTGCAAAG ATCTATGGTG TGTACTCAGA AAAGCAAAAA GA - #CAGAATTT 120- AAAACTCTGG AAGGAGTCAT TACTAGAACA AAGCATGGTG AAAAGGTCAG TC - #TGAGCTCT 180- AAGTGTGCAG AAATTGACCG AGAAATGATC AGTTCTCTTG GGGTTTCCAA GG - #CTGTGCTA 240- AATAATGTCA TTTTCTGTCA TCAAGAAGAT TCTAATTGGC CTTTAAGTGA AG - #GAAAGGCT 300- TTGAAGCAAA AGTTTGATGA GATTTTTTCA GCAACAAGAT ACATTAAAGC CT - #TAGAAACA 360- CTTCGGCAGG TACGTCAGAC ACAAGGTCAG AAAGTAAAAG AATATCAAAT GG - #AACTAAAA 420- TATCTGAAGC AATATAAGGA AAAAGCTTGT GAGATTCGTG ATCAGATTAC AA - #GTAAGGAA 480- GCCCAGTTAA CATCTTCAAA GGAAATTGTC AAATCCTATG AGAATGAACT TG - #ATCCATTG 540# 543- (2) INFORMATION FOR SEQ ID NO:55:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 2886 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA (genomic)- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#5' END OF RAD50 GENOMIC SEQUENCE- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:55:- ATTATGCTTC AATAAATCTG ACTTAAAAAA TGGTCTTGGC CAGGCGCAGT GG - #CTCACACC 60- TGTAATCCCA GCACTTTGGG AGGCCGAGGC GGGTGGATCA CAAGGTTAGG AG - #TTCGAGAC 120- CAGCTTGACC AACATGGTGA AACCCCGTCT CTACTAAAAA TACAAAAAAT TA - #GCCAGGTG 180- TGGTGCCACG TGCCTGTAAT CCCAGCTACT CAGGAGGCTG AGGCAGAAGA AT - #CACTTGAA 240- CGCGGGAGAT GGAGGTTGCA GTGAGCCAAG ATCGCACCAT TGCACTCCAG TC - #TGGGTGAC 300- AGAGTGAGAC TCCATCTCAA AAAAAAAAAA AAAAAAAGTC TCCACTTGAA TA - #GTCAATTA 360- TTCAAAGATA CACAAATGGC CAATAAACAC ATGAAATGAT GCTACTAATA AT - #TATTGAAA 420- TGCAAATCAA AATTACAATG AGGTATCACT TCACACTCAT CAGGATGGCT AC - #CATAAAAA 480- AACATAAAAT AACAAGTGTT GGCAAGCATA TGTAGAAATT GAAACCCTTA TG - #CACTATTG 540- GTGGGAATGT CAAATGGTAC AACCACTGTG GAAAACAGTA TGGCAGTTCC TC - #AAATAATT 600- AAAAATTGAA TTACTGTATG ATCTAATAAT TCCACTTCTG GGTATATACC CA - #AAAGAATT 660- GAAAGCAGGG TCCAGAAGTG ACATTTGTAC ACCAATATAT ATAGCCACAC TA - #TTCACAAT 720- AGCTAAAATG TGAAAGTAAC CCAAATGTCC ATCAATAGAT GGATAAGCAA AA - #TGTGATGT 780- GTATTGTAAT GAATCTTATT CAACCTTAAA AACGACCTGA ATTCTGATAT AT - #GCTACAGT 840- GGTCCCCAAC CTTTTTGGCA CCAGGGACCA GTCTCACGGA AGACAGTTTT TC - #CACAGACA 900- GGAGTGGGGT GATGGTTTTG GGATGAAACT GTTCGACCTC ACATCATCAG GC - #ATTAGATT 960- CTCATAAGGA ATGGGCAAGC TAGATCCCTT GCATGGGGCA ACCTACATCT TT - #CTCATGGG1020- CAGTTCAAAA TACGGTTTGT GCTCCTATGA GAATCTAATG CCCCCACTGA TC - #TGAGGCCC1080- AGCTCGGGTG GTAATGTTCA CTCACCTGCT GCTCACCTCC TACTGTGCCA CC - #AGGTTCCT1140- AACAGGCCAG GTATGCATAC TGGTCAGTGA CCCAGGGGTT GGGGACTGAG CT - #GCAACATG1200- GATGAACCTT GAGGACATTA TAAGTGAAAT GAGCCAGTCA CAAAAAGATA AA - #TACTGTAT1260- GATTCCACTT ATATGAGGTA CTTAGTAAAA AATTATAGAG ACAGTAAGTA GA - #ATGTTGGT1320- TGTCAGGGTT TGGAGGATGT GGGGAGGAAA GGGTTATTGT TTAATGGGTA GT - #TTGTTTTG1380- CAAAGTGAAA AGATTTGTAG AGGTTGAAAG GTGGTGACGG TTGTACGTGA GT - #ATACTTAA1440- CACCACTGAA ATGTACACTT GGTTAAGATA GTAAATTCTT TTTGAGACGG AG - #TCTCGCTC1500- TGTTGCCCAG GCTGGAGTGC AGTGGTGCGG TCTCGGCTCA CTGCAAGCTC CG - #CCTCCCGG1560- GTTCATGCCA TACTCCTGCC TCAGCCTCCT GAGTAGCTGG GACCATCGGC GC - #CTGCCACC1620- ATGCCCGGCT AATTTTTTGT GTTTTCAGTA GAGACGGGGT TTCACCGTGT TA - #GCCAGGAT1680- GGTCTTGATT TCCTGACCTC GTGATCCACC CGTCTCGGCC TCCCAAAGTG CT - #GGGATTAC1740- AGGCGTGAGC CACCGCGCCT GGCCAAGACA GTAAATTTTA TGTGTATTTT AC - #AATTTTTA1800- AAATAAAAAA AGGTCTTTCG TCTTTTCCCA TTGTTTTATT ACATTTGCTT TG - #CCAAGTAA1860- GACATTCCTA TATAATTTTA ATGTTTTGTT CCATTAGTTA TTTTAACTAT TT - #TGTAATAA1920- CTGACACTTT CCGGTTTTTT TAACCTGGTA CAGCAAGAGA CTATTTCTCA CT - #GGTCTTCC1980- CCACTTGCAT CCTTTGGCAC ATACATTTAT GTATTAGGTT CTGTAAATTA TT - #TGCTTGGG2040- ATTGTATGAC TGGAGAAACA TTTCCTACAT TTTTCCAAGG CAGGCAGAGG CA - #AATTATAC2100- CACTACAGTA ATTCCAAATT TGTGTTTCAT TTAAATGTCC TCCACTATTG TT - #TCAGTAAT2160- TTTTATGTAT GTTTCTCTAG GCCCTTAAAT GTGATATCCC TCCATTAAGT TT - #GTTTCCAA2220- GAAAGCAATA TTCTCAGTTA CTTCTGAGAC AGGTAACTTC TCTTTCCCTT AT - #TTTTAAAG2280- ATATCTATTG CTGGGAGCAC TGATCGGAAT GGATTACCTC TACATTCTTC AT - #ATTTGCAG2340- ACTGCTTTTA GTTTTAGTTC CCAGACTTTT GGTCTTAAAG ACGCCTTTAC AC - #TAAAAAAT2400- TACGGGGGAC CTCAAAGAGC GTGTACGTGA GTTATAATTA TCAACATTTA CT - #CAATTAGA2460- AATTAAAATT GGTATTTCTA AGCGCAAGAA TACACATGCG CACATTCCAT TA - #ACCGCCAC2520- TGCAATGGCG TCATCACATG TTATGTGATC ACTGGAAATT ACTACACGAA CG - #TTAGAGAG2580- AGAATGAGAA TGAAAAGGAA AATAGTTTTG ACATGAACTG ACCCCGCTTC CT - #GGGTCTCC2640- AATCCACCCC ACCACTACCC CCATTCCAGG AGTCCCAGGA TCAAGCTTTG GG - #AAGCGCCA2700- TCCGTCACAG GTCTTGGTCT CCCCTTCCAA AAGTCAGTGC CTCTCCAGGC TG - #CCCATCCC2760- CAGCAAAGAT CCGGAAGTCC GCTGCCCCTG GCAACAGCAC CCAGCACCTA GC - #CCTCTGCT2820- TCGCCGTACC GCACCCGGAA GTCGGAGCTG CGCACGCACC GCGGGACTCT GA - #TTTCCCGG2880# 2886- (2) INFORMATION FOR SEQ ID NO:56:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 516 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA (genomic)- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#EXON 1 OF RAD50 GENOMIC SEQUENCE- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:56:- CCAGGAGAGC GGCGTGGACG CGTGCGGGCC TAGAGGCCCA CGTGATCCGC AG - #GGCGGCCG 60- AGGCAGGAAG CTGTGAGTGC GCGGTTGCGG GGTCGCATTG TGGCTACGGC TT - #TGCGTCCC 120- CGGCGGGCAG CCCCAGGCTG GTCCCCGCCT CCGCTCTCCC CACCGGCGGG GA - #AAGCAGCT 180- GGTGTGGGAG GAAAGGCTCC ATCCCCCGCC CCCTCTCTCC CGCTGTTGGC TG - #GCAGGATC 240- TTTTGGCAGT CCTGTGGCCT CGCTCCCCGC CCGGATCCTC CTGACCCTGA GA - #TTCGCGGG 300- TCTCACGTCC CGTGCACGCC TTGCTTCGGC CTCAGTTAAG CCTTTGTGGA CT - #CCAGGTCC 360- CTGGTGAGAT TAGAAACGTT TGCAAACATG TCCCGGATCG AAAAGATGAG CA - #TTCTGGGC 420- GTGCGGAGTT TTGGAATAGA GGACAAAGAT AAGCAAATTA TCACTTTCTT CA - #GCCCCCTT 480# 516 CCAA TGGGGCGGGA AAGACG- (2) INFORMATION FOR SEQ ID NO:57:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 1829 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA (genomic)- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#INTRON 1 OF RAD50 GENOMIC SEQUENCE- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:57:- GTAAGTCTTC AGTAGCCGCC TTCAGTTTAC AGGTCGCTAC ATCTTTCGGA GA - #ATAAAATG 60- GGAAGTTGAG AACTCTCCTT AGGAGCAGAA GCGTCCCTAG GGCTCCACAG GT - #GTAGGCCC 120- TTAAAGTGCC TTAGGGTGTG GCCTGCAGGC TACAGCGACC TTAGGAGTTT GC - #CTGAAGCA 180- GTCCCGGAAG GATGTCCGGA CCTGGCCTGG GGACAAGGTT TACTTAAGAA TC - #CCACGATA 240- CCGGGAGCTG TCGCCGCTCA CTCAGAGTTC AGTTCCCACT GGATGCCCTT TG - #GTCTGTAT 300- TGATGTTTTT AACGCTGTCT CCTTGCTTTC AAAGCATAGC ATTCACTTCC CA - #GTAGTTGT 360- CCCATACAAG AATTCCTTTA AAAGTTATAA AATGATACAT ACATGACTAA AG - #AGTTTCCA 420- AGTATGCCAA CTGTCCAGAC ATAATACATG GAAAATAAAT AAATTCAAAA TG - #TAACTGAT 480- GTAGTGGGGC TTAACTTGGA AAACTTCTCT TCTTAAAACT CAGTCAAAAA TT - #TAACGTTG 540- GTGCACGACT GACTTTTTTT TTTTTTTAAA GCCGTGGGAA TATTTATAAA TT - #TGAATGGA 600- AAGAATAACC AAGAGGCATT CTGGTCAGGA ATAGTGGCTT AAGAAAAAGC AA - #GACGATGT 660- CAGTATAGCA GGGAGAAGAG TCTAAAGGAA GGATTTGTGA AGAGTGTAGA AA - #GAGAGAAG 720- GTTGAGAATT GAATGCCAAA CTTGTTTACT TTTGTTTTTG TAAAAATGTT AT - #TTGTTGAA 780- TGCTTGTTAT GTACTTAGGA TTGTACTAAA TACTAGCAGA AGGGAGAGTA GT - #ACTGTATA 840- GTGTTTATGA GGACTGGCTG CCTCAATACA GCTTTTTCGC TTCATTTATT AG - #TTGTCTGA 900- TTGTTTGCGA GTGACCTCAC TGCTCTGTGC CTTAGTTTTC TCATTTATAA AA - #TGGAGATT 960- AAAAATAGTT TCTACAGCTG GGCACGGTGG CTCACGCCTG TAATCCCAGC AC - #TTTGGGAG1020- GCCGAGGCGG GTGGATCACC TGAGGTCAGG AGTTCGAGAC CAGCCTGGCC AA - #CGTGGCGA1080- AACCCCATCT CTAATAAAAA TACAAAAATT AGCCAGGCGT GGTGGCGCAT GC - #TGTAATCC1140- TAGCTACTGG GGAGGCCGAG GCGGGAGAAT CGCTTGAACC GGGGAGGTGG AG - #GTTGCAGT1200- GAGCCGAGAT CACGCCATTG CACTACACCA GCCTGGGTGA CAGAGGGAGA CT - #CTCTCCCC1260- CCACAAAAAA AAAAAAAAAA AAAAAAAAGT TTCTACAGGC TGGGCATGGT GG - #CTGACGAC1320- TGTAATCCGA GCCGTTTGGG AGGCTGAGGC TGGGGGATTG CTTGAGCCCA GG - #AGGTCGAG1380- AGGTCGAGGC TGCAGTAAGC CATGATCATG CAGCTGCACT GCAGCCTGGG CA - #GCAGAATG1440- AGACCCTGTC TCTTAAACAA AAAGTTCCTA CAGCCTGGAG TTAATGTGAG AA - #TTAAATAA1500- ATGTATGTAA GAGTGCTTAG TACAATACAG TACTTAACTG TTAGCCATTC TT - #ATTATTAA1560- CTTAAATTAG TTTAAAGGGT TTCAGTTGAA AATAATTATT TTTTTCCCAA GT - #AACAATTC1620- TTCATATTAG GATAACTTCT TAGTTATATA GCATTTCTGT GAACTTACAG CA - #TTAACACT1680- TAATCATATT TTTATTACAG GTTTTATAAT GTCAGATTTT ATCTTTTATA GT - #TTCCATGA1740- TAAATAATAT TTTTGTAATG AATTCATATT TTATGGTAAA CTTCTGTGGT TC - #TCTTATAA1800# 1829 TCTA TTTCTTTAG- (2) INFORMATION FOR SEQ ID NO:58:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 84 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA (genomic)- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#EXON 2 OF RAD50 GENOMIC SEQUENCE- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:58:- ACCATCATTG AATGTCTAAA ATATATTTGT ACTGGAGATT TCCCTCCTGG AA - #CCAAAGGA 60# 84ATCC CAAG- (2) INFORMATION FOR SEQ ID NO:59:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 14855 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA (genomic)- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#5' END OF INTRON 2 OF RAD50 GENOMIC SEQUENCE- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:59:- GTAATGGTGC TAGTACAATT TTGTATTTTT ATAATTATAA AAATGATAAT AG - #CTTATTAT 60- AGAAAACTTG GCACTGGAAA ACTATAAAGA GAAATGAAAG TCAGCCCCAC AC - #AGTTTTAG 120- CACCCAGTAG TAACCGTTGT TGACATTTTC ATGTGTTTTC CTCCTCCTTT AA - #ATACTGTT 180- TTATATAGCT GATGTCATAC TCTTAATTTT GTATTCTGGG TTTTTTTCCC CA - #CTTAACAT 240- TATCATGAAG TCCTATGTCA TTAAAAAACT ATCATCTGGG TGTTTGGTAT GT - #AAGTGTTT 300- CTTTTAATCT TTATACTGCT TTGTATGTCT GAGATATTTT CTACTTAAAG TG - #CATGAACA 360- CTTTAGTAGT TATGTAATTT TCTTACATTA GATTGCTTTC AGTTTTTCAT TA - #AAATGTAC 420- CATGATAAGC CAGGCTTGGG GGTGTGTGCC AATACTCCCA GATAGCTCTA GA - #GGCTGAGA 480- TGGGAGGATT GCTTCAGCCC AGGAGTTCAA GGCTAGCCTG GACAATATAG TG - #AGACCCAC 540- TGTCTAGAAA AAAAAGTATC ATGATAAAAA TCTTTGTGTA TGAATCATTG TT - #TGAATTAT 600- GGTGTTTATA CTATTCGTAT GTGTAAAGGA CATAGAATTT GGTCTATAGG TT - #TGTTTTTG 660- CACATATAGA AGTGAAACAA CAATACACAC ACACACACAC ACACACACAC AT - #ATATATAT 720- AGTTTATTCG TTTTTAGTGG GGTCATGTGC CTCTCTAGCC GCTCCCTGAC CC - #CAGTTCCA 780- CTATGTTTTC GTTACGTATT CTTCCAAGCT TTTTTCTGCT TATAAAACCA TG - #TCTACGTG 840- AGCACATAAA TGCATTCACA CATACATATT TTAGCACATT AATATAATTT TA - #TACTTCTA 900- TTTTATTGTT TTTAATTAGT AAATTGTATT CCATTGAGTT TATATCCTGT AG - #TTTATTAA 960- ATGACCCCCT GTTGATTATT ATTTGTTTCT ACCTTAGTGT GATTAAAGAT AA - #CTCTGTAA1020- TTATGAAAAT ATTTATGAAT TTTCCTCTTA GAAATGTAAT AGTATTTAGT AC - #ATTTACTG1080- AGTCCTCTCC ATAATGACTG TTTCCCACCT TCTCTCTCCT TAAATCTACA AT - #CTACTTTC1140- CTTAATTGAT GATCTTGCTT TGTACTTTAT TGAGAAATAG GAAGAATCAA AT - #GAGAATTC1200- CCTTATTTTC CAATCATCAC ATCTACGAAA CTACTGTACA TACGTGCCCA TA - #CTGTTTTT1260- TCTTGGATAA ATTATTTGTT GTTTTATCTA AACATGAACC AGCTCCTTGG AG - #GCTAGATC1320- TCATTGATCC CTCTTATCCA CCCAAGGATT TTGCCCTTCA GTTTTTCCAT CT - #CTCTCCTG1380- GATCAGCAGT TTCTCTTGAT GGATCATTCA CATCAGCATA TAAACATGCT CT - #GGTATCTC1440- TAGTCTTCAA ACAAAAAACT CTCCCTTTAC TCCAATTTAC CCTCTAGCCA TT - #ACCTTTTC1500- TCTGTTCCAA TATATTTCAA AATTCATAAG ATTTGTATGT CCTCATTGTC TT - #TACTTCAT1560- TGACTCCCAT TTTTCCCTCA ATCTACTCCA TTCAGGTTTT CTTTTTTTCC TC - #CACTAAAA1620- GTGCCTTTGT AAGGTCACCA ATAATCTCAA TGTGCCAGAT AGAGTGGTCA GT - #TTCTAATT1680- CTCATTAACA TCTTGTCAGA TTTGACACAG TTGGCTATTT CTTTTTTAAA AT - #ATATTTCC1740- TTCTTGGCTT TTGTGACACT ATAATCTCAT AGTTTCCTTC TTTCTCACTG GC - #TATACTTT1800- AGTCTTTGTT GGGTCTACCT TTGCTTGATT TCTTTTTTTT TATGAGACGG AG - #TCTTGCAC1860- TGTTGCCCAG GCTGGAGTGC AGTGTGGCAT GATCTTGGCT TACTGCAACC TC - #TGTCTCTC1920- AGGTTCAAGC TATTCTTGTG CCTTAGCCTC TTGAGTAGCT GGGATTACGG GT - #GTGCCACC1980- ACACCCAGCT AATTTTTGTA TTTTTAGCAG AGACGGGGTT TCATCATGTT GG - #CCAGGCTG2040- GTCTCAACCT CCTCACCTCA GGTGATCCAC CTGCCTCAGT CTCCCAAAGT GC - #TGGGATTA2100- CAGATGTGAG CCACTGCACC CAACCTGCTT GATTTCTAAA AGCCAGTGTG AC - #ACAAGAGT2160- TGGCCATCTT TGCATTAACC CTCTTCCCTA TCTCTCTTGG ATGAGCTTAT TC - #AGTCTAAC2220- GGCTTTAAGT ACTGGTTATG TGCTGGTAAC TACCACATTT ATATATTTGA CC - #CTGACTTC2280- TTTCCTTAAC TCTAGACATA TATGTCTAGC TGTTTGTTTG GATATTTAAT GG - #GCATCTCA2340- AATTTAACAT GTTCAAAACA GAACTCTTGA TTCCTTGTAC CCACTTCCTG CC - #TACATTCT2400- CAGCTCTGTT ACTACCTCAG TACCCCACCC CCGCCAGTTT TGTAAATGAT GT - #CATCATCC2460- CTACATAAGC AATTCTTACC TACCCTTCTA AAATATGTCA GAATTTGTCT AC - #TTCATTCC2520- ATCGGCCACT GTGTTCCTGT TCCAAGCCAC CATCATATTC CCTTTCAACT AT - #TAGAATCG2580- TCTCCTAACT TATTTTCCTG CCCTCATTCT TGAAGCTCTC TCTTTCTCAC AG - #AGTAATCA2640- GAGTTGTCTT TTAAATATTC ATTCAAGAGG GAATGAGTTG TTCAAAATCT GG - #GAAGAAAC2700- ATTTCATTCA GTCTAGTTGC AGAGTCCCTG AGCATGGTTG GTGTGTTCAA GG - #AATGACAA2760- GGAAGAACAA GGGAAAATGG TAGAAAATAA AGTTAGAAAG ATAGGAGAGA CT - #AGATCCTG2820- TAGGTCCTTG GATTCTAGTC TTATTTAAAT AGGAATCTGT CTATTGGGAG AT - #TTTGAGCA2880- GGGAAAGGAC ATGGTCTGAT TTATCTTTTA AAGTGCTCAG TCTGGTTGCT GA - #GAGAAGAC2940- TGTCCGTAGG TAGCAAAGAT AGGGCAGAGA CAAATTAAGA AGATTTTGTG AT - #GATCCAGG3000- TGAGAAATAT AGGTGGCTTC ATTAAGGTAG TGGTAGAATG GTGAGAAATG TT - #TGGATTTA3060- GGATGTATTT TGAAGATAGA ACCAACAAAT TAGCTAATGG TTTGGATAAT GG - #TGTATGAA3120- AGAAGTAAAA GCATCAAGCA TAACTCCAAA GTTTTTGGCT TGAACAACTG GA - #TAAAATAG3180- TTTTGTCATT TATTATAATA GGGGCACTAT GGAAAAAATA TTTGGGTGGA TC - #TGGTTTAA3240- ACATGCAAAT TAGGGATATG TGTTAAATAT CCAAAGGAGA TGTCCAGTTG GC - #AAGCAGAA3300- GTCTGTTCAG GAAAGAGATT AGGACTGGAG AAAGAAAATT AGGAATCATT AG - #TGTATACA3360- GGTAGTTCCA CATAGTTAAT TTTTAAAGCC TGATGAGATC AAATAGAGAG TG - #AATATGGA3420- AAAGATATTC AAGACCTTAA CCTAGAGCAC TAGAGCCGAT GATGCCTTTA GA - #AATTGGGA3480- AGAGGAGGAG AAGCTAGTAA AAGAGCAATT CGTTAAGTAA GGAAAACTGA GA - #GAGTGGTG3540- TCTTGGAAGA CAAGAGAATA AAGTGTTATA AGGAGGAAAT CATCAACTGT GT - #CAAATATG3600- TTGATAGCTC AAGAAAGAAG AGGAGTGTTT GGATATGTGG AGTCCGTTGT TG - #CTCTTGAC3660- AAAACCAGTT CCAGTAATCA GAGAAAAGAT AAAGAAGTGA AACAGAATTA TT - #TTATGAAT3720- TTTGTTGTAA GTGGACACAG ACATAGGACA GTAGCTGAAG AGGTTAACAG GA - #TAAAGGAA3780- AGTTTTGTTG TTGTTGTTTT ATTGTGTTTT TAAAAGTGGG ATATACTAGA GC - #ATTTGTAG3840- ACTGTTGGGA ATGACTCTGG ACAGAAACAT TGATGCAGGA GAGGGGATAA TT - #ACAGAGCA3900- CAATTCTTGA GTAGGCAAAA AGAGATAAGA TCCATTGCCC AACTGGAGGG GA - #TACCAGGA3960- ACATCCACTG TTATCCATTG TAACAGGGAT TTAGGCAGAT TATATGATTG GA - #AACTTTAG4020- TGGTGAAAGA ATGAGTAAGT TCTCTTTTGA TTGCTTTTAT ATTCTCAAAT GA - #AAAAAGAA4080- ATGAAGTTAC TGGTTGAGAG TGGCAGAAGG GGTTGATTGA GCCTAGAAAA CA - #TAGAATAG4140- TTTTTAACCT CAGTAAGTAA ATTGATTAAG GGAGGTGTTC TGGGATTACA TG - #ACAGTGTC4200- AGGGGTTTTG TGAAAATTTA AAGAGAGACC AGCCATCATG GTTATGTATG TT - #TTTTCAGT4260- CTTGTTCAGC CCAAGCACTG AATAAATTGG AAAGTTGCAT TTATCCATGG TT - #GGGGATTT4320- GGTAAATACT ATGAAGGTAA TGAGAAGCAA GGAATTGAGT ACCGATATGG TT - #TGAATTTG4380- TATCTGCCCA AATCTCATGT CAAATTGTAA CCCCCATTGT TGGAGGAGGG GC - #CTGGTGGG4440- AGGTGATTGA ATCATGGAGG TGGATTTCCC CCTTGCAGTT CTTGTGATAG TA - #AGTTCTCA4500- TGAGATCTGA TTGTTTAAAA GTGTGTAGCA CCTCCCCCTT CACTCTCTTC CT - #CCTGTTCT4560- GGCCGTGTAA GATGTGCCAG CCTCCTCTTC ACCTTCTGCC ATGATTGTAA GT - #TTCCTGAG4620- GCCTCCGCAG TCATGCTTCC TGTACAGCCT GCAGAACCGT GAGCCAATTA AA - #CCTCTTTT4680- CTTTAACCAG TTTCAGGTAT TTCTTTGTAG CAGTGAGAAA ACAGACTAAT GC - #AGAAAGTT4740- GGTACCGAGA GTAGGGTATT GCTATAAAGA TAGCTGAAAA TGTGGAAGTG AC - #TTTGGAAC4800- TGGGTAATGG GTAGAGGTTG GAACAGTTTG GAGGGCTCAA AAGAAGACAG GA - #AGATGAGG4860- AAAAGTTTGG AACTTCCTAG AGACTTGTTA AATTATTTTG ACCAAAATGC TG - #ACAGTGAT4920- ATGAATAATG AAGTCTAGGC TGAGGAGGTC TCAGATGGAG ATAAGGAGCT TA - #CTGAGAAC4980- TGGAGTAAAG GTCACTCTTG CGATGCTTTA GCAAAGAGAC TGGCAGCATT GT - #GCCCCTGC5040- TCTAGGAATC TGTGGAACTT TGAACTTGAA AGAGATGATT TAGAGTATTT GG - #TGGAAGAA5100- ATTTCCAGGC AGCAAAACTT TCAACATGTG GCCTGGCTGC TTCTAGCAGT AT - #ATGCTCAT5160- ATGTGCAAGC AAAGAGATCT GAAACTGGAA CTTATATTTA AAAGGGAAGC AG - #AGCATAAA5220- AGTTTGGAAA ATTTGCACCC TGATCATGTG GTAGAAAAGA AAAACCCATT TT - #CTGGGGAG5280- GAATTCAAGC CGGCTGCAGA AATTTGCATA AGTAAAGAGG AGCAGAATGT TT - #AATAGCCA5340- AGACACTGGG GAAAATGGCT AGAAGGCATT TCAGAGATCT TCACAGCAGC CC - #CTCCCATT5400- ACAGGACACT ACTCCCTGTG TTTCAGCCAC TCCAGCTCCA GCCATGGCTA AA - #AGGGCCCC5460- AGATATATCT TAAGCTGCTG CTCCAGAGGC TGCAAGCTGT AAGCCTTGGC AG - #CTTCCACA5520- TGGTGTTAAG CCTGGGGTTG CGCAGAGAAC AAGAGTTGAG GCTTGGGAGC CT - #CCACCTAG5580- ATTTCAGGGG ATGTATGGAA ACGTCTGGAT GTCCAGGCAG AAGTCTGCAG GA - #CTTGTTGC5640- AGGAGGGACC TGGTTGGGGT GATTGGATCA TGGGGGTAGA TTTCCCCCTT GC - #TGTTCTCA5700- TGATAGTGAG TAAATTCTCA TGAGATCTGG TTGTTTAAAA ATCTGTCACA AT - #TCCCCCTT5760- TACTCTTTTT CTTCTGCTCC AGCCATGTAA GATGTGCCAG CATCCCCTTT GC - #CTTCTGCC5820- ATGATTGTAA GTTTCCTGAG GTCTCCCCAG TCTTGCTTCC TGTATAGCAT GT - #GGAACTGT5880- GAGCCAATTA AACCTCCTTT CATTATAAGT TACCCAGTTT CAGGTTTTTT TT - #TTATAGCA5940- GTGCAAGAAT GTACTTATAC AACCATAATC TTAATATATT GACTTAATCA AT - #CCTCCTGT6000- ATGTAATCAA TGTCTCATCG TTGCATCAGG GCCCTAGCAC CTCATATGGG CT - #GACTCCAT6060- CCCTGTATGC CAGTCTTCCT TATCCTGCGT AGGCTCTTGA CTCTTCATTC TG - #ACTCCCTC6120- ATGGGATGCT TTTCCATTCT GTATACACTT TGACTTCTGG TGCTAGATCA TG - #TCCTCATT6180- CCCCGCCCTT CTCTGATACC AGGTGGCCTC TTGCAGGGAT GCCCACTGTA CT - #CTGACCTG6240- AATCTCCCCA GATCTGTGTC ACTGAGAGGG TCACTCTTCT CAGTCTGATA CT - #TTATACCA6300- GGTGGCTTCT TGCAAGAATG CCGTCTCTAC TCTATGATCT GACTTCCCCC TA - #GCCGACTT6360- AACCCTCAGG TGGGCCCCCT TCTCATCATT ATCAGGCTCT GAATCCCCAC AC - #TATTCCCT6420- GGCGTGGACA CTCTGCTTCT GAGCTGGATC CCCCCTATTT GTGGATTCCT CT - #TTCATCCT6480- GCTGGAACTC TGATACCATT GGACTCTTGA AACTCTGTCT ATGCCAAGCT GT - #TTCCCCAT6540- GAGGGTACCC TTCTCAGCCT ACTCAAGCTC ATTTATTCCA CTCTAGGCTG AG - #TTATAGGT6600- GCCTTAACCT TCAGCTGGCA TGAACACGCA CCTTCTTCTG CCCCACCTAA TG - #GTTTTACA6660- ACTAGATTGT TTGGAGAAAG AAGGGTTTTT CTTATTTTTT ATTTTATTCT TT - #TTGATAGA6720- AATTGTTCTG AAGTATAATA CACATTTCTT TGTTTTAATA ATTCAATCTA AA - #TTACACTT6780- CACTTTTGAA GTGACTCTTC TTCAATAAGA GTGTCAACAA CAATGTAGTG AT - #AGAAATGC6840- TACAAGATAG CCCTTGCTTG AATTCTATTT ACTAATTTGA TGTTTGCCGG GT - #AGCTAGGT6900- CCTCGAAAAG TAGATGCCAT GGAGAAAGAG TATGTGTATT TGGCTTGCTA CT - #CAGGAACA6960- CTGTAAACAA ATTAATTTTT TGCTGCATAA ATACATAGCT CCTTAGTTCA AC - #TACTGTGG7020- ATTAAACCTT CAGCAGAATG CTCTCCTTAT GATGAAATGA CAGAGTCAAG TC - #TGGGCTTT7080- CAAAGCTTTA TACTGACCTC TGGCCACCTC CTCATTGAAA TGTCTGTATC CT - #AAGAGGCT7140- GTTTCTGAGT AGCCAGTTCA GCGACTTCTT CCTCTTTACC TCCATCCTCA AC - #CCTTGTCC7200- AGGCTGCCTT CCTATCTCTC CTCGATTATT CCCTGCTTCA TGTCTTGTCT CA - #GTTCACTC7260- TGTTCACCCT AAAGACAAAA TAATTCTTCT AAAATGCATA TCTACTTCAT GC - #AATTCCCC7320- TGGTTCAAAC CATTTAGTGC CATCACCTTA AATCCAAAAG CCTTACCAAG TT - #TAGAAGGC7380- TGTTAATTTC TGAAACATTT TAGGTTGATA CTCTTCTTTT CCCTACTTTC TA - #TGCCAAAC7440- ATTCTGAAAT TTCTGTAGTC ACGTAGTGAC TCAGATCTTC TCATCTGGTT AA - #CTTCTACC7500- CAGATTGGTA GAAGTTTCAT TTAAACATTC ACTTCCTTTA GACTACCTTC CC - #TGAGCTGT7560- CCTAGATAGG TTAGATGCTC CTGCTTTGTA CTCCCAGATT ATCCTGTGCT TA - #TGATGGTG7620- TTTAGCACAC CTTGTCTACA TTTAACCTAT CTTGCATGCT TCAAAGGAAA AA - #AAGTCTGT7680- CAGTTTGAAC CAAAACAACA CATGAAACCT ACAAAGTGCC TGTAAATATT TG - #TTGAATGA7740- TTAATTGAAT TAGTATCAAA GTTAAATTCA TGCCAAGAAG TCATTAAAAA GT - #CAGCAAAG7800- GATCTTTAAT GATTTTTTTT TTTTAAAGCA GAATCCAGTA CTTGTGATTT GG - #GTTGCAAC7860- AAAATAATGA GTATCACACT TATACTCGCA AGATGAATAA CTGTAACACT GG - #AAAAGTAT7920- GTGAAACAAC TATTTTCAGG CATTGGACCA CAGATAATGC AGGGCTATAT TC - #TTTGAGAA7980- AGGAGAAACA TAAAAGGTGA TTCTGCATTC ATTCCAGCTT TCTACCTGGG AA - #CACTTTGT8040- AAACTTTGGC ACATGGAATT GGAATCCAGT AGAGAGCTGG GCAGAATTGG GC - #ATCACTAG8100- GCAGATGAAA CAAAGATAGG ATTTTGGATT TGCTAAAGTG ACTGGAAATT GT - #AGAGCAGA8160- GTACTGAAGT AGGGTTGTTG TGCAGAGATG GTGTACCAGA AATCTGCATA AG - #GATCTTTT8220- GAGTCTTTGG CCAAATACTA AGCTATCCAT GTATAGGATG AGATTTAATG AG - #GGCTAGTA8280- GAGAACAACT ACCAAGGTGG CAAGTGGGGC TGTGAGTGTT GTATTCTAAA GG - #TCACACAA8340- TGCTGTGAGA CATTTGAGTC CTGATGTGCC AGAATGGAGT GACCTTGTGG AA - #CTCTCCAG8400- TGTTCACTTG AGACCTCAGA AAGGCCCACC TAACAAATAC TGAAACCAGG TT - #TTGATAGA8460- ATCAAGCTGA GTTGCCAGTA AATTAACTGG CTGCTAGAAC AAAACTCAAG AC - #TTTTTAAA8520- GGAAGCCTAC TCAGTCGAAG CTCTCAATGT GGCATCTACA ATGTGCAGAA TA - #TAATTTTA8580- AAAATTAATG GGAATATGCA AAAGAAAATG TGGTCTATAC CTGAGAAGGG AA - #AAGTGAGT8640- AGAAGCAGAT CCAGAGATGA CAGATTTTGG AATTAGCAGA CAAGGATTTT TT - #TTTAAATT8700- TTTTTTAAAT TTTTTTTTTT GAGATGGAGT CTCACTCTGT TTCCCAGGCT GG - #AGTGCAGT8760- GGCACAATCT CGGCTCACTG CAACCTGTGC CTCCCAGGTT CAGGCAATTT TC - #CTGCCTCA8820- GCCTCCCGAG TAGCTGGAAC TACAGGTGCC CACGACCATG CCCGGCTGAT TT - #TTTATTTT8880- TTTATTTTTT ATTTTTAGTA GAGACGGGGT TTCACCATAT TAGCCAACCT GG - #TCTCGAAC8940- TCATGACCTT GTGATCCGCC TGCCTCGGCC TCCCAAAGTG CTGGGATTGC AG - #GCATGAGC9000- CACGACGCCC GACCGGATTT TTTTAAAGCT ATGATAGATA AGCTCAAGGA CT - #TAAAGGAA9060- AAGATGGACA TAATGTGTGG GAAGACATCT AAACAGAGTA ATAAAAACTA TA - #AAAAAAGA9120- CCCAAGAAGC TGAATGCATC ACAAGCAGCA TAAACATAAC TATGTTGTAC AT - #TACATTCA9180- AATTGTTCAA AACTAAATAT AAAATCTTAA AAACAGGTGG AGGAAAAAGT AA - #CACATCAT9240- GCAGAGGGAA AGAATAATGA GTATGATTAC TTCTTAGGAA AAGCAATCTA AA - #CCTGAAAA9300- CAGTGGGACA GCACCTTTAA GGTGCTAGGG AATAAAAGTT AAACTCCTAT AT - #CCAGCAAA9360- AATATTCTTT GAAAATTGGA GGTGAAATGG AGGACATTTT CAGATTTAAA AC - #AAAATGGT9420- AGAGGTAATT TGTTACAGAC AGGCTTGCAC TATAGTAATT GTTAAAGAAA GT - #TTTTGAGG9480- CTGAAGGAAA ATGTCGAAAA TGATTGTAAA TTAGTCCTAG AGTAAAAGCT GC - #TCTAGGTC9540- CCCCTTTACA GACCTTAACA ACAAAGGTTC AAAAGAATCC AACTGTTTGT TG - #CTCAAAAA9600- ACTTAACTGC ATGCCAGAAC AAAGTTCAGT ACTCATTAAA GGAATAAAAC AA - #AATCTTTC9660- ACCCAACAAT ACAAAATTCA CAATCAAAAG TTAACAGGCA TCCAAAGAAG CA - #GGGAAATA9720- GGACCCATAA TCAGAGAAAA ATCAATCATA TGAACAGATC CAAAATGAAA GA - #AATAATAG9780- AATTAGTAGA TAAGAACCCT AAAACCTTAT TATAACTCTT ATAAATATGC TC - #ATAGATAT9840- AAAGGAAAAC ATAAGCATAA TGAGAAAAAT GGAAAATAAT TTTAAAAACC CA - #AATAAACG9900- GAATAATGGT GTTTTGTATA TAATGGTACA AATAGGTTAA AAGCAAAAGG AT - #TGAAAAAA9960- TATACTGTGC CAGCTAATGA AAAGAAAGCT GAAGTGACCA TATTAATACC AG - #ACAGAAGA10020- CATCAGAACT AGGGAAAATG AAACATTTTA TGATGAGAAG AGGTCAATTT AA - #TGCAAGGA10080- CACAAAAATT CTAAATGTAA AACTTCCAAA TATATGAGGC AGAAACCTAT GG - #AACAGAAT10140- GGAGAAATAC ACAAATCTGC AAGGTCAATT GGAGATCTCA ATACCCCTCT CA - #GTAGAGAA10200- AAGAAGCAGA TGAAATATCA GTAAGTATAT GGAAAATTTT AACAACACTG TT - #AACCAAAT10260- CAACCTGATT GACATTTATA GGACATTCCA TTGAACGATA GCAGAATACA CT - #TTATTTTC10320- AAGTGCATGT GGAACATTCT GTAAGATAGA CCAACATTCT GGACTGTAAA AC - #AAGTGTCA10380- ATAAATTTAT AAGGAGTAAA GTCATAGATA ATGTATTCTG TGACTACACC AG - #AATCAGTA10440- GCAGAAAAGT ATCCGGAAAA TCCCCAAATA ATTGAAAAAT TAAGCAGCAT AC - #TTCTAAAT10500- ATTACATGGA TCAAAAAAGG AATCACAAGG GAAATTAGAA AAAATACTTT AA - #ATGAATCA10560- AAAATATAGC ATGTAAAAAT ATGTGGGGTG CAGCTAGATA ATGCTTAGAG AG - #ATACGGTA10620- GAAAAGAAAC CAATCAGTAT AATTTGCCAC ATTAACAGAA TAAAAAAGAA AT - #ATCATATG10680- AACACCAATA GATACAGAAA ACGCATTTCA ATTTAATAGT CTTTCGTGGT AA - #AAACCCTC10740- AGCATAACTG ATGGAGGAAT ATTAATTCCT GAATAATTCA GTCCAAAATC CG - #TTAGGTGT10800- GGCTGAGTGA GGAAGGCATC CACAAAAACA AGCTGTGACA GCCTGGTGGG GG - #ATTGGAGC10860- CCAAGTAAGG AATCTATGAG TTTATACTGA TACAAGAAAA TGGGGGGGGA AA - #TGGAGAAA10920- GAGCAAAGCC CCTTATACTA GAACCTTAAC TAATATAAAA GGAATAATGG AA - #CTAGAAAA10980- TTACTATAGG CATACCTTAG ATATTGCAGG TTAAGTTCTA ATGGATGGCG GT - #CTTGTCTA11040- CATTGAAAAT CTGTTGTTTA GTGTAGCTAC CTTCATCAAT TACCTGAGCT AG - #ATCTTCTG11100- GATAACTTGC TGCAGCTCCT GCATCAGCAC TTGCTGCTTC ACCTCGCACT TT - #TATGTTGT11160- GGAGACAGCT TCTTTCTTTA AGCCTCATGA ACCAACCATT GCTAGCTTCC AA - #CTTTTCTT11220- TGCAGCTTCT TTACTTCTCT CAGCCTTCAT AGAATTGCAG AGAGTTGGGG CT - #TTGCTCTG11280- GATTAGGTTT TGGCCTGAGG GAATGTTGTG GCTGGTTTAA TCTATCCCAA CT - #ACTAAAAC11340- TTTCTCCATA TCAGCAGTAA GGCTGTTTCA CTTTCTTATC ATTTGTGTGT TC - #ACTAAAGT11400- AGCACTTTTA ATTTTATTCA AGAACTTTTC CTTTGCCCTC ACAACTCAGC TA - #ACTGATGA11460- AAGAGGCCTA ACTTTCAACC TGTTTTGGAT TTTGACATGC TTTTCTCAAC TA - #AGCTTAAT11520- CATTTCTAGT TTTTGATTTA AAACGAGATG TTTGACTCTT CTTTCGCTTA AA - #CACTTAGG11580- GGCTGTTGTA GGGTTACTAA TTGGCCTAAT TTCCATATTA TTGTGTCTCA GG - #CAATCAGG11640- TTCCAAGGAG AGGGAGAGAG ACGGGAATGG CAGGTCAGTA AAGCAGTCAG GA - #CACACACG11700- TTAATGGATT AAGTTCACCT CTTATATGTG GATGGTTTGT GGCACACAAA CA - #ATTACAGT11760- AGTAACATCA AAGATCACTT ATCACAGATC ACTATAACAG ATACAATAAT AA - #TGAAAAAG11820- TTTGAAATAT TGTGAGAATT ACCAAAATGT GACACAGAGA CACAAAGTGA GC - #ACATGCTG11880- TTGGAAAAAT GGCACCGATA GACTTGTTAG ATGCAGGGTT GCCACAAACC TC - #TGAAGAGC11940- ACAATAAGAT GGGGTATGCC TGTATTTGAT AGCTGTCATA ATAATAATTC AT - #TCAGGTAA12000- GAAACAGTAG ATGCTAAAAC TAATGGAAGA AAGTTTGATG AAGTATGAGA TA - #GTTGTATG12060- GTCTCTGCAT CTCTCCCTCA AATTATTAAT TAATTGTAAA GAAAAATTTT TT - #GGTGAAGC12120- TAGGAGATAC ACCTTTATCA AGAGATTGAA GTTAGTCTAG GCAACATGGT GA - #ACCACATC12180- TCTACAAAAA CTACAAAAAT TGGCGGGGTG TGGTGGCATG CACCTATAGT CC - #CAGCTACT12240- TGGGGGGCTG AGGTAGGAGG ATTGCTTATG ACTCAGAGGT CGTGGATGCA GT - #GAGCTGTG12300- TTCATGCCAC TGCACTCCAG CCTGGATGAC AAAGTGAGAC CCTGTCTCAA AA - #AAATAAAT12360- AAAGGGATTG AAGTTAATAC CCTCCGTAAT GAGATAAATG GAAATGATGT CC - #TGTCTGAT12420- GAGATGCAGT AAAAGGAACT CATCATCGCT TGTATAATAT TCTTGCCAAA GA - #TACATAAC12480- CTGATTCTAG TCGTGAGGAA ATATTACCCA AATTTTGGGA GGTATTCTGC AA - #AATAATGG12540- TCTGTACTTT TCAAAATTAT CAGTCATGAA AGTCAAGGAA AATCTGAGCA AC - #TATTTCAG12600- GCTGAAAGAA AGTAAAGAGA CATAACCACC AAATACAAAG TGTAATTCTG AA - #CTGAATCC12660- TTTTGCTCTA AAGGACGTAC TGGGACAAGT GAATTAGGCT GTAGAAAAAG AA - #AAAAACAA12720- TCAGTATAAT TTGCCACAGT AATAGAATAA AGAAGAAAAA TCATATGAGC AT - #CAATAGAT12780- ACAGAAAAAG CTTTTCAATT TAATACTCAT TCATGATAAA AACTCTCAGC AT - #AACTAATG12840- GATGAATAGT TATTCATTCC TGATTAATTC AGTCCAAAAG CCATTAGGTA GG - #ACTGAGTG12900- AGGAAGGCAT CCACAGAAGT ACCCTAGGGA TGAATAGATG ATAGAATTAG TA - #GATAAGAA12960- CCTTAAAATC TTATTATAAA TCTTATAACT ATGTTCATAG ATATAAATAA AA - #ACATAAAA13020- ATAAAAACAT GAGAAAAATG GAGGACAATA ACCAAAAAAC CCTAAATAAA GT - #AAAAGGAA13080- TAACAGTGTT TTTATATATA ATAGTACAGA TGGGTTTAAA ACAAAAGGAT GG - #GAAAAATA13140- TACCGTGCCA GCTAATGAAA AGAATGCTGA AGTGACCATA TTAATATAAG AC - #AGAAGACA13200- TCAGAAAAAA TAGGTGATTA TATGATATTT GAATGTCTGT TCATTGTTGG TC - #TTTTAGGT13260- CTTATAAGAT GATGGTCATT TTCTACTACT TTAAGGGAGC ATATTAAATT TT - #TTTCAACA13320- GACTTTAAAC TTTATTTTGT AGATCAGCTT CGGGTTTATA GCAAAATTGA GC - #AGAAAGTA13380- CAGTTTCTGT ATATTCCCTG CCTGTACACA CACAACCTCC TCTACTATCA GC - #ATCTAACT13440- TTTTGTAGAT ACTTTGCCTC ATTCAAATAA TCCAGGGTAA TCTTTCTATT TT - #AAAGTCAA13500- GTGATTGACA CCCCAGTTCC ATCTGTAATG TTAATTCTCT TTTGCTGTGT AA - #TGTAACAT13560- TCACAAATTC AAGGGATTAG AATGTGGACA TCTTTGGAGA ACCATTATTT TA - #TATGCCAC13620- AGCTGAGTTA ATGGTAACTT ATCACATTTT GGAACAACTG GCAAAACTTG AA - #TGGGATTT13680- GTGGACCATG TGGTAATAAT ATATCAGTAT CAGTTTCCTG ATTTTTGTTG TT - #GAAAATGT13740- CCTTGTTTTG TAGGAAATAC TGGTGTTGGG ACATCAGATC AGCAACTTAC TC - #TCATGTGG13800- TTTGGGGGGC AGGAAAGCTA TGTATACTGT AGTTCTGTGT ATTACTCCAT TT - #TCACACTG13860- CTGTTAAAGA CATACCCAAG ACTGGGCAAT TTACAAAAGA AAGAGGTTTA AT - #GGACTTAC13920- AGTTCCACGT GGCTGGGGAG GCCTCACAAT CATGGTGGAA GGTGAAAGTC AT - #GTCTCACA13980- TGGTGGCAAA TGAGAGCTTG TGCAGGAAAA TTCCCCCTTA TAATGACCAT CA - #GATCTCGT14040- GAGACTTACT ATCATGAGAA CAGCACAGGA AAGACCTGCC CCCGTGATTC AA - #TTATCTCC14100- CACCTGGTTT CTCCCACAAC ACATGGGGAT TCAAGATGAG ATTTGAGTGG AG - #ACACAGCC14160- AAACCATATG ATTCCACCCC TGGCCCCTCC CAAATCTCAT GTCCTCACAT TT - #CAAAACCA14220- ATCATGCCTT CCCAACAGTC CCCCAAAGTC TTATTTTAGC ATTAATTCAG AA - #GTCCACAG14280- TCCAGAGTCT TACCCAAGAT AAGGCAAGTC CCTTCTGCCT ATGCGCCTGT AA - #ACTCAAAA14340- GCAAGTTAGT TACTTCTTAG ATACAATGGG GATACAGGCA TTGGGCAAAT AC - #AGCCATTC14400- CAAATGGGAG AAATTGGCCA AAACAAAGGG GCTACAGGCC CCGTGCAAGT CC - #GAAATTCA14460- GTGGGGCAGG TGTATCTTAA AGCTCCAGAA TGATCTCCTT TGACTCCATG TC - #TCACATCC14520- AGGTCACTCT GATGCAAGAG GTGGGCTTCC ATGGCCTTGG GCAGCTCCAC TT - #CTGGCTTT14580- GCAGGGTATA GCCTCCTTCC TGGCTGTTTT CACAGGCTGG TGTTGAGTGC CT - #GCAGTTTT14640- TCCAGGTGCA CAGTGCAAGC TGTCAGTGGA TCTATTATTC TGGGGGATCT AC - #CAGTCTGG14700- AGGACAGTGG CTGTCTTCTC ACAGCTCCAC TAGGCAGTCC CCTCCATAGG AA - #CTCTGTGG14760- GGTTTCAACC CCACATTTCC CTTCCATATT GCCCTAGCAG AGGTTTTCCA TA - #AGGGCCCC14820# 14855 TCTG CCTGGGCATC CAGGT- (2) INFORMATION FOR SEQ ID NO:60:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 231 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA (genomic)- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#3' END OF INTRON 2 OF RAD50 GENOMIC SEQUENCE- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:60:- ATACCTGATC TCCTAATGAT GCTGAATAAA GGAGGTAGAT AGTATATCAT TT - #TTGTAAAT 60- TAATTAAACA GTATTCTTCT ATATTTTGGA TAGCATGTAA AAATATCACT CA - #TTTTGGAT 120- GTTTTTCTTT TTGTTCCCTC ATTTTGGGTA AGATTGCTTA TGCCTTTTTC TC - #AGAACCAA 180# 231TAAAGTA ACATAAGTTT TTTCTGTGTT TTCCTTCAAA G- (2) INFORMATION FOR SEQ ID NO:61:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 152 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA (genomic)- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#EXON 3 OF RAD50 GENOMIC SEQUENCE- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:61:- GTTGCTCAAG AAACAGATGT GAGAGCCCAG ATTCGTCTGC AATTTCGTGA TG - #TCAATGGA 60- GAACTTATAG CTGTGCAAAG ATCTATGGTG TGTACTCAGA AAAGCAAAAA GA - #CAGAATTT 120# 152 TCAT TACTAGAACA AA- (2) INFORMATION FOR SEQ ID NO:62:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 266 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA (genomic)- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#5' END OF INTRON 3 OF RAD50 GENOMIC SEQUENCE- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:62:- GTAGGTGTTT ATATGATATT TGAATTTCTG TTCATTTTCA GTCTTTTAGG TC - #TGTAAGTT 60- GATGGTTGTT TTCTACTATA AGTTTAGGGG AGCATATTAA ATTTTTTTCA AT - #AGACTTTA 120- GACTTTATTT TTTTAGAGCA GTTTTGGGTT TATAGCAAAA TTGGGCAGAA AG - #TACTGAGC 180- TTCCATTTTC TCCCTACCCC CACGCACACA CAGCCTCCTC CACTATGAAC AT - #TTGATTTT 240# 266 TCAG TTAAAT- (2) INFORMATION FOR SEQ ID NO:63:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 250 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA (genomic)- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#3' END OF INTRON 3 OF RAD50 GENOMIC SEQUENCE- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:63:- GTCCCAAATA TGTAAAAAAT AAATTCTGGC TTCCTTTCCT GAACTACTTT GT - #TTTACATA 60- TCTTTTCATC TGTGAACCGT TAAATAGTTT AAGAGTTACA CTTTTTAGCA TG - #ATGAAGCC 120- ATTTCTAACG GGATAGGTGA AGGGCCTTTT TTTTTATTCT TTTAAAGAAG TA - #CAGTATGA 180- ATTGATTAAG CAATAGAATA GATACACTGA AGGTTATTTT ACATATATTC TT - #GATTTTCA 240# 250- (2) INFORMATION FOR SEQ ID NO:64:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 186 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA (genomic)- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#EXON 4 OF RAD50 GENOMIC SEQUENCE- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:64:- GCATGGTGAA AAGGTCAGTC TGAGCTCTAA GTGTGCAGAA ATTGACCGAG AA - #ATGATCAG 60- TTCTCTTGGG GTTTCCAAGG CTGTGCTAAA TAATGTCATT TTCTGTCATC AA - #GAAGATTC 120- TAATTGGCCT TTAAGTGAAG GAAAGGCTTT GAAGCAAAAG TTTGATGAGA TT - #TTTTCAGC 180# 186- (2) INFORMATION FOR SEQ ID NO:65:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 359 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA (genomic)- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#INTRON 4 OF RAD50 GENOMIC SEQUENCE- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:65:- GTTTGTAACC CTTAAATAGA CTTTGTAGTC CATTAAGTTA TTGAACTGTG TT - #TGCAATTT 60- GGATGCTTCT TTTTAACAGA AAAAATTTAA AAAGCAGAAA GGTCATCAGT TA - #CTACCTCT 120- CATCCAGCAG CAACCATTGG GCATATTTTC TTTCACTTGT CTTTCTGTGC GT - #ATATTTAT 180- TTACCTGATT GACAGTATAA ATGTAATTTT TTTCACTTAC CATTATGTCA TA - #GGCATTTT 240- ACAAGTTATT AAAAACTCAT TGTAACTGTA ATCTTAGTGA CAGCATAATA TC - #CCACTGTA 300- TGAATATATA CCATAATTTA CTTTGCCAGA AATTTGATTT TTGTTTCATA TC - #TTCAAAG 359- (2) INFORMATION FOR SEQ ID NO:66:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 205 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA (genomic)- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#EXON 5 OF RAD50 GENOMIC SEQUENCE- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:66:- ATACATTAAA GCCTTAGAAA CACTTCGGCA GGTACGTCAG ACACAAGGTC AG - #AAAGTAAA 60- AGAATATCAA ATGGAACTAA AATATCTGAA GCAATATAAG GAAAAAGCTT GT - #GAGATTCG 120- TGATCAGATT ACAAGTAAGG AAGCCCAGTT AACATCTTCA AAGGAAATTG TC - #AAATCCTA 180# 205 CCAT TGAAG- (2) INFORMATION FOR SEQ ID NO:67:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 243 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA (genomic)- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#5' END OF INTRON 5 OF RAD50 GENOMIC SEQUENCE- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:67:- GTAACTTGAT TTTATTTTTA ATTGACAAAA ATTGTATATC TTTATGGTAT AC - #AGCATGAT 60- GTTTTGATAT AAGTATACAT CGTGGACTGG CTAGGTGATG CTGCCAACTT AC - #TGATTTAG 120- TGTATGATGG TGTTTTTGAG GTGCTCCAGT GGCTTCTGTT TCTATCAGCT GT - #CCCTCCTG 180- TTCAGCTACT GACGGGGTGG TGCGTAACGG CAAAAGCACC GCCGGACATC AG - #CGCTATCT 240# 243- (2) INFORMATION FOR SEQ ID NO:68:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 6623 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA (genomic)- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#3' END OF INTRON 5 OF RAD50 GENOMIC SEQUENCE- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:68:- TTTGAATCAT GAAGTAGAAA ATATATATAT ATTTTTAATG ATGGCCATGC AT - #AGAAATAT 60- ATTGCAAGGG CTTCTGGGAG GAGGTAGGGC TGAGGTGGGC CTTGAAGAAT GG - #GAAGAAAT 120- CAAGTCAGCA AACTAGAAGA CATTTTATAC ATGTTTGTAT TTATTTATTT AT - #TTATTTTT 180- GAGATGGAGT TTCACTTTTG TTGCCCAGGC TGGAGTGCAG TGGCACGATC TC - #GGCTCACT 240- GCAACCTCTG CCTCCCGGGT TCAAGCAATT CTCCCACTTA GCCTCCAGGG TA - #GCTGGGAT 300- TACAGGCATG AGCCACCACG CCCGGCTAAA TAAAAAAAAA AAATAGAATT TT - #TTGTATTT 360- TTAGTAGAGA CGGGGTTTCT CCATGTTGGT CAGGCTGGTC GCGAACTCCC GA - #CCTCAAGT 420- GATCTGCCCG CCTCGGCCTC CCAAAGTGCA GGGATTACAG GCGTGAGCCA CC - #GCACCTGG 480- AAATGTTTGT ATTTATTTTG ACTTTTCTTT TAAAAGTAAT ATGTGCCCCT AG - #TAAAAAAG 540- TTATAAAAGG ATATTAGGTG AAAAGTAAAA GATAGTCTTC CATTTCTCAT CT - #CTAACCTT 600- CCAGAGTATA TTTTACCTGC AACTTTTTTT AACTGCATAT ATACAATACA TA - #TGTATATA 660- CAAACATTCA CTTGTATGTA TGTGCATATT TACCTTTACA AGCTTAATCA GA - #ACAGGATT 720- ATGAGAGGAA GAGTCTGGGT TAAGTAAATC AATATAAAAG GAGTAAATGA CC - #AATATGAA 780- TCGGGGTCAG ATTATAGAAA GCTAATGGAT TTCAGACTTA GTTCAATAGA CA - #GAAGAGTG 840- GAAGACTATG TTATATTTTA GGATGAGTTG TCCTGATAAC TCTGTGTGGG TC - #CCGTGGTA 900- ATTACCAAGA TATTAGAACA GATTTCCTTT TTTTTTCTTC TTTCCCCCTT GC - #CCCACTCC 960- ACGTTTTATT TTCTTGAGGA GCATCTTGGT TGGAGAGATG ACAAGCACAT GT - #AATGGTAA1020- GGCAGAGAAA AAAACAAGAC CTGTAGGAGC TCTGAGGATA AAGAAAGAGA AT - #TTCTATCT1080- GAGGTAGCCA GAGAGGATTT CATAGGACTG AATTTGGCCA TGACTTTTTT GA - #TCATAAAT1140- GAGTAAGTCA TTGGAGACAT AGAGACAGTA AAATCCAAGC TGTCTTTGAA CA - #CTGTCAAG1200- GAAATCCATA TTGTTGAAAT GAAGCATTTA TATTGGAAAT GATGTCAAGG TA - #GGGCTAAA1260- TGATAATACC TAGGATTTAG TGAGTGGTGC CAAGATTCTA ACCAAGGCTG TA - #GCAGAGGT1320- TGAGGTATTT ATTTACTTGT TTGTGTTTAA TTGTGAGTAA TTCTCCAAGG GT - #TTAATATT1380- CTTCTCTGTA TCCTCAGAGC CTAGCCTAGT GCCTGGCACA TAGCAGGTGG TT - #CAATAAAT1440- GTTTATTAAG TAGATGACTT CCAAAGTCCT TTTTTTTAGC TCTGACATGT GA - #AGATTCTT1500- CCCTTCATAG AACCCAATTA AAGTTTGGGT CAAATCACCT TCCCAGAAAA GA - #CTACGTCC1560- TTTCAACCAT GCACTAGAAT GCATCCTTTC CCATTTTTAC TGATTCCCTT TA - #TCTTCGGG1620- AACTCTCACT CTCTCATAAA CTACTTTATT ACCATCCCAC CATATCCTGT CC - #TCTTTTTT1680- TGGCCTACTT AGATCTGTTT TCCTTTCTTG CCTTAAATGG GAATTGCTAG AG - #GAATATGT1740- TTCTAACTTT TTTTTTCTGC ACACAAGTTC ATGGTCCTTC TATACTTGAT AG - #CCCAGCTG1800- CTCTATTTTT TTTATCTCAT TTCACACTGG CACCTAAGCT TTAAACCCTT GG - #CTGTTTTT1860- GTTATTGTTG TCTGCCTGCT TGTCCTAGCT CCTTTTACTA GGTGTGTACT CT - #GGGGATAG1920- AACCTATGTT TTGTGCTCTG AGATTAGAAC CAAAACACAG ATGTCAAAGA AG - #GAATTCAG1980- GGGATCTGGT GACTGGCTGG ATTTAAGGAA TGAAGCAGGT AGAGATGTCA TG - #AAAGATCC2040- AAGCCCAGAT GATTATCATA ATGTTTGTGC TACCAAGAGG CAGTGAAAAC AC - #TGATGGAA2100- AGAAACTGAG CACTTTGTAG AGTATCATAG TAGAGCTGTT AGTATTCATT GC - #TCTTAAGT2160- ATCCATCCAG TTATATTTGT TAGACTCTAC TCAAAAGGTA TTTTCTGAGT AC - #AGAATTTT2220- TTTCACAAGT GGTGCAAATG GTCTCATTAA TTGAATGTTT ACTGCCTAAC AC - #TAACCCGA2280- GTGCTTTAAA ATGTATAATG TAAACTCCAT AGTAACTGTG AGGTTGTATA GG - #CAGGAAAA2340- CTGAGGTACA GGTATTCACA GTGGAAATAA GGGTTAAAGG TAGGATTTGA GT - #CCTCTGAT2400- TCCTAAGTTT ATACCTTTTT TTCTTTTTAA GTCAAGTTTA TTAAGGTATA AT - #ATATATAT2460- GGTAAAATCC ACCCTTTTTA GAGTATAAAT TCTATGAGTT AGGACATATG CA - #TACAGTAG2520- CATAACCATC ACTAAAATGA AGATGTAGAA TATTTCAGTC ACTCCAAAAA GT - #TCTCTCAA2580- AGTCCTTGCA GTCAGTCCTC TCCCCTGCTC CCATCCATAG TAACCACTAA TT - #TGTTTTCT2640- GTCATTATAG TTTTGCCTTT TCCAGAGAGT GGCACATATA TAGAATCATA CA - #GTATGCAG2700- ACTTTTGTGT CTGGGATTTA TCTATGTTGC TGCATGTGTG AGTAATTCAT TC - #CTTTTTTT2760- TTTTTTTTTT TTTGAGACGG AGTTTCACTC TTATTGCCCA GGCTGGAGTG CA - #ATGGCATG2820- ATCTCGGCTC ACTGCAACCT CCGTCTCCCA GGTTCAAGCA ATTCTCCTAC CT - #CAGCCTCC2880- CAAGTAGCTG GGATTACAGG CATGTGCCAC CATACCCAGC TAATTTTTTT TG - #TATTTTTA2940- GTAGAGACGG GGTTTCTCCA TGTTGGTCAG GCTGGTCTCG AACTCCCAAC CT - #CAGATGAT3000- CTGCCCACCT CGGCCTCCCA AAGTGCTGGG ATTACAGGTG TGAGCCACTG TG - #CCCGGCAA3060- TTCATTCCTT TTTATTGTGG AGGAGCATTC CTTCCATTGT ATCATGTATT AT - #AATTTTTT3120- TCCTCATCCA TTCTGTGGCT GATGGACATT AAGTTGTTTT TGGTTGAACT AG - #TTTACAGT3180- CCCTCCAACA GTGTAAAAGT GTTCCTCTTT CTCCACATCC TCTCCAGCAC CT - #GTTGTTTC3240- CTGATTTTTA TTGATCGCCA TTCTAACTGG TGTGAGATGA TATCTCATTG TG - #GTTTTGAT3300- TTGCATTTCT CTGATGGCCA GTGATGATGA GCATTTTTTC ATGTGTCTGT TG - #TCTGCATA3360- AATCTCTTCT TTTGAGAAGT GTCTGTTCAT ATCCTTCACC CACTTTTTGA TG - #GGGTTGTT3420- TGTTTTTTTC TTGTAAATTT GTTTGAGTTC TTTGTAGATT CTGGATATTA GC - #CCTTTGTC3480- AGATGAGTTG ATTGCAAAAA TGTTCTCCCA TTCTGTAGGT TGCTTGTTCA CT - #CTGATGGT3540- AGTTTCTTTT GCTGTGCAGA AGCTCTTTAG TTTAATTAGA ACCCATTTGT CA - #GTGTGGCG3600- ATTCCTCAAG GATCTAGAAA TAGAAATACC ATTTGACCCA GCCATCCCAT TA - #CTGGGTAT3660- ATACCCAAAG GATTATAAAT CATGCTGCTA TAAAGACACA TGCACATGTA TG - #TTTATTGC3720- AGCACTACTC ACAATAGCAA AGACTTAGAA CCAACCCAAA TGTCCAATGA TG - #ATAGACTG3780- GATTAAGAAA ATATGGCACA TATACACCAT GGAATACTAT GCAGCCATAA AA - #AATGATGA3840- GTTCATGTCC TTTGTAGGGA CATGGATGAA GCTGGAAACC ATCATTCTCA GC - #AAACTACC3900- GCAAGAACAA AAAACCAAAC ACCGCATGTT CTCACTCATA GGTGGGAATT GA - #ACAATGAG3960- AACACTTGGA CAGACACAGG AAGGGGAACA TCACACACTG GGTCCTGTTG TG - #GGGTGGGG4020- GGAGGGAGGA GGGATAGCAT TAGGAGATAC ACCTAATGTA AATGACGAGT TA - #ATGGGTGC4080- AGCACACCAA CATGGCACAT GTATACATAT GTAACAAACC TGCATGTTGT GC - #ACATGTAC4140- CCTCGAACTT AAAGTATAAT AAAAAGAAAT AAGTTGTTTT CGGCTTTGGG TT - #GTTACAGA4200- TAAAACTGCT ATAAACTTCT GTATACAGGT CTTTGGATAA CTTTAGGACT CG - #GGTTGCTA4260- GGTCGTGTGG TAAATATATG TTTAACCTTA TAAGTTACCA GATGGCTGTA CC - #ATCTGGTA4320- CCACTTCATA GTCCTACCAA CAATATACCA ACAATTTATG GGAATGTAAT TG - #CTCTGCAT4380- TCTCATCCCC ACTTAGTACT GTCAGTCTTT TTCATTTTAG CCATAACAGT AG - #GGGTGTGG4440- TAGTGTCTCA TTGTGACATT GTGAGGTTGT ATTTCTTTAT ATTTTTAATT TG - #TGTTTTCC4500- TAGTTGATCA GTCAATTGAT TATTGATTTT GAGCATCTTT TCATGTATTT AT - #TTGCCACC4560- TGAATATCTT CGTTAGTAAA ATATAAAAGT CTTTTGCCTA TTTTTCAATG TT - #ATTTATTT4620- ATTGGTCATT TTATTATTGA GCTGTGAGAG TTCTTTTTTT TTTTTTTTTT TT - #TCTTGTTT4680- TTTGAGACAG GGTCTCGCTG TCTTACCCAG GCCAGAGTGC AGTGGTGTGA TC - #TTGGCTCA4740- CTGCAACCTC TGACTCCCAG GCTCAAGTGA TCCTTCCACC TCAGTCTCCC AC - #GTAGCTGG4800- GACTACAGGC ACACACTCAC CACACCGGTG AGACTTGTAG AGGCAAGGTC TC - #ACCAGGTT4860- ACCCAGGCTG GTCTCAAACT TCTGGGCTCA AGCAATCAGC CTGCCTCAGT CT - #CCCAAAGT4920- GCTGGGATTA CAGGTGTGAG CTACAGTGCC AGGCAGAGAG TTCTAAATAT GT - #TCTGGATA4980- CAAGCCCTTT ATCAGATATT GGTTTTGCAG ATATTTCTTA ACTGCTTTTC AG - #AGGACAGG5040- AGTTTTAAAT TTTGATCAGG TACAGTTTAT AAACTTTTTT CTCTTATGGT TT - #ATACTTTT5100- TGTTTATTAT TTAGGAAGTC TTTGACCCAG TGTCACAAAA ATATTCTTCA GT - #GTTTTCCT5160- CTAAAAGTTT TATAGTTTGA GTTCTTACAA TTAAGTATAT GCTTCATTTC AG - #AATCTTAA5220- TATGATATGA GGTAAAAGTT GAGGTTTACT TTCTTACATA CAAATGTCCA CT - #TCTTCTAG5280- CACCCAGAGC CTAGTCATTA TGATACCCTG CCTTCTAATC TTATTGTTAT CT - #TGTCTCCC5340- AATCTTAACT ATACAATTTT GTACAAGTCA GTTAAGTCCT TTGAATTTCC TG - #CTTAGTAT5400- ATACTTTTGT GAGGATTAGA GAGAATTTAT AGCAGCACCT AGTACAGTGT CT - #GGAACATA5460- GCAGACATTC AATCAGTGAT ACCTGTGACT GTTGCTCTTG GTAAAATTAT TT - #TTTTCAAA5520- TCTCTCTTTC GTTTAGCTAA CATTGAACAC CTATTGCATG TTCTGGGGAT AC - #ATTAGGGA5580- ACAAAGTAAA CAAAGTTTCT GTTTTTAGGT TCATTTGTAT ATGAACGTTT AC - #GTTCATAT5640- ACAAATCACA AGCTATACTA TTAGTATAAT TTTAATAAAT TATGTTAAAG TC - #GAGGATGC5700- ATTTTGGTGC AATTATGAAA GCTTGCAATT GCTGTCTAAG CATTCCAATA AC - #TTCATATG5760- TTAGTTTAAA ATTAGGTTCT GCTGGGCATG GTGGTACATA CTTATAGTCT CA - #GCTACTTG5820- GAGGCTGAGG TGGGAGGAAC ACTTGAGCCC AGGAGTTCAA GTTGTATTGC AC - #TGTTATTG5880- CACCTGTGAA TAGCCACTCC AGCCAGGGCA ACATAGCAAG ACCTTGTCTC TG - #CATTTGAA5940- ATAATAATAA TAAAAGTAGG TTGTAAAAAT GTCTTAGAAG AAGAGTTGGT CA - #GTTTTGGA6000- ATCATAGAGG CAAACACTAG AAGAATATCC CCAGCATCAT CCAATAAGAG AA - #TGCCCCGA6060- ACCAGATCCC AGTATTCCTG GGAGATGAGG CAACCAGCTG TCTCTGGAAG CG - #AGCCTCAG6120- AGCAGGCCAC TGAGCTCCCT TGTTGTACTT TACTTGCTCA GAGTCCTCTG TG - #GTTGAGCA6180- AGCTTTGGAT TAAAGTATAC TCTTCATGTA AATTTGCCTA TAGGCTCAGA AT - #GCATTGGT6240- AACTCACCAT GAATTTCTAG CCTTCTCAGT AGTCCTGACT TAAAAAAATA CA - #TTAAATAG6300- TTACCTTTTT AAGGATTAAG TAACTCTAAA TGCCCAATGA ATGAATAATG AC - #TTTTGTGG6360- CAGGTGTTGA GGACAGGACA TGGTGTTTGG AGTTAGAAGT GGAATTTAAT TC - #CTGCTTCT6420- CTCTACTAGC TGTGAGGACT TGGGCCAAGT TACTTAATGT CTCTGAACTT CA - #GTTTCTCT6480- AGGCCTGCTC TACAGTGTTA TTGTTAGCCT TAAATGAGAT CACTTTTACT AA - #ATGCCTGG6540- ACCTGGAGTA TCTTACTTGT CTTCATCTAT CAGCCATGTA AGCTATAGTG AG - #TTTTATTT6600# 6623TTTT CAG- (2) INFORMATION FOR SEQ ID NO:69:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 129 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA (genomic)- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#EXON 6 OF RAD50 GENOMIC SEQUENCE- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:69:- AATCGTCTAA AAGAAATTGA ACATAATCTC TCTAAAATAA TGAAACTTGA CA - #ATGAAATT 60- AAAGCCTTGG ATAGCCGAAA GAAGCAAATG GAGAAAGATA ATAGTGAACT GG - #AAGAGAAA 120# 129- (2) INFORMATION FOR SEQ ID NO:70:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 233 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA (genomic)- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#INTRON 6 OF RAD50 GENOMIC SEQUENCE- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:70:- GTTTGTGGTG GTAGAATTTT GTTCTGCTTC AAAATTTTGG GATTATTGTA AT - #GAACTTTA 60- TTTGAATCCA TTTTGCCATC CACATTGGAA AAAAACAAAT ACAGATCTTG TT - #ACTTCTAT 120- GTATATGTTA AAATGAAGGA TATTGAATAA GGTTTGGTTT ATATTTGATA CC - #TCAAAGTG 180- ATCATATTTT CTTATGTTTG TACATTAAAG CTTTTTATTT TGGTGTTACA CA - #G 233- (2) INFORMATION FOR SEQ ID NO:71:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 166 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA (genomic)- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#EXON 7 OF RAD50 GENOMIC SEQUENCE- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:71:- GTTTTTCAAG GGACTGATGA GCAACTAAAT GACTTATATC ACAATCACCA GA - #GAACAGTA 60- AGGGAGAAAG AAAGGAAATT GGTAGACTGT CATCGTGAAC TGGAAAAACT AA - #ATAAAGAA 120# 166GGA AAAATCAGAA CTGCTTGTTG AACAGG- (2) INFORMATION FOR SEQ ID NO:72:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 597 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA (genomic)- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#INTRON 7 OF RAD50 GENOMIC SEQUENCE- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:72:- GTAGGACAAA ATGTTTATTT GGTCGTTTTT CCTACTATGA TGTTATACAT TT - #TCTGTATG 60- AATGAAGAAT CTCCAAGGAC TTATGCTGAG TGAAAAGCCA ATCTTAAAAG GC - #TATACACA 120- GTATGTTTCC ATTTATATAA CATTTTTATA ATGTCAAAAT TTTAGAAATA GT - #GGAGAAAT 180- TAGTGGTTGC CAGGGATACT GGGTAAGAGA AAGGACAGGA GGGAGCTAGG TA - #TGGTTATG 240- ATTAGAACAA AAAGAGAGTC CTTGTAGTAT TGGAACTGTT CAGTATCTTG AC - #TGCCATAG 300- TGGATATATG AACCGACACA GGTGATAAAA TTATATAGAA CTTAATATAC AC - #ACATCCAC 360- ATGCTCAGGG GTACAAATAA AATTGGGGAA ATTTGAATAA GATTGATGAA TT - #ATATCAAT 420- ATCAGTATTC TGGTTGTGAT ATTTTACTGC AGTTTTGCAA AATGTTATCA TT - #GGGAGAAA 480- CTGGGCAAAA TGTACAAGAG ACACACTGCA TTATTTTTTA TAACTCGTGA AT - #CTGCAGCT 540- ATCTCAACTT TTTAAGCACC AGTTGAAAAA AAAATTATGA GATTTTTTTT TT - #AAAAG 597- (2) INFORMATION FOR SEQ ID NO:73:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 194 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA (genomic)- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#EXON 8 OF RAD50 GENOMIC SEQUENCE- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:73:- GTCGTCTACA GCTGCAAGCA GATCGCCATC AAGAACATAT CCGAGCTAGA GA - #TTCATTAA 60- TTCAGTCTTT GGCAACACAG CTAGAATTGG ATGGCTTTGA GCGTGGACCA TT - #CAGTGAAA 120- GACAGATTAA AAATTTTCAC AAACTTGTGA GAGAGAGACA AGAAGGGGAA GC - #AAAAACTG 180# 194- (2) INFORMATION FOR SEQ ID NO:74:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 750 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA (genomic)- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#INTRON 8 OF RAD50 GENOMIC SEQUENCE- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:74:- GCAAGTATTT TGAAATACAG TATTTGTTAT TTTGTTTGCA TCATATTCTC TA - #CTTGAATT 60- GTTTTAATTT TTGGTTGGAC TCCATTTTGG CATATTTTTC TATTAGTGTT AG - #GATAAAAT 120- CTGCTACAAG GCAGAAAAAC CTTTATTGAA GCAAATGTTC TTAAGTGTAT AA - #AGATAAAA 180- ATATGAAGAA AATGTAAACC TACATTTTTT ATTTGGTTTT AAGTAAAAAT TT - #TTAAAAAC 240- TAATTGCAGA GAAAACATTT GCTCACAGTT AATGATTATC TCTGGGTAAT GG - #TTTTGATT 300- GTTTTTAAAA TACAGTCTTG AACCACATGT TTTGGTCAGT GATAGACCAC AT - #ATTTGACA 360- TTGGTCCCAT AAAATTATAA TACTGTATTT TACTGTATGT TTTCTGTGTT TA - #GATATGTT 420- TAGATACATA AATACTTATC ATCATGTTAC AGTTGCCAAA GTATTCAGTA CA - #GTAATATG 480- CTGTATAGGT TTGTAGCCCA TAAACAATAG GCTATACCAT ATAGTCTATG TG - #TGTATTAA 540- ACTATACCAT GTAGGCTTAT GTAAATACAT TCTGATGTTC ACACAATGAT AA - #AATTGCCT 600- AATGATGCAT TTCTTGGAAT ATATCCCTGC TGAGCAACAC ACGACTGTAC TT - #TTTTGTAT 660- TTTCTTCAGT GTACATATAT TCCTTTTGCA ATTAAAAAAC TTAAATTGTT TA - #GTAAATTA 720# 750 ACAT ATGCATTTAG- (2) INFORMATION FOR SEQ ID NO:75:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 207 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA (genomic)- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#EXON 9 OF RAD50 GENOMIC SEQUENCE- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:75:- AATGACTTTG CAGAAAAAGA GACTCTGAAA CAAAAACAGA TAGATGAGAT AA - #GAGATAAG 60- AAAACTGGAC TGGGAAGAAT AATTGAGTTA AAATCAGAAA TCCTAAGTAA GA - #AGCAGAAT 120- GAGCTGAAAA ATGTGAAGTA TGAATTACAG CAGTTGGAAG GATCTTCAGA CA - #GGATTCTT 180# 207 TCAT AAAAGCT- (2) INFORMATION FOR SEQ ID NO:76:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 1386 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA (genomic)- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#INTRON 9 OF RAD50 GENOMIC SEQUENCE- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:76:- GTAAGATATT GTTTGAATAA TCTAATAATT TTAAGATATA ATACTTTTAG AA - #GTATTTTG 60- TCTATTTTTG ATCCTAAGAT TATAGCATTT TAATAAAAAC ATCAACTTTG TC - #TTATTCTC 120- ATGTAAAATG AATTCATCTG AATATCTTGA TCTTCTGACT CTTTGGTTCT AC - #AACCCGAT 180- AGCCTGAAAA TTAGAATCAC ATAGGGAGCT TTTTAAAGAT ACTGTACTCA GA - #CCTTAAAG 240- CTTCAGACCT TCCAAATCAA AATCTCTGAG AATGGGGCAT AGAAATGTAC AT - #TCAAAACA 300- CAACAAAACT GGCTAATTCT TATGAGCACC TTGATTAAGA ACACTTACCA GG - #CCGGGTGC 360- GGTGTCTCAC ACCTGTAATC CCAGCACTTT GGGAAGCCAA GGCAGGCAGA TA - #ACGTGAGG 420- TCAGGAGTTC AAGACCTGTC CAGCCAACAT GGTGAAACCC CGTCTCTACT AA - #AAATACAA 480- AAATTAGCTG GGCGTGGTGG CGTGTGCCTG TAATCCCAGC TACTTGGGAG GC - #CAGGGCAG 540- GAGAATCGCT TGAACCTGGG AGGCAGAGGT TGCAGTGAGC CAAGATTGCG CC - #ACTGCTCT 600- CCAGCCTGGG TGACAGAGTG GGACTCCATC TCAAAAAAAA GAAAAAGAAC AC - #TTGCCAAA 660- GTTTTAAAAA AGCAAGTATT TTTCCTCTAG GTCACACACG TTGTAATTCT AG - #ATGATTTT 720- TGCTGTATTA TTACTTTTTC TGTGTTAAAA ACTTTCTTAG CCAATCTTTT CA - #GGTATTTC 780- CATATTTTCT TTCTTGCTTC TAGTCTGTCC TCCTTCTTCA CATCTCCATT AC - #CAAAGTAA 840- GCATTCTAAA GCATGGCAAA CTTCTTAAAG CCCATCTTGA TAATTTATGT AA - #ACATTTAT 900- TTTTGCTCCA TAACTCACCA TTGTAGCATA CATTTTTGTC AGTTTAGCAC TT - #CATCAGTG 960- TTGTCTTGTT GGGGTGGGGA GATACTTGGT CAGGGACCAC ATCACACTAT TT - #TTATAGTT1020- TCTACATACC AGGCAATATA GTGAATTACA TGGGGACATA ATAAATATTT AA - #TTGTTGAC1080- TGAGGACTCA CTAATCTGTG TACTTAGACA CATGTCTCCT AATTTTACAG TA - #ATTCTCAC1140- ATTTCTTTCC TGTTTGACCC TTCTAGGTTT ATTTACTAAT TCTCTACCAT TA - #TAACATAG1200- TAAGGTCACT TTAATAAGAT ATACCTTAGA GCATATATAG TGCCTTATGT TT - #TTTTCTCT1260- TGTTGGATGC AAACAGTAAT ATTTGGAACA TTCTGAGGAG TAGTTAATTT CT - #AATACACT1320- TTGTCATTAT TTTAATTCTT GCACAAAATA TATAACACCT TTGCATTTGT AT - #GAATTATT1380# 1386- (2) INFORMATION FOR SEQ ID NO:77:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 183 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA (genomic)- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#EXON 10 OF RAD50 GENOMIC SEQUENCE- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:77:- GAACGTGAGT TAAGCAAGGC TGAGAAAAAC AGCAATGTAG AAACCTTAAA AA - #TGGAAGTA 60- ATAAGTCTCC AAAATGAAAA AGCAGACTTA GACAGGACCC TGCGTAAACT TG - #ACCAGGAG 120- ATGGAGCAGT TAAACCATCA TACAACAACA CGTACCCAAA TGGAGATGCT GA - #CCAAAGAC 180# 183- (2) INFORMATION FOR SEQ ID NO:78:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 470 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA (genomic)- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#INTRON 10 OF RAD50 GENOMIC SEQUENCE- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:78:- GTATGATTTT TCTTTTTGTT CTAATTATAC TGTCTGGTAC TTAAAATAGC CT - #ACCTTGCA 60- CTCATAAGTC ATAGACTATA AGGTATTAAG TTGGTATTGA CTATATTTTA GA - #GGCTAAGT 120- GAGCTTAGTA CTCTATATAA TAGACTTTCA AGCTTAAAAG TTATTGTTTA AT - #TACAAAAA 180- GTTAATACAG AAATGTATAT ATATGTATAT ACACACATGC ACATTACTGT TA - #ACTTTTAA 240- CATACACAAA TTTTAAAATT TTATATTGTT CGACTTGGTA CTCCACTCTT AA - #GGCTTAGA 300- AAGACCATCC CCACTTGAAG ACTTTAAGAA CTTTAAGAAA TTTTATATTT TA - #TTTTCATA 360- TTTTTATAGT TTTAAGCTTA GAACTTTAGT CAGTCTAGAA TTTATTTTTG TT - #CTTGATAT 420# 470GACTTT ATTTTTAAAA GATTTTTTTT TTACCTATAG- (2) INFORMATION FOR SEQ ID NO:79:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 158 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA (genomic)- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#EXON 11 OF RAD50 GENOMIC SEQUENCE- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:79:- GCTGACAAAG ATGAACAAAT CAGAAAAATA AAATCTAGGC ACAGTGATGA AT - #TAACCTCA 60- CTGTTGGGAT ATTTTCCCAA CAAAAAACAG CTTGAAGACT GGCTACATAG TA - #AATCAAAA 120# 158 GGGA CAGACTTGCC AAATTGAA- (2) INFORMATION FOR SEQ ID NO:80:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 386 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA (genomic)- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#5' END OF INTRON 11 OF RAD50 GENOMIC SEQUENCE- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:80:- GTAAGTTGCA ACATTTGGAG ATGTAATAGA AATCTCTTAT TTCATGCTTA CC - #TGTTTAAT 60- TGTTTTAAAA TAATTTATTG TCATGAAATG GTATGTTATA TTGATAAACT TT - #AGTTCTTA 120- CATACAAGGA GACTTCAGAA AGTTCATGGA AAAATGGAAT TAAAAGATAA AA - #ATTTTAAA 180- TAAACTGTAT TTCTCAACAT AAGCTCCATC AAGTTCAAGA CTCTTCTGAG CA - #GTGATACC 240- AGCAATTTAG TTCAGTCCTA AAGAACTGAG GGTCCTGGGA ATTTAACCAT GT - #CAGTGTAG 300- TCTTTTTTAC ATTGCTAGCA TAAAAATGGG TGCCCTTTAA AGATTTTTTT AA - #GATTAAGA 360# 386 GAGC CAAATC- (2) INFORMATION FOR SEQ ID NO:81:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 247 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA (genomic)- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#3' END OF INTRON 11 OF RAD50 GENOMIC SEQUENCE- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:81:- CAGGCAGAAT TCTGTGTACA TTTTTCTGGG AGCAGGCCCA TGAGTAGGAC TG - #GCAGGTGA 60- GTCAGTGTCC TAGGGGGAGA GTTAAGGCAG AAGTGGACTA GTCCCTCAAC TT - #CTGAAAAA 120- AATTATTTGG TCATACCAAA CTCTTGTCAT GATTTGTTGG CAGAATTTGT CT - #TGTTTTTG 180- CCTACTCAAA TTTTCAAACT AATTTCTCCT ATTTTAAAAT GAAAATCCAT AT - #TTGCTCTT 240# 247- (2) INFORMATION FOR SEQ ID NO:82:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 176 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA (genomic)- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#EXON 12 OF RAD50 GENOMIC SEQUENCE- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:82:- CAAGGAACTA GCTTCATCTG AGCAGAATAA AAATCATATA AATAATGAAC TA - #AAAAGAAA 60- GGAAGAGCAG TTGTCCAGTT ACGAAGACAA GCTGTTTGAT GTTTGTGGTA GC - #CAGGATTT 120- TGAAAGTGAT TTAGACAGGC TTAAAGAGGA AATTGAAAAA TCATCAAAAC AG - #CGAG 176- (2) INFORMATION FOR SEQ ID NO:83:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 528 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA (genomic)- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#INTRON 12 OF RAD50 GENOMIC SEQUENCE- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:83:- GTAAGTTGTC TACTTTATAT TATCAGGATA CTTTGACACC TTTGAATTTT CA - #TTCACAGG 60- TAACTGTTAA GGATGGGGAA TTTAAAAACC TGGTTATGGA GCCTAATGGC TT - #GGATTTCA 120- GTCCTGGCTC TACAACTTAC TCACTGTGTG ACTTTAGGCA AGTTACTGAA AC - #CTTCCTGT 180- GTTTCATTGT CTATAAAATG AGGACACAAC TACCACCTGT GGTACTGAGG TG - #TGAATGAG 240- ATTGTAATTA TAAAGCCCTT AGAACAGTGC CTGGCACATA GAAAGCTCTC AG - #TAGGCATT 300- TTGTTATACT TATAATGTGT TACCAAAAAA TATTTATACA AATCTGAATG TA - #TCATGCTC 360- TTTGGAAGCG AATATCGGAA TTTTAAATAT CAGAATTTTT ATTTCTTTTA TA - #ATATATTT 420- ATAAAGCAAG AATAATCATA TATTTATAGA AAAAGATACA ACCGTATTCA GA - #ATACTGTA 480# 528CATT GGTGATATAA TTTATTTTCT TAAAATAG- (2) INFORMATION FOR SEQ ID NO:84:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 238 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA (genomic)- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#EXON 13 OF RAD50 GENOMIC SEQUENCE- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:84:- CCATGCTGGC TGGAGCCACA GCAGTTTACT CCCAGTTCAT TACTCAGCTA AC - #AGACGAAA 60- ACCAGTCATG TTGCCCCGTT TGTCAGAGAG TTTTTCAGAC AGAGGCTGAG TT - #ACAAGAAG 120- TCATCAGTGA TTTGCAGTCT AAACTGCGAC TTGCTCCAGA TAAACTCAAG TC - #AACAGAAT 180- CAGAGCTAAA AAAAAAGGAA AAGCGGCGTG ATGAAATGCT GGGACTTGTG CC - #CATGAG 238- (2) INFORMATION FOR SEQ ID NO:85:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 267 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA (genomic)- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#5' END OF INTRON 13 OF RAD50 GENOMIC SEQUENCE- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:85:- GTAAGAATGG GATTTACCTT CACTGTACAT GTAGCAGCAC ATTGTAAAAG GT - #ACCCATCT 60- CATGCCTGGG CAGATGGTAG TTACTCAGTA AGGACTCTGA GCTGGTATGC CC - #TGTCTTAT 120- ATCACTTCTA TGATAAGAAG ATTCAATTAT TTTGTTTAAA GATAAGCTTG TT - #TCCTGTCT 180- TTTTTTCTTT TTCTTTTTTT TTCCTGAGAC AGAGTCTCTC TCTGTCACCT AA - #GCTGGAGT 240# 267 GGCT CCATTGC- (2) INFORMATION FOR SEQ ID NO:86:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 266 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA (genomic)- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#3' END OF INTRON 13 OF RAD50 GENOMIC SEQUENCE- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:86:- TCTCTCCTTA AGATACTTGT TAATTACAAA GACTAAAACA GTAACTTTAC AG - #TGGAGAAA 60- CCTGGCCAAC ACCATCTAAG CCAAGTGAAT AAGGATTAAC ATCATCAGTA AT - #AAGACATA 120- TTGATATCAT GATTCCATAT CCACTGATAT GATACCCTGA AAAGAACACA AT - #GTCACTTC 180- TGTGGTATTC TTCCTAAAAA TACATAACCT CAGTCTAACT GTGAGAAACA TC - #AGATACTT 240# 266 TTCT ATTTAG- (2) INFORMATION FOR SEQ ID NO:87:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 190 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA (genomic)- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#EXON 14 OF RAD50 GENOMIC SEQUENCE- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:87:- GCAAAGCATA ATTGATTTGA AGGAGAAGGA AATACCAGAA TTAAGAAACA AA - #CTGCAGAA 60- TGTCAATAGA GACATACAGC GCCTAAAGAA CGACATAGAA GAACAAGAAA CA - #CTCTTGGG 120- TACAATAATG CCTGAAGAAG AAAGTGCCAA AGTATGCCTG ACAGATGTTA CA - #ATTATGGA 180# 190- (2) INFORMATION FOR SEQ ID NO:88:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 430 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA (genomic)- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#INTRON 14 OF RAD50 GENOMIC SEQUENCE- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:88:- GTAAGTTTAT TGTAGTTTAA GGCAGAATAA AACTTGTTCC ATGGTGGCTT GA - #ATTTGAAG 60- TGTGAGAGTT AAAAATAGTA GCTAGTATTC AGGTACAGGT TGTGTTTAGA AT - #TCCCCATC 120- CTGAATTTCA GATACCCTCA GGGAGAAACT GCTTAGTTTA CATCCCTGGG TT - #TAAACTTT 180- TTAATTCATA AATTTAAAAA TTAAGACAGT TCTGTTTGTT TTTCATCTTT AG - #TCAGCTTC 240- CTTTTGTTTA CATCATTTGA ATTGCTGATA ATTAATTTCA CTTTTATCCT AT - #TAAACTTT 300- GCTAAAATTG TATCTAGAAA TGGTTTATAA GTTTAGATTT AAAAAATAAA TG - #ATAAGAGC 360- AATTAATTTT TAAAGATTTT GAATAATGCA GTAAGTTTAT TAAAGGAAAT CA - #TTTTGTTA 420# 430- (2) INFORMATION FOR SEQ ID NO:89:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 127 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA (genomic)- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#EXON 15 OF RAD50 GENOMIC SEQUENCE- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:89:- ATGGAACTTA AAGATGTTGA AAGAAAAATT GCACAACAAG CAGCTAAGCT AC - #AAGGAATA 60- GACTTAGATC GAACTGTCCA ACAAGTCAAC CAGGAGAAAC AAGAGAAACA GC - #ACAAGTTA 120# 127- (2) INFORMATION FOR SEQ ID NO:90:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 261 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA (genomic)- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#5' END OF INTRON 15 OF RAD50 GENOMIC SEQUENCE- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:90:- GTAATACAGT CTGTGTCCTT CTGTACTCAT AGAGACTTTG ACATTGCGAG CA - #CATGCCTT 60- TTACAGTCAA TTTTATATCT GTTACATGGA CAACGAAGTT CCTTCCTGTC CA - #CATATATT 120- TGCTCTTTTT TTCTGAAAAG CATCACTTCT CTTTGTTCTC TTACTTTGCA CA - #ACAGATTT 180- TGAACAGTAG GAGAGTATGA AATAAGCTGT ATTCTCTTTT CCTTTTTTTT TT - #TTTTAAGA 240# 261GC C- (2) INFORMATION FOR SEQ ID NO:91:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 284 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA (genomic)- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#3' END OF INTRON 15 OF RAD50 GENOMIC SEQUENCE- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:91:- CCCCAAAGTG CTGGGATAAC AAGTGTGAGC CAGTGCGCCT GGCCATGAGC TG - #TATTCTTT 60- CTCATTCATA CCTGCCCTGT AAGCTTTTCC CTGTGAGTGG CCAGCAGGGA AC - #ATCAAGCT 120- GATTTGAGAA CTAGCAGGGT TCTCATTGTA TTTTTGTTGC AGTGGGTGGG GC - #CCACAGAA 180- ATAGCATTTG TGGATTCCAT AGACCGATAA AAATGGGAAG AATGATACAA AT - #AGTATTTT 240#284 ATTA CTGTGATAAT ATGTTTTTGT GTAG- (2) INFORMATION FOR SEQ ID NO:92:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 194 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA (genomic)- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#EXON 16 OF RAD50 GENOMIC SEQUENCE- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:92:- TTTCTAGTAA GATTGAATTG AATCGTAAGC TTATACAGGA CCAGCAGGAA CA - #GATTCAAC 60- ATCTAAAAAG TACAACAAAT GAGCTAAAAT CTGAGAAACT TCAGATATCC AC - #TAATTTGC 120- AACGTCGTCA GCAACTGGAG GAGCAGACTG TGGAATTATC CACTGAAGTT CA - #GTCTTTGT 180# 194- (2) INFORMATION FOR SEQ ID NO:93:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 239 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA (genomic)- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#5' END OF INTRON 16 OF RAD50 GENOMIC SEQUENCE- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:93:- GTAAGAATAT CCATACATGT TTTTTGTAAA ATTATTTTAA TTATTTATTT TT - #ATTTTTAT 60- TTTTTGAGAC AGTCTCGTTC TGTCACCCAG GCTGGAGTGC AGTAGCACGA TC - #TCGGCTCA 120- CTGCAACCTC CATCTCCTGG GTTCAAGTGA TTCTCTTGCC TCAGCCTCTG GA - #GTAGCTGG 180- GATTACAGGC GTGCACCACC ATGCCTGGCT AATTTTTGTT CTTTTAGTAG AA - #ACGGGTT 239- (2) INFORMATION FOR SEQ ID NO:94:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 367 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA (genomic)- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#3' END OF INTRON 16 OF RAD50 GENOMIC SEQUENCE- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:94:- GTTGAAGCCA CACGCTAATA TAATTGGGAG CACATGGCCT AGATTAAGAT CA - #AATTAGTG 60- GTTGATGCAG TATAGCATGC GTAGTGGTTA AGAGCGTGAA CTCTGGAGCT GG - #ACTGGGTT 120- AAAATCTTGG CTGCTTCATT TACTGGCTGT TGTGACCCTG GACAAATCAT TC - #TCTGTGTC 180- TGTTTGCTCG TTTGAAATAT AGGACTGAAA ATGATGGTAC TGTCCTCATA GG - #GTCATTGA 240- AAGGAGCAAA TGAGTTGACT TTTAGAGCCT GGCACATAGA AAGTGCTTTT AT - #TAAGACTG 300- TGAAGTCTGA CCCCTAAAGT AAGATAATGG AATATTATAT AATACTTTAT CT - #TTTTTATA 360# 367- (2) INFORMATION FOR SEQ ID NO:95:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 111 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA (genomic)- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#EXON 17 OF RAD50 GENOMIC SEQUENCE- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:95:- GATGCTAAAG AGCAGGTAAG CCCTTTGGAA ACAACATTGG AAAAGTTCCA GC - #AAGAAAAA 60# 111ACAAAAA AAATACAAGC AACAAAATAG CACAGGATAA A- (2) INFORMATION FOR SEQ ID NO:96:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 391 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA (genomic)- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#INTRON 17 OF RAD50 GENOMIC SEQUENCE- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:96:- GTAAGATTTC ATTTATATAT TTACTTATCA AATATCTGTA TTAAACTTAT GT - #TCATAGCA 60- CCACGTCGGA CACTTATTTC ACATGAAATT AAATAGCATA AGATAAATAG TA - #TTTTCAGA 120- TTCATGGTAT AATTTTGACA TTAGAAATTC TTGTTAGAAC AAGGATTTGA TG - #TAAATTAT 180- TTTGCTGCTT GATCTACAAT AGAAGTTAAG AAATGAGACT AATTAATCAA TT - #CCTATAGG 240- TGAGAAAGGG ACTTGTCTGC GATCATAAAA TTCAGTAGTG GTGGAAACTG GA - #ACCCAATG 300- TTCATAACTT CCCAGCCAGT GTTTTACTGT GCTCTCCTGT TATGTGCCCT TA - #AGTACAAC 360# 391 AATA TTTTTCTACA G- (2) INFORMATION FOR SEQ ID NO:97:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 93 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA (genomic)- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#EXON 18 OF RAD50 GENOMIC SEQUENCE- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:97:- CTGAATGATA TTAAAGAGAA GGTTAAAAAT ATTCATGGCT ATATGAAAGA CA - #TTGAGAAT 60# 93 AAGA CGACTATAAG AAG- (2) INFORMATION FOR SEQ ID NO:98:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 73 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA (genomic)- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#INTRON 18 OF RAD50 GENOMIC SEQUENCE- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:98:- GTAATTTAAA ACTTAAAATT ATTTATTTGA TTGTATTTTT ATTCATGTGC TT - #AAAGAATT 60# 73- (2) INFORMATION FOR SEQ ID NO:99:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 114 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA (genomic)- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#EXON 19 OF RAD50 GENOMIC SEQUENCE- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:99:- CAAAAAGAAA CTGAACTTAA TAAAGTAATA GCTCAACTAA GTGAATGCGA GA - #AACACAAA 60- GAAAAGATAA ATGAAGATAT GAGACTCATG AGACAAGATA TTGATACACA GA - #AG 114- (2) INFORMATION FOR SEQ ID NO:100:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 249 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA (genomic)- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#5' END OF INTRON 19 OF RAD50 GENOMIC SEQUENCE- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:100:- GTAGGTCTGT TTTGCTTATG ATATCACTTA CACCTATGAC ATTCTTTTCT AT - #AGTTTTAT 60- TTTCAATAGA AGATCCATTG AATAGAAATG CAAAAAGGAA AGAGGCCAAG CG - #TGGTGGCT 120- CACACCTGTA ATCCCTGCAC TTTGGAAGGC CGAGGCGGGT GGATCACTTG AG - #GCCAGGAG 180- ATCAAGACCA GCCTGGCCAA CACAGTGAAA CCCTGTCTGT ACTGAAAATA CA - #AAAATTAG 240# 249- (2) INFORMATION FOR SEQ ID NO:101:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 5543 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA (genomic)- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#3' END OF INTRON 19 OF RAD50 GENOMIC SEQUENCE- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:101:- TCACATGCTT TATGCAAGCA TGGTAGTTAA TGCCTTTAAA AACTATACCA TT - #TCTCTGTT 60- CTTACTGTTT TAAACAAAAT TTACTATTTG AATGCCTTAA CCACTTGGTT AT - #AAGTGGTT 120- GCTTAAAATC ATTTGGAAGA TTAGTTACAT TAGTTTTCTG CTGGGTCTCT TT - #CTGTACCA 180- CCAAGAATTT CAAATATATG AAATATCAGT CAAAGGGAGA TCAAATCTCT GC - #CTGGCCTA 240- ATACATATTG AATAACTGTA TAAATTTATG ATGCATATAT AACAAAATAA TT - #ATCACTAG 300- CTTTTATGTA GTTGCCTATA TAAAAATCAC AATCTGTAAA TTCGCAGCAG CT - #CTCTGTAT 360- ATATATACGA AATTGTTAAG ATTAATGATC TATGACCCCT TTTAAAGTGA TG - #GTCTAAAC 420- TTAGTGGATC TGATGGTATT AGTTTACTTT GTAACCTTCC TTGTTCCAGA AA - #TTATTTAC 480- TTAGTTATAT ACAATAGAGC AAAGATAAAT GTATTTCAAA TTAATGGGAA AA - #CAAGGCAG 540- TGTAGAAATA AGGGCAAGAA AGTAATGAAA CCAGGAGAGA AGTGTATAAA AA - #GTATGCAT 600- GAAGTCTGAT ATGCTTGCTG AAGATTCTAG TAGTCAAATA AAGAGAGGAG GC - #CAGGCGCA 660- GTGACTCATG CCTGTAATCC CAGCACTTTG GGAGGCCAAG GCAGACGGAT CA - #CCTGAGGT 720- CAGGAGTTCA AGACTAGCCT GGCCAATATG GTAAAACCCC ATCTCTACTG AA - #AATAGAAA 780- AATTAGCCAG GTGTGGTGAC ACGCGCCTGT AATCCCAGGT ACTCAGGAGG CT - #GAGGCAGG 840- AGAATCGCTT GAACCTGGGA GGCAGAGATT GCAGTGAGCC GAGATCACAC CA - #TTGCACTT 900- CAGCCTGGGT GACAAGAGTG AAACTCCGTC TCAAACAAAC AAACAAACAA AC - #AGAAACAA 960- AAACAGCCAG GCGTGGTGGC TCACGCCTGT AATCCCAGCA CTTTGGGAGG CC - #AAGGCGGG1020- CAGATCACGA GGTCAGGAGA TCGAGACCAT CCTGGCTAAC ACGCCGAAAC CC - #CGTCTCTA1080- CTAAAAAATA CAAAAAATTA GCCAGGCCTG GTGGTGGGCG CCTGTAGTCC CA - #GCTACTCA1140- GGAAGCTGAG GCAGGAGAAT GGCGTGAACC TGGGAGGCAG AGCTTGCAGT GA - #GCCGAGAT1200- CGCACCACTG CACTCCAGCC TGGGTGACAG AGCCAGACTC CGTCTTAAAA AA - #AAAAAAAA1260- AAAAAAAAAA GTCACAATTA GTCAAGATTC ACATTGTGTC AATGCTAAAA GA - #AAACCAGT1320- TTCCTATACT GACTACAGGA TAATGTCTCT ATTCATAGAA AGGAAGACAT GT - #ATAGTCTT1380- CAACAGACTT CGCAGGGCTT TAAAAAAAAT ACAGTGTATC TCAGCATCAT TA - #TTCCTTGA1440- TACGAGGTTC TGTAGAGGGT GGTATGATTG AAGCCTGAAG TAAATGTTAA TG - #TTTAGAAA1500- GCAAAGGTTC TTAGCTAGGG GCACCTGTAA ATCGTCTGAG TTTTTCCACT TC - #TAGGTATA1560- GAACTAAGAA AATTGAAAAC ATATGTTCCC ACAACAACTT GTACAAGAAT GC - #TCATAGCA1620- GCATTATTTG TAATAGTCAA AATATGGACA CACCCAAATG GCCATCAACT GA - #TGATCAGA1680- TAAACAAAAT GTGGTATACC CATACAATGG AATATTATTC AGCCATAAAA AG - #GATACATG1740- CTACCACATG AATGAACCCT TAAAACATGC TAAGCAAAAG AAGCCAGTCA CA - #AAAGGTCA1800- CATAATGTAC GATTCCACTT ATAATAAATG TACAGATTAG GTAAATCCAG TG - #ACAGCAGA1860- TTAATGTTTC CAGGGGGCTA GAGGTGAGGA AGGAATAGAG TGACTGCTAT TG - #AATATGAG1920- ATTTCCTTTT GGGATGATCA AATGCTCTGG AATTGGATAG TGGTGATGGT TG - #TATAACCT1980- TGTAAATAAA GTAAAACTGC TAAATTGTAC ACGTTTAAAC AGTGAATTTT GT - #GGAATATT2040- AATTACATCT CAGTTTTTAA AAAATGACTT AGGTTATTAA AAATACATGT GT - #TGGCCGGG2100- CACAGTGGCT CATGCCTGTA ATCCTAGCAC TTTGGGAGGC CGAGGCGGGC AG - #ATTGCTTG2160- AGCCTGGGAG TTCCAGACTA TCCTGGGCAA TATGGCGAAA CCCCATCTCT AC - #AAAAAAAT2220- TAGCCAGGTG TGATGGTGCA TACCTGTAGT CCCAGCTACT CAGGAGGCTG AG - #GTGGGAGG2280- ATTGCTTGAG CTGGGGAGTT CAAGGCTGCA GTGAGCCCTT ACTACGCCAC TG - #CACTCCAG2340- CCTGGGCAAC AGAGCAAGAC CCTGTCTCAA AAAATATATA TATATATATG TC - #TATGTCTC2400- CAATCCACAC CAGTAAATCA GAATCTTGGG GGTTTGGGCA GAGATATGTG TG - #TTTTGTTG2460- AAATTCCTTA GAGGTTCTAA TATATCCCTT TAGCTGTCAA TAACTGAGCC AG - #CACTGGAT2520- GGACTGCATA GCTTTCAGGC AGTCTTGTAG AAGTGGTGTT ATTCCCAGCT AG - #ACTTTTGG2580- TGGACATTGG ACTGTAATCT GTTCAGCATG CCACTCTCTC ACAGGTATCT AG - #AATGCAGC2640- TAATTTTTAT GTTTCCATAG GTGACCAGCT GCATGCATTA ACTGTCATCT GA - #GTTGGATG2700- ATTGGGGTTA ATATTTAAGA GCTGAGGAGC CTAACAGTCA CTTATTTACG TA - #CTGATTTA2760- AGCCCTGCTA AATTTAGTCC ACAGAATAAA ATAATTTGGA AACTTAACTG CC - #TTTCTCAG2820- TTTTCAGCTG AAGGAATATA TGAAGAGAAC TGTAGGTGAC CTGACTTGTC CA - #AGGTCACA2880- AAAAGTAGTA ACAGGTAGAA CTGGACCCTA CACTATCAAA TTTCTAGTAG AA - #TGGAAAAA2940- CATTTGTGGT ATACTATAAC TGCATCTGAT TTTTTTTCCC TTCCTTTCTC TG - #ATACATTT3000- TGTAGACTAT AATTGGAATT CTCACTGCTT ACAGTACAAA GGACAAATTT GA - #CCCAAAAG3060- GCATTTTATT AGCAATTATT GAGTCAGGCA CTATACTGAT TACATACACT CA - #TTCCTTTA3120- ATCTTCACAA TAGTCTTTTT TTTTTTTTTT TTTTTTTTAA ATTAGATGGA GT - #CTTGCTCT3180- CTCACCCAGG CTGGAGTGCA GTGGCACAAT CTCGGCTCAC TGCAACATTC GC - #CTCCCGGG3240- TTCAAGTGAT TCTCCTGCCT CAACCTGCCT GGGGCTACAG GCGAGTGCCA CC - #AGGCCTGG3300- CTAATTTTTG TATTTTTAGT AGAGGTGGGG TTTCACTATG TTGGCCAGGA TG - #ATCTCGAA3360- CTCCTGACCT CAAGTAATCC ATCTGCCTTG GCCTCCCAAA GTGCTGGGAT TA - #CAGGTATG3420- AGCCACCACG CCCGGCCACA CAATAGTTCT TTATGATAGA TAGTATCATT AT - #TGACCATG3480- TTATAAGCAA ACTGAGGTTC AGAGAATTTA AACTAATTTG CCCAAAGTTA TC - #CAGTTTAA3540- AAGTAATAAC ACTGTGATTT GAGCCTAGAT GTATCTGACT TCAAAGCATT AC - #ACTCTTGA3600- TGTGGTATAT ACTGTCTTTC AAAACTAGAA GAATAATGGA AGCTGACCTA AA - #ACAAAGAA3660- ATGCCTAGCT GTCTGGTAAC AATGCAGGTA GACAGACCAG CAACAATATT TT - #GTGCCAAA3720- AATCAGTCTC ATCTAAAAAT GTGATAGCAC TTTAAAGAGT CCTTTCATGC AA - #TTGTGAAA3780- ACAAATTCAA ATGTTCTGGG GTATTAGATG AAAGTAAGCA GTAGCACATT CC - #CTTGTTCC3840- TAATAAGGAA CAACAAGCAT AGTACCCCAT AGTAGAACCT TGGTAAGTCA CA - #CCAGCTAC3900- AGTGGTACAT TAGATTGCTT TAGCAACAAA GGACATTTAT AACCATGTCA TT - #TTAGTCAC3960- CTTTAACTGC CTATAATAAT GCCTTTAGTA GATACATATT CAGTTGTCTC GG - #TATCTCTG4020- GGAGGGATTG GTTCCAGGAT CCCCCGATAA AACAGATACC GAAATCTAGG AT - #GCTCAAGT4080- CCCTTATATA AAATGGCATA TCTAGTGTTT ACATATAGCC TATCCATATC CT - #CTGATATA4140- CTTTAATCTC TAGATTGCTT TTGATATTAA TATGTAAATG ATACGTAGTT TT - #TATATTGT4200- ATTATTTTAA ATTTGTATTT TTTTATTGTA CTATTACTTT TTATTTTTTT TC - #CCCAATAT4260- TTTTGATCCA TGGTTAGTTG AATCCGTAGA TGTGGACCCT GTGGATAAAT TG - #TATGTTTA4320- TATTATTTCC AGGAAAAATG AAAGTAGCCT TACTTTGTGA CTGTTAAAAA AG - #AAAAAAAA4380- AACTCTAAAA ATAGTCACGC ATAGAGGGGC AGGATTGGAT ATGAACATTA AG - #CATGTGAG4440- AGAAATCCTT GATTTCCCTC TCTCATCTAC CAGTCCCTGG CCTTTACTGT TG - #GTGCAAGA4500- TATTGCCACA GGTCTGTCCA TCTCTCTCAC TTCCCATGTC ACTGAGTTTA GC - #TTAGCTGC4560- AAGGGCTATT GCAGGAGGGT CCCAGCTCCC TCTTTGAGAA ATCCTTACTC CA - #AATTCAGA4620- ATAAGTTTTC TATACACATG ATTTGTGGGC CAAATCACCC TTCTTTCTGC AG - #GAAATTTT4680- TTTTCCTCTA AATTCCAAAG AATCAACTTA AAAACTGTTT TCTAATGATT GT - #CTCTTGAC4740- AACATAGTTC ATTTTAATCA CCAGGAAAAC CACTGAAATA ATTTTGTTGT TG - #TTGCTGCT4800- GCTGCTAAGT GTTATTGAGT CTCTTTTGAA GGACAAAACT ACTCAACAAG AA - #CAGCCAAT4860- TTTTTGAAAT TTCATTTCGG TGGCTAAGGA GGTACCAAGT TCATAGATAT AT - #GCTACTAT4920- TGTGGCACTT CTTACTGCCT TGAGTGATTA CAATTTGTCA ACCTAAAGGT AG - #AAGTTGCA4980- GGTAACATAT ACCTAACAGG TTCTAATGGT CTTGGTACAT GTTGGGAGAC AG - #AACTAGGA5040- CGAAAAAGTT GGGGAAGACT TCAGTAGTAG TATTGATCTC TTATAATCTT TC - #AGGTCAGT5100- AGGCTTTATC ATGGGGTTCC TATGCAAAAT GATCCACTGG GGATGTAGGT AT - #TAAAATAT5160- CTAGTTATAT TTTTAATTTC ACCATTTAAA ATGTCTGTTT TGTATGTTTT TA - #ATACTTTA5220- TAAGTAAATA AGTACACAGA TATATGCTCA AATCTTTATG AGACTCCCCA TC - #AAACAGTA5280- GACCTGGTTT TTAGATTATG GTTGTGAAAG AGCAGTAAAA GCTGCGCTAC AG - #GAGGTATT5340- ACACTTGTCA CTGTGGATGG GGATGGGCCA TCCAGATTGC CCCAGACCTG TA - #GATTCCTT5400- CACACTGGCT TATTCTCCCT CTGTTGAATT TCACATGATT CTAAGTAAGA CA - #GAAATGGC5460- ACTTGCTGTC ACCAGTTGCC TGTTACAGAT TTCATGTTAG TAACTTGGTT AT - #TTTTGTTA5520# 5543CCTT TAG- (2) INFORMATION FOR SEQ ID NO:102:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 128 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA (genomic)- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#EXON 20 OF RAD50 GENOMIC SEQUENCE- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:102:- ATACAAGAAA GGTGGCTACA AGATAACCTT ACTTTAAGAA AAAGAAATGA GG - #AACTAAAA 60- GAAGTTGAAG AAGAAAGAAA ACAACATTTG AAGGAAATGG GTCAAATGCA GG - #TTTTGCAA 120# 128- (2) INFORMATION FOR SEQ ID NO:103:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 1939 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA (genomic)- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#INTRON 20 OF RAD50 GENOMIC SEQUENCE- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:103:- GTATGCTTTT AAAATAATCT TCAGTTTAAA TAAACGTCTT TATTACTGGA AT - #GTGAAGAA 60- TATTAAATAC CTGTTTTAAA AGAATTTTAG CCTCAGCCTG GTATCCTTTG AG - #AGTTACTA 120- GAAGGTGAAC AGTGTTTGGA TACAATTATA TTTCATGGCC TTAAGAACTT TA - #TTACTGAA 180- GAAGTGATAT AGAATTGGTA ATCACACTGT AGTGATGGGC CTTAGTTATT CA - #GTATTGAA 240- CATGCTTAGC CCCCATACAT CTGCTAGCCT GCTGCACAGA ATAGTGGTAC TA - #AGCATAAA 300- GAATATGGAG CTGTGGACCT TGTCTGGGTC AGAGCTTGTA CAGTCTATAA TA - #TTGTCAAT 360- GGAGTTGTTG CCAGAGTGAT TTATCCACAG AGATTCATTT TAGATTTTCT CA - #TTTGTAAT 420- TATGTGTCCA CCAGAGCATT TCTTTTGAAA GATGAGCCTC ATTCTTCCTT TA - #TCTGGTCT 480- TATTGTTACT TATTGTAGTT GCTACCTTCC TGGTACAGCA GAAAAGATTT TA - #TTCCTGCC 540- TTGACTGCCT TAGAGTTAGT TGCCTTAGGA ATTCTGTAAG AACCTTGTTG AT - #GCTAAGGC 600- ACTAGACTGG TATAAAAGGT TGTACTAGGC AAATACTTAG ATTGTCAACC AC - #CTCAGCTG 660- GTTAAATCCA GGCCTCTCAT TTATTAAACC CTTCCTTGTA GAGTTTTCAT GT - #CTTCTTGA 720- ATTTATACAG AAATCTGAAT GAAAAAATGC CCAGGCTTTT CTAAAGGATA TA - #GTAAAGTG 780- AATTTTAATT TATAAAGCCT AACAAATGGT TAATCCTGTG TTTTGGTTAA GT - #ACTCTTAG 840- CTATTTAAAA TCTCTTTCCT ATATCAGGGA AATCAGATTT TTAACTAGAA GA - #GCTCATCA 900- TCTTCAGAGT CTTCATTTTT GTATGCATTA TGCACACTTA GACCCAGAAA AA - #TCACAGAG 960- GAAATTATGA TGAAAGCCAA GAATGTGACC CTAATATCCT AGTTCCCAAG CC - #TCAGTTCT1020- TTTACACGAT ACTCTCCATG GCAAGTTGGA AAAGTAATGC TTCTAGAAGA AA - #TTTTGATA1080- TAAAATAATA TATTCGTGGC TACTAAAGAC CAAAACCAGA TATTTAAAAA AT - #TTCTTCTG1140- TAATTGGTAC ATAACAGTAC TTTTTACATT CATTCACATT ACTAAGTACA AC - #TATTTTTC1200- AAACGTTTCT TCAACCAGGA CATAACAGAA ATGCCAACAA GACTTGTAAT CC - #AGTCGACT1260- CTGTAAGGAT GCCCATAAGC TTGAGAGTAG TGCCTGACAC ATAAGAGGAT GC - #TTAATAAG1320- TGATAATAAA TAAATGAAGA TTTTTAAAGC ATACATTGAA ATTTGTATAA TC - #TGCCAAAA1380- TATCAGAAAA GTTTGAATAT TTTACTTTTT TGGTCATTAT TATGGTTTTT AC - #ACTTGTGC1440- AAGAGAAATT TTGTTTTCAT GGAGGAATCT AAATTTTTAA TAAGTATTAC TG - #CAGAAAAT1500- TAATATATGA TTTAATTCGT ATTGTGCCTT TGACATGAGC AAAATGATGA TG - #AAGCCTGT1560- TATCCATAAC TTCTTAGTGT TGATAATTGT GCATTCTCAG TTCACAATCA GA - #AGATTGTG1620- AATTTGTAAT ATTAATCACC AGAGTGCTTT ACTTAGCGTC TAAAGGCCAG GA - #ACTTTATC1680- AGTGATCACA TGCTATGAGG GTTCTGTAAT ACACAAAATT AGCTATTTAG CA - #ACCTATGT1740- GCGGCAGAGA TATGGAAGGA AGAGAGGGGT TTTCTTTAGT ACCAAAGCCC TA - #AATAATAA1800- GCAAGGAGAG ACTCTGTTAT AATATACTGA TTGCTAAGGA GAATGATACT TA - #ACCTATCT1860- AAAGAAATCT ATGACTTTTC CACTTCAGGT TGTTAAAAGC TAAAAAATGG TC - #CTCATTTG1920# 193 - #9- (2) INFORMATION FOR SEQ ID NO:104:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 225 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA (genomic)- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#EXON 21 OF RAD50 GENOMIC SEQUENCE- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:104:- TGAACATCAG AAGTTGGAAG AGAACATAGA CAATATAAAA AGAAATCATA AT - #TTGGCATT 60- AGGGCGACAG AAAGGTTATG AAGAAGAAAT TATTCATTTT AAGAAAGAAC TT - #CGAGAACC 120- ACAATTTCGG GATGCTGAGG AAAAGTATAG AGAAATGATG ATTGTTATGA GG - #ACAACAGA 180# 225GG ATATTTATTA TAAGACTCTT GACCA- (2) INFORMATION FOR SEQ ID NO:105:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 13158 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA (genomic)- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#5' END OF INTRON 21 OF RAD50 GENOMIC SEQUENCE- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:105:- GTAAGTATTA GACTGGGGAT TTTCTTATTG CAGTTAATAT TAACTAACAT AC - #TTTAGTCA 60- TCTTTTCTCT CATTTTTTTC TTTTTTTCTT TTTTATTTTT TGAGACAGAG TT - #TCACTCTT 120- GTTTCCCAGG CTGGAGTGCA ATGGCACGAT CTCAGCTCAC TGCAACCTCT GC - #CTCCCGGG 180- TTCAAATGAT TCTCCTGCCT CATCCTCCCA AGTAGCTGGT ATTACAGGTG CA - #TGCCACCA 240- CGCTGGGCTA ATCTTGTATT TTTAGTAGAG ACGGGGTTTC TCCATGTAGG TC - #AGGCTGGT 300- CTCGAACTCC TGACCTGAGG TGATCCACCC GCCTCGGCCT CCCAAAGTGC TG - #GGATTACA 360- GGCATGAGCC ACTGCGCCCA GCCCCTCATT TTTTCTCTTT AAATATGGTA TT - #TTATGTAT 420- ACCATGGATT GGAAAATATA TGTATGTATG TATGTAAACA CACACTAGCT TA - #AGTTATGA 480- AGTTAAGATA TAAAGCATAT TAATATCTAC GAGTATTCAT GATACTACCT CC - #CTCTAACC 540- AATCTACCAT TATCACTGAT TGGCATCCAC TTAGATGCTC CCTTCTTATC TC - #AACCTTCT 600- GTCATCCCCA TTCCCTATAA CCAGTGACAA AGATTTTTAC TTTCTCTGCT TT - #TTTAAAAA 660- ACAGTTTTAT CATATATATG TCATATTTTG AGCTTTTTAA AAATGATATG AT - #ATTCTAGG 720- ACTTGCTTTT TTATTTGGAT TTGCTTTTGT TTATCCATGT TGTTTATGGC CG - #TAGTTGAT 780- TCATTTTCAC TGATGTACAT AATCTACTAT GGGAATAGAC CACAATGCAT TC - #ATTCTCCT 840- ACAGATGGAC ATTTGGGGTT TTTTTCCAGG TCTTGTCATG TCTTCTGGAG GA - #AAGGTATA 900- AGGTTATATT TGTGGGAGTG CATTGTGGAG TATGCTCAAT TTTACAAAAT AA - #TATTGTTT 960- TCCAGAAATG ACTACTGATT TATACCACTA GCAGTATATA AGGGTTTATT TG - #ATGGATCC1020- TCTGACATTG GTTTTATAAA TTTCTTAATG TTTGCCAACC TCATAGGTTT AA - #AATGATGA1080- ATCGTTGTTT ATACATTATT AGTCTTGTCT TTTTGTGTGT TTTGGGACAG AG - #TCTCTCTT1140- TGTCACCTAG GCTAGAGTGC AATGGTGCAA TCATAGTTCA GTGTAACCTC AA - #ACTCCTGG1200- GCTCAGGCAT TCCTCCCACT TCGGCCTCCC AAAGTGCTGG GGTCACAGGT GT - #GAGGCATT1260- GTTCCTGGCC CTATTGGTCT TTTCTTATTG ATTTAAATGT GTTCTTTATC TC - #TTCTGCAT1320- TTCAATTCCT TTTCAGTTAT ATGTATTACA AATGTCTTTT CAAACATTAT GC - #TTATCTTT1380- TTTACTTAGC ATCTTTTGAT GACACTGGAT TTGATTTTGA GTTAGTTGAA TT - #TAGCAGCC1440- TTTTCTGGTT AGCTCTTTGT GTGTCTTGTT AAGAAATCCT TCCCTACTCC TC - #TCTCTCTC1500- TCTCTCTCTC TCTCTCTACT CCTCTCTCTC TCTCTCTCTC TCTATATATA TA - #TATATAAA1560- GATATATATA TATAAAGATA TATATATATA TAGAGAGAGA GAGAGAGAGA TA - #TATCTTTT1620- TTTTTTTTGA GACGGAGTCT CACTCAGTCG CCCAGGCTGG AGTGCAGTGG CG - #CCATCTCG1680- GCTCACTGCA AGCTCTGCCT CCCAGGTTCA CGCCATTCTC CTGCCTCAGC CT - #CCTGAGTA1740- GCTGGGACTA CAGGCGCCCG CCACTACGCC CGGCTAATTT TATTGCATTT TT - #AGTAGAGA1800- TGGGGTTTCA CCGTGTTAGC CAGGATGGTC TCGATTTCCT GACCTCGTGA TC - #CACCTGTA1860- TTGGCCTCCC AAAGTGCTGG GATTACAGGC GTGAGCTGCC ACGCCCTACT TC - #TATATTTT1920- TGTCTAAAAG TTTTAAATTT TGCCTTTCAC ATGTAAGTAC ATTTAAGTAT TT - #AATTCTAA1980- GTTGAATTTT TTCCGTTATG AATAACTGGT TGTCTTGGCT CTATTTATTG TA - #GACTATCC2040- TTCTCTCAGT GACCTACAGT GTCATTTCTG TCATATATCA GAATTCCCTA TG - #TGCCTGGG2100- TTGGCCTGGG TTCTCTGTTC TACTTAATTC ATCACTTTGT CTATCTCTGT GC - #CATTTCTC2160- TCACCATCTT AATTACATAT AGCAGAATTT TCTTTATCCA GTGTATGTCT GT - #CTTTTAAC2220- CAGTGAATTT AGGCCTTTCA TATTCATTCT GATTACTCAA TTGAGTTGGA TT - #TATTTCTG2280- CCATCTTTTT TTCCTTTCCT GCCTTTTTGA GATGGATTTA TTTTTCTTGA CT - #CCTCCTTT2340- TTCCCTTCTT TGGGTTATCC AGTTGACCAT ATAACATGGG GATTAGGGAC AC - #TAAGCCCC2400- CCACGCAGTC AGAAATCCAC ATATAACTTT TGATTCCCTC AGAACTTAAC TA - #CTAATAGC2460- CTACTGTTGA CTGGAAGCCT TACTGATAAC AGAAACAGTT GATTAACATA TA - #TTTTGTAT2520- GTTATGTGTA TTATATGCAG TATTCTTTCA CAATAAAGTA AACTGGAGAC AA - #GAAAAAAT2580- TATAAGGGAA AATATATTTT CTGTTAAGTG GAAATGAATC ATCATAAAGG TC - #TTCATCCT2640- TGTCCTCTTC ACATTGAAGA GGAGGAGGAA GAAGAGGAGG GGTCAGTCTT GC - #TGTCTCGG2700- ATGGCAGAGG TGGAAGAAAA TCTACATAAA CATAGACCCA CATGGTTCAA AC - #CTGTGTTC2760- AAGGATCGGT TGTATTCTAC TTTAGTTATT TGAGTGTTTA CTTTTTAATT TT - #TAAATACT2820- TATTTGACTT AAAATCATAT GCATTAGTTC TCAAAGTGGT CGTGGAGCAC CA - #TTATCAGT2880- ATCACCTTGG AACATGTTAG AAATGCCTCT CAGCTTCTAC CCCAGACCTC GA - #TCAAAAAT2940- TTGAGAGGTA GGGCCCAGCA GTCTATTTTT GACAGACATT TTGGGTGATT CT - #GATGCACA3000- TCAAAGTTTA AAAACCATAG CTTTAATGTG AATTGTTTTA TCTTTTTCCT GA - #ATACTAAT3060- TATCTTCTCT CATCTGCATT ATTTCTTTTG TCTAATATTT TAGTTTTACC TT - #GTTTTTAA3120- ATCATCACAA ATGAGTAATA ATTATTGTGG TGGTTTCATA AGCCCGCATG TT - #TCCCAATT3180- TCTTTGTTCA TTCTTGCTTT TTAAATCCCA CTCCTCCCTT CTTTAGGTTC AG - #TTTTCTTT3240- TTTTGGAGTA TATTCTTCAA TAGTTTTTTC AGTGAATGAC TGTTAGTGGT AA - #ACAATCAG3300- TCTTTGAGAA GTTTTTCCCC TTAATTTGAT AGTTTAGCTG AGCATAGAGT TC - #TAGATTGA3360- CAGTTTTGTT CTCTTGGCAC TTTGAAAATA TTTCATTTTT TGTTGGCCTC TA - #TGGTTACA3420- GTTGAGAAAT CATTTTAATT ATTCCTTTAA AAGTAATCTG CCTTTTTCCC CT - #GGTTCTCT3480- TAGGATTTTT CCCTTTGTCT TCAGTGTTCT GTATTTTTAT AATAGTGTGT CT - #AGACTCAG3540- CTTTAGTTCT TCTGCTCATA AATTATGCTT TTTGATCTGA GGATTGATAT CT - #TCCATCAA3600- TTTTGGGGAT TTTTCATACA TTATCTCTTC AAATATTATT CTTTCTCCAT TT - #CTCACTAT3660- TTTCCCCTTC TTCACTTTTT ATTAGACATA ACCTCCTCTT TCCTCTACAT TG - #CTTAACCC3720- CTCTTGCATA TACTGGGCTC TGGGTAAATA TCTTGTTAAA TAAATTATTT AG - #CTGCTACT3780- TATACTGCCT ATTGAGTTGT CATTTTTTCC TCCATTTTTT TCTATAAGTT CT - #ATTTTGTT3840- CTTTTTCAGA AACTCACATG GTTTTTTTAT AATTTTTTTT TTTTAAAACA GA - #GTCTGGCT3900- CTGTCGCCCA GGCTAGAGTG CAGTGGCATG ATCTCGGCTC ACTGCAGCCT CC - #ACCTCCTG3960- AGTTCAAGCA GTTCTCATTC CTCAGCCTCC CAGATAGCTG GAATTACAGA TG - #CATGCCAC4020- CACTCGGCTA ATTTTTGTAT TTTTATTACA GATGGGGTTT TGTCATGTTG CC - #CCGGCTGG4080- TCTTGAACTC CTGGCCTCAA GCGATCCTCC TGCCTAGGTC TCCCAAAATG CT - #AGGATTAC4140- AGATGCGAGC CACTGCGCCA GGCCTATGAT GTATTTTCTT CCTTTGTATT TT - #GATTCCTT4200- CTTGAATGTG TCTTTACTCA TTTTATACAC ATTTTATACC TAGGCCTCCC AA - #AGTGCTAG4260- GATTACAGAT GTGAGCCACT GTGCCAGGCT TATGATGTAT TTTCTTCCTT AG - #TATTTTGA4320- TTCCTTCTTG AATGTGTCTT TACTCATTTT AACTATACAC ATTTTATATT CT - #CTTTCAGA4380- TTGTTATTTT TTAATTTCAC ATTTTGAGGA GTCTGCTTCT GCTGTTTTGT AT - #GTTGATTC4440- TATCCCCTAG TGAAGTTTCT GTGTTTTATT AACATTTAAT TGTGTGCTTA TC - #TTTAGTAG4500- TGTTGTTTTT TCTATGAGAC TCCCTTGTGA CCTTTCCTTG TAGAGGTCCA TC - #TACACAGA4560- AATTTTGGTT TTATATTAAC TAAGAGCTCC AGAGAAAACA TTGGCCTGCA TG - #TAGGGTTT4620- TTGTTAATTT CTTAGTTGGT AGGTTCCTAG ACTATACTCA CTGGTAGCAT AA - #CTTTGAAC4680- CCCAAAACTA TATAAAGCAT TTGCCCAAGA CTTTGAATTT TCAACTCATT AA - #TTTTCCAC4740- TCTTTCATTG AGGATTGATG TTATAGCTCT TGAAGAGTCC CATTTTTTGT GT - #GTTGGGAG4800- TCACTTCTAA TCTTCTTCCT TACTTGGGTC CTATCCTTCA TCTTCTGTCC TG - #GATGATAA4860- GAACCAATCC CTAGGTTATA AAAACAATAA CGCCAAGTTC ATGGCTGGGC AC - #GGTGGCTC4920- ATGCCTGTAA GCCCAGCACT TTGGGAGACC GAGGTGGGCG GATCACTTGA GG - #TGAGGAGT4980- TCAAGACCAG CCTGGCCAAC ATGGTGAAAC CCCGTCTGTA CTAAAAAAAA TA - #CAAAAATT5040- AGCTGGCTGT AGTGGTGCAC ACCTGTAATG CCAGCTACTC AGGAGGCTGA GG - #CAGGAGAA5100- TCGCTTGAAC TGGGAAGTAG AGGTTGCAGT GAGCCAAGAT TGCACCACTG CA - #CTCCAGCC5160- TGGGCAACAG AACGAGACTC TGTCTCAAAA CTAACAATAA CAGTAATAAT AA - #TAACCCCA5220- AGTTTAGTTT GTCTGTCAGG TTACATACTG ACTGGTCTGG TTTTCACTTC TA - #TCTTCGTT5280- TCTATTATGT AGGGATTTCC CTTTCTTTCT TGTGAGCTCA ACTATGAATT TA - #AAATAAGT5340- TTTGTTATAA GTCTATCTAG TAGTTCTGTT CATTTGTGGC AGGAGAATTA TT - #ACTTACCT5400- TAGATTTTGG TGGTGGTTGT TTTTTCCAGA ATGGCAAATA TCTTCCTTAG CA - #CTAAGAGA5460- GTTACACAGA GAGCTTCTCT TCTAAGACTT CTGGTCAGAT ACAGCATAGT CA - #ACAGACCA5520- ACCTGAGCAG TGGCATTCAG ACCACAGGGC TCAGGAAGAC AGGAGAACTC TG - #GTTTCAGT5580- ATGAGGACTT TTTTAGTTAG TGATGATAAC AAAGGTGGTC CCAGAATTGC CT - #AGGCATAT5640- TTTTGGCATA TACAAGTTTT AGGAAGTACG TAATCATGTA AGACAAATTA GA - #TCCATTTA5700- CTGTGAAATA TTGGGAGTGA GCCAATTAAC ATGTTATTTT TTAAAAATAA AT - #TATACTAA5760- GATTTTTGTT AGATTAAGTT TAACTTTTAA AACAATTTTT TGAGAGTATT CC - #ATGGATAT5820- ATCTTTTGTC CCATTTCATT GTGAGTGGGT ACGTTAACAT TACAATGTTC CC - #TGGGTCCA5880- AAATGGCTCA TAGAATTATA TGCCTGCACC AAATGAGAAC TTTTGTTTTT TA - #ACTTCTTT5940- GAATATTGCC ATCTCTCCTA GATATTAGAT CCAGCAGTTT AAAGTGGTTA GT - #CTTGGAAT6000- TTAAGGTGCT GAAACAAGAA CATAAGCAAA ACTTAAGGAA TTCTTGCCCA GT - #AGACTACA6060- CATACATATA TTTGTTTTTT GTTTTTTGGT TTTTTTTGCC TTTAATAATT CT - #TTTTAGTC6120- TTCTCAGCTA CCTCATTTAT GCCTTTAGGG GACTTTTTAG TTTTTCTTAG TT - #CTTTAACA6180- ACAGATGCTG TGTATCTAAT AGACTTATCA AACATTCATT GAGCATTAAG GA - #ATAGGAGA6240- TCCAGTAACT TCTAGCAAGG ATATTATAGT TTATTTGAAG AGACACAAAT CA - #AAACAGAT6300- TTTTGTTGGT AAAAACCTAT TTTGCCAGGC TTAGTGCTTA CGCCTGTAAT CC - #TAGCACTT6360- TGGGAGTCCA AAGTGGGTGG ATTGCTTAAG TCCAGGAGTT TGAGACCAAC CT - #GGGCAACA6420- TGGCGAAACC CCATCACTAC AAAAAAATAC AAAAATTATC TGGGCGTGGT AG - #CACACACC6480- TGTAATCCCA GCTACTCAGA AGCCCGTGGC GGGTTGCAAT GAGCCAAGAT TG - #TGCCAGTG6540- CACTCCAGCG TGGGTGACAG AAAGAGACCC TGTCTCAAAA AAAAAAAAAA AA - #AAAAAATC6600- ACCAAAACTT CTTTTTGGAA TAAGATAAGT TGGTTGTGAT GGAAAAATAA AA - #ATGGATAT6660- TAAAAGCAAG ACATTGGACT TTGTATAAAA GTCCAACATG ATAAGTTTTA CC - #TTTTTTAA6720- AAAGCCTCAG AAGTCCATAA TACATGGTTA AAAGTGCTGT CTCTGAACAC TA - #CAGATGTC6780- CAGATTTTGA ATTCTTTTTT TTTTTTTTTG AGACGGAGTC TCGCTCTGTC GC - #CCAGGCTG6840- GAGTGCAGTG GCGGGATCTC GGCTCACTGC AAGCTCCGCC TCCCGGGTTC AC - #GCCATTCT6900- CCTGCCTCAG CCTCCCAAGT AGCTGGGACT ACAGGCGCCC GCCACTACGC CC - #GGCTAATT6960- TTTTGTATTT TTAGTAGAGA CGGGGTTTCA CCGTTTTAGC CGGGATGGTC TC - #GATCTCCT7020- GACCTCGTGA TCCGCCCGCC TCGGCCTCCC AAAGTGCTGG GATTACAGGC GT - #GAGCACCG7080- CGCCCGGCCG AATTCTTTTT TTTAAAAAAA GTTTTATTCT TATTTTTTAT GG - #CTATATAG7140- CCGGTATATT TATGTGGTAC GTGAGATATT TTGATGCAGG CATACAATGC AT - #AATAATCA7200- CATCAGGGTA AATGAGGTTT CCATCACCTC AAGCATTTAT CCTTCCTTTT GT - #TACAGACA7260- TTCCAATTAT ACTATTTAGT TATTTTTAAA TGTACAATAC ATTGTTGACT GT - #AGTCACTC7320- TGTTGTGCTA TAATATACTA GATCTTATTC TTACTATATT TTTGTACTTG TT - #AACCATCT7380- CCACTGCCCT TCCTAGTCTC TGGTAACTAT CATCTCCACT ATCTCCATGA GT - #TCAATTGT7440- TTTAATTTTT CACTCCCACA AATGAATGAG AACATGCAAA GTTTGTCTTT CT - #GTGCCTGG7500- CTTATTTCAC CTAACATAAT GTCCTTCAGT TCCATCCATG TTATTCCAGA TG - #ACAGGATC7560- TCATTTTATT TTATGGCTGA ATAGCACTCC ATTGTATATA TGAACAACTT TT - #TTTTTTTT7620- TTGAGACGGA GTCTCTGTCT CCCAGGCTGA AGTGCAGTGG TGTGATTTCA GC - #TCACTGCA7680- ACCTCCACCT CAGCCTCCGA GTAGCTGGAA TTACAGGTTC CTGCCACCAC AC - #CTGGCTAA7740- TTTTTGTATT TTTAGTAGAA ACAGGGTTTT GCCATGTAGG CCATATTGAT CT - #CGAACTCC7800- TGACCTCAAA TGATCCACCC GCCTCAGCCT CCCACAGTGC TGGAATTAGA CG - #TGAGCCAC7860- CGCGCCCGAG AGGAACCACA TTTTCTTTAT CCATTTATCT GTTGATGGAC AC - #TTAGGTTG7920- CTTCCAAATC TTAGGTATTA TGAACAGTGC TGCAATAAAT ATGGGAGTGC AG - #ATATCTCC7980- TCAACCTAAT GATTTCATTT CCTTTGCGTA AATATCCAGT AAGTGGGATT GC - #AGAATCAT8040- ATGGTAGTTC TGTCTTTAGT TTTTTTAGGA ACCTCCATAC TATTCTCCAT AG - #TGGTGATT8100- TTGAGTCCTG ACTGAAGATA TTTAGCAAAT TATTTAGACA CTCTGAGTTT CC - #GTTTCCTC8160- ATCTATAAAA TAGAATTTTT AAAAATCTAT ACTATTATTC AGTATAGAGT CA - #GAAAAGCT8220- CAGAGGCGAT TTAGTCCAGC TTCCTTTGTC ATGTTCCATT CTTTAATGTA AG - #TTAAGTTC8280- TTAAATTCTC TATTCTTTAA TAGCACTAAA GAACTAAATT CATTAAGAAA AC - #GTAGGTTT8340- CTGTTCCCAT TTAAACATTC TTTGAGGTTG AGGGCTGTGC ATAGAAGACA AT - #AATAGCAA8400- TTGAATACTA CATGATAGCA TAATCGATTT AATTATTGTA TCTAACTCTG TT - #TTAAAGGG8460- CAAGTATTTA TCAGACAGAT TAAGCAGGCT ACCCAAGATT ACCCAGGTAA AT - #GGTAGAGA8520- TAAAATTAGA TATCAGAACC ACTGTGACAT GCTGCTACCA TAGTGGCCCC CT - #GCTTTTTT8580- TTTTATTTTT CTGGAGACGG AGTCTCACTG GTTCTCTCAG CTCTCTCAGG CT - #GGAGTGCA8640- GTGGCGTGAT CTCTGCTCAC TGTAACCTCT GCCTCTTGGG TTCAAGCGAT TC - #TCATGCCT8700- CAGCCTTCTA AGTAGCTGGG ATTACAGGCA TGTGCTACCA CACTGGGCTA AT - #TTTTGTAT8760- TTTTAGTAGA AACGAGGTTT CGCCATGATG ACCAGGCTAG TTTTGAACTC CT - #GGCCTCAA8820- GTGATCCACC CTCCTCAGCC TCCCAAAGTG CTGGGATTAC GGGCATGACC TT - #TTTTTATA8880- ACCGTTAAAA AACTAGTATT TATATAAAAG CATTTTAACT GTTACTTATA CT - #TCCTGGTT8940- TAGAACCATA ACTTATTTCT ATATATTTTG TAACTCTTCA GTGAGGTGCT TG - #TGTACATA9000- ATACATAGTT GTATATTAGG ATTTTGTTCA ATAAAAATTT GAGTACATAA AT - #GCTTGATA9060- CTGTTCTAGA TACTAAGTAT ATAAGGATGA AGAAACAAAA TTAAGAAATA AA - #TTAATAAC9120- AAAATGGGTA GTAGTGGTAG GTATTACAGT GAAAATGAAC AATGTGAGCA TA - #ACAGATGG9180- GCCTTTAAGC TGGGACCTGA TTGATGAGAA GGGAGCAAGA TATGCAAAAA AT - #GGGGTGCA9240- GGCGTTCCAG GTAGAGAGAA TAGTTACTGC AGCAGCCAAG ACCAGTACGA AC - #AGAAAGTG9300- TTCAAGGACC AGGAAGAAGG CAAGCATGGG TGGAATATAG TCAGGGATAG AC - #CATTCCCA9360- GAGTATGTCA TGCCTTGTAG CCTTGGTAAA CAAACAGTTT TATTTCATTC TA - #ACTGCATT9420- GGGCAGTCAC TGGAGGGTTT GAAGCAGGGA AGTAATATAA TCTGATTTCT AG - #TTGGAAGA9480- AATTGCACTG GCTGCTGGGT GTGGAGAATG GATTGTAAAG GGCAAGAGTA AA - #AGCAGAGA9540- CTGATGAGGA GACTTGTAGT AACCAAGAGA TGGTGGTGGG CTAGATCAGG TG - #GTAGCAGT9600- GAAAATGGAG AGAAGTGATA GACTTGGGAT TTGTTCTGGA GAGAGAGTTG AC - #AGGCCTTG9660- CTTCTGAATT GAGTGTAAGG GAGGGAAAGT AAAATAACCA AAGGTTGCTC CT - #ACATATTT9720- TTGCTTGAAC AACAGGATAT TGGGAGAACA GGTTGCCATT CCCTAAAATG GG - #TGGGACTG9780- GGGAGAGAAA ATCAGTAGTT CCGTTTTGTA CACTTTAAGT TTGAAGTGCC TG - #TAGATATC9840- TAAGCAGAGC TGTCAAGCAG GCAGTTGGAT ATATAACCTC GAGCCTAGAG TT - #CAAGTGAA9900- AGGTGTACAC TGGGGAGTCA TCAGCATATC CACGGCATTT AACCCATGAG AT - #GAGATCAC9960- ATGTGGAATG AGCATAGAGA GAGAAGGGAA AGGTCCCACC ACTAGTTATG TT - #TGCAAATC10020- CAGTAAATAA GCAGCTGGTG ATGTGGGAAA AGATTTTAAA AGATGTGGTA TC - #TTGAAAAC10080- CAAGTGAAGC AAATATATCA AGAATCTAAT GCTATTTGGA GTCAAATAAG AT - #AAGGACTA10140- AGAAGTGGCC CTTAAATTTG ACAAAATGGA AGTTGTTAAT GACTGAGGAG CA - #GTCAGTGG10200- CACAGTTGGA ACTGAAGCCC GGTCAAGTTG GGTGGGGAGA GAATGGGTAG TA - #AGAAATGG10260- AGACAGCAGC CGGGCACGGT GGCTCACACC TGTAATCCCA GCACTTTGGG AG - #GCCAGGGC10320- GGGTGGATCA CCTGAAGTCA GGAGTTCGAG ACCAGCCTGA CCAACATGGG GA - #AACCACGT10380- CTCTACTAAA AATGCAAAAA TTAGCTGGGC CTGGTGGTGC CTAGCCTGTA AT - #CCCAGCTA10440- CTCAGGAGGC TGAGGCAGGA GAATCGCCTG AACCCGGGAG GCGGAGGTTG CA - #GTGAGCCA10500- AGATCGTGCC ATTGTACTCC AGCCTGGGCA ACAAGAGAAA AAAACTGTCT CA - #GAAAAAAA10560- AAAGAAAAAG AAATGGAGAC AGAGAATATA GATAATTCTT ATAACAACTT CT - #CCTGTGAC10620- GGGGAGCAAG AAAAATGGGG CAATGGTTAG AGTGGACCAG GGACCAAGTT AA - #ATAGGCAG10680- GTTGGTTTTG TTTTCAATTT TACTTGTAAG TATTTTGCTG CAAGGTCAGC TC - #TTCTCTTA10740- CAGCCCATTG ACCTGCAGAC CTGGGGTTTC ATATGTATTC ACTGAATAGA AA - #AACATACG10800- TAGGAGCTCT CCAGCTATCC CTGCATACCC TGAGAACCAG TGGCAGCAGG AA - #TAAGAATT10860- CCCTTCACTT CCAAGATTAG GCTATAAGAG AAAAAATAAA AAAGAATTCA AC - #AACCCTTG10920- CTCTGCCACT TTCTTGTCAG GCTCTGGGAA AACAGGAATA TCTTTCCCTG TC - #CCTCCTCC10980- AAACTGCTGA CAGTCTGTCT GATGGAGACC TTGGTAGGTG CTCCATAGTC TG - #TTTTTGAC11040- CTGGGCCTGG GATAAGAAGG AAGGGCTTTT CAGCAGAGAA AAGTGCCTCA GT - #CACAGAGG11100- CATGCTGAGC AGAATGAGGA CCTATGAGGG AGCTTGGTGG AGCCTGGCGG GG - #TGGAGAGG11160- TACAGGAGTG CTTTCTAGCA ATTTAGGCTT GTTAAGGAAC AAAGCCAGGC TG - #TTTACTGA11220- GTTCTCTTAC CTGGTACTCA GATGGATTCT TCTAAATGAA AAGAGGTGAT AC - #AAATTTCC11280- CCAAAATTGA GTCTTTGTGG CTTATGCTCG CAAACAGTGG CCTTCTCAAG AT - #TTATACGG11340- TGAGCCCTAA ATTTGCCTTC TCACCCAGAA GAAAGTAAGG TACAAAATTT CC - #CTCATTCT11400- TTCACGTCTT AGAATAAAGC ATGCAGTCAG TGTAATTGTT GCGTTCAGCT GT - #CTATTTAA11460- GGTAACACAG GAAGTCAGCA GTGCATTTTC AAGAAAAGCT GATTACCATC TG - #TTATTAGT11520- AATCATCTAA AAACATCACT AAGATAAGCA TTGGCAGTGG TCAGAGACAC AT - #AGATGAAA11580- AGGGGGAAAT TATCCATCAT TTGGAATGTA TTACCCCATA CTAATACAAT AT - #ACCAATTT11640- AAATGATGTT AGAATATATC ACTCAAGATA TGGTGTTCTA CCCCATGCCC AA - #AATGTTCT11700- ACTCTCATTT TTCCCCAGAT GTGGAAGGTT GCATATTAGG TAATACTTTT TT - #TTTTTTTT11760- TTGAGACAGA GTTTCGCTCT TTTTGCCCAG GCTGGACTCC AATGGTGCGA TC - #TCAGCTCA11820- CTGCCATCTC CACCTCCCGG GTTCAAGCAA TTCTTCTGCC TCGGCCTCCC AA - #GTAGCTGG11880- GATTACAGGC GCCTGCCACC ACACCCGGCT AATTTTTTGT ATTTTAAGTA GA - #GACGGGGT11940- TTCACCATGT TGGCCAGGAT GGTCTTGATC TCTTGACCTT GTGATCCACC TG - #CCTTGGCC12000- TCCCAAAGTG CTGGGATTAC AAGCATGAGC CACGCACCTG GCCAGGTCAT GC - #TTCTTTTA12060- AGACTCATTG TAAACACGTA ACCTTTACAG TTTTGCATCC AAGGTAGCCA GC - #TTTCTGTG12120- AGGCTCTTCA GAGCCTGGGT CCCTGCATTC GAGGGGAGCT TCAGATGAGG GC - #TTTATTCA12180- GGGCTCACCT TAGAGTCACC ATCTCTATCA TGACCATGGA TGCAGTAAGG TT - #TCACAGTA12240- GCTCCTGCAA CCTCAAGAGG GTAGATTACA AAACCCAAAG ATAGCCAGTG GT - #GTTTCACA12300- CCTAAACAAA TGTTTATCTT GCCATAGTGA TTGAACCATA GGCTGAATTG TA - #AAAGCTGA12360- TGTTTGGGAG TCTAGCTAAA GAAAACTAAG TTAATAGGTT TAAAGAAGCA AG - #AGCTGGAA12420- GGGTCTTCTC CTGGAAGGTG AGATATTGGT CTGTGGGGTG TCCAAGGGAG AG - #AATCCAGT12480- CATGGGTTCT TAGCTTCTCT TTCTGGTTGG ACCAGTAAAG CCTCTTCCTC AT - #CCCTCTTT12540- TCTGCTCATC ACTAGAGACA AAACTAAAAA CCATGGCTTC AGTCTGCTAA AA - #GCCTAGAA12600- CAAAACAGAA CAACAAAATA AGGCAGGCTG GACAAGCTTG TTAAGACTTT CA - #TGGATTAC12660- CAGAAATATA AATGCCATTA AAGCCATCAT TTTTCCTCAT AAAATGCAAT CG - #ATTGTTAC12720- TGAAATTTTT AATGAAATCT TTCAGACTCT TAATGAGTAT TTAAATATCA GA - #CTAAAGTA12780- ATTTATAAAT CATTATTTTC TGAGCTCCGA GAGAGTCTCA CTTTTTTTTT TT - #TTTTTTTT12840- TAAGACAGAG TCTGGCTCTG TCACCCAGGC TGGAGTTCAT TCTTGCAAAC TC - #GGCTCACT12900- GTAACCTCCA CCTCCCAGGT TCAAGCGATC CTCCTGCCTC AGCCTCCCAA AT - #AGCTGGGA12960- TTACAGGTGC CCACCACCAC ACCGGCTAAT TTTTGTATTT TTAGTAGAGA TA - #GAGTTTTA13020- CCATGTTGGC CAGGGTGGTC TCTAACATCT GACCTCAAGT GATTTACCCA CC - #TTGGCCTC13080- CCAAAGTGCT GGGATTACAG GCGTGAGCAC CTCACCTGGC CTCTCACTTT AA - #GAGCCAGT13140# 131 - #58- (2) INFORMATION FOR SEQ ID NO:106:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 230 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA (genomic)- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#3' END OF INTRON 21 OF RAD50 GENOMIC SEQUENCE- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:106:- CCTGGAGCAC TAGAAATAAG CCTGCCAATT TTCAGTATTA GCCAAGCAGC AA - #AGTTTTGC 60- TGCTGTTTAT TTTTGTAGCT CTTACTATAT TCTACTTTTA CCATTGAAAA TA - #TTGAGGAA 120- GTTATTTATA TTTCTATTTT TTATATATTA TATATTTTAT GTATTTTAAT AT - #TACTATTA 180# 230TTATAT ATATGAAGTA CCAATGACTT CCTTTTCCAG- (2) INFORMATION FOR SEQ ID NO:107:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 86 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA (genomic)- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#EXON 22 OF RAD50 GENOMIC SEQUENCE- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:107:- AGCAATAATG AAATTTCACA GTATGAAAAT GGAAGAAATC AATAAAATTA TA - #CGTGACCT 60# 86 CGTG GACAAG- (2) INFORMATION FOR SEQ ID NO:108:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 233 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA (genomic)- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#5' END OF INTRON 22 OF RAD50 GENOMIC SEQUENCE- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:108:- GTGAGTACCA TGGTGTATCA CAAATGCTCT TTCCAAAGCC CTCTCCGCAG CT - #CTTCCCCT 60- TATGACCTCT CATCATGCCA GCATTACCTC CCTGGACCCC TTTCTAAGCA TG - #TCTTTGAG 120- ATTTTCTAAG AATTCTTATC TTGGCAACAT CTTGTAGCAA GAAAATGTAA AG - #TTTTCTGT 180- TCCAGAGCCT AACAGGACTT ACATATTTGA CTGCAGTAGG CATTATATTT AG - #C 233- (2) INFORMATION FOR SEQ ID NO:109:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 179 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA (genomic)- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#3' END OF INTRON 22 OF RAD50 GENOMIC SEQUENCE- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:109:- TGGCCAGACC ACCAGGCTCT TGAATCCTCC CAGCCAGAGA AAGAGTTTCC AC - #ACCAGCCA 60- TTGTTTTCCT CTGGTAATGT CAGCCTCATC TGTTGTTCCT AGGCTTACTT GA - #TATGTTTG 120- TAAATGACAA AAGGCTACAG AGCATAGGTT CCTCTAAAAT ATTCTTCTTC CT - #GTGTCAG 179- (2) INFORMATION FOR SEQ ID NO:110:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 143 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA (genomic)- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#EXON 23 OF RAD50 GENOMIC SEQUENCE- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:110:- ATATTGAATA CATAGAAATA CGGTCTGATG CCGATGAAAA TGTATCAGCT TC - #TGATAAAA 60- GGCGGAATTA TAACTACCGA GTGGTGATGC TGAAGGGAGA CACAGCCTTG GA - #TATGCGAG 120# 143ACAA AAG- (2) INFORMATION FOR SEQ ID NO:111:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 2448 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA (genomic)- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#INTRON 23 OF RAD50 GENOMIC SEQUENCE- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:111:- GCAGGTATCT CAAAAGCCTG GGGAGCCAAC TCACCCAAGT AACTGAAAGA GA - #GAAACAAA 60- CATCAGTGCA GTGGAAGCAC CCAAGGCTAC ACCTGAATGG TGGGAAGCTC TT - #TGCTGCTA 120- TATAAAATGA ATCAGGCTCA GCTACTATTA TTACACTCTC CTGAAGCTAA CC - #AACATTTC 180- CTGCAACATT ATGTAGACTT TTAAAAGAAG GGCCTGAAGC ATTCTCACAG GA - #TAGGCTAA 240- ATGTAGAACA AGAAGCTGAA GACCCGTTAG AGTTTTCATG GCACTCCTTA TC - #AGAATAAG 300- GTCACTGTCT CATCAGTTAT AAGACATACC ACTATTTTAT GTGCCAGCAG GA - #ATGAAAAA 360- ATGCAATTAT AACCATAAGA TGTTTCAGAA TCAATGACAT AATAGTATTG CA - #AACCAGAT 420- TCTAGCTTAA GCTAGAATGA ATATTCCAGT ATAGTAAGGA GTCTCATTAA GA - #AAGTAGCC 480- CCTCATAGAA CTAAGTCCCT ACCACAGCAT ACACAAAGAC TTAGCTGCTG GG - #TCAGGCCA 540- TCTGGCTTCA GGTAAGGCTC TGTGAGGACA GCCTACATTG GAAATCAGGA AG - #AGGAATGA 600- AGTTTTAAAG AATCAGGAAT ATGGCATCCT TGGGGAACAA GGCTGGATCC TT - #CACTGTGC 660- ACAGGTTTGT AACAAAGATG TCACAGATAC TTGAGCTTTC TGCTTTCAGA TC - #AAGGCAGA 720- AGATTACACT TGATAACACC TCTAGGCCCT TGACTTTTTT TAAATAAAAT TC - #TAAAATCA 780- TAGAAATAGA TGCTTACATT ATCTAACTCA TTTTCATAGT TTGCAGTTTT TG - #CTTAAAGA 840- ACATGCCATG CAGCTGGGCA TGGTGTCTCA CACCTGTAAT CGCAGCACTT TG - #GAAGGCCG 900- AGGCGGGCAG ATCACCTGAG GTCAGGAGTT CGAGACCAGC CTAACATGGT GA - #AACTCCGT 960- CTCTATTAAA AATACAAAAA TTAGCTGGGC ATGGTAGCAT GTGCCTGTAA TC - #CCAGCTAC1020- TCGGGAGGCT GAGGCAGGAG AATTGCTTGA ACCTGGGAGG CGGAGGTTGC AG - #TGAGCCGA1080- GATCGTGCCA TTGCACTCCA GCCCAGGCAA CAAGAGCGAA ACTCCGTCTC AA - #AAAAAAAA1140- AAAAAAAAGA ACATGCCATG CATATATGTA TTATGTTGTC AGCCTAGACA GC - #TGATCCCA1200- ATTTAAAGCA TCTGCAGATT ACTGTCTAAA TCATAGTCTA CAAAAATGAC AA - #ACTTGTGA1260- TCTGTAATCA GTATCCCTAC GTGCTTTGAT GATTTTTAGT GGTAATTATA AA - #TGAGAAAA1320- TACAGAGTTT GAAACATGGT CTCTTTGAAT TAAAAATACT TTCAAAAATA TC - #TTGAGGAA1380- AAAGATTTTT TGTAGCTATT CTGAGTTATG AAAATTAATT AGCAATAATT GT - #CTCCTTGG1440- TGTGAGGGGA GAGAACAAAT AATGGAGGTG GGCCTCCAGC CTACCTAACA CT - #GGCTTTTG1500- CTGAGGCTCT AGCAGCCAGC CAGGGGCTCT GCATGTGAGT GGGTGGTGGT AG - #AGTTGACA1560- GCAGTTTGGA TTCAAAGACA GGAAGGAAAT GCCTGTCCCT CACAGGGCCA AG - #CTGTGGCC1620- CTGTCTTCTG GCTTGCCTAG GCATTAAAGA AAAGACATAA ACTATTCTAA AA - #TTACCAAC1680- TCACTGATGT GTGCGCACCC ACCCACAAAC TGAGGGGGAA AGGGGACTTA CA - #GCTCACAC1740- CAGAGTAGTT TATACTTCCT AGAATAGCCC TACTCTCTCA ATTCTGTGTG TC - #TTGTATCC1800- TCAGATGGTT TCAGTGGGTC TGAGGGTTTT AGTATTAGGT TTCTAGTAAC CA - #CGAAAATG1860- CCTAACAGTT CCAGTTACTT GGATTTTCTA CAGGTAAGCT TAACTGAAAC CA - #CATTTCTA1920- TACTCCTGAT ACTTTGACCT AGGATTTTCT TTTTTATTCT CTCAGTCTCA GG - #ATTATACA1980- CAAGAATATG GAAATTTAAA GGTAGCAGAG AAAAAGTGAG AGGCTCTAGA AA - #ACGTGTCG2040- AAGTTTTCTA ACAGATCCCA TTATCAGGCA AATAGCCAGG TCAAGAATTT TT - #AAGGTTGC2100- TCATCTTACA GGATTATTAA AATTACAGAT AAATGGCATT GTCTCTGTTT CT - #AGCCTTTG2160- GTCTCAAGTT GGTTGTAGCT GATGTAATTT TTTATGTGAG AGCATCAGCG TT - #GTTCTGAG2220- CATTTTGTTT TGTGGTGAAT GATAGGCTGA GATCATGCAG GTTCTCCTTC TG - #GAGGACAT2280- AAGAATCTGG TCCCAGTGCT GGGCTCTCCC AGAGGGCAGT GCTTTACCTA AC - #AGTGAACC2340- TGTGACGTTT CCCACTTTTC CCTGCTGAAA AGATCATGTC AGGACTGCTT GC - #CTGCCATG2400# 2448GCTG GGCTTCTCAC ATAGGGGCTT TTTTCCAG- (2) INFORMATION FOR SEQ ID NO:112:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 134 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA (genomic)- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#EXON 24 OF RAD50 GENOMIC SEQUENCE- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:112:- GTATTAGCCT CACTCATCAT TCGCCTGGCC CTGGCTGAAA CGTTCTGCCT CA - #ACTGTGGC 60- ATCATTGCCT TGGATGAGCC AACAACAAAT CTTGACCGAG AAAACATTGA AT - #CTCTTGCA 120# 134- (2) INFORMATION FOR SEQ ID NO:113:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 1371 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA (genomic)- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#INTRON 24 OF RAD50 GENOMIC SEQUENCE- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:113:- GTAAGTATCT CTTGCACATG CTCTGGTTGA GTAAGTATCT CACATTTGGG GA - #CAGGTTGT 60- GATAGTTCTT CAAAACCAAG AGAGTTCTGT GATGAAAACG TTCTCTAGCT GT - #GTTCCCCA 120- CTTCTTGGGG AAGCCAGTTG GTGCCAGGCC CTGGGCTTTA CCTTTTGATA GT - #AATTCTTC 180- AGATCCCTCC TAAAGGAACT AGATGGTGAA CAGCAGCCCC AGACACATCC TG - #CAGCTCCC 240- CAAGTGTGTT CACAGGGAGA GAGTCACTGT GAGGGGTTCC TGGCCTGGTT TT - #CCTGTAAA 300- CCTACCAGAG GAACCCACAT GTCATGCACA GCAATTAGCA TGCCCTGCTA AG - #ACATCTGC 360- AGGTAGTGGT AGTGGGTTTA GGACTGTCTC CCCAGCTTTC CACATGTGTC AG - #AGAACTGT 420- GAGGAATGAC AGAGCTCTTA CTCAAAAAGC TTATTTGAGA TTAGGTAAAG TC - #CAGTGAGG 480- GTAAAATTGC ACACCTTTTA CCACATTCAC CTGGGGTCAG TGTAGACGCC AA - #GGTTGTCA 540- AGCAGCTCTT GCATAAGGAC TATGCTGGCA GAGAAAAAGG CAGTTTCCCT GA - #GGTCAAAG 600- GAGGTGTTTC AGGCACTCCT GGCTCCAGAC AGTCCCTTTC TGGCAGAGAG GG - #CCAGAAGG 660- AGAGCTCAGC AGCGCAGGGC CACCTTTCTG CAGCCATCAT CACAAGTAAG GG - #CGAGTGCT 720- TTTGAAACCT CAAATGCATC CAGCTCCAGG AAGGGGATAA GTGGCTAGCT AA - #AAGAAAAA 780- GTCTTTCAGG TTTCAGTCAC ATTGCTGGTT ACCTCAGCAA AATGTTCCCA GA - #ACACCCAC 840- TCAGGTCCCT GTGTGTCATA GTAATGATGC ATCTAGTGAC TGGTGGTGGC AG - #AATTCTAA 900- GTAGACCCAG CTCTTAAGAA AGCAGTGTTA TTCCCCTTAC CTGTAGTTTG TC - #TTTATTAC 960- TTTTAAATTT TTCTTCCAGA GAAAAGTAGT AACAGGTCAG GAAAATCCCA GG - #CGAAGGAG1020- TAAGCCTTCT ATAGTTGAAC AGTTTGGATA TTAAGGAAAA CTCAATAAAA TA - #TTTATACC1080- TGCTTTAGTG AGAACTTCTG ATCTGGAAGA AACTAGTTCT TGTATTCCTG TG - #AGTCCCTA1140- AGCCAGACCT AAGTGAGGAG TCAGGCCATG TGTCCCTACT GTCTGGAGAG GA - #GAAGAGAC1200- TCCTGCCTGG CTGCCTGAAG GCCTGGGGCC ACCCCTCCAC TTCCTGCAGG GT - #AGCTGGGG1260- CCCTGACACA CAGCACAAGT TCATGTGTCT GACAAGGTTT GCGGTGACTT TT - #CAAATCAA1320# 1371CTCTTTA CTAATAATAT GTTCTGAATA TATTGTTGCA G- (2) INFORMATION FOR SEQ ID NO:114:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 1730 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA (genomic)- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#EXON 25 OF RAD50 GENOMIC SEQUENCE- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:114:- GATAATAAAA AGTCGCTCAC AGCAGCGTAA CTTCCAGCTT CTGGTAATCA CT - #CATGATGA 60- AGATTTTGTG GAGCTTTTAG GACGTTCTGA ATATGTGGAG AAATTCTACA GG - #ATTAAAAA 120- GAACATCGAT CAGTGCTCAG AGATTGTGAA ATGCAGTGTT AGCTCCCTGG GA - #TTCAATGT 180- TCATTAAAAA TATCCAAGAT TTAAATGCCA TAGAAATGTA GGTCCTCAGA AA - #GTGTATAA 240- TAAGAAACTT ATTTCTCATA TCAACTTAGT CAATAAGAAA ATATATTCTT TC - #AAAGGAAC 300- ATTGTGTCTA GGATTTTGGA TGTTGAGAGG TTCTAAAATC ATGAAACTTG TT - #TCACTGAA 360- AATTGGACAG ATTGCCTGTT TCTGATTTGC TGCTCTTCAT CCCATTCCAG GC - #AGCCTCTG 420- TCAGGCCTTC AGGGTTCAGC AGTACAGCCG AGACTCGACT CTGTGCCTCC CT - #CCCCAGTG 480- CAAATGCATG CTTCTTCTCA AAGCACTGTT GAGAAGGAGA TAATTACTGC CT - #TGAAAATT 540- TATGGTTTTG GTATTTTTTT AAATCATAGT TAAATGTTAC CTCTGAATTT AC - #TTCCTTGC 600- ATGTGGTTTG AAAAACTGAG TATTAATATC TGAGGATGAC CAGAAATGGT GA - #GATGTATG 660- TTTGGCTCTG CTTTTAACTT TATAAATCCA GTGACCTCTC TCTCTGGGAC TT - #GGTTTCCC 720- CAACTAAAAT TTGAAGTAGT TGAATGGGGT CTCAAAGTTT GACAGGAACC TT - #AAGTAATC 780- ATCTAAGTCA GTACCCACCA CCTTCTTCTC CTACATATCC CTTCCAGATG GT - #CATCCAGA 840- CTCAGAGCTC TCTCTACAGA GAGGAAATTC TCCACTGTGC ACACCCACCT TT - #GGAAAGCT 900- CTGACCACTT GAGGCCTGAT CTGCCCATCG TGAAGAAGCC TGTAACACTC CT - #CTGCGTCT 960- ATCCTGTGTA GCATACTGGC TTCACCATCA ATCCTGATTC CTCTCTAAGT GG - #GCATTGCC1020- ATGTGGAAGG CAAGCCAGGC TCACTCACAG AGTCAAGGCC TGCTCCCTGT AG - #GGTCCAAC1080- CAGACCTGGA AGAACAGGCC TCTCCATTTG CTCTTCAGAT GCCACTTCTA AG - #AAAAGCCT1140- AATCACAGTT TTTCCTGGAA TTGCCAGCTG ACATCTTGAA TCCTTCCATT CC - #ACACAGAA1200- TGCAACCAAG TCACACGCTT TTGAATTATG CTTTGTAGAG TTTTGTCATT CA - #GAGTCAGC1260- CAGGACCATA CCGGGTCTTG ATTCAGTCAC ATGGCATGGT TTTGTGCCAT CT - #GTAGCTAT1320- AATGAGCATG TTTGCCTAGA CAGCTTTTCT CAACTGGGTC CAGAAGAGAA TT - #AAGCCCTA1380- AGGTCCTAAG GCATCTATCT GTGCTAGGTT AAATGGTTGG CCCCCAAAGA TA - #GACAGGTC1440- CTGATTTCTA GAACCCGTGA CTGTTACTTT ATACAGCAAA GGAAACTTTG CA - #GATGTGAT1500- TAAAGCTAAG GACCTTAAGA CAGAGTATCC TGGGGGTGGT GGTGGGGTGG GG - #GGGGGTCC1560- TAAATGTAAT CACGAGTAAG ATTAAGAGCA AATCAATTCT AGTCATATAT TA - #AACATCCA1620- CAATAACCAA GATATTTTTA TCCCAAGAAT GCAAGATTTC AGAAAATGAA AA - #ATCTGTTG1680# 1730ATAATA AAACCGAAGG TGAAAAAAAT TCTGAAAAAA- (2) INFORMATION FOR SEQ ID NO:115:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 7705 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA (genomic)- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#3' END OF RAD50 GENOMIC SEQUENCE- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:115:- TTCTAGCAGC TATATTTGAT AAAATTCAAC ATCTCCTAGC TTTAGCAAAC TC - #ACAGTTTT 60- GCAAATAATA TTTTCTTAAT GTTATCTGTT GCTAAATCAA AATTAAACAG TC - #ATCTTAAC 120- TGCAAAATAA AACATTTCTC AGTAAATATT AAAGCCAGTT ACCTTCTATC AA - #CATGTTAA 180- TGAAAGTGCT AGTTGTTGCA GCAAAGAATA ACAAAGGCAA TACACGATCA AT - #ATAGGCAG 240- TGAAACAAAA GTATCATTTG CAAGTTAAAA CAGACTTCCC AATTTTAAAT CT - #GGTTTCCC 300- CCTGAATATG TGGCATCCTT GGCAGCACTT CTGAGAGTGG CTGCTTTCAT TC - #CAAGAAGC 360- CCATGGGTTT GGAGGTGGGA TAGGTGCCTT TCTGGCTTCT CATTGCTGCT TC - #TAGATCAG 420- TCTCCAAATA TCCCCCTTCC CCACATTGGA ATGAATAGCC ATCACAGCAT GG - #ATGGAGGT 480- TAGAATGAGC CAGACTGCCT GGGCTCAAAT CCTAGCACAC CACTCACTAG CT - #GGGGACCT 540- TGAGCAAGTT ATTTGTCCTG TTTTCTGTTT CCTTATATGT AAAAGTGGGT AA - #AATGGTAC 600- ATATTTTGTA GGGTTGTTAT GAAGATTGAA TGACATTATT TACAAACTGC TT - #AGAACTGC 660- TTGCCACCTA CTAAATACTG TGTAAGTGTT CAAGAAAAAG CTGTCTTCAT TT - #CACTCTTG 720- TTGCAGTTAT CTTTCATTCC CAGCTTGGTC ACTCCCTCTT ATTTGTTGAA GA - #GTTTAGCT 780- CCCGGTTCAG TGTCACCCCA TTACTAATAA TCATTGCTGA TTTCAATATC CA - #AGTGATGG 840- TCTAATACAA CTCCTTGGCC TCTCAGTCTT TTTTATTTTT TGAGGTGGAG TC - #TTGCTCTG 900- TCACCCAGGC TGGAGTGCAA TGGCACCATC TCAGCTCACT GCAACCTCTG CC - #TCCCTGAT 960- ACAAGCAATC CTCCTGCCTC AGCCTCCCAA GTAGCTAGGA TTACAGGCAT GT - #ACCACCAC1020- ACCAGGCTAA TTTTTGTATT TTAGTAGAGA CAGGGTTTCG CCTTGTTGGC CA - #GGCTGGTC1080- TTGAACGTCT GGCCTCAAGT GATCTGCCTA CCTTGGCCTC CCTCAGCCCC TT - #TTTGTTTC1140- CTCCAGTGAG AAGATACTCA GTTCTATGGT CTTATTCTAG AGCCCCGTCC TT - #TTAATAAC1200- AATAACTGCA CCCCTCCAAA ATCTCAGTTT TAAGCATCTC ACTCTCCAAT AA - #CCCCATGG1260- TGTCTACAAT TTTCCTGTGG TCCTCAACCC CAGCAATTCT TTGACCCCAC TG - #AGATTTCA1320- ATCCATTGAT TCTATGGCTT TTTCACAGGT TGTTTCCCTG ATGCCTGTAC TT - #CTCTCCTT1380- ATTCAACTTA AATTCCATGG CTCATCATTA TGTCACCCTC CACTGCATTG TA - #CTCAAACT1440- GTCCCGACAA TCCCCAGCCC TACTGGAATC CAGCTCTGCC TCCTCCCTGC AA - #CACCTGCA1500- CATCCCGTTT CCTTTGCTGT TTCCTCCTCA TTTCCCTGGC CCCTCAATGT CA - #CAGGTTTT1560- AGTACTCAGA GTCTGCACCT CTTTTCTTCT CTGTGCTCAC TTATTTGGTG AT - #CTCATCCA1620- GTCTCATAGC TTTAAATTAT CTTAGTTTGG GTTCTCCCAG AAGCAGAGCG TA - #AAACAATG1680- CTTCACGTGA AAGTAATCAG TAGGAAATTG GGGAAATTGT GTATGAAAGA GA - #AAGCAGCC1740- AATGAAAAGT TTACTATTAA GCCAGCTACG GTAAGTGGGC AATTAGAGTT TG - #GTGCCCCA1800- GGGAGACTCT GGGGAGTTTG GCAAAATATA TACCTCAGAA TTATCCCACC TA - #AGGGGCAA1860- GAGACCTGGA GTATTTATAT AACAACTTGC CAGGGTTACT GAGTGAAGGC TA - #TTCTAGCA1920- CATGTTAGTT ACTGGCTTGC CATGTGTACC GACACAGCTG CTTTCCACAG TT - #TAAAAAGA1980- AAGTCTGAGC AACATAGTGA CATCCCATCT TTACATAAAA TTTTTAAAAA AT - #TAGCAAGG2040- CATGGTGGTG CACACCTGTA GTCTCAGCTA CTTGGCTGAG ATAGGATCCC TG - #GAGTCTGA2100- GGGTTCAAGG CTGCAGTGAG CTGTGATTTG TGCCACTGCA CCCCAGCCTG GG - #TGGGTGGC2160- AGAGTGAGAC CCTGTCTAAA AAGACAAAAA AAAAAAAAAA AAAAAAGCAG CA - #GCAGCTGA2220- AAGTTGGCAG GAGCACACTG GCAGTTCCTA GGATCATAGG ATATAGGCAG GG - #CACTGACC2280- ACTCCTACAA CCACCATCTA TACACTGATA ACTCATAAAT GTTTGTGTCC AA - #TCCAGATC2340- TCTCCTAAAT GCTTGACTGA TATATTCAGC TGCCTGTGGA TAACTGGGCA TC - #TATCTGCA2400- CTTGAATATC TAATAAACGT CTAAAACTTA AAATGACCAA AACCAGTCTT TC - #TCCCAGAA2460- CTTGAATCTC TTCTGTTAAT GGCAACTCCA TTATTCCAAT TGCTCAGGCA AA - #AATTGGCA2520- TTATCCTTGA TTCTTTATCT TACATCTTAT ATCTAATTCG TCAGTTTAAT AC - #TATGGGTT2580- CAATTTTCAA AACATCCGGA ATCTGACCAT GCCTCACCAT TTAAACCAGC AG - #TCCCCAAC2640- CATTTTGGCA CCAGAGACCG ATTTAGTGGA AGACAATTTT TCCATGGACG GG - #TGGGGTGA2700- GGGGGATGGT TTCGGGATGA AACTGTTCCA TCTCAGATCA TCAGGCATTA GT - #CAGATTCT2760- CATAAGGAGC ACGCAACCTA GATCCCTCAC GTGCAAATTC ACAATAGAGT TT - #GCACTCCC2820- GTGAGAATCT AATGCCACCA CCAATCTGAT AGGAGGTAGA GCTCAGGCGG TA - #ATGCTCCC2880- TCACCTGTCA CTCACCTCCT GTTGTGCGAC TCTGTTCCTA ACAGGCTGAG GA - #CAGGTAAT2940- GGTCTGCAGC CCGGGGGTTG GGGACCCCTG ATCTAAACCA TCATTGCTCT GG - #TCCAAGCC3000- ACTGCCATCT CTAACCTGAA TAATCTGAGT AACCACGTAA CTGCTCCCAC TG - #ATTTGGGG3060- CCTGCTCCCT GTAGTTCTCA ACACAGCAGC CAGTGATCTT TTTAAAAAGT AA - #CTCAAGAA3120- AATGTGTTTC TCACAGGGGT GTGGGTTAGC AATTTCGAAA TTTTTATGTA CA - #TACTAAAG3180- TCAAACAAAT ACATACCTGT GTTGTAGATA ATACGAACTG AGTTTCTCAC TG - #TTGGAAAA3240- AGGTGTTTGC ATATCAGGAA AGGAGGCCAT AAAAAGAACC CCTTGGTGTT GA - #TTGAATCC3300- AAAGGATCTG TACAAATTTA TAATTTTAAT ATCTAAAGGA TTTCTACTTC CA - #TAAGGGTG3360- GAGTAAAAGC CATCCAAAAT CTGCTTCTTC ATAAAAGCAA TAAGACTGGC AA - #AAATGTCA3420- AAATCAACTT TTTCAGAACT TTGGAAATTA ACTAATGGAT AGCGACAAAC TG - #AGGTGTGT3480- TTATTAAAGG AAAACAGCTG AATCTCAGAG CAGAAAGTGG CATTTTAAGT TG - #CCCTAATC3540- CCATGCCCTT CTCTCTTAAT CCATGGTAAC TTGAAAACCA ACAGCCCTCT TA - #GTATCTGT3600- GAAAATCAGC AACCTAGTAG CCACTGGAGG AGACAGAATA GATTTGGAGG TC - #CCCCAGAT3660- CTCCACTACT AGAGAACTGC CTCTATTTGT CTTGTCTGGC AACTCACTGA AA - #AGCTCCAT3720- TTTCAGGACC TATCTTTATT TGACTTAACT CAGAGCTCAC TCTGAAAACA GC - #CCTTCCTG3780- CAGAATAATC AGTGGCAACT GATTAACCCT GTGGCTGCCT GAGGCAGCGT TA - #CCAGGTGG3840- AGCTAACAAA AGGCTGACCA AGAAACTTAA AAGGAAAAAT CTGGGAAGAA GA - #TGTCCACG3900- GGAGCTTTGA CAAGCTCAAG CATATTCCTG GGAATCTAGA AGTCCATGTG CA - #TGTGCAGG3960- GATGTATGCA TGTCCTGAGA GGGTCCTAAG CTCTCATCTC TGACTGACCT TG - #AAACTCAA4020- TTCATGCCAG AAATGAAGAT AAAGGCAGTT GTAAACTGTC TGCTGACACA TC - #AATGACAT4080- GACTCCACAA ATACACACAC ATGCACACAC TTGACAAAAG CTAGAAAATT TA - #TTGGTTCA4140- AGGCATTAGA AAGAAATATC TGTCCAATTA TTCGCTTACC CACTAGGCTG AG - #TAGAGACT4200- TCAGGAACCA AACATGACAA AGCATATAGA ATTTGCAGAA TTAGTCCAGG AA - #AGACACAG4260- AACAAACCAA CAGCAGCAAC AATAAGAAAT AGTAACAGGT GCAAGCCCTG GA - #GAGTAGGT4320- AATCTGACTT CAATAATTGA TAGAGTATTT AAAACAAGAC ACACAAAGAA CA - #GGAACATC4380- TGACCCATGC CATAAACAGC AATTTAAAAA ACAGTCAATA GAAACAATCT AT - #GAGGAAGC4440- CCAGATGTTA GACTTACTAG GCAAAGACTT TAGATATCAG CTATTATAAA CA - #TGTTCAAG4500- GAACTAACAG AAACAAAGTC TAAAGAATTA AAGGAAATTA TGAGAATGAT GT - #TTCACCAA4560- ATTATCAGGA CTATCAGTAA GGAGACAAAC ATTATAAAAA AGAATCAAAT AG - #ATATTCTG4620- GAGTTGAGAA ATACAGTAAT GGAAATAAAA ATTCACTAGA TGGGGGTCAA CA - #GCAAATTT4680- GAACTGGCAG AAGAAAGAAT CAGTGAGTTC AAAGACCGGT CAATTGAGAT TA - #TACAGTCT4740- GAGGAATAGA CAGAAGAATG AAGAAAAATG AAGAGAGCTT CAGAGACCTT TG - #AGACACTA4800- TCAAGTGTAC CAAAATGCCA AGTATACCAA TCATAATGAG AATCCCAGAA GA - #GAGAGAGA4860- GAGAAAGGAG CAGAAAGACT ATTTGAAGAA ATAGTAGCCC AAAACTTCCC AA - #ATTTTATG4920- AAAACATTAA TCTTCGTATC CAAGAAATTG AACAAACTCC AAGTAGGGTA AA - #CTCAAAGG4980- GATTCACATT TAGATGCATC ATGGTCAAAT TGTTGAAAAA GAGATCTCAA AC - #GAAAGAAG5040- CAAGTAAAGC TAAGAAGTGA CTTCTCTTAA GAAACAATGC AGGCCTGAAA GC - #AGTGAGAT5100- GACATATTCA AAGTGCTGAA TGAAAAAGAC TATCAACCAA GAATTATTTT TG - #CAGTGGTG5160- CAATCATAGC TCACTGTAGC TTCAAACTCC TGGGCTCAAG CAATTCTCTT TC - #CTCAGCCT5220- CTCAAATAGG ACTACCAGCA TGTGCCACCA CACTCAAAAA AAAAAATTTT TT - #AAGAGACA5280- GGGGGTCTTG CTGTCTTGCC CAGGCTGGTC TTAAACTCCT AGTCTTAAGC AG - #TCCTCCCA5340- CCTTGGCCTC CCAAAGTGCT GGGATTAAGG TGTGGGCTAC TGTGCCCAGC CT - #CAATCAAG5400- AATTCTGTAT CCAGAAAAAC TGTCCTTCAA AAACAAGAAA TGAAGACACT CC - #CATATAAA5460- CAAACATTGT GATAATCTGT CTTCACCAGA CTTGCCCTAC AAGAAATATA AA - #AGGAGAAT5520- GAATCCTTTA GGGTAAAATG AAACTAGACT CAAATGCTCA TGAATACTCA AA - #TAAAGAGT5580- ACTGGTAAAG GTAAATATAT AGGTAATATA AAAGTATAAA TGTATTTTGG GG - #GCTGGGAG5640- CAGTGGCTCA TGCCTGTAAT CCCAACACTT TGAGAGGCCG AGGTGGGCGG AT - #CACCTGAG5700- GTCAGGAGTT TGAGACCAGC CTGCCCAACA TGGTGAAACC CTGTCTCTAC TA - #AAAATACA5760- AAAAATCAGC CAGGCGTTGT GGTGGGCGCC TGTAATCCCA GCTACTCAGG AG - #GCTGAGGC5820- AGGAGAATCT CTTGAACCCA GGAGGCGGAG GTTGCGGTGA GCTGAGATCA CG - #CCACTGCA5880- CTCCAGCCTT GGTGACAAGA GCAAAACTCG GTCTCAAAAA AAAAAAAAAA GT - #ATTTTGGG5940- TTGTAACTCT TTTCCTACAT GATTGAAAGG GAACTGCATT AAGAATTTTA AC - #ACTGTTGA6000- TGGGCTTATA ATGTATAAAA ATATAATTTA TATGACAATA ATGCTACAAA AG - #AGAGAGGC6060- AACAGAGCTA TATAGGAACT TTTGAAATGG AAATTAAGTT GACATTCATC TA - #AATTAAGG6120- TGTTCATTTG TAATCCCCAG GGTAACCACT AAGAAAATAA TGAAAACTTA TA - #GTGAAAGT6180- AACAAAGTTA TTTAAAGAGG GCCCAGTGTG ATGACACCCC AGTAATAATG AG - #GACACCTA6240- CTTCCAAGAT CTCGATTTTA AAACACGCTC TTCAATAAAA AGAACTCTGG CT - #CCTTGGTG6300- AAGTGGTTGA CTTCAGGGCT GAGGCAAGGA AAATACAAAA TGACCCTAGA AT - #TTTTTGTG6360- GTGCCAGAAA TTAAGAAAAT ATTTTTTTTA AAAAAAAAGG TAGAGTTTGT TC - #AAAGAACA6420- CAGAACCCAA CCTGAAGTAA CTCCCAATGA TCAAAGGTAG AACAATTTGA GA - #AACAAAAT6480- AAAGACAGTA TTGGATTATA ACCGATAGAG TAAAATAAAT ATTCATGAAC TT - #ATGTGGCT6540- ATACACAAGT ACTTACTTTA AAAAAAATGA GGGACAAGGA CAGCACTTCT TT - #ATAGTAGA6600- ATTACAAGTA ATAAATGTAG AAGGAAAGGG AAAAAGAAAA GTCATCACTA GG - #CAAATACC6660- ACAATAAAAA TCATTTCAGA CAAGAGTCAC TGATGAAGCT AATATTAGTA GG - #CACAAATC6720- TGAGAAAAAA TTTATATAAT CTCAAACTAT CTTTCCCAAT ATATTAACTA AA - #AAGGGAAA6780- GATAGTAATT TTATCATGGA AGAACCTGAC AGAAACCATC TTAACCAAGT GG - #TCAGGGTC6840- AACATCACCA ATAAGAAGGC ATGTACCTCA TGAACCCTGT GACCTGATGC AG - #TGAGAAGG6900- CCCCAACTTC ATCTCTGTGA AAATGTAGAA CCTCAGTGCA ATTAGGAGAA AA - #CACCAAGG6960- GGACCAAACT GAGGAACATT TGACAGCATA ACTCATCAGT ATTCCTGGAA AA - #TGTAAGCG7020- TTATGAAAGA CAAGACTGAG GAACCATTCA GACTGCAGGA GACCAAAGAG AA - #TTAACTCA7080- ATGCACTGTG AGATCCTGGG TTGATCTTGA AACTGAAAAA GGATGTGAAT GG - #AAACACTG7140- GTGAGATTAG AATAGGATCC AGTTTACTTA ATAAATCCAT GCTCATTTTT CT - #GTTTTTGA7200- TCATTGCACT ATGATTATGT AATGTGTTAC CATTGGGAGA AGCTGGGTAA GT - #GGAGGGGA7260- TATGGAAACT GTCTGTACTA TTTTTGTATC TTTTCCGTAA ATATAACGTT AA - #TTCAAATT7320- TTTTTAAAAA AAGAAAAAAG GTAAATTGAG TCATGTCACT CCTCTGCTCA AA - #ACCTCCAG7380- TGGCTCCCTA TGTCACTCAT CATGAAATCC TCAGTCCTCT CAATGGCTTA CA - #AGTCTCCA7440- TATGCTCTGG ACATACTTCT CTGACAGTAT CTTCTCCCAT GCCTCCCCTC AC - #TCCTTCTG7500- GCTTTCCTTG CTAATTCTCA GCACAGTGGG CATTTTCCTG CTTTGGTGCT AC - #TATGGTTT7560- GAGTGTATGT TTCCCTCCAA AATTCATACA TTGGAACTTA ATCCCCAAGG TG - #ATGCTATT7620- AAGAAGTGGG GCACTTAAAA GGTGATTAGG CCATGGAGGA ATGGGATTCA TG - #ACCTCATA7680# 7705 AAAG TTCTT- (2) INFORMATION FOR SEQ ID NO:116:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#SSCP RAD50 PRIMER R1UAL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:116:#21 CGCC T- (2) INFORMATION FOR SEQ ID NO:117:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 24 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#SSCP RAD50 PRIMER R2UAL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:117:# 24GAAG ACTT- (2) INFORMATION FOR SEQ ID NO:118:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 24 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#SSCP RAD50 PRIMER R3UAL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:118:# 24GTTC TCTT- (2) INFORMATION FOR SEQ ID NO:119:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 26 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#SSCP RAD50 PRIMER R4UAL ISOLATE:#ID NO:119:xi) SEQUENCE DESCRIPTION: SEQ# 26 GCAC CATTAC- (2) INFORMATION FOR SEQ ID NO:120:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 24 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#SSCP RAD50 PRIMER R5UAL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:120:# 24AAGT AACA- (2) INFORMATION FOR SEQ ID NO:121:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 26 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#SSCP RAD50 PRIMER R6UAL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:121:# 26 AAAC ACCTAC- (2) INFORMATION FOR SEQ ID NO:122:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 24 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#SSCP RAD50 PRIMER R7UAL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:122:# 24CTGA AGGT- (2) INFORMATION FOR SEQ ID NO:123:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 24 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#SSCP RAD50 PRIMER R8UAL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:123:# 24TTAA GGGT- (2) INFORMATION FOR SEQ ID NO:124:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 24 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#SSCP RAD50 PRIMER R9UAL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:124:# 24ATAT ACCA- (2) INFORMATION FOR SEQ ID NO:125:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 22 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#SSCP RAD50 PRIMER R10AL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:125:# 22TAC TT- (2) INFORMATION FOR SEQ ID NO:126:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 24 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#SSCP RAD50 PRIMER R11AL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:126:# 24ATAG TGAG- (2) INFORMATION FOR SEQ ID NO:127:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 24 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#SSCP RAD50 PRIMER R12AL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:127:# 24CTAC CACC- (2) INFORMATION FOR SEQ ID NO:128:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 24 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#SSCP RAD50 PRIMER R13AL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:128:# 24TTAC ACAG- (2) INFORMATION FOR SEQ ID NO:129:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 24 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#SSCP RAD50 PRIMER R14AL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:129:# 24CTTC ATTC- (2) INFORMATION FOR SEQ ID NO:130:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 24 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#SSCP RAD50 PRIMER R15AL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:130:# 24CTCA ACTT- (2) INFORMATION FOR SEQ ID NO:131:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 27 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#SSCP RAD50 PRIMER R16AL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:131:# 27 CAAA ATACTTG- (2) INFORMATION FOR SEQ ID NO:132:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 27 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#SSCP RAD50 PRIMER R17AL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:132:# 27 TATG CATTTAG- (2) INFORMATION FOR SEQ ID NO:133:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 27 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#SSCP RAD50 PRIMER R18AL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:133:# 27 CAAA AATAGAC- (2) INFORMATION FOR SEQ ID NO:134:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 27 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#SSCP RAD50 PRIMER R19AL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:134:# 27 GAAT TATTGAC- (2) INFORMATION FOR SEQ ID NO:135:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 24 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#SSCP RAD50 PRIMER R20AL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:135:# 24TAAG TACC- (2) INFORMATION FOR SEQ ID NO:136:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 27 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#SSCP RAD50 PRIMER R21AL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:136:# 27 GGAG ATATAGA- (2) INFORMATION FOR SEQ ID NO:137:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 27 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#SSCP RAD50 PRIMER R22AL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:137:# 27 TGTT GCAACTT- (2) INFORMATION FOR SEQ ID NO:138:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 24 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#SSCP RAD50 PRIMER R23AL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:138:# 24GTTG GCAG- (2) INFORMATION FOR SEQ ID NO:139:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 24 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#SSCP RAD50 PRIMER R24AL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:139:# 24TATC CTGA- (2) INFORMATION FOR SEQ ID NO:140:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 25 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#SSCP RAD50 PRIMER R25AL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:140:# 25 GAAT ACTGT- (2) INFORMATION FOR SEQ ID NO:141:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 25 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#SSCP RAD50 PRIMER R26AL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:141:# 25 TCCC ATTCT- (2) INFORMATION FOR SEQ ID NO:142:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 25 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#SSCP RAD50 PRIMER R27AL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:142:# 25 AACT GTGAG- (2) INFORMATION FOR SEQ ID NO:143:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 25 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#SSCP RAD50 PRIMER R28AL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:143:# 25 AATA AACTT- (2) INFORMATION FOR SEQ ID NO:144:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 27 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#SSCP RAD50 PRIMER R29AL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:144:# 27 TTAT TAAAGGA- (2) INFORMATION FOR SEQ ID NO:145:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 24 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#SSCP RAD50 PRIMER R30AL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:145:# 24GACA CAGA- (2) INFORMATION FOR SEQ ID NO:146:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 26 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#SSCP RAD50 PRIMER R31AL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:146:# 26 ATTA CTGTGA- (2) INFORMATION FOR SEQ ID NO:147:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 24 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#SSCP RAD50 PRIMER R32AL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:147:# 24CTGT CTAA- (2) INFORMATION FOR SEQ ID NO:148:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 24 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#SSCP RAD50 PRIMER R33AL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:148:# 24AAAG TAAG- (2) INFORMATION FOR SEQ ID NO:149:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 24 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#SSCP RAD50 PRIMER R34AL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:149:# 24AACA TAAG- (2) INFORMATION FOR SEQ ID NO:150:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 24 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#SSCP RAD50 PRIMER R35AL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:150:# 24CCTT AAGT- (2) INFORMATION FOR SEQ ID NO:151:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 26 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#SSCP RAD50 PRIMER R36AL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:151:# 26 ATAT CATAAG- (2) INFORMATION FOR SEQ ID NO:152:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 24 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#SSCP RAD50 PRIMER R37AL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:152:# 24AACT TGGT- (2) INFORMATION FOR SEQ ID NO:153:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 24 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#SSCP RAD50 PRIMER R38AL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:153:# 24AAGA CGTT- (2) INFORMATION FOR SEQ ID NO:154:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 24 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#SSCP RAD50 PRIMER R39AL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:154:# 24TCAG GTTG- (2) INFORMATION FOR SEQ ID NO:155:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 24 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#SSCP RAD50 PRIMER R40AL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:155:# 24TAAT ACTT- (2) INFORMATION FOR SEQ ID NO:156:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 24 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#SSCP RAD50 PRIMER R41AL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:156:# 24CCTT TTCC- (2) INFORMATION FOR SEQ ID NO:157:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 24 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#SSCP RAD50 PRIMER R42AL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:157:# 24TGGT ACTC- (2) INFORMATION FOR SEQ ID NO:158:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 24 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#SSCP RAD50 PRIMER R43AL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:158:# 24GGTT CCTC- (2) INFORMATION FOR SEQ ID NO:159:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 24 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#SSCP RAD50 PRIMER R44AL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:159:# 24AGAT ACCT- (2) INFORMATION FOR SEQ ID NO:160:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 24 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#SSCP RAD50 PRIMER R45AL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:160:# 24CACA TAGG- (2) INFORMATION FOR SEQ ID NO:161:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 24 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#SSCP RAD50 PRIMER R46AL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:161:# 24TGCA AGAG- (2) INFORMATION FOR SEQ ID NO:162:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 26 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#SSCP RAD50 PRIMER R47AL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:162:# 26 TCAA AGAAGG- (2) INFORMATION FOR SEQ ID NO:163:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 26 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#SSCP RAD50 PRIMER R48AL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:163:# 26 TGAC ACAATG- (2) INFORMATION FOR SEQ ID NO:164:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 24 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#Primer 2B-8) INDIVIDUAL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:164:# 24AGTC AAGG- (2) INFORMATION FOR SEQ ID NO:165:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 29 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#Primer A106-ARNDIVIDUAL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:165:# 29 ATCT TGGATATTT- (2) INFORMATION FOR SEQ ID NO:166:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 26 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#Primer B4-2) INDIVIDUAL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:166:# 26 TGTT GTCCTC- (2) INFORMATION FOR SEQ ID NO:167:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 24 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#Primer N6Z-1 INDIVIDUAL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:167:# 24GAGA AGGA- (2) INFORMATION FOR SEQ ID NO:168:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 29 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#Primer N6Z-2 INDIVIDUAL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:168:# 29 ATAC TTTGGCACT- (2) INFORMATION FOR SEQ ID NO:169:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 24 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#Primer G10-2 INDIVIDUAL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:169:# 24TTGC GTCC- (2) INFORMATION FOR SEQ ID NO:170:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#Primer G10-14INDIVIDUAL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:170:#21 ACCT G- (2) INFORMATION FOR SEQ ID NO:171:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 39 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#Primer G10-N INDIVIDUAL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:171:# 39 GACT CCAGGTCCCT GGTGAGATT- (2) INFORMATION FOR SEQ ID NO:172:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 32 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#Primer G10-C1INDIVIDUAL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:172:# 32 ATTG AATCCCAGGG AG- (2) INFORMATION FOR SEQ ID NO:173:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 25 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#Primer A106-21NDIVIDUAL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:173:# 25 ACTC GGTAG- (2) INFORMATION FOR SEQ ID NO:174:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 37 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#Primer S1(C) INDIVIDUAL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:174:# 37 CCTA GCCCTCTGCT TCGCCGT- (2) INFORMATION FOR SEQ ID NO:175:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 37 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: DNA- (iii) HYPOTHETICAL: NO- (iv) ANTI-SENSE: NO- (vi) ORIGINAL SOURCE:#Primer S2(C) INDIVIDUAL ISOLATE:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:175:# 37 ACGG TTACTACTGG GTGCTAA__________________________________________________________________________

Human RAD50 gene and methods of use thereof

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Non-Patent Literature Citations (28)

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Entry
Genbank Loci: R92967; L46900; N70974; H93370; L43399; L42096.
Clonetech 1995 Catalog pp. 32, 80-81 and 96-97.
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