Genomic organization of the ATM locus involved in ataxia-telangiectasia.
The ATM gene, involved in the genetic disorder ataxia-telangiectasia (AT), has been identified recently. This gene is suspected to predispose to malignancy and is located in a chromosomal region that we have recently found deleted in 50 to 60% of breast and lung carcinomas. Because of its location and its function, the ATM gene is a strong candidate tumor suppressor or modifier gene of chromosome region 11q23. In this study, we define its genomic structure. The aim was to establish the basis for the development of mutation scanning methods based on DNA instead of RNA. We found that the gene spans a region of approximately 70-80 kb and is composed of 37 exons, ranging in size from 64 to 324 bp. Nucleotide sequences of all exon/intron boundaries were determined. With this information, it will be possible to develop simple genetic tests for the identification of homozygotes and heterozygotes, as well as determine whether the gene is involved in the pathogenesis of breast and other carcinomas.
Jefferson Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
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D001260:Ataxia Telangiectasia / Q000235:genetics*; D064007:Ataxia Telangiectasia Mutated Proteins; D001483:Base Sequence; D018797:Cell Cycle Proteins; D002880:Chromosomes, Human, Pair 11; D017931:DNA Primers / Q000737:chemistry; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins; D005091:Exons; D016147:Genes, Tumor Suppressor; D006801:Humans; D007438:Introns; D008969:Molecular Sequence Data; D017346:Protein Serine-Threonine Kinases; D011506:Proteins / Q000235:genetics*; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D017931:DNA Primers; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D011506:Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases