Ataxia-telangiectasia (group A): localization of ATA gene to chromosome 11q22-23 and pathogenetic implications.
Ataxia-telangiectasia (AT) is an autosomal recessive disorder resulting from a single defective gene in each family. Complementation studies suggest that the same syndrome is associated with defects of at least four AT genes (ATA, ATC, ATD and ATE). The syndrome is multifaceted and involves the cerebellum, skin, immunological system, chromosomes, cancer susceptibility, radiosensitivity, premature ageing and serum alphafetoprotein levels. In order to further develop understanding of how these seemingly unrelated physiological systems interact in this disease, we attempted to localize the gene by linkage analysis, using a single large Group A AT family to screen 171 genetic markers and 30 additional AT families to confirm any positive linkages. We found a linkage to AT (Group A) with genetic markers on chromosome 11q22-23. This region of the human genome is syntenic with a large region of the mouse genome on chromosome 9 and includes such "candidate" genes as THY1, NCAM, CD3G-D-3, ets-1, and APOA1-C3-A4. In addition, studies of human chromosomes identify fragile sites in this region as well as breakpoints associated with translocation 4: 11 and 9; 11 in acute non- lymphocytic leukemias. The pathogenetic implications of this localization to 11q22-23 are considered.
Department of Pathology, UCLA School of Medicine 90024.
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Gatti
D000818:Animals; D000954:Antigens, Surface / Q000235:genetics; D001053:Apolipoproteins / Q000235:genetics; D001260:Ataxia Telangiectasia / Q000175:diagnosis / Q000235:genetics*; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics; D002872:Chromosome Deletion; D043283:Chromosome Fragile Sites; D002873:Chromosome Fragility; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11 / Q000648:ultrastructure; D005315:Fetal Diseases / Q000175:diagnosis; D005796:Genes; D006580:Genetic Carrier Screening; D005819:Genetic Markers; D006801:Humans; D008126:Lod Score; D051379:Mice / Q000235:genetics; D008818:Mice, Neurologic Mutants / Q000235:genetics; D008957:Models, Genetic; D011296:Prenatal Diagnosis; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins / Q000235:genetics; D050783:Proto-Oncogene Proteins c-ets; D013045:Species Specificity; D018800:Thy-1 Antigens; D014157:Transcription Factors
D000954:Antigens, Surface; D001053:Apolipoproteins; D015816:Cell Adhesion Molecules, Neuronal; C494041:ETS1 protein, human; C494042:Ets1 protein, mouse; D005819:Genetic Markers; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D018800:Thy-1 Antigens; D014157:Transcription Factors