Publication Date:
1995-06-23
Description:
A gene, ATM, that is mutated in the autosomal recessive disorder ataxia telangiectasia (AT) was identified by positional cloning on chromosome 11q22-23. AT is characterized by cerebellar degeneration, immunodeficiency, chromosomal instability, cancer predisposition, radiation sensitivity, and cell cycle abnormalities. The disease is genetically heterogeneous, with four complementation groups that have been suspected to represent different genes. ATM, which has a transcript of 12 kilobases, was found to be mutated in AT patients from all complementation groups, indicating that it is probably the sole gene responsible for this disorder. A partial ATM complementary DNA clone of 5.9 kilobases encoded a putative protein that is similar to several yeast and mammalian phosphatidylinositol-3' kinases that are involved in mitogenic signal transduction, meiotic recombination, and cell cycle control. The discovery of ATM should enhance understanding of AT and related syndromes and may allow the identification of AT heterozygotes, who are at increased risk of cancer.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Savitsky, K -- Bar-Shira, A -- Gilad, S -- Rotman, G -- Ziv, Y -- Vanagaite, L -- Tagle, D A -- Smith, S -- Uziel, T -- Sfez, S -- Ashkenazi, M -- Pecker, I -- Frydman, M -- Harnik, R -- Patanjali, S R -- Simmons, A -- Clines, G A -- Sartiel, A -- Gatti, R A -- Chessa, L -- Sanal, O -- Lavin, M F -- Jaspers, N G -- Taylor, A M -- Arlett, C F -- Miki, T -- Weissman, S M -- Lovett, M -- Collins, F S -- Shiloh, Y -- HG00882/HG/NHGRI NIH HHS/ -- NS31763/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1995 Jun 23;268(5218):1749-53.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Human Genetics, Sackler School of Medicine, Tel Aviv University, Israel.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7792600" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acid Sequence
;
Ataxia Telangiectasia/*genetics
;
Ataxia Telangiectasia Mutated Proteins
;
Cell Cycle
;
Cell Cycle Proteins
;
Chromosome Mapping
;
Chromosomes, Artificial, Yeast
;
*Chromosomes, Human, Pair 11
;
Cloning, Molecular
;
DNA, Complementary/genetics
;
DNA-Binding Proteins
;
Female
;
Genetic Complementation Test
;
Genetic Predisposition to Disease
;
Heterozygote
;
Humans
;
Male
;
Meiosis
;
Molecular Sequence Data
;
Neoplasms/genetics
;
Nucleic Acid Hybridization
;
Phosphatidylinositol 3-Kinases
;
Phosphotransferases (Alcohol Group Acceptor)/chemistry/*genetics/physiology
;
*Protein-Serine-Threonine Kinases
;
Proteins/chemistry/*genetics/physiology
;
Radiation Tolerance
;
Sequence Deletion
;
Signal Transduction
;
Tumor Suppressor Proteins
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
Permalink
