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Localization of an ataxia-telangiectasia gene to chromosome 11q22–23

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Abstract

Ataxia-telangiectasia (AT) is a human autosomal recessive disorder of childhood1,2 characterized by: (1) progressive cerebellar ataxia with degeneration of Purkinje cells; (2) hypersensitivity of fibroblasts and lymphocytes to ionizing radiation3; (3) a 61-fold and 184-fold increased cancer incidence in white and black patients, respectively4; (4) non-random chromosomal rearrangements in lymphocytes; (5) thymic hypoplasia with cellular and humoral (IgA and IgG2) immunodeficiencies; (6) elevated serum level of alphafetoprotein; (7) premature ageing; and (8) endocrine disorders, such as insulin-resistant diabetes mellitus. A DNA processing or repair protein is the suspected common denominator in this pathology5. Heterozygotes are generally healthy; however, the sensitivity of their cultured cells to ionizing radiation is intermediate between normal individuals and that of affected homozygotes6. Furthermore, heterozygous females are at an increased risk of breast cancer7,8. These findings, when coupled with an estimated carrier frequency of 0.5–5.0%, suggest that (1) as many as one in five women with breast cancer may carry the AT gene7 and that (2) the increased radiation sensitivity of AT heterozygotes may be causing radiation therapists to reduce the doses of radiation used for treating cancer in all patients10. To identify the genetic defect responsible for this multifaceted disorder, and to provide effective carrier detection, we performed a genetic linkage analysis of 31 families with AT-affected members. This has allowed us to localize a gene for AT to chromosomal region 11q22-23.

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References

  1. Boder, E. & Sedgwick, R. P. Pediatrics 21, 526–554 (1958).

    CAS  PubMed  Google Scholar 

  2. Boder, E. in Ataxia-telangiectasia: Genetics, Neuropathology and Immunology of a Degenerative Disease of Childhood (eds Gatti, R. A. & Swift, M.) 1–61 (Liss, New York, 1985).

    Google Scholar 

  3. Painter, R. B. in Ataxia-telangiectasia: Genetics, Neuropathology and Immunology of a Degenerative Disease of Childhood (eds Gatti, R. A. & Swift, M.) 89–100 (Liss, New York, 1985).

    Google Scholar 

  4. Morrell, D., Cromartie, E. & Swift, M. J. natn. Cancer Inst. 77, 89–92 (1986).

    CAS  Google Scholar 

  5. Hanawalt, P. & Painter, R. in Ataxia-telangiectasia: Genetics, Neuropathology and Immunology of a Degenerative Disease of Childhood (eds Gatti, R. A. & Swift, M.) 67–71 (Liss, New York, 1985).

    Google Scholar 

  6. Paterson, M. C., MacFarlane, S. J., Gentner, N. E. & Smith, B. P. in Ataxia-telangiectasia: Genetics, Neuropathology and Immunology of a Degenerative Disease of Childhood (eds Gatti, R. A. & Swift, M.) 73–87 (Liss, New York, 1985).

    Google Scholar 

  7. Swift, M., Reitnauer, P. J., Morrell, D. & Chase, C. L. New Engl. J. Med. 316, 1289–1294 (1987).

    Article  CAS  Google Scholar 

  8. Pippard, E. C., Hall, A. J., Barker, D. J. & Bridges, B. A. Cancer Res. 48, 2929–2933 (1988).

    CAS  PubMed  Google Scholar 

  9. Swift, M. et al. Am. J. hum. Genet. 39, 573–583 (1986).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Norman, A., Fagan, R. A. & Chan, S. L. Am. J. Oncol. 11, 84–88 (1988).

    Article  CAS  Google Scholar 

  11. Jaspers, N. G. J., Painter, R. B., Paterson, M. C., Kidson, C. & Inoue, T. in Ataxiatelangiectasia: Genetics, Neuropathology and Immunology of a Degenerative Disease of Childhood (eds Gatti, R. A. & Swift, M.) 147–162 (Liss, New York, 1985).

    Google Scholar 

  12. Jaspers, N. G. J., Gatti, R. A., Baan, C., Linssen, P. C. M. L. & Bootsma, D. Cytogenet. Cell Genet. (in the press).

  13. Ginter, D. N. & Tallapragada, R. in Medical Genetic Studies of the Amish (ed. McKusick, V.) 144–145 (Johns Hopkins Univ. Press, Baltimore, 1978).

    Google Scholar 

  14. Gatti, R. A. et al. Hum. Immun. 22, 145–150 (1988).

    Article  CAS  Google Scholar 

  15. Ott, J. Analysis of Human Genetic Linkage (Johns Hopkins Univ. Press, Baltimore, 1985).

    Google Scholar 

  16. Hodge, S. E., Anderson, C. E., Neiswanger, K., Sparkes, R. S. & Rimoin, D. L. Am. J. hum. Genet. 35, 1139–1155 (1988).

    Google Scholar 

  17. Smith, C. A. B. Ann. hum. Genet. 27, 175–182 (1963)

    Article  CAS  Google Scholar 

  18. Donis-Keller, H. et al. Cell 51, 319–337 (1987).

    Article  CAS  Google Scholar 

  19. Nakamura, Y. et al. Science 235, 1616–1622 (1987).

    Article  ADS  CAS  Google Scholar 

  20. Lange, K., Boehnke, M. & Weeks, D. E. Programs for Pedigree Analysis Department of Biomathematics, University of California, Los Angeles (1988).

    Google Scholar 

  21. Gordon, J. W. et al. Cell 50, 445–454 (1987).

    Article  CAS  Google Scholar 

  22. Spangrude, G., Heimfeld, S. & Weissman, I. L. Science 241, 58–62 (1988).

    Article  ADS  CAS  Google Scholar 

  23. Williams, A. F. Nature 314, 579–580 (1985).

    Article  ADS  CAS  Google Scholar 

  24. Gunter, K. C. et al. Nature 362, 505–507 (1987).

    Article  ADS  Google Scholar 

  25. Acton, R. T., Addis, J., Carl, G. F., McClain, L. D. & Bridges, W. F. Proc. natn. Acad. Sci. U.S.A. 75, 3283–3287 (1978).

    Article  ADS  CAS  Google Scholar 

  26. Garson, J. A., Beverly, P. C. L., Coakham, H. B. & Harper, E. I. Nature 298, 375–377 (1982).

    Article  ADS  CAS  Google Scholar 

  27. Kameko, Y. et al. Blood 67, 484–491 (1986).

    Google Scholar 

  28. Hagemeijer, A., Hahden, K., Sizoo, W. & Abels, J. Cancer Genet. Cytogenet. 5, 95–105 (1982).

    Article  CAS  Google Scholar 

  29. Rovigatti, U., Watson, D. K. & Yunis, J. J. Science 232, 398–400 (1986).

    Article  ADS  CAS  Google Scholar 

  30. Yunis, J. J., Brunning, R. D., Howe, R. B. & Lobell, M. New Engl. J. Med. 311, 812–818 (1984).

    Article  CAS  Google Scholar 

  31. Davisson, M. T. & Roderick, T. H. Mouse News Letter 81, 1–8 (1988).

    Google Scholar 

  32. Prochazka, M., Leiter, E. H., Serreze, D. V. & Coleman, D. L. Science 237, 286–289 (1987).

    Article  ADS  CAS  Google Scholar 

  33. Swift, M. in Ataxia-telangiectasia: Genetics, Neuropathology and Immunology of a Degenerative Disease of Childhood (eds Gatti, R. A. & Swift, M.) 133–146 (Liss, New York, 1985).

    Google Scholar 

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Authors and Affiliations

  1. Department of Pathology, UCLA School of Medicine, Los Angeles, California, 90024, USA

    Richard A. Gatti, Patrick Charmley, Ozden Sanal, Ellen Susi & Shan Wei

  2. Children's Medical Center, Tulsa, Oklahoma, USA

    Izzet Berkel

  3. Department of Pediatrics, UCLA School of Medicine, Los Angeles, California, USA

    Elena Boder & Robert S. Sparkes

  4. Virginia Mason Research Center, Seattle, Washington, USA

    Gary Braedt & Patrick Concannon

  5. Department of Microbiology and Immunology, UCLA School of Medicine, Los Angeles, California, USA

    Patrick Charmley

  6. Department of Pediatrics, Hacettepe University, Ankara, Turkey

    Fugen Ersoy & Ozden Sanal

  7. Department of Biomathematics, UCLA School of Medicine, Los Angeles, California, USA

    Tatiana Foroud, Kenneth Lange & Daniel E. Weeks

  8. Department of Cell Biology and Genetics, Erasmus University, Rotterdam, The Netherlands

    Nicholas G. J. Jaspers

  9. Howard Hughes Medical Institute, Salt Lake City, Utah, USA

    G. Mark Lathrop, Mark Leppert, Yusuke Nakamura, Peter O'Connell & Ray White

  10. Cross Cancer Institute, Edmonton, Canada

    Malcolm Paterson

  11. Department of Biology, UCLA, Los Angeles, California, USA

    Winston Salser & Shan Wei

  12. Hospital for Joint Diseases, New York, New York, USA

    Jack Silver

  13. Department of Medicine, UCLA School of Medicine, Los Angeles, California, USA

    Robert S. Sparkes

  14. University of South Carolina, Charleston, South Carolina, USA

    Freda Yoder

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  1. Richard A. Gatti
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  7. Fugen Ersoy
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  10. Kenneth Lange
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  13. Yusuke Nakamura
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  14. Peter O'Connell
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  15. Malcolm Paterson
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  16. Winston Salser
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  17. Ozden Sanal
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  18. Jack Silver
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  19. Robert S. Sparkes
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  20. Ellen Susi
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  22. Shan Wei
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Gatti, R., Berkel, I., Boder, E. et al. Localization of an ataxia-telangiectasia gene to chromosome 11q22–23. Nature 336, 577–580 (1988). https://doi.org/10.1038/336577a0

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  • DOI: https://doi.org/10.1038/336577a0

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