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

Richard A. Gatti, Izzet Berkel, Elena Boder, Gary Braedt, Patrick Charmley, Patrick Concannon, Fugen Ersoy, Tatiana Foroud, Nicholas G J Jaspers, Kenneth Lange, G. Mark Lathrop, Mark Leppert, Yusuke Nakamura, Peter O'Connell, Malcolm Paterson, Winston Salser, Ozden Sanal, Jack Silver, Robert S. Sparkes, Ellen Susi & 4 others Daniel E. Weeks, Shan Wei, Ray White, Freda Yoder

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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.

Original languageEnglish (US)
Pages (from-to)577-580
Number of pages4
JournalNature
Volume336
Issue number6199
StatePublished - 1988
Externally publishedYes

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Ataxia Telangiectasia
Chromosomes
Genes
Heterozygote
Lymphocytes
Radiation
Premature Aging
Cerebellar Ataxia
Genetic Linkage
Purkinje Cells
Radiation Tolerance
Ionizing Radiation
Immunoglobulin A
Cultured Cells
Neoplasms
Diabetes Mellitus
Hypersensitivity
Breast
Fibroblasts
Immunoglobulin G

ASJC Scopus subject areas

  • General

Cite this

Gatti, R. A., Berkel, I., Boder, E., Braedt, G., Charmley, P., Concannon, P., ... Yoder, F. (1988). Localization of an ataxia-telangiectasia gene to chromosome 11q22-23. Nature, 336(6199), 577-580.

Localization of an ataxia-telangiectasia gene to chromosome 11q22-23. / Gatti, Richard A.; Berkel, Izzet; Boder, Elena; Braedt, Gary; Charmley, Patrick; Concannon, Patrick; Ersoy, Fugen; Foroud, Tatiana; Jaspers, Nicholas G J; Lange, Kenneth; Lathrop, G. Mark; Leppert, Mark; Nakamura, Yusuke; O'Connell, Peter; Paterson, Malcolm; Salser, Winston; Sanal, Ozden; Silver, Jack; Sparkes, Robert S.; Susi, Ellen; Weeks, Daniel E.; Wei, Shan; White, Ray; Yoder, Freda.

In: Nature, Vol. 336, No. 6199, 1988, p. 577-580.

Research output: Contribution to journalArticle

Gatti, RA, Berkel, I, Boder, E, Braedt, G, Charmley, P, Concannon, P, Ersoy, F, Foroud, T, Jaspers, NGJ, Lange, K, Lathrop, GM, Leppert, M, Nakamura, Y, O'Connell, P, Paterson, M, Salser, W, Sanal, O, Silver, J, Sparkes, RS, Susi, E, Weeks, DE, Wei, S, White, R & Yoder, F 1988, 'Localization of an ataxia-telangiectasia gene to chromosome 11q22-23', Nature, vol. 336, no. 6199, pp. 577-580.
Gatti RA, Berkel I, Boder E, Braedt G, Charmley P, Concannon P et al. Localization of an ataxia-telangiectasia gene to chromosome 11q22-23. Nature. 1988;336(6199):577-580.
Gatti, Richard A. ; Berkel, Izzet ; Boder, Elena ; Braedt, Gary ; Charmley, Patrick ; Concannon, Patrick ; Ersoy, Fugen ; Foroud, Tatiana ; Jaspers, Nicholas G J ; Lange, Kenneth ; Lathrop, G. Mark ; Leppert, Mark ; Nakamura, Yusuke ; O'Connell, Peter ; Paterson, Malcolm ; Salser, Winston ; Sanal, Ozden ; Silver, Jack ; Sparkes, Robert S. ; Susi, Ellen ; Weeks, Daniel E. ; Wei, Shan ; White, Ray ; Yoder, Freda. / Localization of an ataxia-telangiectasia gene to chromosome 11q22-23. In: Nature. 1988 ; Vol. 336, No. 6199. pp. 577-580.
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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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T1 - Localization of an ataxia-telangiectasia gene to chromosome 11q22-23

AU - Gatti, Richard A.

AU - Berkel, Izzet

AU - Boder, Elena

AU - Braedt, Gary

AU - Charmley, Patrick

AU - Concannon, Patrick

AU - Ersoy, Fugen

AU - Foroud, Tatiana

AU - Jaspers, Nicholas G J

AU - Lange, Kenneth

AU - Lathrop, G. Mark

AU - Leppert, Mark

AU - Nakamura, Yusuke

AU - O'Connell, Peter

AU - Paterson, Malcolm

AU - Salser, Winston

AU - Sanal, Ozden

AU - Silver, Jack

AU - Sparkes, Robert S.

AU - Susi, Ellen

AU - Weeks, Daniel E.

AU - Wei, Shan

AU - White, Ray

AU - Yoder, Freda

PY - 1988

Y1 - 1988

N2 - 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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