Skip to main content
PMC home page
American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1995 Jul;57(1):112–119.

Localization of an Ataxia-Telangiectasia Gene to an −500-kb Interval on Chromosome 11q23.1: Linkage Analysis of 176 Families by an International Consortium

Ethan Lange, Anna-Lise Borresen, Xiaoguang Chen, Luciana Chessa, Sujata Chiplunkar, Patrick Concannon, Sugandha Dandekar, Steven Gerken, Kenneth Lange, Teresa Liang, Carmel McConville, Jeff Polakow, Oscar Porras, Galit Rotman, Ozden Sanal, Sepideh Sheikhavandi, Yosef Shiloh, Eric Sobel, Malcolm Taylor, Milhan Telatar, Sharon Teraoka, Aslihan Tolun, Nitin Udar, Nancy Uhrhammer, Lina Vanagaite, Zhijun Wang, Beth Wapelhorst, Jocyndra Wright, Huan-Ming Yang, Lan Yang, Yael Ziv, Richard A Gatti
PMCID: PMC1801232  PMID: 7611279

Abstract

We describe a 20-point linkage analysis map of chromosome 11q22-23 that is based on genotyping 249 families (59 CEPH and 190 A-T). Monte Carlo linkage analyses of 176 ataxia-telangiectasia (A-T) families localizes the major A-T locus to the region between S1819(A4) and S1818(A2). When seven nonlinking families were excluded from subsequent analyses, a 2-lod support interval of ∼500 kb was identified between S1819(A4) and S1294. No recombinants were observed between A-T and markers S384, B7, S535, or S1294. Only 17 of the international consortium families have been assigned to complementation groups. The available evidence favors either a cluster of A-T genes on chromosome 11 or intragenic defects in a single gene.

Full text

PDF
112

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ambrose H. J., Byrd P. J., McConville C. M., Cooper P. R., Stankovic T., Riley J. H., Shiloh Y., McNamara J. O., Fukao T., Taylor A. M. A physical map across chromosome 11q22-q23 containing the major locus for ataxia telangiectasia. Genomics. 1994 Jun;21(3):612–619. doi: 10.1006/geno.1994.1321. [DOI] [PubMed] [Google Scholar]
  2. Charmley P., Foroud T., Wei S., Concannon P., Weeks D. E., Lange K., Gatti R. A. A primary linkage map of the human chromosome 11q22-23 region. Genomics. 1990 Feb;6(2):316–323. doi: 10.1016/0888-7543(90)90572-c. [DOI] [PubMed] [Google Scholar]
  3. Foroud T., Wei S., Ziv Y., Sobel E., Lange E., Chao A., Goradia T., Huo Y., Tolun A., Chessa L. Localization of an ataxia-telangiectasia locus to a 3-cM interval on chromosome 11q23: linkage analysis of 111 families by an international consortium. Am J Hum Genet. 1991 Dec;49(6):1263–1279. [PMC free article] [PubMed] [Google Scholar]
  4. Gatti R. A., Berkel I., Boder E., Braedt G., Charmley P., Concannon P., Ersoy F., Foroud T., Jaspers N. G., Lange K. Localization of an ataxia-telangiectasia gene to chromosome 11q22-23. Nature. 1988 Dec 8;336(6199):577–580. doi: 10.1038/336577a0. [DOI] [PubMed] [Google Scholar]
  5. Gatti R. A., Boder E., Vinters H. V., Sparkes R. S., Norman A., Lange K. Ataxia-telangiectasia: an interdisciplinary approach to pathogenesis. Medicine (Baltimore) 1991 Mar;70(2):99–117. [PubMed] [Google Scholar]
  6. Gatti R. A., Lange E., Rotman G., Chen X., Uhrhammer N., Liang T., Chiplunkar S., Yang L., Udar N., Dandekar S. Genetic haplotyping of ataxia-telangiectasia families localizes the major gene to an approximately 850 kb region on chromosome 11q23.1. Int J Radiat Biol. 1994 Dec;66(6 Suppl):S57–S62. [PubMed] [Google Scholar]
  7. Gatti R. A., McConville C. M., Taylor A. M. Sixth international workshop on ataxia-telangiectasia. Cancer Res. 1994 Nov 15;54(22):6007–6010. [PubMed] [Google Scholar]
  8. Hauge X. Y., Evans G. A., Litt M. Dinucleotide repeat polymorphism at the D11S528 locus. Nucleic Acids Res. 1991 Apr 25;19(8):1964–1964. doi: 10.1093/nar/19.8.1964. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hauge X. Y., Grandy D. K., Eubanks J. H., Evans G. A., Civelli O., Litt M. Detection and characterization of additional DNA polymorphisms in the dopamine D2 receptor gene. Genomics. 1991 Jul;10(3):527–530. doi: 10.1016/0888-7543(91)90431-d. [DOI] [PubMed] [Google Scholar]
  10. Jaspers N. G., Gatti R. A., Baan C., Linssen P. C., Bootsma D. Genetic complementation analysis of ataxia telangiectasia and Nijmegen breakage syndrome: a survey of 50 patients. Cytogenet Cell Genet. 1988;49(4):259–263. doi: 10.1159/000132673. [DOI] [PubMed] [Google Scholar]
  11. Julier C., Nakamura Y., Lathrop M., O'Connell P., Leppert M., Litt M., Mohandas T., Lalouel J. M., White R. A detailed genetic map of the long arm of chromosome 11. Genomics. 1990 Jul;7(3):335–345. doi: 10.1016/0888-7543(90)90167-s. [DOI] [PubMed] [Google Scholar]
  12. Komatsu K., Kodama S., Okumura Y., Koi M., Oshimura M. Restoration of radiation resistance in ataxia telangiectasia cells by the introduction of normal human chromosome 11. Mutat Res. 1990 Mar;235(2):59–63. doi: 10.1016/0921-8777(90)90058-d. [DOI] [PubMed] [Google Scholar]
  13. Kwiatkowski D. J., Henske E. P., Weimer K., Ozelius L., Gusella J. F., Haines J. Construction of a GT polymorphism map of human 9q. Genomics. 1992 Feb;12(2):229–240. doi: 10.1016/0888-7543(92)90370-8. [DOI] [PubMed] [Google Scholar]
  14. Lange K., Sobel E. A random walk method for computing genetic location scores. Am J Hum Genet. 1991 Dec;49(6):1320–1334. [PMC free article] [PubMed] [Google Scholar]
  15. Lathrop G. M., Lalouel J. M., Julier C., Ott J. Strategies for multilocus linkage analysis in humans. Proc Natl Acad Sci U S A. 1984 Jun;81(11):3443–3446. doi: 10.1073/pnas.81.11.3443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Litt M., Kramer P., Hauge X. Y., Weber J. L., Wang Z., Wilkie P. J., Holt M. S., Mishra S., Donis-Keller H., Warnich L. A microsatellite-based index map of human chromosome 11. Hum Mol Genet. 1993 Jul;2(7):909–913. doi: 10.1093/hmg/2.7.909. [DOI] [PubMed] [Google Scholar]
  17. Litt M., Sharma V., Luty J. A. Dinucleotide repeat polymorphism at the D11S35 locus. Nucleic Acids Res. 1990 Oct 11;18(19):5921–5921. doi: 10.1093/nar/18.19.5921-a. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. McConville C. M., Byrd P. J., Ambrose H. J., Stankovic T., Ziv Y., Bar-Shira A., Vanagaite L., Rotman G., Shiloh Y., Gillett G. T. Paired STSs amplified from radiation hybrids, and from associated YACs, identify highly polymorphic loci flanking the ataxia telangiectasia locus on chromosome 11q22-23. Hum Mol Genet. 1993 Jul;2(7):969–974. doi: 10.1093/hmg/2.7.969. [DOI] [PubMed] [Google Scholar]
  19. Meyn M. S. High spontaneous intrachromosomal recombination rates in ataxia-telangiectasia. Science. 1993 May 28;260(5112):1327–1330. doi: 10.1126/science.8493577. [DOI] [PubMed] [Google Scholar]
  20. Nakamura Y., Leppert M., O'Connell P., Wolff R., Holm T., Culver M., Martin C., Fujimoto E., Hoff M., Kumlin E. Variable number of tandem repeat (VNTR) markers for human gene mapping. Science. 1987 Mar 27;235(4796):1616–1622. doi: 10.1126/science.3029872. [DOI] [PubMed] [Google Scholar]
  21. Rotman G., Savitski K., Vanagaite L., Bar-Shira A., Ziv Y., Gilad S., Uchenik V., Smith S., Shiloh Y. Physical and genetic mapping at the ATA/ATC locus on chromosome 11q22-23. Int J Radiat Biol. 1994 Dec;66(6 Suppl):S63–S66. [PubMed] [Google Scholar]
  22. Sanal O., Lange E., Telatar M., Sobel E., Salazar-Novak J., Ersoy F., Morrison A., Concannon P., Tolun A., Gatti R. A. Ataxia-telangiectasia: linkage analysis of chromosome 11q22-23 markers in Turkish families. FASEB J. 1992 Jul;6(10):2848–2852. doi: 10.1096/fasebj.6.10.1634048. [DOI] [PubMed] [Google Scholar]
  23. Sanal O., Wei S., Foroud T., Malhotra U., Concannon P., Charmley P., Salser W., Lange K., Gatti R. A. Further mapping of an ataxia-telangiectasia locus to the chromosome 11q23 region. Am J Hum Genet. 1990 Nov;47(5):860–866. [PMC free article] [PubMed] [Google Scholar]
  24. Sobel E., Lange K. Metropolis sampling in pedigree analysis. Stat Methods Med Res. 1993;2(3):263–282. doi: 10.1177/096228029300200305. [DOI] [PubMed] [Google Scholar]
  25. Swift M., Morrell D., Massey R. B., Chase C. L. Incidence of cancer in 161 families affected by ataxia-telangiectasia. N Engl J Med. 1991 Dec 26;325(26):1831–1836. doi: 10.1056/NEJM199112263252602. [DOI] [PubMed] [Google Scholar]
  26. Telatar M., Concannon P., Tolun A. Dinucleotide repeat polymorphism at the NCAM locus. Hum Mol Genet. 1994 May;3(5):842–842. doi: 10.1093/hmg/3.5.842. [DOI] [PubMed] [Google Scholar]
  27. Uhrhammer N., Concannon P., Huo Y., Nakamura Y., Gatti R. A. A pulsed-field gel electrophoresis map in the ataxia-telangiectasia region of chromosome 11q22.3. Genomics. 1994 Mar 15;20(2):278–280. doi: 10.1006/geno.1994.1165. [DOI] [PubMed] [Google Scholar]
  28. Uhrhammer N., Lange E., Porras O., Naeim A., Chen X., Sheikhavandi S., Chiplunkar S., Yang L., Dandekar S., Liang T. Sublocalization of an ataxia-telangiectasia gene distal to D11S384 by ancestral haplotyping in Costa Rican families. Am J Hum Genet. 1995 Jul;57(1):103–111. [PMC free article] [PubMed] [Google Scholar]
  29. Vanagaite L., Savitsky K., Rotman G., Ziv Y., Gerken S. C., White R., Weissenbach J., Gillett G., Benham F. J., Richard C. W., 3rd Physical localization of microsatellite markers at the ataxia-telangiectasia locus at 11q22-q23. Genomics. 1994 Jul 1;22(1):231–233. doi: 10.1006/geno.1994.1370. [DOI] [PubMed] [Google Scholar]
  30. Weissenbach J., Gyapay G., Dib C., Vignal A., Morissette J., Millasseau P., Vaysseix G., Lathrop M. A second-generation linkage map of the human genome. Nature. 1992 Oct 29;359(6398):794–801. doi: 10.1038/359794a0. [DOI] [PubMed] [Google Scholar]
  31. Ziv Y., Rotman G., Frydman M., Dagan J., Cohen T., Foroud T., Gatti R. A., Shiloh Y. The ATC (ataxia-telangiectasia complementation group C) locus localizes to 11q22-q23. Genomics. 1991 Feb;9(2):373–375. doi: 10.1016/0888-7543(91)90268-j. [DOI] [PubMed] [Google Scholar]

Articles from American Journal of Human Genetics are provided here courtesy of American Society of Human Genetics

RESOURCES