Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Analysis of 7 polymorphic markers at chromosome 11q22-23 in 35 ataxia telangiectasia families; further evidence of linkage

  • 31 Accesses

  • 20 Citations


Ataxia telangiectasia (A-T) is an autosomal recessive disorder characterised by progressive neurological degeneration, oculocutaneous telangiectasia, immunodeficiency and a high incidence of lymphoid tumours. A prerequisite to gaining a complete understanding of the basic defect that results in these features is the localization of the gene(s) involved. We report here a linkage analysis using seven polymorphic markers, which map to 11q22–23, on a sample of 35 consecutively obtained families from the British Isles showing this disorder. In a pairwise analysis, the strongest support for linkage was a lod score of 4.01 at zero recombination from Thy-1. This result supports a previous report showing linkage of the A-T gene to 11q22–23. We have also obtained evidence in a multipoint analysis for a more centromeric A-T-linked locus in the region between YNB 3.12/CJ52.208 and 2-7-1D6. This observation is also supported by inspection of the haplotypes of selected recombinants.

This is a preview of subscription content, log in to check access.


  1. Aurias A, Dutrillaux B (1986) Probable involvement of immunoglobulin superfamily genes in most recurrent chromosomal rearrangements from ataxia telangiectasia. Hum Genet 72:210–214

  2. Baer R, Heppell A, Taylor AMR, Rabbitts PH, Boullier B, Rabbitts TH (1987) The breakpoint of an inversion chromosome 14 in a T cell leukaemia; sequences downstream of the immunoglobulin heavy chains locus implicated in tumorigenesis. Proc Natl Acad Sci USA 84:9069–9073

  3. Boder E (1985) Ataxia telangiectasia: an overview. In: Gatti RA, Swift M (eds) Ataxia telangiectasia: genetics, neuropathology and immunology of a degenerative disease of childhood. Liss, New York, pp 1–63

  4. Budarf M, Sellinger B, Griffin C, Emanuel BS (1989) Comparative mapping of the constitutional and tumor-associated 11;22 translocations. Am J Hum Genet 45:128–139

  5. Butterworth SV, Taylor AMR (1986) A subpopulation of t(2;14) (p11;q32) cells in ataxia telangiectasia B lymphocytes. Hum Genet 73:346–349

  6. Charmley P, Foroud T, Wei S, Concannon P, Weeks DE, Lange K, Gatti R (1990) A primary linkage map of the human chromosome 11q22–23 region. Genomics 6:316–323

  7. Cox R, Hosking P, Wilson J (1978) Ataxia telangiectasia, evaluation of radiosensitivity in cultured skin fibroblasts as a diagnostic test. Arch Dis Child 53:386–390

  8. Feinberg AP, Vogelstein B (1983) A technique for radiolabelling DNA restriction fragments to high specificity. Anal Biochem 132:6–13

  9. Garson JA, Beverly PCL, Coakham HB, Harper EI (1982) Monoclonal antibodies against human T lymphocytes label Purkinje neurones of many species. Nature 298:375–377

  10. Gatti RA, Lathrop GM, Salser W, Silver J, Lalouel JM, White R (1987) Location of Thy-1 with respect to a primary linkage map of chromosome 11q (abstract). (9th International Workshop on Human Gene Mapping) Cytogenet Cell Genet 46:618

  11. Gatti RA, Berkel I, Boder E, Braedt G, Charmley P, Concannon FE, Foroud T, Jaspers NGJ, Lange K, Lathrop M, 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 336:577–580

  12. Heppell A, Butterworth SV, Hollis RJ, Kennaugh AA, Beatty DW, Taylor AMR (1988) Breakage of the T cell receptor α chain locus in non-malignant clones from patients with ataxia telangiectasia. Hum Genet 79:360–364

  13. Hollis RJ, Kennaugh AA, Butterworth SV, Taylor AMR (1987) Growth of large chromosomally abnormal T cell clones in ataxia telangiectasia patients is associated with translocation at 14q11. Hum Genet 76:389–395

  14. Jaspers NGJ, Gatti RA, Baan C, Linssen PCML, Bootsma D (1988) Genetic complementation analysis of ataxia telangiectasia and Nijmegen breakage syndrome: a survey of 50 patients. (Human Gene Mapping 9.5: update to the 9th International Workshop on Human Gene Mapping) Cytogenet Cell Genet 49:259–263

  15. Kennaugh AA, Butterworth SV, Hollis R, Baer R, Rabbitts TH, Taylor AMR (1986) The chromosome breakpoint at 14q32 in an ataxia telangiectasia t(14;14) T cell clone is different from the 14q32 breakpoint in Burkitt's and an inv(14) T cell lymphoma. Hum Genet 73:254–259

  16. Kunkel LM, Smith KP, Boyer SH, Borgaonkar DS, Wachtel SS, Miller OJ, Boreg WR, Jones HW, Rary JM (1975) Analysis of human Y chromosome specific reiterated DNA in chromosome variants. Proc Natl Acad Sci USA 74:1245–1249

  17. Lathrop GM, Lalouel J-M, Julier C, Ott J (1984) Strategies for multilocus linkage analysis in humans. Proc Natl Acad Sci USA 81:3443–3446

  18. Leppert M, O'Connell P, Nakamura Y, Lathrop GM, Maslen C, Litt M, Cartwright P, Lalouel JM, White R (1987) A partial primary genetic linkage map of chromosome 11 (abstract). (9th International Workshop on Human Gene Mapping) Cytogenet Cell Genet 46:648

  19. Murnane JP, Painter RB (1982) Complementation of the defects in DNA synthesis in irradiated and unirradiated ataxia telangiectasia cells. Proc Natl Acad Sci USA 79:1960–1963

  20. Savage PD, Jones C, Silver J, Geurts von Kessel AHM, Gonzalez-Sartmiento R, Palm L, Hanson CA, Kersey JH (1989) Mapping studies and expression of genes located on human chromosome 11, band q23. Cytogenet Cell Genet 49:289–292

  21. Sedgwick RP (1982) Carcinofetal proteins in ataxia telangiectasia: a cancer report. In: Bridges BA, Harnden DG (eds) Ataxia telangiectasia — a cellular and molecular link between cancer, neuropathology and immune deficiency. Wiley, Chichester, pp 387–391

  22. Shiloh Y, Ziv Y, Frydman M, Portnoi S, Nakamura Y, Foroud T, Gatti RA (1989) The ataxia-telangiectasia (A-T) locus in Jewish and Arab A-T patients localizes to 11q22–23. Am J Hum Genet 45:161

  23. Southern EM (1975) Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol 98:502–517

  24. Spector BD, Filipovich AH, Perry GS, Kersey JH (1982) Epidemiology of cancer in ataxia telangiectasia. In: Bridges BA, Harnden DG (eds) Ataxia telangiectasia: a cellular and molecular link between cancer, neuropathology and immune deficiency. Wiley, Chichester, pp 103–138

  25. Swift M, Morrell D, Cromartie E, Chamberlin AR, Skolnick MH, Bishop DT (1986) The incidence and gene frequency of ataxia telangiectasia in the United States. Am J Hum Genet 39:573–583

  26. Taylor AMR (1982) Cytogenetics of ataxia telangiectasia. In: Bridges BA, Harnden DG (eds) Ataxia telangiectasia — a cellular and molecular link between cancer, neuropathology and immune deficiency. Wiley, Chichester, pp 53–82

  27. Taylor AMR, Butterworth SV (1986) Clonal evolution of T cell chronic lymphocytic leukaemia in a patient with ataxia telangiectasia. Int J Cancer 37:511–516

  28. Taylor AMR, Flude E, Laher B, Stacey M, McKay E, Watt J, Green SH, Harding AE (1987) Variant forms of ataxia telangiectasia. J Med Genet 24:669–677

  29. Waldmann TA, McIntire KR (1972) Serum alpha-foeto protein levels in patients with ataxia telangiectasia. Lancet II:1112–1115

  30. Waldmann TA, Broder S, Goldman CK, Frost K, Korsmeyer SJ, Medici MA (1983) Disorders of B cells and helper T cells in the pathogenesis of the immunoglobulin deficiency of patients with ataxia telangiectasia. J Clin Invest 71:282–295

  31. Wegner RD, Metzger M, Hanfield F, Jaspers NGJ, Baan C, Magdorf K, Kunze J, Sperling K (1988) A new chromosomal instability disorder confirmed by complementation studies. Clin Genet 33:20–32

  32. Wei S, Rocchi M, Archidiacono N, Sacchi N, Romeo G, Gatti RA (1990) Physical mapping of the chromosome 11q region containing the ataxia-telangiectasia locus. Cancer Genet Cytogenet 46:1–8

  33. Woods CG, Bundey SE, Taylor AMR (1990) Unusual features in the inheritance of ataxia telangiectasia. Hum Genet 84:555–562

Download references

Author information

Correspondence to C. M. McConville.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

McConville, C.M., Woods, C.G., Farrall, M. et al. Analysis of 7 polymorphic markers at chromosome 11q22-23 in 35 ataxia telangiectasia families; further evidence of linkage. Hum Genet 85, 215–220 (1990). https://doi.org/10.1007/BF00193199

Download citation


  • Internal Medicine
  • Metabolic Disease
  • Linkage Analysis
  • Strong Support
  • Complete Understanding