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

Tissue specificity of chromosomal rearrangements in ataxia-telangiectasia


Cytogenetic studies of lymphocytes and fibroblasts from individuals with ataxia-telangiectasia (AT) demonstrate spontaneous chromosomal breakage. In the AT lymphocytes, this damage results in a high frequency of balanced rearrangements involving chromosome bands 7p14, 7q35, 14q12, and 14q32. The T-cell receptor α, β, and γ chain gene complexes and the immunoglobulin heavy chain gene complex, all of which may be functional in lymphocytes, have been localized to these bands. To assess the relationship between genes at these breakpoints and the entirety of the AT phenotype, we undertook a detailed cytogenetic analysis of fibroblasts and lymphocytes from seven AT homozygotes. Our findings indicate that the rearrangements present in the lymphocytes are not commonly observed in the fibroblasts, despite the increased instability of chromosomes from these cells relative to lymphocytes. Furthermore, the changes in the fibroblasts are neither consistent within nor between patients, suggesting that chromosome rearrangement occurs more randomly in this tissue. Therefore, differential site-specific damage in separate tissues may generate the distinct features of the disease in those tissues and may account for the pleiotrophic effects of the AT gene.

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


  1. Al Saadi A, Palutke M, Kirshnakumar G (1980) Evolution of chromosomal abnormalities in sequential cytogenetic studies of ataxia telangiectasia. Hum Genet 55:23–29

  2. Aurias A (1981) Analyse cytogenetique de 21 cas d'ataxic telangiectasie. J Genet Hum 29:235–247

  3. Aurias A, Dutrillaux B, Buriot D, Lejeune J (1980) High frequencies of inversions and translocations of chromosome 7 and 14 in AT. Mutat Res 69:369–374

  4. Baer R, Chen K-C, Smith SD, Rabbitts TH (1985) Fusion of an immunoglobulin variable gene and a T-α cell receptor constant gene in the chromosome 14 inversion associated with T-cell tumors. Cell 43:705–713

  5. Beatty-De Sana JW, Hoggard MJ, Cooledge JW (1975) Non-random occurrence of 7–14 translocation in human lymphocyte cultures. Nature 255:242–243

  6. Benn PA (1977) Population kinetics of chromosomally abnormal human fibroblast sub-populations. Cytogenet Cell Genet 19:136–145

  7. Cohen MM, Kohn G, Dagan J (1973) Chromosomes in ataxia telangiectasia. Lancet II:1500

  8. Cohen MM, Shaham M, Dagan J, Shmueli E, Kohn G (1975) Cytogenetic investigations in families with ataxia telangiectasia. Cytogenet Cell Genet 15:338–356

  9. Cohen MM, Sagi M, Ben Zur Z, Schaap T, Voss R, Kohn G (1979) Ataxia telangiectasia: chromosomal stability in continuous lymphoblastoid cell lines. Cytogenet Cell Genet 23:44–52

  10. Croce CM, Isobe M, Palumbo A, Puck J, Ming J, Tweardy D, Erikson J Davis M, Rovera G (1985) Gene for α chain of human T-cell receptor: location on chromosome 14 region involved in T-cell neoplasms. Science 277:1044–1047

  11. Davey MP, Bertness V, Nakahara K, Johnson JP, McBride OW, Waldmann TA, Kirsh IR (1988) Juxtaposition of the T-cell receptor α-chain locus (14q11) and region (14q32) of potential importance in leukemogenesis by a 14;14 translocation in a patient with T-cell chronic lymphocytic leukemia and ataxia-telangiectasia. Proc Natl Acad Sci USA 85:9287–9291

  12. Denny CT, Hollis GF, Hecht F, Morgan E, Link MP, Smith SD, Kirsch IR (1986a) Common mechanism of chromosome inversion in B- and T-cell tumors: relevance to lymphoid development. Science 234:197–200

  13. Denny CT, Yoshikai Y, Mak TW, Smith SD, Hollis GF, Kirsch IR (1986b) A chromosome 14 inversion in a T-cell lymphoma is caused by site-specific recombination between immunoglobulin and T-cell receptor loci. Nature 320:549–551

  14. De Wald GW, Noonan KJ, Spurbeck JL, Johnson DD (1986) T-Lymphocytes with 7;14 translocations: frequency of occurrence, breakpoints and clinical and biological significance. Am J Hum Genet 38:520–532

  15. Gatti RA, Aurias A, Griscelli C, Sparkes RS (1985) Translocations involving 2p and 22q in ataxia-telangiectasia. Dis Markers 3:169–175

  16. Gatti RA, Berkel I, Boder E, Braedt G, Charmley P, Concannon P, Ersoy F, 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

  17. Hayashi K, Schmid W (1975) Tandem duplication of q14 and dicentric formation by end-to-end chromosome fusions in AT. Humangenetik 30:135–141

  18. Hecht F, McCaw BK, Koler RD (1973) Ataxia telangiectasia: clonal growth of translocation lymphocytes. N Engl J Med 289:286–291

  19. Hecht F, McCaw BK, Peakman D, Robinson A (1975) Non-random occurrence of 7–14 translocations in human lymphocyte cultures. Nature 255:243–244

  20. Hustinx TWJ, Scheres JMJC, Weenaes CMR, Haar BGA ter, Jonsson AH (1979) Karyotype instability with multiple 7/14 and 7/7 rearrangements. Hum Genet 49:199–200

  21. Isobe M, Erikson J, Emanuel BS, Nowell PC, Croce CM (1985) Location of gene for subunit of human T-cell receptor at band 7q35, a region prone to rearrangements in T-cells. Science 228:580–582

  22. Kirsch IR, Morton CC, Nakahara K, Leder P (1982) Human immunoglobulin heavy chain genes map to a region of translocation in malignant B lymphocytes. Science 216:301–303

  23. Kohn PH, Whang-Peng J, Levis WR (1982) Chromosomal instability in ataxia telangiectasia. Cancer Genet Cytogenet 6:289–302

  24. LeBeau MM, Diaz MO, Rowley JD, Mak TW (1985) Chromosomal localization of human T-cell receptor β-chain genes. Cell 41:335

  25. Mengle-Gaw L, Willard HF, Smith CI, Hammarstrom L, Fischer P, Sherrington P, Lucas G, Thompson PW, Baer R, Rabbits TH (1987) Human T-cell tumors containing chromosome 14 inversion or translocation with breakpoints proximal to immunoglobulin joining regions at 14q32. EMBO J 6:2273–2280

  26. Morgan R, Jarzabek B, Jaffe JP, Hecht BK, Sandberg AA (1986) Telomeric fusion in pre-T-cell acute leukemia. Hum Genet 73:260–263

  27. Morton CC, Duby AD, Eddy RL, Shows TB, Seidman JG (1985) Genes for β chain of human T-cell antigen receptor map to regions of chromosomal instability in T-cells. Science 228:582–585

  28. Moyzis RK, Buckingham JM, Cram LS, Dani M, Deaven LL, Jones MD, Meyne J, Ratliff RL, Wu JR (1988) A highly conserved repetitive DNA sequence, (TTAGGG)n, present at the telomeres of human chromosomes. Proc Natl Acad Sci USA 85:6622–6626

  29. Murre C, Waldmann RA, Morton CC, Bongiovanni KF, Waldmann TA, Shows TB, Seidman JC (1985) Human γ chain genes are rearranged in leukemic T-cells and map to the short arm of chromosome 7. Nature 316:549–552

  30. O'Connor RD, Brown MG, Francke U (1982) Immunologic and karyotypic studies in ataxia telangiectasia: specificity of break points on chromosomes 7 and 14 in lymphocytes from patients and relatives. In: Bridges BA, Harnden DG (eds) Ataxia telangiectasia: a cellular and molecular link between cancer, neuropathology and immune deficiency. Wiley, Chichester, pp 259–270

  31. Oxford JM, Harnden DG, Parrington JM, Delhanty JDA (1975) Specific chromomome aberrations in ataxia telangiectasia. J Med Genet 12:251–262

  32. Painter RB, Young BR (1980) Radiosensitivity in ataxia telangiectasia: a new explanation. Proc Natl Acad Sci USA 77:7315–7317

  33. Pfeiffer RA (1970) Chromosomal abnormalities in ataxia telangiectasia (Louis Bar's syndrome). Humangenetik 8:302–306

  34. Rary JM, Bender MA, Kelly TE (1975) A 14/14 marker chromosome lymphocyte clone in ataxia telangiectasia. J Hered 66:33–35

  35. Ray JH, German J (1983) The cytogenetics of the “chromosome-breakage syndromes”. In: German J (ed) Chromosome mutation and neoplasia. Liss, New York, pp 135–167

  36. Russo G, Isobe M, Pegoraro L, Finan J, Nowell PG, Croce CM (1988) Molecular analysis of a t(7;14)(q35;q35) chromosome translocation in a T cell leukemia of a patient with ataxia telangiectasia. Cell 53:137–144

  37. Scheres JMJC, Hustinx TWJ, Weemaes CMP (1980) chromosome 7 in ataxia telangiectasia. J Pediatr 97:440–441

  38. Schmid W, Jerusalem F (1972) Cytogenetic findings in two brothers with ataxia-telangiectasia (Louis Bar's syndrome). Arch Genet 45:49–52

  39. Seabright M (1971) A rapid banding technique for human chromosomes. Lancet II:971–972

  40. Sparkes RS, Como R, golde DW (1980) Cytogenetic abnormalities in ataxia-telangiectasia with T-cell chronic lymphocytic leukemia. Cancer Genet Cytogenet 1:329–338

  41. Spector BD, Filipovich AH, Perry III 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

  42. Taylor AMR, Oxford JM, Metcalfe JA (1981) Spontaneous cytogenetic abnormalities in lymphocytes from thirteen patients with ataxia telangiectasia. Int J Cancer 27:311–319

  43. Wallace C, Bernstein R, Pinto MR (1984) Non-random in vitro 7;14 translocations detected in a routine cytogenetic series. 12 examples and their possible significance. Hum Genet 66:157–161

  44. Welch JP, Lee CLY (1975) Non-random occurrence of 7–14 translocations in human lymphocyte cultures. Nature 255:241–242

  45. Yunis JJ, Soreng AL (1984) Constitutive fragile sites and cancer. Science 226:1199–1204

  46. Zech L, Haglund U (1978) A recurrent structural aberration t(7;14) in phytohemagglutinin-stimulated lymphocytes. Hereditas 89:69–73

  47. Zech L, Gahrton G, Hammarstrom L, Juliusson G, Mellstedt H, Robert KH, Smith CIE (1984) Inversion of chromosome 14 marks human T-cell chronic lymphocytic leukemia. Nature 308:858–860

Download references

Author information

Correspondence to R. R. Schreck.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Kojis, T.L., Schreck, R.R., Gatti, R.A. et al. Tissue specificity of chromosomal rearrangements in ataxia-telangiectasia. Hum Genet 83, 347–352 (1989). https://doi.org/10.1007/BF00291379

Download citation


  • Heavy Chain
  • Chromosomal Rearrangement
  • Cytogenetic Analysis
  • Cytogenetic Study
  • Chromosome Band