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. 1991 Jul 1;88(13):5907–5911. doi: 10.1073/pnas.88.13.5907

Functional complementation of ataxia-telangiectasia group D (AT-D) cells by microcell-mediated chromosome transfer and mapping of the AT-D locus to the region 11q22-23.

C Lambert 1, R A Schultz 1, M Smith 1, C Wagner-McPherson 1, L D McDaniel 1, T Donlon 1, E J Stanbridge 1, E C Friedberg 1
PMCID: PMC51987  PMID: 2062869

Abstract

The hereditary human disease ataxia-telangiectasia (AT) is characterized by phenotypic complexity at the cellular level. We show that multiple mutant phenotypes of immortalized AT cells from genetic complementation group D (AT-D) are corrected after the introduction of a single human chromosome from a human-mouse hybrid line by microcell-mediated chromosome transfer. This chromosome is cytogenetically abnormal. It consists primarily of human chromosome 18, but it carries translocated material from the region 11q22-23, where one or more AT genes have been previously mapped by linkage analysis. A cytogenetically normal human chromosome 18 does not complement AT-D cells after microcell-mediated transfer, whereas a normal human chromosome 11 does. We conclude that the AT-D gene is located on chromosome 11q22-23.

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Selected References

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

  1. BODER E., SEDGWICK R. P. Ataxia-telangiectasia; a familial syndrome of progressive cerebellar ataxia, oculocutaneous telangiectasia and frequent pulmonary infection. Pediatrics. 1958 Apr;21(4):526–554. [PubMed] [Google Scholar]
  2. Colbère-Garapin F., Ryhiner M. L., Stephany I., Kourilsky P., Garapin A. C. Patterns of integration of exogenous DNA sequences transfected into mammalian cells of primate and rodent origin. Gene. 1986;50(1-3):279–288. doi: 10.1016/0378-1119(86)90332-x. [DOI] [PubMed] [Google Scholar]
  3. Evans G. A., Lewis K. A. Physical mapping of complex genomes by cosmid multiplex analysis. Proc Natl Acad Sci U S A. 1989 Jul;86(13):5030–5034. doi: 10.1073/pnas.86.13.5030. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Henning K. A., Schultz R. A., Sekhon G. S., Friedberg E. C. Gene complementing xeroderma pigmentosum group A cells maps to distal human chromosome 9q. Somat Cell Mol Genet. 1990 Jul;16(4):395–400. doi: 10.1007/BF01232467. [DOI] [PubMed] [Google Scholar]
  5. Hoeijmakers J. H., Odijk H., Westerveld A. Differences between rodent and human cell lines in the amount of integrated DNA after transfection. Exp Cell Res. 1987 Mar;169(1):111–119. doi: 10.1016/0014-4827(87)90230-8. [DOI] [PubMed] [Google Scholar]
  6. Ishizaki K., Oshimura M., Sasaki M. S., Nakamura Y., Ikenaga M. Human chromosome 9 can complement UV sensitivity of xeroderma pigmentosum group A cells. Mutat Res. 1990 May;235(3):209–215. doi: 10.1016/0921-8777(90)90076-h. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. 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]
  9. Kaur G. P., Athwal R. S. Complementation of a DNA repair defect in xeroderma pigmentosum cells by transfer of human chromosome 9. Proc Natl Acad Sci U S A. 1989 Nov;86(22):8872–8876. doi: 10.1073/pnas.86.22.8872. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. Lichter P., Ledbetter S. A., Ledbetter D. H., Ward D. C. Fluorescence in situ hybridization with Alu and L1 polymerase chain reaction probes for rapid characterization of human chromosomes in hybrid cell lines. Proc Natl Acad Sci U S A. 1990 Sep;87(17):6634–6638. doi: 10.1073/pnas.87.17.6634. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Lohrer H., Blum M., Herrlich P. Ataxia telangiectasia resists gene cloning: an account of parameters determining gene transfer into human recipient cells. Mol Gen Genet. 1988 Jun;212(3):474–480. doi: 10.1007/BF00330852. [DOI] [PubMed] [Google Scholar]
  13. Mayne L. V., Jones T., Dean S. W., Harcourt S. A., Lowe J. E., Priestley A., Steingrimsdottir H., Sykes H., Green M. H., Lehmann A. R. SV 40-transformed normal and DNA-repair-deficient human fibroblasts can be transfected with high frequency but retain only limited amounts of integrated DNA. Gene. 1988 Jun 15;66(1):65–76. doi: 10.1016/0378-1119(88)90225-9. [DOI] [PubMed] [Google Scholar]
  14. McConville C. M., Formstone C. J., Hernandez D., Thick J., Taylor A. M. Fine mapping of the chromosome 11q22-23 region using PFGE, linkage and haplotype analysis; localization of the gene for ataxia telangiectasia to a 5cM region flanked by NCAM/DRD2 and STMY/CJ52.75, phi 2.22. Nucleic Acids Res. 1990 Aug 11;18(15):4335–4343. doi: 10.1093/nar/18.15.4335. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Paterson M. C., Smith P. J. Ataxia telangiectasia: an inherited human disorder involving hypersensitivity to ionizing radiation and related DNA-damaging chemicals. Annu Rev Genet. 1979;13:291–318. doi: 10.1146/annurev.ge.13.120179.001451. [DOI] [PubMed] [Google Scholar]
  16. Pinkel D., Straume T., Gray J. W. Cytogenetic analysis using quantitative, high-sensitivity, fluorescence hybridization. Proc Natl Acad Sci U S A. 1986 May;83(9):2934–2938. doi: 10.1073/pnas.83.9.2934. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Rudolph N. S., Latt S. A. Flow cytometric analysis of X-ray sensitivity in ataxia telangiectasia. Mutat Res. 1989 Mar;211(1):31–41. doi: 10.1016/0027-5107(89)90104-8. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. Saxon P. J., Schultz R. A., Stanbridge E. J., Friedberg E. C. Human chromosome 15 confers partial complementation of phenotypes to xeroderma pigmentosum group F cells. Am J Hum Genet. 1989 Apr;44(4):474–485. [PMC free article] [PubMed] [Google Scholar]
  20. Saxon P. J., Stanbridge E. J. Transfer and selective retention of single specific human chromosomes via microcell-mediated chromosome transfer. Methods Enzymol. 1987;151:313–325. doi: 10.1016/s0076-6879(87)51026-6. [DOI] [PubMed] [Google Scholar]
  21. Schultz R. A., Saxon P. J., Glover T. W., Friedberg E. C. Microcell-mediated transfer of a single human chromosome complements xeroderma pigmentosum group A fibroblasts. Proc Natl Acad Sci U S A. 1987 Jun;84(12):4176–4179. doi: 10.1073/pnas.84.12.4176. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Seabright M. A rapid banding technique for human chromosomes. Lancet. 1971 Oct 30;2(7731):971–972. doi: 10.1016/s0140-6736(71)90287-x. [DOI] [PubMed] [Google Scholar]
  23. Swift M. Genetic aspects of ataxia-telangiectasia. Immunodefic Rev. 1990;2(1):67–81. [PubMed] [Google Scholar]
  24. Zampetti-Bosseler F., Scott D. The response of normal and ataxia-telangiectasia cells to bleomycin: relationships between chromosome damage, cell cycle delay and cell killing. Mutat Res. 1985 Aug;151(1):89–94. doi: 10.1016/0027-5107(85)90187-3. [DOI] [PubMed] [Google Scholar]
  25. 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]

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