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A method for constructing radiation hybrid maps of whole genomes

Abstract

In radiation hybrid mapping, chromosomes in human–rodent hybrid cells are fragmented by X–rays and fragments rescued by fusion of the donor cell to a recipient rodent cell. The co–retention frequencies of markers in 100–200 hybrids are used to map individual chromosomes, but mapping the whole genome in this way is impractical. We have reverted to the original protocols of Goss and Harris and have produced a panel of 44 hybrids using irradiated human fibroblasts as donors. This panel has been used to make a map of human chromosome 14 containing 40 ordered markers. The map integrates previously published maps and localizes nine new markers. We suggest that the construction of a high resolution map of the whole human genome is feasible with a single panel of 100–200 hybrids.

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References

  1. Walter, M.A. & Goodfellow, P.N. Radiation hybrids: irradiation and fusion gene transfer. Trends Genet. 9, 352–356 (1993).

    Article  CAS  PubMed  Google Scholar 

  2. Goss, S.J. & Harris, H. New method for mapping genes in human chromosomes. Nature 255, 680–684 (1975).

    Article  CAS  PubMed  Google Scholar 

  3. Willard, H.F., Goss, S.J., Holmes, M.T. & Munroe, D.L. Regional localization of the phosphoglycerate kinase gene and pseudogene on the human X chromosome and assignment of a related DNA sequence to chromosome 19. Hum. Genet. 71, 138–143 (1985).

    Article  CAS  PubMed  Google Scholar 

  4. Cox, D.R., Burmeister, M., Price, E.R., Kim, S. & Myers, R.M. Radiation hybrid mapping: a somatic cell genetic method for constructing high-resolution maps of mammalian chromosomes. Science 250, 245–250 (1990).

    Article  CAS  PubMed  Google Scholar 

  5. Barrett, J.H. Genetic mapping based on radiation hybrid data. Genomics 13, 95–103 (1992).

    Article  CAS  PubMed  Google Scholar 

  6. Wigler, M., Pellicer, A., Silverstein, S. & Axel, R. Biochemical transfer of single-copy eucaryotic genes using total cellular DNA as donor. Cell 14, 725–731 (1978).

    Article  CAS  PubMed  Google Scholar 

  7. Benham, F. et al. A method for generating hybrids containing nonselected fragments of human chromosomes. Genomics 4, 509–517 (1989).

    Article  CAS  PubMed  Google Scholar 

  8. Warrington, J.A. et al. A radiation hybrid map of 18 growth-factor, growth-factor receptor, hormone receptor, or neurotransmitter receptor genes on the distal region of the long arm of chromosome-5. Genomics 13, 803–808 (1992).

    Article  CAS  PubMed  Google Scholar 

  9. Siden, T.S., Kumlien, J., Schwartz, C.E. & Rohme, D. Radiation fusion hybrids for human chromosomes 3 and X generated at various irradiation doses. Somat. Cell. molec. Genet. 18, 33–44 (1992).

    Article  CAS  PubMed  Google Scholar 

  10. Boehnke, M., Lange, K. & Cox, D.R. Statistical methods for multipoint radiation hybrid mapping. Am. J. hum. Genet. 49, 1174–1188 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. NIH/CEPH Collaborative Mapping Group. A comprehensive genetic-linkage map of the human genome. Science 258, 67–86 (1992).

  12. Weissenbach, J. et al. A 2nd-generatlon linkage map of the human genome. Nature 359, 794–801 (1992).

    Article  CAS  PubMed  Google Scholar 

  13. Cox, D.W. Report of the first International workshop on human chromosome 14 mapping 1993. Cytogenet. Cell Genet. 66, 2–9 (1994).

    CAS  PubMed  Google Scholar 

  14. Goodfellow, P.J., Povey, S., Nevanlinna, H.A. & Goodfellow, P.N. Generation of a panel of somatic cell hybrids containing unselected fragments of human chromosome 10 by X-ray irradiation and cell fusion: application to Isolating the MEN2A region in hybrid cells. Somat. Cell. molec. Genet. 16, 163–171 (1990).

    Article  CAS  PubMed  Google Scholar 

  15. Ceccherini, I. et al. Construction of a map of chromosome 16 by using radiation hybrids. Proc. natn. Acad. Sci. U.S.A. 89, 104–108 (1992).

    Article  CAS  Google Scholar 

  16. Sefton, L., Arnaud, D., Goodfellow, P.N., Simmler, M.C. & Avner, P. Characterization of the central region containing the X-inactivation center and terminal region of the mouse X chromosome using irradiation and fusion gene transfer hybrids. Mamm. Genome 2, 21–31 (1992).

    Article  CAS  PubMed  Google Scholar 

  17. Gorski, J.L., Boehnke, M., Reyner, E.L. & Burright, E.N. A radiation hybrid map of the proximal short arm of the human x-chromosome spanning incontinentia-pigmenti-1 (ip1) translocation breakpoints. Genomics 14, 657–665 (1992).

    Article  CAS  PubMed  Google Scholar 

  18. Lawrence, S., Morton, N.E. & Cox, D.R. Radiation hybrid mapping. Proc. natn. Acad. Sci. U.S.A. 88, 7477–7480 (1991).

    Article  CAS  Google Scholar 

  19. Westerveld, A., Visser, R.P.L.S., Khan, P.M. & Bootsma, D. Loss of human genetic markers in man-Chinese hamster ovary cells. Nature New Biol. 234, 20–22 (1971).

    Article  CAS  PubMed  Google Scholar 

  20. Cotter, F.C., Hampton, G.M., Nasipuri, S., Bodmer, W. & Young, B. Rapid isolation of human chromosome-specific DNA probes from a somatic cell hybrid. Genomics 7, 257–263 (1990).

    Article  CAS  PubMed  Google Scholar 

  21. Orita, M., Sekiya, T. & Hayashi, K. DNA sequence polymorphisms in Alu repeats. Genomics 8, 271–278 (1990).

    Article  CAS  PubMed  Google Scholar 

  22. Powell, S.J., et al. Human bradykinin b2-receptor-nucleotide-sequence analysis and assignment to chromosome-14. Genomics 15, 435–438 (1993).

    Article  CAS  PubMed  Google Scholar 

  23. Polymeropoulos, M.H., Xiao, H., Rath, D.S. & Merril, C.R. Dinucleotide repeat polymorphism at the human cardiac beta-myosin gene. Nucl. Acids Res. 19, 4019 (1991).

    PubMed  PubMed Central  Google Scholar 

  24. Byth, B.C., Meijers, J.C.M. & Cox, D.W. A (ca)n repeat polymorphism in the protein-c inhibitor (pci) gene. Hum. molec. Genet. 2, 1752–1752 (1993).

    PubMed  Google Scholar 

  25. Byth, B.C. & Cox, D.W. A (ca)n repeat polymorphism at the 5′ end of the alpha-1-antitrypsin gene (pi). Hum. molec. Genet. 2, 1752–1752 (1993).

    PubMed  Google Scholar 

  26. Yamada, Y. et al. Human somatostatin receptor genes-localization to human chromosome-14, chromosome-17, and chromosome-22 and identification of simple tandem repeat polymorphisms. Genomics 15, 449–452 (1993).

    Article  CAS  PubMed  Google Scholar 

  27. Weber, J.L., Kwitek, A.E. & May, P.E. Dinucleotide repeat polymorphism at the D14S34 locus. Nucl. Acids Res. 18, 4638 (1990).

    PubMed  PubMed Central  Google Scholar 

  28. Jordan, S.A., McWilliam, P., O'Briain, D.S. & Humphries, P. Dinucleotide repeat polymorphism attheD14S42 locus. Nucl. Acids Res. 19, 1171 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Sharma, V., Smith, L., Allen, L., Magenis, R.E. & Litt, M. Dinucleotide repeat polymorphism at the D14S43 locus. Nucl. Acids Res. 19, 1722 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Luty, J.A. & Litt, M. Dinucleotide repeat polymorphism at the D14S45 locus. Nucl. Acids Res. 19, 4308 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Wang, Z. & Weber, J.L. Continuous linkage map of human chromosome 14 short tandem repeat polymorphisms. Genomics 13, 532–536 (1992).

    Article  CAS  PubMed  Google Scholar 

  32. Hudson, T.J. et al. Isolation and chromosomal assignment of 100 highly Informative human simple sequence repeat polymorphisms. Genomics 13, 622–629 (1992).

    Article  CAS  PubMed  Google Scholar 

  33. Polymeropoulos, M.H., Ziao, H., Ide, S.E. & Merril, C.R. Dinulceotide repaet polymorphism at the D14s99E locus. Hum. molec. Genet. 2, 490 (1993).

    Article  CAS  PubMed  Google Scholar 

  34. Zhao, B. et al. The human gene for apurinic/apyrimldinic endonuclease (HAP1): sequence and localization to chromosome 14 band q12. Nucl. Acids Res. 20, 4097–4098 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Walter, M., Spillett, D., Thomas, P. et al. A method for constructing radiation hybrid maps of whole genomes. Nat Genet 7, 22–28 (1994). https://doi.org/10.1038/ng0594-22

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