Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

High resolution localization of recombination hot spots using sperm typing

Abstract

We have applied sperm DNA typing to determine the distribution of crossover events within a one megabase region of the short arm of human chromosome 4 near the locus for Huntington disease. A total of 29 recombinants were detected among 602 sperm typed after whole genome amplification. These recombinants were typed for seven polymorphic markers. The 280 kilobase D4S10–D4S126 interval was found to undergo recombination at a 6–9–fold greater rate per unit of physical distance than the adjacent 720 kb D4S126–D4S127 interval. Sperm typing has the potential to dissect mammalian recombination hot spots to the point where DNA sequence analysis may reveal the molecular basis for hyperrecombination.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Donis-Keller, H. et al. A genetic linkage map of the human genome. Cell 51, 319–337 (1987).

    Article  CAS  PubMed  Google Scholar 

  2. Laurie, D.A. & Hulten, M.A. Further studies on chiasma distribution and interference in the human male. Ann. hum. Genet. 49, 203–214 (1985).

    Article  CAS  PubMed  Google Scholar 

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

  4. Li, H. et al. Amplification and analysis of DNA sequences in single human sperm. Nature 335, 414–417 (1988).

    Article  CAS  PubMed  Google Scholar 

  5. Allitto, B.A. et al. Increased recombination adjacent to the Huntingdon disease-linked D4S10 marker. Genomics 9, 104–112 (1991).

    Article  CAS  PubMed  Google Scholar 

  6. Locke, R.A. et al. A genetic linkage map of the chromosome 4 short arm. Somat. Cell molec. Genet. 19, 95–101 (1993).

    Article  CAS  PubMed  Google Scholar 

  7. Zhang, L. et al. Whole genome amplification from a single cell: Implication for genetic analysis. Proc. natn. Acad. Sci. U.S.A. 89, 5847–5851 (1992).

    Article  CAS  Google Scholar 

  8. Petes, T.D., Malone, R.E. and Smyington, L.S. . in The Molecular and Cellular Biology of the Yeast Saccharomyces (eds Broach, J., Jones, E.W. & Pringle, J.R.) 407–521 (Cold Spring Harbor Press, New York, 1991).

    Google Scholar 

  9. Bryda, E.C., Depart, J.A., Sant'Angelo, D.B., Murphy, D.B. & Passmore, H.C. Multiple sites of crossing over within the Eb recombinational hot spot in the mouse. Mamm. Genome 2, 123–129 (1992).

    Article  CAS  PubMed  Google Scholar 

  10. Henke, A., Fischer, C. & Rappold, G.A. Genetic map of the human pseudoautosomal region reveals a high rate of recombination in female meiosls at the Xp telomere. Genomics 18, 478–485 (1994).

    Article  Google Scholar 

  11. Rouyer, F. et al. The pseudoautosomal region of the human sex chromosomes. Cold Spring Harbor Symp. Quant. Biol. 51, 221–228 (1986).

    Article  CAS  PubMed  Google Scholar 

  12. Page, D.C. et al. Linkage, physical mapping and DNA sequence analysis of pseudoautosomal loci on the human X and Y chromosomes. Genomics 1, 243–256 (1987).

    Article  CAS  PubMed  Google Scholar 

  13. Westphal, E.M. et al. Tyrosine aminotrasferase and chymotrypsinogen B are linked to haptoglogin on human chromosome 16q: Comparison of genetic and physical distances. Genomics 1, 313–319 (1987).

    Article  CAS  PubMed  Google Scholar 

  14. Bowcock, A.M. et al. High recombination between two physically close human basement membrane collagen genes at the distal end of chromosome 13q. Proc. natn. Acad. Sci. U.S.A. 85, 2701–2705 (1988).

    Article  CAS  Google Scholar 

  15. Sefton, L., Kelsey, G., Kearney, P., Povery, S. & Wolfe, J. A physical map of the human PI and AACT genes. Genomics 7, 382–388 (1990).

    Article  CAS  PubMed  Google Scholar 

  16. Benger, J.C. et al. Localization and genetic linkage of the human immunoglobulin heavy chain genes and the creatine kinase brain (CKB) gene: identification of a hot spot for recombination. Genomics 9, 614–622 (1991).

    Article  CAS  PubMed  Google Scholar 

  17. Janson, M. et al. Detailed physical map of human chromosomal region 11q12–13 shows high meiotic recombination rate around the MEN1 locus. Proc. natn. Acad. Sci. U.S.A. 88, 10609–10613 (1991).

    Article  CAS  Google Scholar 

  18. Shutler, G.G., MacKenzie, A.E. & Korneluk, R.G. The 1.5 Mb region spanning the myotonlc dystrophy locus shows uniform recombination frequency. Am. J. hum. Genet. 54, 104–113 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Oudet, C., Hanauer, A., Ciemens, P.I., Caskey, T. & Mendel, J.L. Two hot spots of recombination in the DMD gene correlate with the deletion prone regions. Hum. molec. Genet. 1, 599–603 (1992).

    Article  CAS  PubMed  Google Scholar 

  20. Hubert, R. et al. Sperm typing allows accurate measurement of the recombination fraction between D3S2 and D3S3 on the short arm of human chromosome 3. Genomics 12, 683–687 (1992).

    Article  CAS  PubMed  Google Scholar 

  21. McCombie, W.R. et al. Expressed genes, Alu repeats and polymorphisms in cosmids sequenced from chromosome 4p16.3. Nature Genet. 1, 348–353 (1992).

    Article  CAS  PubMed  Google Scholar 

  22. Cui, X. et al. Gene-centromere mapping by PCR analysis of individual oocytes. Genomics 13, 713–717 (1992).

    Article  CAS  PubMed  Google Scholar 

  23. Bates, G.P. et al. Characterization of a yeast artificial chromosome contig spanning the Huntingdon's disease gene candidate region. Nature Genet. 1, 180–187 (1992).

    Article  CAS  PubMed  Google Scholar 

  24. Zuo, J., Robbins, C., Taillon-Miller, P., Cox, D.R. & Myers, R.M. Cloning of the Huntington disease region in yeast artificial chromosomes. Hum. molec. Genet. 1, 149–159 (1992).

    Article  CAS  PubMed  Google Scholar 

  25. Baxendale, S. et al. A cosmid contig and high resolution restriction map of the 2 megabase region containing the Huntington's disease gene. Nature Genet. 4, 181–186 (1993).

    Article  CAS  PubMed  Google Scholar 

  26. Weber, H.I. & May, P.E. Abundant class of human DNA polymorphisms which can be typed using the polymerase chain reaction. Am. J. hum. Genet. 44, 388–396 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Litt, M. & Luty, J.A. A hypervariable microsatellite revealed by in vitro amplification of a dinucleotide repeat within the cardiac muscle actin gene. Am. J. hum. Genet. 44, 397–401 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Gusella, J.F. et al. A polymorphic DNA marker genetically linked to Huntington's disease. Nature 306, 234–238 (1983).

    Article  CAS  PubMed  Google Scholar 

  29. Stapleton, P.M. Sequence analysis of three polymorphic regions in the human genome detected by the G8 probe for RFLPs associated with Huntington's disease. Nucl. Acids Res. 16, 2735 (1988).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Li, H., Cui, X. & Arnheim, N. Analysis of DNA sequence variation in single ceils. Methods — a companion to Methods in Enzymology (ed. N. Arnheim) 2, 49–59 (Academic Press, 1991).

    Google Scholar 

  31. Cui, X. et al. Single sperm typing: determination of genetic distance between the G-gamma globin and parathyroid hormone loci. Proc. natn. Acad. Sci. U.S.A. 86, 9389–9393 (1989).

    Article  CAS  Google Scholar 

  32. Hubert, R., Weber, J., Schmitt, K., Zhang, L. & Amheim, N. A New Source of polymorphic DNA markers for sperm typing: analysis of microsatellite repeats in single cells. Am. J. hum. Genet. 51, 985–991 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hubert, R., MacDonald, M., Gusella, J. et al. High resolution localization of recombination hot spots using sperm typing. Nat Genet 7, 420–424 (1994). https://doi.org/10.1038/ng0794-420

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng0794-420

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing