Skip to main content

Thank you for visiting 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.

Human recombination hot spots hidden in regions of strong marker association


The fine-scale distribution of meiotic recombination events in the human genome can be inferred from patterns of haplotype diversity in human populations1,2,3,4,5 but directly studied only by high-resolution sperm typing6,7,8. Both approaches indicate that crossovers are heavily clustered into narrow recombination hot spots. But our direct understanding of hot-spot properties and distributions is largely limited to sperm typing in the major histocompatibility complex (MHC)7. We now describe the analysis of an unremarkable 206-kb region on human chromosome 1, which identified localized regions of linkage disequilibrium breakdown that mark the locations of sperm crossover hot spots. The distribution, intensity and morphology of these hot spots are markedly similar to those in the MHC. But we also accidentally detected additional hot spots in regions of strong association. Coalescent analysis of genotype data detected most of the hot spots but showed significant differences between sperm crossover frequencies and historical recombination rates. This raises the possibility that some hot spots, particularly those in regions of strong association, may have evolved very recently and not left their full imprint on haplotype diversity. These results suggest that hot spots could be very abundant and possibly fluid features of the human genome.

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

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Prices vary by article type



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

Figure 1: Patterns of LD and historical recombination in a 206-kb interval around minisatellite MS32.
Figure 2: LD and sperm crossover profiles across NID.
Figure 3: LD and sperm crossover profiles near minisatellite MS32.
Figure 4: Impact of crossover frequencies on strengths of pairwise marker association.
Figure 5: Testing whether sperm crossover frequencies are compatible with coalescent estimates of historical recombination rates.


  1. Chakravarti, A. et al. Nonuniform recombination within the human beta-globin gene cluster. Am. J. Hum. Genet. 36, 1239–1258 (1984).

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Gabriel, S.B. et al. The structure of haplotype blocks in the human genome. Science 296, 2225–2229 (2002).

    Article  CAS  Google Scholar 

  3. Reich, D.E. et al. Human genome sequence variation and the influence of gene history, mutation and recombination. Nat. Genet. 32, 135–142 (2002).

    Article  CAS  Google Scholar 

  4. Crawford, D.C. et al. Evidence for substantial fine-scale variation in recombination rates across the human genome. Nat. Genet. 36, 700–706 (2004).

    Article  CAS  Google Scholar 

  5. McVean, G.A. et al. The fine-scale structure of recombination rate variation in the human genome. Science 304, 581–584 (2004).

    Article  CAS  Google Scholar 

  6. Jeffreys, A.J., Ritchie, A. & Neumann, R. High-resolution analysis of haplotype diversity and meiotic crossover in the human TAP2 recombination hotspot. Hum. Mol. Genet. 9, 725–733 (2000).

    Article  CAS  Google Scholar 

  7. Jeffreys, A.J., Kauppi, L. & Neumann, R. Intensely punctate meiotic recombination in the class II region of the major histocompatibility complex. Nat. Genet. 29, 217–222 (2001).

    Article  CAS  Google Scholar 

  8. May, C.A., Shone, A.C., Kalaydjieva, L., Sajantila, A. & Jeffreys, A.J. Crossover clustering and rapid decay of linkage disequilibrium in the Xp/Yp pseudoautosomal gene SHOX. Nat. Genet. 31, 272–275 (2002).

    Article  CAS  Google Scholar 

  9. Jeffreys, A.J. & May, C.A. Intense and highly localized gene conversion activity in human meiotic crossover hot spots. Nat. Genet. 36, 151–156 (2004).

    Article  CAS  Google Scholar 

  10. Wang, N., Akey, J.M., Zhang, K., Chakraborty, R. & Jin, L. Distribution of recombination crossovers and the origin of haplotype blocks: the interplay of population history, recombination, and mutation. Am. J. Hum. Genet. 71, 1227–1234 (2002).

    Article  CAS  Google Scholar 

  11. Phillips, M.S. et al. Chromosome-wide distribution of haplotype blocks and the role of recombination hot spots. Nat. Genet. 33, 382–387 (2003).

    Article  CAS  Google Scholar 

  12. Stumpf, M.P. Haplotype diversity and SNP frequency dependence in the description of genetic variation. Eur. J. Hum. Genet. 12, 469–477 (2004).

    Article  CAS  Google Scholar 

  13. Jeffreys, A.J., Murray, J. & Neumann, R. High-resolution mapping of crossovers in human sperm defines a minisatellite-associated recombination hotspot. Mol. Cell 2, 267–273 (1998).

    Article  CAS  Google Scholar 

  14. Kong, A. et al. A high-resolution recombination map of the human genome. Nat. Genet. 31, 241–247 (2002).

    Article  CAS  Google Scholar 

  15. Li, N. & Stephens, M. Modeling linkage disequilibrium and identifying recombination hotspots using single-nucleotide polymorphism data. Genetics 165, 2213–2233 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Fearnhead, P., Harding, R.M., Schneider, J.A., Myers, S. & Donnelly, P. Application of coalescent methods to reveal fine-scale rate variation and recombination hotspots. Genetics 167, 2067–2081 (2004).

    Article  CAS  Google Scholar 

  17. Stephens, M. & Donnelly, P. A comparison of Bayesian methods for haplotype reconstruction from population genotype data. Am. J. Hum. Genet. 73, 1162–1169 (2003).

    Article  CAS  Google Scholar 

  18. Gyapay, G. et al. The 1993-94 Généthon human genetic linkage map. Nat. Genet. 7, 246–339 (1994).

    Article  CAS  Google Scholar 

  19. Morton, N.E. Outline of Genetic Epidemiology (Karger, Basel, 1982).

    Google Scholar 

  20. Reich, D.E. et al. Linkage disequilibrium in the human genome. Nature 411, 199–204 (2001).

    Article  CAS  Google Scholar 

  21. Sabeti, P.C. et al. Detecting recent positive selection in the human genome from haplotype structure. Nature 419, 832–837 (2002).

    Article  CAS  Google Scholar 

  22. Akey, J.M. et al. Population history and natural selection shape patterns of genetic variation in 132 genes. PLoS Biol. 2, e286 (2004).

    Article  Google Scholar 

  23. Wall, J.D., Frisse, L.A., Hudson, R.R. & Di Rienzo, A. Comparative linkage-disequilibrium analysis of the beta-globin hotspot in primates. Am. J. Hum. Genet. 73, 1330–1340 (2003).

    Article  CAS  Google Scholar 

  24. Ptak, S.E. et al. Absence of the TAP2 human recombination hotspot in chimpanzees. PLoS Biol. 2, 849–855 (2004).

    Article  CAS  Google Scholar 

  25. Winckler, W. et al. Comparison of fine-scale recombination rates in humans and chimpanzees. Science 308, 107–111 (2005).

    Article  CAS  Google Scholar 

  26. Ptak, S.E. et al. Fine-scale recombination patterns differ between chimpanzees and humans. Nat. Genet. 37, 429–434 (2005).

    Article  CAS  Google Scholar 

  27. Stumpf, M.P. & McVean, G.A. Estimating recombination rates from population-genetic data. Nat. Rev. Genet. 4, 959–968 (2003).

    Article  CAS  Google Scholar 

  28. Kauppi, L., Jeffreys, A.J. & Keeney, S. Where the crossovers are: recombination distributions in mammals. Nat. Rev. Genet. 5, 413–424 (2004).

    Article  CAS  Google Scholar 

  29. Dean, F.B. et al. Comprehensive human genome amplification using multiple displacement amplification. Proc. Natl. Acad. Sci. USA 99, 5261–5266 (2002).

    Article  CAS  Google Scholar 

  30. Griffiths, R.C. & Marjoram, P. An ancestral recombination graph. In IMA Volume on Mathematical Population Genetics (eds. Donnelly, P. & Tavaré, S.) 257–270 (Springer, Berlin/Heidelberg/New York, 1996).

    Google Scholar 

Download references


We thank J. Blower and volunteers for providing semen and blood samples; S. Mistry for oligonucleotide synthesis; K. Holloway for DNA samples; C. May for website design; A. Webb for bioinformatics advice; P. Fearnhead, C. Freeman, J. Marchini and C. Spencer for coalescent analyses; and colleagues for discussions. This work was supported by grants to A.J.J. from the Medical Research Council, the Royal Society and the Louis-Jeantet Foundation and to P.D. from the US National Institutes of Health, the Nuffield Trust and the Wolfson Foundation.

Author information

Authors and Affiliations


Corresponding author

Correspondence to Alec J Jeffreys.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Jeffreys, A., Neumann, R., Panayi, M. et al. Human recombination hot spots hidden in regions of strong marker association. Nat Genet 37, 601–606 (2005).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


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