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Human recombination hot spots hidden in regions of strong marker association

Nature Genetics volume 37, pages 601–606 (2005)Cite this article

Abstract

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.

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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.

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Acknowledgements

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.

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  1. Maria Panayi

    Present address: National Genetics Reference Laboratory, St. Mary's Hospital, Hathersage Road, Manchester, M13 0JH, UK

Authors and Affiliations

  1. Department of Genetics, University of Leicester, Leicester, LE1 7RH, UK

    Alec J Jeffreys, Rita Neumann & Maria Panayi

  2. Department of Statistics, University of Oxford, Oxford, OX1 3TG, UK

    Simon Myers & Peter Donnelly

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Correspondence to Alec J Jeffreys.

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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). https://doi.org/10.1038/ng1565

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