Meiotic recombinations contribute to genetic diversity by yielding new combinations of alleles. Recently, high-resolution recombination maps were inferred from high-density single-nucleotide polymorphism (SNP) data using linkage disequilibrium (LD) patterns that capture historical recombination events1,2. The use of these maps has been demonstrated by the identification of recombination hotspots2 and associated motifs3, and the discovery that the PRDM9 gene affects the proportion of recombinations occurring at hotspots4,5,6. However, these maps provide no information about individual or sex differences. Moreover, locus-specific demographic factors like natural selection7 can bias LD-based estimates of recombination rate. Existing genetic maps based on family data avoid these shortcomings8, but their resolution is limited by relatively few meioses and a low density of markers. Here we used genome-wide SNP data from 15,257 parent–offspring pairs to construct the first recombination maps based on directly observed recombinations with a resolution that is effective down to 10 kilobases (kb). Comparing male and female maps reveals that about 15% of hotspots in one sex are specific to that sex. Although male recombinations result in more shuffling of exons within genes, female recombinations generate more new combinations of nearby genes. We discover novel associations between recombination characteristics of individuals and variants in the PRDM9 gene and we identify new recombination hotspots. Comparisons of our maps with two LD-based maps inferred from data of HapMap populations of Utah residents with ancestry from northern and western Europe (CEU) and Yoruba in Ibadan, Nigeria (YRI) reveal population differences previously masked by noise and map differences at regions previously described as targets of natural selection.
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McVean, G. A. et al. The fine-scale structure of recombination rate variation in the human genome. Science 304, 581–584 (2004)
Myers, S., Bottolo, L., Freeman, C., McVean, G. & Donnelly, P. A fine-scale map of recombination rates and hotspots across the human genome. Science 310, 321–324 (2005)
Myers, S., Freeman, C., Auton, A., Donnelly, P. & McVean, G. A common sequence motif associated with recombination hot spots and genome instability in humans. Nature Genet. 40, 1124–1129 (2008)
Baudat, F. et al. PRDM9 is a major determinant of meiotic recombination hotspots in humans and mice. Science 327, 836–840 (2010)
Myers, S. et al. Drive against hotspot motifs in primates implicates the PRDM9 gene in meiotic recombination. Science 327, 876–879 (2010)
Parvanov, E. D., Petkov, P. M. & Paigen, K. Prdm9 controls activation of mammalian recombination hotspots. Science 327, 835 (2010)
O’Reilly, P. F., Birney, E. & Balding, D. J. Confounding between recombination and selection, and the Ped/Pop method for detecting selection. Genome Res. 18, 1304–1313 (2008)
Kong, A. et al. A high-resolution recombination map of the human genome. Nature Genet. 31, 241–247 (2002)
Kong, A. et al. Detection of sharing by descent, long-range phasing and haplotype imputation. Nature Genet. 40, 1068–1075 (2008)
Kong, A. et al. Parental origin of sequence variants associated with complex diseases. Nature 462, 868–874 (2009)
Dempster, A. P., Laird, N. M. & Rubin, D. B. Maximum likelihood from incomplete data via the EM algorithm. J. R. Stat. Soc. B 39, 1–38 (1977)
The International HapMap Consortium A haplotype map of the human genome. Nature 437, 1299–1320 (2005)
Lang, M. R., Patterson, L. B., Gordon, T. N., Johnson, S. L. & Parichy, D. M. Basonuclin-2 requirements for zebrafish adult pigment pattern development and female fertility. PLoS Genet. 5, e1000744 (2009)
Broman, K. W., Murray, J. C., Sheffield, V. C., White, R. L. & Weber, J. L. Comprehensive human genetic maps: individual and sex-specific variation in recombination. Am. J. Hum. Genet. 63, 861–869 (1998)
Kong, A. et al. Sequence variants in the RNF212 gene associate with genome-wide recombination rate. Science 319, 1398–1401 (2008)
Akey, J. M. Constructing genomic maps of positive selection in humans: where do we go from here? Genome Res. 19, 711–722 (2009)
Stefansson, H. et al. A common inversion under selection in Europeans. Nature Genet. 37, 129–137 (2005)
Devlin, B. & Roeder, K. Genomic control for association studies. Biometrics 55, 997–1004 (1999)
We thank D. Reich for discussion and suggestions.
The authors are all employees of deCode Genetics, a biotechnology company that provides genetic testing services, and own stocks or stock options in the company.
The maps constructed in this study are available at http://www.decode.com/addendum.
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Kong, A., Thorleifsson, G., Gudbjartsson, D. et al. Fine-scale recombination rate differences between sexes, populations and individuals. Nature 467, 1099–1103 (2010). https://doi.org/10.1038/nature09525
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