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Fine-scale recombination rate differences between sexes, populations and individuals

Abstract

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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Figure 1: Determining recombination locations.
Figure 2: Sex differences in recombinations.
Figure 3: Sex-specific recombination rates and genes.

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Acknowledgements

We thank D. Reich for discussion and suggestions.

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Authors and Affiliations

Authors

Contributions

A.K. and K.S. planned and directed the research. A.K. wrote the first draft of the paper and, with K.S., U.T. and A.H., wrote most of the final version. D.F.G. improved previous phasing procedures and, with G.M., made the recombination calls. G.T. created the maps and, with M.L.F., assisted A.K. in the analyses. U.T., Aslaug J., A.S., Adalbjorg J., K.T.K. and G.B.W. performed experiments providing information on sequences at the PRDM9 gene. A.G. did the variant imputations. G.M. and S.A.G. determined the locations and intensities of genomic features. A.H. assisted in the study on selection.

Corresponding authors

Correspondence to Augustine Kong or Kari Stefansson.

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Competing interests

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.

Additional information

The maps constructed in this study are available at http://www.decode.com/addendum.

Supplementary information

Supplementary Information

The file contains Supplementary Notes 1-10, Supplementary Tables 1-6, Supplementary Figures 1-4 with legends and additional references. (PDF 656 kb)

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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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