Populations and Individuals

Abstract

Meiotic recombinations contribute to genetic diversity by yielding new combinations of alleles. Recently, high-resolution recombina-tion maps were inferred from high-density single-nucleotide poly-morphism (SNP) data using linkage disequilibrium (LD) patterns that capture historical recombination events 1,2 . The use of these maps has been demonstrated by the identification of recombination hotspots 2 and associated motifs 3 , and the discovery that the PRDM9 gene affects the proportion of recombinations occurring at hot-spots 4–6 . However, these maps provide no information about indi-vidual or sex differences. Moreover, locus-specific demographic factors like natural selection 7 can bias LD-based estimates of recom-bination rate. Existing genetic maps based on family data avoid these shortcomings 8 , 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 recombina-tions with a resolution that is effective down to 10 kilobases (kb). Comparing male and female maps reveals that about 15% of hot-spots in one sex are specific to that sex. Although male recombina-tions result in more shuffling of exons within genes, female recombinations generate more new combinations of nearby genes. We discover novel associations between recombination character-istics 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 previ-ously described as targets of natural selection. To perform a large, family-based recombination study, one chal-lenge is to phase the genotypes of the parents when the grandparents are not genotyped. One solution is to use genotyped nuclear families with two or more offspring, which in essence uses the children to phase the parents. However, resolution can be diminished and difficulties can arise when two or more offspring have recombinations that are close to each other. We capitalized on recent methodological advances that led to the successful determination of parental origins of over 97% of the heterozygous genotypes of 38,167 Icelanders typed on Illumina SNP arrays, many of them with ungenotyped parents 9,10