Recombination rates in admixed individuals identified by ancestry-based inference

Abstract

Studies of recombination and how it varies depend crucially on accurate recombination maps. We propose a new approach for constructing high-resolution maps of relative recombination rates based on the observation of ancestry switch points among admixed individuals. We show the utility of this approach using simulations and by applying it to SNP genotype data from a sample of 2,565 African Americans and 299 African Caribbeans and detecting several hundred thousand recombination events. Comparison of the inferred map with high-resolution maps from non-admixed populations provides evidence of fine-scale differentiation in recombination rates between populations. Overall, the admixed map is well predicted by the average proportion of admixture and the recombination rate estimates from the source populations. The exceptions to this are in areas surrounding known large chromosomal structural variants, specifically inversions. These results suggest that outside of structurally variable regions, admixture does not substantially disrupt the factors controlling recombination rates in humans.

Figure 1

Sketch of the haplotype-copying Hidden Markov model used to detect ancestry switch points. (a) Yellow and blue represent the chromosomal segments of different ancestry and the shades of each color represent different haplotypes from each ancestry. Recombination creates a mosaic of haplotypes regardless of origin but recombination events between haplotypes of different ancestries leave signatures that can be detected in descendant, admixed individuals. (b) The genotypes observed for such an individual form observed states of a Hidden Markov model in which underlying states are based on which haplotypes from a reference population each allele of the genotype is copied.

Figure 2

Sensitivity and specificity of inference. (a) Estimated number of switches (${\overline{c}}_{jk}^{(i)}$) between neighboring SNPs obtained for a simulated individual with two ancestry switches (vertical dashed lines). Below, the comparison at the 50-kb scale of the estimated rates (r_jk) and the underlying recombination map used to perform the simulations for this segment. Both maps are normalized to the same total rate. (b) The inferred number of switch points (${\overline{c}}_{jk}^{(i)}$) as function of the size of the interval between locations j and k. The black line represents the median for symmetric intervals around a single, isolated switch point. The red line represents the median for intervals with zero simulated switch points and which are located at least 1 Mb away from the closest switch point. Dashed lines mark the 2.5% and 97.5% quantiles. (c) Comparison of the inferred rates (r_jk) with the true rates across all segments at 10-kb (blue), 50-kb (orange) and 1-Mb (red) scales. The 2.5% and 97.5% quantiles are shown with dashed lines. All maps have been normalized to the same total rate for comparison.

Figure 3

Comparison of the African admixture-based map to existing maps. (a) Example of 1-Mb–scale map from 50 Mb of chromosome 1. (b) Example of 50-kb–scale map from the 2.5-Mb section of chromosome 1 indicated by the gray box in a. (c) Proportion of the total recombination in various proportions of sequence intervals at the 50-kb scale.

Figure 4

Population differences in recombination patterns. (a–d) Independent of scale, the AfAdm map correlates better (a) and shares more hotspots (c) with the HapMapYRI than the HapMapCEU map. In contrast, the deCODE map correlates better (b) and shares more hotspots (d) with the HapMapCEU than the HapMapYRI map. Hotspots are defined as the 50-kb intervals with the top 1% largest rates.

Figure 5

Recombination rates in notable genomic locations. (a) The region with the largest deficit of the AfAdm map just outside the known inversion on chromosome 8p23.1–8p22 (gray). (b) The region with a large deficit of the AfAdm map on chromosome 9 near the boundary of multiple known polymorphic inversions. (c) The inversion on chromosome 17q21.31 (gray). (d) A region on chromosome 14 with an elevated average European-ancestry proportion (gray) framed by local peaks of recombination.