Reconstructing recent population history while mapping rare variants using haplotypes

Haplotype-based methods are a cost-effective alternative to characterize unobserved rare variants and map disease-associated alleles. Moreover, they can be used to reconstruct recent population history, which shaped distribution of rare variants and thus can be used to guide gene mapping studies. In this study, we analysed Illumina 650 k genotyped dataset on three underrepresented populations from Eastern Europe, where ancestors of Russians came into contact with two indigenous ethnic groups, Bashkirs and Tatars. Using the IBD mapping approach, we identified two rare IBD haplotypes strongly enriched in asthma patients of distinct ethnic background. We reconstructed recent population history using haplotype-based methods to reconcile this contradictory finding. Our ChromoPainter analysis showed that these haplotypes each descend from a single ancestor coming from one of the ethnic groups studied. Next, we used DoRIS approach and showed that source populations for patients exchanged recent (< 60 generations) asymmetric gene flow, which supported the ChromoPainter-based scenario that patients share haplotypes through inter-ethnic admixture. Finally, we show that these IBD haplotypes overlap with asthma-associated genomic regions ascertained in European population. This finding is consistent with the fact that the two donor populations for the rare IBD haplotypes: Russians and Tatars have European ancestry.