Yin yang haplotypes revisited - long, disparate haplotypes observed in European populations in regions of increased homozygosity.

Objectives: Yin yang haplotypes differ at every SNP. A previous study provided striking examples of these haplotypes, but claimed that their distribution across the genome could be attributed to chance. When we studied regions of homozygosity (ROHs) we found haplotypes that tended to differ at several SNPs simultaneously but did not subject this to formal testing. Here, we formally assess whether haplotypes from these regions provide evidence for the yin yang effect.

Method: We identified 20 regions where ROHs are common in a sample of European subjects and studied the most frequent haplotypes of SNPs with high minor allele frequency. We calculated the average 'disparity' between all haplotype pairs using a 'disparity score' calculated as 2(d), where d is the number of SNPs at which a pair of haplotypes differ. We also studied these SNPs in HapMap samples.

Results: Overall, there was highly significant evidence for excess haplotype disparity. Three of the HapMap populations with European ancestry also had statistically significant haplotype disparity scores.

Conclusion: Locations where ROHs are frequent harbour long common haplotypes showing surprising disparity. We believe these haplotypes must represent ancient founder effects and could be valuable for elucidating features of a population's history.