Accurate genome-wide phasing from IBD data

Abstract

As genotype databases increase in size, so too do the number of detectable segments of identity by descent (IBD): segments of the genome where two individuals share an identical copy of one of their two parental haplotypes, due to shared ancestry. We show that given a large enough genotype database, these segments of IBD collectively overlap entire chromosomes, including instances of IBD that span multiple chromosomes, and can be used to accurately separate the alleles inherited from each parent across the entire genome. The resulting phase is not an improvement over state-of-the-art local phasing methods, but provides accurate long-range phasing that indicates which of two haplotypes in different regions of the genome, including different chromosomes, was inherited from the same parent. We are able to separate the DNA inherited from each parent completely, across the entire genome, with 98% median accuracy in a test set of 30,000 individuals. We estimate the IBD data requirements for accurate genome-wide phasing, and we propose a method for estimating confidence in the resulting phase. We show that our methods do not require the genotypes of close family, and that they are robust to genotype errors and missing data. In fact, our method can impute missing data accurately and correct genotype errors.