A Novel Method for Across-Chromosome Phasing without Relative Data

Across-chromosome phasing identifies which haplotypes of different chromosomes come from the same parent. This differs from within-chromosome phasing, which uses linkage disequilibrium patterns to determine which alleles were co-inherited within each chromosome but does not match haplotypes across different chromosomes. While across-chromosome phasing can be conducted using genotypes from parents or close relatives, current methods perform poorly for samples of unrelated individuals. Here, we introduce a novel approach for across-chromosome phasing that employs a window-based SNP-similarity metric, eliminating the need for data from close relatives or detection of identical-by-descent haplotypes.

Using UK Biobank offspring with both parents genotyped as a gold standard, we evaluated the performance of our method by phasing the offspring without using parental data. In genomic data with no within-chromosomal phase errors, our algorithm achieved a mean across-chromosome phasing accuracy of 95%, with 53% of individuals phased perfectly. When data was pre-phased computationally using a standard within-chromosomal phasing algorithm, mean accuracy for across-chromosome phasing dropped to 83.1%. Thus, our method is limited primarily by the accuracy of within-chromosome phasing, and can approach near perfect across-chromosome phasing accuracy as within-chromosome phasing accuracy improves.