Haplotype-resolved genome sequencing: experimental methods and applications

摘要

Human genomes are diploid and, for their complete description and interpretation, it is necessary not only to discover the variation they contain but also to arrange it onto chromosomal haplotypes. Although whole-genome sequencing is becoming increasingly routine, nearly all such individual genomes are mostly unresolved with respect to haplotype, particularly for rare alleles, which remain poorly resolved by inferential methods. Here, we review emerging technologies for experimentally resolving (that is, 'phasing') haplotypes across individual whole-genome sequences. We also discuss computational methods relevant to their implementation, metrics for assessing their accuracy and completeness, and the relevance of haplotype information to applications of genome sequencing in research and clinical medicine.