Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA.
Department of Molecular and Medical Genetics, Oregon Health &Sciences University, Portland, Oregon 97239, USA.
Nat Rev Genet. 2015 Jun;16(6):344-58. doi: 10.1038/nrg3903. Epub 2015 May 7.
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.
人类基因组是二倍体的，为了完整描述和解释它们，不仅需要发现它们所包含的变异，还需要将其排列到染色体单倍型上。尽管全基因组测序变得越来越常规，但几乎所有这些个体基因组在单倍型方面都大多没有得到解决，特别是对于稀有等位基因，这些基因仍然很难通过推断方法来解决。在这里，我们回顾了用于在个体全基因组序列中实验性解决（即“定相”）单倍型的新兴技术。我们还讨论了与它们的实现相关的计算方法、评估其准确性和完整性的指标，以及单倍型信息与基因组测序在研究和临床医学中的应用的相关性。
