Institute for Systems Biology, Seattle, WA 98109, USA.
Am J Hum Genet. 2011 Sep 9;89(3):382-97. doi: 10.1016/j.ajhg.2011.07.023.
Assignment of alleles to haplotypes for nearly all the variants on all chromosomes can be performed by genetic analysis of a nuclear family with three or more children. Whole-genome sequence data enable deterministic phasing of nearly all sequenced alleles by permitting assignment of recombinations to precise chromosomal positions and specific meioses. We demonstrate this process of genetic phasing on two families each with four children. We generate haplotypes for all of the children and their parents; these haplotypes span all genotyped positions, including rare variants. Misassignments of phase between variants (switch errors) are nearly absent. Our algorithm can also produce multimegabase haplotypes for nuclear families with just two children and can handle families with missing individuals. We implement our algorithm in a suite of software scripts (Haploscribe). Haplotypes and family genome sequences will become increasingly important for personalized medicine and for fundamental biology.
通过对包含三个或更多孩子的核心家庭进行基因分析，几乎可以对所有染色体上的所有变体进行等位基因分配到单倍型。全基因组序列数据通过将重组分配到精确的染色体位置和特定的减数分裂，实现了几乎所有测序等位基因的确定性定相。我们在两个各有四个孩子的家庭中展示了这个基因定相过程。我们为所有孩子及其父母生成单倍型；这些单倍型跨越了所有基因分型的位置，包括罕见变体。变体之间的相位（交换错误）错误分配几乎不存在。我们的算法还可以为只有两个孩子的核心家庭生成多兆碱基的单倍型，并且可以处理有缺失个体的家庭。我们在一套名为 Haploscribe 的软件脚本中实现了我们的算法。单倍型和家族基因组序列对于个性化医疗和基础生物学将变得越来越重要。
