Chromosomal Haplotypes by Genetic Phasing of Human Families
Chromosomal Haplotypes by Genetic Phasing of Human Families
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DOI：
10.1016/j.ajhg.2011.07.023
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发表时间：
2011-09-09
影响因子：
9.8
通讯作者：
Smit, Arian F. A.
中科院分区：
文献类型：
--
作者：
Roach, Jared C.;Glusman, Gustavo;Smit, Arian F. A.
通过对有三个或更多孩子的核心家庭进行遗传分析，可以将所有染色体上几乎所有变异的等位基因分配到单倍型。全基因组序列数据允许将重组分配到精确的染色体位置和特定的减数分裂，从而实现几乎所有测序的等位基因的确定性相位。我们在两个各有四个孩子的家庭中展示了这个基因阶段的过程。我们为所有的孩子和他们的父母生成单倍型；这些单倍型跨越所有基因型位置，包括罕见的变异。变体之间的相位分配错误（开关错误）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产生多碱基单倍型，也可以处理有失踪人员的家庭。我们在一套软件脚本（Haploscribe）中实现我们的算法。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。
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.