Detection of sharing by descent, long-range phasing and haplotype imputation.
Detection of sharing by descent, long-range phasing and haplotype imputation.
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DOI：
10.1038/ng.216
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发表时间：
2008-09
期刊：
影响因子：
30.8
通讯作者：
Stefansson K
中科院分区：
文献类型：
--
作者：
Kong A;Masson G;Frigge ML;Gylfason A;Zusmanovich P;Thorleifsson G;Olason PI;Ingason A;Steinberg S;Rafnar T;Sulem P;Mouy M;Jonsson F;Thorsteinsdottir U;Gudbjartsson DF;Stefansson H;Stefansson K
尽管已经开发了用于对基于群体的样品进行定相的方法，但是关于单核苷酸多态性（SNP）的串的相位的不确定性在遗传分析中产生了复杂性。然而，这些方法只能有效地对少数SNP进行定相，并且当应用于跨越许多连锁不平衡（LD）区块的SNP时变得不可靠。在这里，我们展示了如何对Illumina芯片进行基因分型的35，528名冰岛人中的一大部分同时对1000多个SNP进行相位分析。此外，在近亲和远亲之间通过血统（IBD）相同的单倍型，例如由10次或更多次减数分裂分开的那些单倍型，通常可以可靠地检测。这种方法在研究大样本集的复发性突变和精细重组的遗传方面特别强大。该方法的进一步扩展使我们能够对未进行基因分型的个体进行长单倍型。
Uncertainty about the phase of strings of single nucleotide polymorphisms (SNPs) creates complications in genetic analysis although methods have been developed for phasing population-based samples. However, these methods can only phase a small number of SNPs effectively, and become unreliable when applied to SNPs spanning many linkage disequilibrium (LD) blocks. Here we show how to phase more than one thousand SNPs simultaneously for a large fraction of the 35,528 Icelanders genotyped by Illumina chips. Moreover, haplotypes that are identical by descent (IBD) between close and distant relatives, e.g. those separated by 10 meioses or more, can often be reliably detected. This method is particularly powerful in studies of the inheritance of recurrent mutations and fine-scale recombinations in large sample sets. A further extension of the method allows us to impute long haplotypes for individuals who are not genotyped.