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Imputation of Single-Nucleotide Polymorphisms in Inbred Mice Using Local Phylogeny

机译:利用局部系统发育技术估算近交小鼠单核苷酸多态性

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摘要

We present full-genome genotype imputations for 100 classical laboratory mouse strains, using a novel method. Using genotypes at 549,683 SNP loci obtained with the Mouse Diversity Array, we partitioned the genome of 100 mouse strains into 40,647 intervals that exhibit no evidence of historical recombination. For each of these intervals we inferred a local phylogenetic tree. We combined these data with 12 million loci with sequence variations recently discovered by whole-genome sequencing in a common subset of 12 classical laboratory strains. For each phylogenetic tree we identified strains sharing a leaf node with one or more of the sequenced strains. We then imputed high- and medium-confidence genotypes for each of 88 nonsequenced genomes. Among inbred strains, we imputed 92% of SNPs genome-wide, with 71% in high-confidence regions. Our method produced 977 million new genotypes with an estimated per-SNP error rate of 0.083% in high-confidence regions and 0.37% genome-wide. Our analysis identified which of the 88 nonsequenced strains would be the most informative for improving full-genome imputation, as well as which additional strain sequences will reveal more new genetic variants. Imputed sequences and quality scores can be downloaded and visualized online.
机译:我们提出了使用一种新方法的100个经典实验室小鼠品系的全基因组基因型估算。使用通过小鼠多样性阵列获得的549,683个SNP位点的基因型,我们将100个小鼠品系的基因组划分为40,647个间隔,这些间隔没有历史重组的迹象。对于这些间隔中的每一个,我们都推断出本地的系统发育树。我们将这些数据与1200万个基因座相结合,并通过全基因组测序在12个经典实验室菌株的常见子集中最近发现了序列变异。对于每个系统发育树,我们确定了与一个或多个测序菌株共享叶节点的菌株。然后,我们估算了88个未测序基因组中每个基因组的高可信度和中等可信度基因型。在自交系中,我们估算了全基因组中92%的SNP,其中高可信区中的71%。我们的方法产生了9.77亿新基因型,在高可信度区域中每个SNP的错误率估计为0.083%,在全基因组范围内为0.37%。我们的分析确定了88个未测序菌株中的哪一个将对改善全基因组插补最为有用,以及哪些其他菌株序列将揭示更多新的遗传变异。估算序列和质量得分可以在线下载和可视化。

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