Resequencing of 200 human exomes identifies an excess of low-frequency non-synonymous coding variants
Resequencing of 200 human exomes identifies an excess of low-frequency non-synonymous coding variants
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DOI：
10.1038/ng.680
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发表时间：
2010-11-01
期刊：
影响因子：
30.8
通讯作者：
Wang, Jun
中科院分区：
文献类型：
--
作者：
Li, Yingrui;Vinckenbosch, Nicolas;Wang, Jun
靶向捕获结合大规模并行外显子组测序是一种有前途的方法，以确定涉及人类性状的遗传变异。我们报告了来自丹麦的200个个体的外显子组测序，靶向捕获18，654个编码基因，每个个体外显子组的序列覆盖率平均为12倍。平均而言，约95%的目标区域被至少一个读取覆盖。我们在样本人群中鉴定了121，870个SNP，其中包括53，081个编码SNP（cSNP）。使用SNP调用的统计方法和基于我们的群体数据的等位基因频率的估计，我们推导出具有大于0.02的次要等位基因频率的cSNP的等位基因频率谱。我们发现在低频范围内（次要等位基因频率在2%和5%之间），有害的非同义cSNP超过同义cSNP 1.8倍。这种过度对于X连锁SNP更为明显，表明有害取代主要是隐性的。
Targeted capture combined with massively parallel exome sequencing is a promising approach to identify genetic variants implicated in human traits. We report exome sequencing of 200 individuals from Denmark with targeted capture of 18,654 coding genes and sequence coverage of each individual exome at an average depth of 12-fold. On average, about 95% of the target regions were covered by at least one read. We identified 121,870 SNPs in the sample population, including 53,081 coding SNPs (cSNPs). Using a statistical method for SNP calling and an estimation of allelic frequencies based on our population data, we derived the allele frequency spectrum of cSNPs with a minor allele frequency greater than 0.02. We identified a 1.8-fold excess of deleterious, non-syonomyous cSNPs over synonymous cSNPs in the low-frequency range (minor allele frequencies between 2% and 5%). This excess was more pronounced for X-linked SNPs, suggesting that deleterious substitutions are primarily recessive.