Large-scale whole-genome sequencing of the Icelandic population
Large-scale whole-genome sequencing of the Icelandic population
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DOI：
10.1038/ng.3247
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发表时间：
2015-05-01
期刊：
影响因子：
30.8
通讯作者：
Stefansson, Kari
中科院分区：
文献类型：
--
作者：
Gudbjartsson, Daniel F.;Helgason, Hannes;Stefansson, Kari
在这里，我们描述了从2，636名冰岛人的全基因组测序中获得的见解，中位数深度为20倍。我们发现了2000万个SNP和150万个插入-缺失（indels）。我们描述的密度和频谱的序列变异的功能注释，基因的位置，途径和保护得分。我们证明了在冰岛的纯合性和罕见的蛋白质编码变异过剩。我们将这些变异归因于104，220名个体，次要等位基因频率为0.1%，并发现MYL 4中的隐性移码突变会导致早发性房颤，ABCB 4中的几个突变会增加肝脏疾病的风险，以及GNAS中的一个内含子变异与增加相关母系遗传时的促甲状腺激素水平。这些数据提供了一种研究设计，可用于确定人类基因组序列的变异如何引起人类多样性。
Here we describe the insights gained from sequencing the whole genomes of 2,636 Icelanders to a median depth of 20x. We found 20 million SNPs and 1.5 million insertions-deletions (indels). We describe the density and frequency spectra of sequence variants in relation to their functional annotation, gene position, pathway and conservation score. We demonstrate an excess of homozygosity and rare protein-coding variants in Iceland. We imputed these variants into 104,220 individuals down to a minor allele frequency of 0.1% and found a recessive frameshift mutation in MYL4 that causes early-onset atrial fibrillation, several mutations in ABCB4 that increase risk of liver diseases and an intronic variant in GNAS associating with increased thyroid-stimulating hormone levels when maternally inherited. These data provide a study design that can be used to determine how variation in the sequence of the human genome gives rise to human diversity.