Whole-genome sequence variation, population structure and demographic history of the Dutch population
Whole-genome sequence variation, population structure and demographic history of the Dutch population
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DOI：
10.1038/ng.3021
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发表时间：
2014-08-01
期刊：
影响因子：
30.8
通讯作者：
Wijmenga, Cisca
中科院分区：
文献类型：
--
作者：
Francioli, Laurent C.;Menelaou, Andronild;Wijmenga, Cisca
全基因组测序能够完整表征遗传变异，但稀有等位基因的地理聚类需要研究许多不同的人群。在这里，我们描述了荷兰基因组（GoNL）项目，在该项目中，我们对250个荷兰亲子家庭的全基因组进行了测序，并构建了一个包含2040万个单核苷酸变异和120万个插入和缺失的单倍型图谱。中间覆盖度（类似于13 x）和三重设计能够广泛表征结构变异，包括先前分类不佳的中等大小事件（30-500 bp）和从头突变。我们证明了单倍型的质量提高了独立样本的插补精度，特别是对于较低频率的等位基因。种群遗传学分析显示了全国范围内的精细结构，并支持多次古代迁徙，与海平面和洪水的历史变化一致。GoNL项目说明了单种群全基因组测序如何提供遗传变异的详细特征，并可能指导未来种群研究的设计。
Whole-genome sequencing enables complete characterization of genetic variation, but geographic clustering of rare alleles demands many diverse populations be studied. Here we describe the Genome of the Netherlands (GoNL) Project, in which we sequenced the whole genomes of 250 Dutch parent-offspring families and constructed a haplotype map of 20.4 million single-nucleotide variants and 1.2 million insertions and deletions. The intermediate coverage (similar to 13x) and trio design enabled extensive characterization of structural variation, including midsize events (30-500 bp) previously poorly catalogued and de novo mutations. We demonstrate that the quality of the haplotypes boosts imputation accuracy in independent samples, especially for lower frequency alleles. Population genetic analyses demonstrate fine-scale structure across the country and support multiple ancient migrations, consistent with historical changes in sea level and flooding. The GoNL Project illustrates how single-population whole-genome sequencing can provide detailed characterization of genetic variation and may guide the design of future population studies.