Whole-genome sequence variation, population structure and demographic history of the Dutch population

被引：485

作者：

Francioli, Laurent C. ^{[1
]}

Menelaou, Andronild ^{[1
]}

Pulit, Sara L. ^{[1
]}

Van Dijk, Freerk ^{[2
,3
]}

Palamara, Pier Francesco ^{[4
]}

Elbers, Clara C. ^{[1
]}

Neerincx, Pieter B. T. ^{[2
,3
]}

Ye, Kai ^{[5
,6
]}

Guryev, Victor ^{[7
]}

Kloosterman, Wigard P. ^{[1
]}

Deelen, Patrick ^{[2
,3
]}

Abdellaoui, Abdel ^{[8
]}

Van Leeuwen, Elisabeth M. ^{[9
]}

Van Oven, Mannis ^{[10
]}

Vermaat, Martijn ^{[11
,12
]}

Li, Mingkun ^{[13
]}

Laros, Jeroen F. J. ^{[11
,12
]}

Karssen, Lennart C. ^{[9
]}

Kanterakis, Alexandros ^{[2
,3
]}

Amin, Najaf ^{[9
]}

Hottenga, Jouke Jan ^{[8
]}

Lameijer, Eric-Wubbo ^{[6
]}

Kattenberg, Mathijs ^{[8
]}

Dijkstra, Martijn ^{[2
,3
]}

Byelas, Heorhiy ^{[2
,3
]}

Van Settenl, Jessica ^{[1
]}

Van Schaik, Barbera D. C. ^{[14
]}

Bot, Jan ^{[15
]}

Nijman, Isaac J. ^{[1
]}

Renkens, Ivo ^{[1
]}

Marscha, Tobias ^{[16
]}

Schonhuth, Alexander ^{[16
]}

Hehir-Kwa, Jayne Y. ^{[17
]}

Handsaker, Robert E. ^{[18
,19
]}

Polak, Paz ^{[18
]}

Sohail, Mashaal ^{[18
,20
]}

Vuzman, Dana ^{[21
]}

Hormozdiari, Fereydoun ^{[12
]}

Van Enckevort, David ^{[12
]}

Mei, Hailiang ^{[22
]}

Koval, Vyacheslav ^{[6
]}

Moed, Ma-Tthijs H. ^{[2
,3
]}

Van der Velde, K. Joeri ^{[9
,22
]}

Rivadeneira, Fernando ^{[18
,22
,23
]}

Estrada, Karol ^{[22
]}

Medina-Gomez, Carolina ^{[9
]}

Isaacs, Aaron ^{[18
,19
]}

McCarroll, Steven A. ^{[6
]}

Beekrnan, Marian ^{[6
]}

De Craen, Anton J. M. ^{[6
]}

机构：

[1] Univ Med Ctr Utrecht, Ctr Mol Med, Dept Med Genet, Utrecht, Netherlands

[2] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands

[3] Univ Groningen, Univ Med Ctr Groningen, Genom Coordinat Ctr, Groningen, Netherlands

[4] Columbia Univ, Dept Comp Sci, New York, NY 10027 USA

[5] Washington Univ, Genome Inst, St Louis, MO USA

[6] Leiden Univ, Med Ctr, Dept Med Stat & Bioinformat, Sect Mol Epidemiol, Leiden, Netherlands

[7] Univ Groningen, Univ Med Ctr Groningen, European Res Inst Biol Ageing, Groningen, Netherlands

[8] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands

[9] Erasmus MC Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands

[10] Erasmus MC Univ, Med Ctr, Dept Forens Mol Biol, Rotterdam, Netherlands

[11] Leiden Univ, Med Ctr, Dept Human Genet, Leiden Genome Technol Ctr, Leiden, Netherlands

[12] Netherlands Bioinformat Ctr, Nijmegen, Netherlands

[13] Max Planck Inst Evolutionary Anthropol, Dept Evolutionary Genet, Leipzig, Germany

[14] Acad Med Ctr, Dept Clin Epidemiol Biostat & Bioinformat, Bioinformat Lab, Amsterdam, Netherlands

[15] SURFsara, Amsterdam, Netherlands

[16] Life Sci Grp, Ctr Wiskunde & lnformat, Amsterdam, Netherlands

[17] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, Nijmegen, Netherlands

[18] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Ctr Neurosci, Nijmegen, Netherlands

[19] Harvard & MIT, Broad Inst, Program Med & Populat Genet, Cambridge, MA USA

[20] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA

[21] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Genet,Dept Med, Boston, MA USA

[22] Erasmus MC Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands

[23] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA

[24] Erasmus MC Univ, Med Ctr, Dept Clin Genet, Rotterdam, Netherlands

[25] Univ Med Ctr Utrecht, Brain Ctr Rudolf Magnus, Dept Neurol, Utrecht, Netherlands

[26] Rinat Pfizer Inc, San Francisco, CA USA

[27] Leiden Univ, Med Ctr, Dept Clin Genet, Leiden, Netherlands

[28] Leiden Univ, Med Ctr, Dept Human Genet, Forens Lab DNA Res, Leiden, Netherlands

[29] BGI Shenzhen, Shenzhen, Peoples R China

[30] BGI Europe, Copenhagen, Denmark

[31] Univ Copenhagen, Dept Biol, Copenhagen, Denmark

[32] Univ Copenhagen, Novo Nordisk Fdn, Ctr Basic Metab Res, Copenhagen, Denmark

[33] Legal Pathways Inst Hlth & Bio Law, Aerdenhout, Netherlands

[34] Columbia Univ, Dept Syst Biol, New York, NY USA

[35] Leiden Univ, Med Ctr, Dept Human Genet, Leiden, Netherlands

[36] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Dept Epidemiol, Utrecht, Netherlands

来源：

NATURE GENETICS | 2014年 / 46卷 / 08期

基金：

欧洲研究理事会;

关键词：

VARIANTS; RARE; IMPACT; COMMON; MUTATIONS; EVOLUTION; FRAMEWORK; GENOTYPE;

D O I：

10.1038/ng.3021

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：818 / 825

页数：8

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