Whole-genome sequence variation, population structure and demographic history of the Dutch population
Top Cited Papers
- 29 June 2014
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Genetics
- Vol. 46 (8), 818-825
- https://doi.org/10.1038/ng.3021
Abstract
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 ( ∼ 13×) 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.Keywords
This publication has 82 references indexed in Scilit:
- Where genotype is not predictive of phenotype: towards an understanding of the molecular basis of reduced penetrance in human inherited diseaseHuman Genetics, 2013
- Imputing Amino Acid Polymorphisms in Human Leukocyte AntigensPLOS ONE, 2013
- Length Distributions of Identity by Descent Reveal Fine-Scale Demographic HistoryAmerican Journal of Human Genetics, 2012
- Five Years of GWAS DiscoveryAmerican Journal of Human Genetics, 2012
- A Fast, Powerful Method for Detecting Identity by DescentAmerican Journal of Human Genetics, 2011
- Genetic Heterogeneity in Human DiseaseCell, 2010
- Simultaneous Genotype Calling and Haplotype Phasing Improves Genotype Accuracy and Reduces False-Positive Associations for Genome-wide Association StudiesAmerican Journal of Human Genetics, 2009
- Correlation between Genetic and Geographic Structure in EuropeCurrent Biology, 2008
- Initial sequencing and analysis of the human genomeNature, 2001
- Basic Local Alignment Search ToolJournal of Molecular Biology, 1990