Geographical structure and differential natural selection among North European populations
Open Access
- 5 March 2009
- journal article
- Published by Cold Spring Harbor Laboratory in Genome Research
- Vol. 19 (5) , 804-814
- https://doi.org/10.1101/gr.083394.108
Abstract
Population structure can provide novel insight into the human past, and recognizing and correcting for such stratification is a practical concern in gene mapping by many association methodologies. We investigate these patterns, primarily through principal component (PC) analysis of whole genome SNP polymorphism, in 2099 individuals from populations of Northern European origin (Ireland, United Kingdom, Netherlands, Denmark, Sweden, Finland, Australia, and HapMap European-American). The major trends (PC1 and PC2) demonstrate an ability to detect geographic substructure, even over a small area like the British Isles, and this information can then be applied to finely dissect the ancestry of the European-Australian and European-American samples. They simultaneously point to the importance of considering population stratification in what might be considered a small homogeneous region. There is evidence from FST-based analysis of genic and nongenic SNPs that differential positive selection has operated across these populations despite their short divergence time and relatively similar geographic and environmental range. The pressure appears to have been focused on genes involved in immunity, perhaps reflecting response to infectious disease epidemic. Such an event may explain a striking selective sweep centered on the rs2508049-G allele, close to the HLA-G gene on chromosome 6. Evidence of the sweep extends over a 8-Mb/3.5-cM region. Overall, the results illustrate the power of dense genotype and sample data to explore regional population variation, the events that have crafted it, and their implications in both explaining disease prevalence and mapping these genes by association.Keywords
This publication has 41 references indexed in Scilit:
- Genes mirror geography within EuropeNature, 2008
- Correlation between Genetic and Geographic Structure in EuropeCurrent Biology, 2008
- A Single SNP in an Evolutionary Conserved Region within Intron 86 of the HERC2 Gene Determines Human Blue-Brown Eye ColorAmerican Journal of Human Genetics, 2008
- A second generation human haplotype map of over 3.1 million SNPsNature, 2007
- Genome-wide detection and characterization of positive selection in human populationsNature, 2007
- Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controlsNature, 2007
- A high-resolution HLA and SNP haplotype map for disease association studies in the extended human MHCNature Genetics, 2006
- Principal components analysis corrects for stratification in genome-wide association studiesNature Genetics, 2006
- A haplotype map of the human genomeNature, 2005
- Detecting recent positive selection in the human genome from haplotype structureNature, 2002