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Geographical structure and differential natural selection among North European populations.

McEvoy, BP, Montgomery, GW, McRae, AF, Ripatti, S, Perola, M, Spector, TD, Cherkas, L, Ahmadi, KR, Boomsma, D, Willemsen, G, Hottenga, JJ, Pedersen, NL, Magnusson, PK, Kyvik, KO, Christensen, K, Kaprio, J, Heikkilä, K, Palotie, A, Widen, E, Muilu, J, Syvänen, AC, Liljedahl, U, Hardiman, O, Cronin, S, Peltonen, L, Martin, NG and Visscher, PM (2009) Geographical structure and differential natural selection among North European populations. Genome Res, 19 (5). pp. 804-814.

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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 F(ST)-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.

Item Type: Article
Authors :
NameEmailORCID
McEvoy, BPUNSPECIFIEDUNSPECIFIED
Montgomery, GWUNSPECIFIEDUNSPECIFIED
McRae, AFUNSPECIFIEDUNSPECIFIED
Ripatti, SUNSPECIFIEDUNSPECIFIED
Perola, MUNSPECIFIEDUNSPECIFIED
Spector, TDUNSPECIFIEDUNSPECIFIED
Cherkas, LUNSPECIFIEDUNSPECIFIED
Ahmadi, KRk.ahmadi@surrey.ac.ukUNSPECIFIED
Boomsma, DUNSPECIFIEDUNSPECIFIED
Willemsen, GUNSPECIFIEDUNSPECIFIED
Hottenga, JJUNSPECIFIEDUNSPECIFIED
Pedersen, NLUNSPECIFIEDUNSPECIFIED
Magnusson, PKUNSPECIFIEDUNSPECIFIED
Kyvik, KOUNSPECIFIEDUNSPECIFIED
Christensen, KUNSPECIFIEDUNSPECIFIED
Kaprio, JUNSPECIFIEDUNSPECIFIED
Heikkilä, KUNSPECIFIEDUNSPECIFIED
Palotie, AUNSPECIFIEDUNSPECIFIED
Widen, EUNSPECIFIEDUNSPECIFIED
Muilu, JUNSPECIFIEDUNSPECIFIED
Syvänen, ACUNSPECIFIEDUNSPECIFIED
Liljedahl, UUNSPECIFIEDUNSPECIFIED
Hardiman, OUNSPECIFIEDUNSPECIFIED
Cronin, SUNSPECIFIEDUNSPECIFIED
Peltonen, LUNSPECIFIEDUNSPECIFIED
Martin, NGUNSPECIFIEDUNSPECIFIED
Visscher, PMUNSPECIFIEDUNSPECIFIED
Date : May 2009
Identification Number : https://doi.org/10.1101/gr.083394.108
Uncontrolled Keywords : Europe, European Continental Ancestry Group, Genetics, Population, Genome-Wide Association Study, Genotype, Geography, Humans, Polymorphism, Single Nucleotide, Principal Component Analysis, Selection, Genetic
Related URLs :
Depositing User : Symplectic Elements
Date Deposited : 17 May 2017 09:48
Last Modified : 17 May 2017 14:45
URI: http://epubs.surrey.ac.uk/id/eprint/825185

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