期刊
HUMAN HEREDITY
卷 76, 期 3-4, 页码 162-177出版社
KARGER
DOI: 10.1159/000360855
关键词
HLA; Population genetics; European; Caucasian; Demographic history; Genetic diversity; Human populations; Linkage disequilibrium; Multi-allelicloci; Natural selection; Population data; Phenotypic variation; HLA haplotypes; HLA-NET; EUROSTAM
资金
- Swiss National Science Foundation (SNSF) [31003A_144180, 10CO11_145293]
- European COST Action [BM0803 'HLA-NET']
- FP-7-Health-2012 program [305385 EUROSTAM]
- Swiss National Science Foundation (SNF) [10CO11_145293] Funding Source: Swiss National Science Foundation (SNF)
Objectives: HLA genes are highly polymorphic in human populations as a result of diversifying selection related to their immune function. However, HLA geographic variation worldwide suggests that demographic factors also shaped their evolution. We here analyzed in detail HLA genetic variation in Europe in order to identify signatures of migration history and/or natural selection. Methods: Relationships between HLA diversity and geography were analyzed at 7 loci through several approaches including linear regression on gene diversity and haplotype frequencies. Regional variation was also assessed on HLA multi-locus phenotypes through structure analysis. Deviation from neutrality was tested by resampling. Results: Geographic distance was a strong predictor of HLA variation at 5 loci (A, B, C, DRB1 and DPB1) in Europe, and latitude significantly shaped HLA gene diversity and haplotype frequencies. Whereas the main level of genetic diversity was found within populations, both HLA gene frequencies and phenotypic profiles revealed regional variation, Southeast Europe, Great Britain and Finland being the most distinctive. Effects of natural selection were suggested at the DQ loci. Conclusions: HLA regional variation was observed in Europe and can be related to population history, locus HLA-A providing by far the strongest signals. This new HLA map of Europe represents an invaluable reference for disease-association studies and tissue transplantation. (C) 2014 S. Karger AG, Basel
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