title: A new HLA map of Europe: Regional genetic variation and its implication for peopling history, disease-association studies and tissue transplantation.
abstract: OBJECTIVE
  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.
authors.affiliation: Laboratory of Anthropology, Genetics and Peopling History, Department of Genetics and Evolution - Anthropology Unit and Institute of Genetics and Genomics in Geneva (IGE3), University of Geneva, Geneva, Switzerland.
authors.forename: Alicia
authors.initials: A
authors.lastname: Sanchez-Mazas
authors.forename: Stéphane
authors.initials: S
authors.lastname: Buhler
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Nunes
mesh_terms: D004194:Disease / Q000235:genetics*; D005060:Europe; D056726:Genetic Association Studies; D056426:Genetic Loci; D014644:Genetic Variation; D005828:Genetics, Population; D005843:Geography; D006680:HLA Antigens / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D016014:Linear Models; D010641:Phenotype; D014180:Transplantation
chemical_list: D006680:HLA Antigens