Genetic polymorphism and linkage disequilibrium of the HLA-DP region in Basques from Navarre (Spain).

In this work, a sample of 116 individuals from an autochthonous Basque population (northern Navarre, Spain) was typed at the DNA level for HLA-DPA1 and HLA-DPB1 loci, with the aim of analysing the genetic polymorphism and the linkage disequilibrium (LD) of the HLA-DP region. In this Basque subpopulation, the most frequent alleles were 0103 (0.767) and 0201 (0.185) for DPA1 locus, whereas for DPB1 locus the 0401 allele was predominant (0.307). Accordingly, the most frequent haplotype was DPA10103-DPB10401 (0.300), which showed a significant LD. However, the haplotypes that most differentiated the sample of Navarre from other worldwide populations already analysed were DPA10105-DPB11901 (0.011) and DPA10201-DPB17601 (0.021), both of which showed a strong LD. Analysis of the relationships between populations based on data provided by HLA-DPA1 and HLA-DPB1 loci revealed a high genetic affinity between the Basque samples (North Navarre and Guipúzcoa), which, in turn, tend to plot separately from the remaining European populations. Gene frequency clines for DPB101, DPB104 and DPB111 alleles among European populations are reported for the first time. These alleles showed maximum values of F(ST) (0.033, 0.034 and 0.025, respectively). Various evolutionary forces were considered in discussing the origin of the spatial structuring of the gene frequencies: (i) gene flow, argued from the hypotheses of Post-glacial recolonization from southern Europe or the demic diffusion of farmers from the Near East into Europe, and (ii) the existence of selective pressures that could have generated genetic microdifferentiation.