High-resolution characterization of 12 classical and non-classical HLA loci in Southern Brazilians.

The human leukocyte antigen (HLA) are the most polymorphic genes in the human genome. Because of their importance for antigen recognition, HLA molecules play a central role in host defense and graft rejection upon transplantation. The aim of this study was to characterize allelic diversity of the classical HLA genes HLA-A, -B, -C, -DRA, -DRB1, -DQA1, -DQB1, -DPA1, -DPB1, and the non-classical class I genes HLA-E, -F and -G at high-resolution for a population of predominantly European ancestry from Curitiba, Brazil. Genotyping of 108 individuals was performed by next-generation sequencing on the MiSeq platform and also by Sanger sequencing. The genotype distributions of all loci were in accordance with Hardy-Weinberg equilibrium (P > 0.05) and a total of 202 HLA variants at second field resolution were observed for the 12 loci. The strongest linkage disequilibrium (r = 1.0, P < 10 ) was observed for the following pairs of alleles: HLA-B42:01:01 ~ HLA-DRB103:02:01; HLA-B14:02:01 ~ HLA-C08:02:01; B42:01:01 ~ HLA-C17:01:01; HLA-DRB103:01:01 ~ HLA-DQB102:01:01 ~ DRB103:01:01 ~ HLA-DQB102:01:01; DRB113:01:01~ HLA-DQB106:03:01 and HLA-DRB109:01:02 ~ HLA-DQA103:02. This is the first study to characterize all 12 HLA genes at high resolution in a single population. On the basis of the allelic frequencies of worldwide populations and principal component analysis, we confirmed the similarity of the study population to European and other Euro-descendant populations.