Genetic Mechanisms Involved in the Generation of HLA Alleles in Brazilians: Description and Comparison of HLA Alleles

Abstract

BackgroundThe HLA genes show high levels of diversity as indicated by the number of HLA alleles. There are almost 11,000 classical HLA-A, -B, -DRB1 alleles in populations around the world, making the search for compatible donors difficult. HLA diversity is generated by different genetic mechanisms, such as point mutations, which result in single nucleotide polymorphisms, insertion and deletion, and recombination. The aim of this study was to describe genetic mechanisms involved in the generation of HLA alleles in Brazilians. MethodsTwenty-six alleles indentified in the Brazilian bone marrow donors were include in the study. Data regarding new HLA alleles by sequence-based typing were also used to elucidate what genetics mechanism was involved in the HLA variability. The new alleles were officially named by the World Health Organization Nomenclature Committee. ResultsThe new alleles described were HLA-DRB1*11:04:14, HLA-A*33:117, and HLA-B*41:48. The DRB1*11:04:14 allele was generated by synonymous point mutation at codon 48. The A*33:117 allele was generated by nonsynonymous nucleotide mutation leading to amino acid substitution at codon 74. The B*41:48 allele was generated by an intralocus gene conversion between the HLA alleles from groups HLA-B*13, B*35, B*53, or B*58 and an allele from the HLA-B*41 group. ConclusionsDifferent genetic mechanisms introduce new mutant HLA alleles into the human population requiring attentive and rigorous specialists and the use of different methodologies to identify these mutations in HLA typing routine.