High-resolution characterization of classical and non-classical HLA diversity reveals important admixture in Brazilian indigenous.

Abstract

Understanding linkage disequilibrium (LD) patterns involving both classical and non-classical HLA genes across diverse ethnic backgrounds provides valuable insights into genomic block inheritance, ancestry inference in admixed populations, and the genetic architecture of immune-mediated diseases. We performed high-resolution typing of classical and non-classical HLA genes using next-generation sequencing in 80 Brazilian Indigenous from 24 families belonging to 24 distinct geographical indigenous communities. Gene copy number analysis was conducted in hemizygous and homozygous samples to confirm zygosity. Allelic and haplotypic frequencies, as well as Hardy-Weinberg equilibrium, were assessed in 50 unrelated individuals, while haplotypes were manually inferred through familial segregation analysis in the remaining families. Extensive allelic and haplotypic diversity was observed, with limited sharing across families and several haplotypes not previously described in the Brazilian population. In addition, haplotypes commonly reported in other ethnic groups were identified, likely reflecting the high degree of genetic admixture in Brazil. These findings contribute to the inclusion of Brazilian Indigenous populations in high-resolution immunogenetic studies and may have implications for ancestry inference, disease association analyses, and donor selection strategies in transplantation.