Immunogenetics of HLA-B: SNP, allele, and haplotype diversity in populations from different continents and ancestry backgrounds

• Autor(a) principal: Silva, Nayane dos Santos Brito [UNESP]
• Data de Publicação: 2023
• Outros Autores: Souza, Andreia da Silva [UNESP], Andrade, Heloisa de Souza, Pereira, Raphaela Neto [UNESP], Castro, Camila Ferreira Bannwart [UNESP], Vince, Nicolas, Limou, Sophie, Naslavsky, Michel Satya, Zatz, Mayana, Duarte, Yeda Aparecida de Oliveira, Mendes-Junior, Celso Teixeira, Castelli, Erick da Cruz [UNESP]
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNESP
• Texto Completo: http://dx.doi.org/10.1111/tan.15043; http://hdl.handle.net/11449/249062
• topic: evolutionary aspects; haplotypes; HLA-B; NGS; polymorphism; variability; worldwide populations

HLA-B is among the most variable gene in the human genome. This gene encodes a key molecule for antigen presentation to CD8+ T lymphocytes and NK cell modulation. Despite the myriad of studies evaluating its coding region (with an emphasis on exons 2 and 3), few studies evaluated introns and regulatory sequences in real population samples. Thus, HLA-B variability is probably underestimated. We applied a bioinformatics pipeline tailored for HLA genes on 5347 samples from 80 different populations, which includes more than 1000 admixed Brazilians, to evaluate the HLA-B variability (SNPs, indels, MNPs, alleles, and haplotypes) in exons, introns, and regulatory regions. We observed 610 variable sites throughout HLA-B; the most frequent variants are shared worldwide. However, the haplotype distribution is geographically structured. We detected 920 full-length haplotypes (exons, introns, and untranslated regions) encoding 239 different protein sequences. HLA-B gene diversity is higher in admixed populations and Europeans while lower in African ancestry individuals. Each HLA-B allele group is associated with specific promoter sequences. This HLA-B variation resource may improve HLA imputation accuracy and disease-association studies and provide evolutionary insights regarding HLA-B genetic diversity in human populations.