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

Author(s):Show less -

Silva, Nayane dos Santos Brito ; Souza, Andreia da Silva ; Andrade, Heloisa de Souza ; Pereira, Raphaela Neto ; Castro, Camila Ferreira Bannwart ; Vince, Nicolas ; Limou, Sophie ; Naslavsky, Michel Satya ; Zatz, Mayana ; Duarte, Yeda Aparecida de Oliveira ; Mendes-Junior, Celso Teixeira ; Castelli, Erick da Cruz

• Document type: Journal article
• Source: HLA; v. 101, n. 6, p. 13-pg., 2023-04-02.

Abstract

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. (AU)

• FAPESP's process: 17/19223-0 - KIR2DL4, KIR3DL2, KIR3DL3, LILRB1 (ILT2) and LILRB2 (ILT4) variability and haplotypes in a Brazilian population sample from the São Paulo state
• Grantee: Erick da Cruz Castelli
• Support Opportunities: Regular Research Grants
• FAPESP's process: 13/17084-2 - Evaluation of MHC Class I genes variability, regulation and evolutive history
• Grantee: Erick da Cruz Castelli
• Support Opportunities: Regular Research Grants
• FAPESP's process: 21/02815-8 - Genetic diversity of HLA class II genes in worldwide populations and detection of variants that influence the expression profile of these genes
• Grantee: Nayane dos Santos Brito Silva
• Support Opportunities: Scholarships in Brazil - Doctorate