Full-Length Next-Generation Sequencing of 11 HLA Loci of More Than 1000 Individuals From Clinical Cohorts in East and West Africa

HLA loci have been implicated in several diseases, including HIV-1, from different world populations. It is necessary to characterise HLA allele variation at the population level prior to investigating associations linked to human diseases. In global databases, limited high-resolution HLA allele types generated by next-generation sequencing (NGS) have been described for populations from African countries. We sought to expand our NGS-based HLA genotyping database to include a total of 1023 participants from multiple clinical studies using a contiguous full-length gene sequencing approach. Collectively we describe HLA genotypes of individuals from Kenya (N = 375), Uganda (N = 338), Nigeria (N = 139), Tanzania (N = 89) and Mozambique (N = 82). Overall, we identified 362 unique HLA alleles across 11 loci with the most frequent at each locus being A*02:01:01, B*53:01:01, C*04:01:01, C*06:02:01, DPA1*01:03:01, DPB1*01:01:01, DQA1*01:02:01, DQB1*06:02:01, DRB1*15:03:01, DRB3*02:02:01, DRB4*01:03:01 and DRB5*01:01:01. A total of 24 novel alleles (HLA-A (2), B (1), C (1), DPA1 (4), DPB1 (6), DQA1 (3), DRB1 (6) and DRB3 (1)) were identified, including 3 (C*07:1218, DQA1*01:190 and DPB1*1820:01) with non-synonymous changes affecting the peptide binding groove of HLA molecules. This expansion of NGS based HLA data at the African population level will improve our understanding of human genetic variation and provide insights for disease association, vaccine development and targeted personalised therapies.