Full-length next-generation sequencing of HLA class I and II genes in a cohort from Thailand

The human leukocyte antigen (HLA) genes are highly variable and are known to play an important role in disease outcomes, including infectious diseases. Prior knowledge of HLA polymorphisms in a population usually forms the basis for an effective case-control study design. As a prelude to future disease association analyses, we report HLA class I and II diversity in 334 unrelated donors from a Dengue vaccine efficacy trial conducted in Thailand. Long-range PCR amplification of six HLA loci was performed on DNA extracted from saliva samples. HLA-A,-B,-C, -DPB1, -DQB1 and -DRB1 were genotyped using a next-generation sequencing method presented at the 17th International HLA and Immunogenetics Workshop. In total, we identified 201 HLA alleles, including 35 HLA-A, 57 HLA-B, 28 HLA-C, 24 HLA-DPB1, 21 HLA-DQB1 and 36 HLA-DRB1 alleles. Very common HLA alleles with frequencies greater than 10 percent were A*11:01:01, A*33:03:01, A*24:02:01, B*46:01:01, C*07:02:01, C*01:02:01, C*08:01:01, DPB1*05:01:01, DPB1*13:01:01, DPB1*04:01:01, DPB1*02:01:02, DQB1*03:01:01, DQB1*05:02:01, DQB1*03:03:02, DRB1*12:02:01, DRB1*09:01:02, and DRB1*15:02:01. A novel HLA allele, B*15:450, had a non-synonymous substitution and occurred in more than one donor. Population-based full-length NGS HLA typing is more conclusive and provides a sound foundation for exploring disease association in a given population.