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

• Published in: Human immunology 2018-11, Vol.79 (11), p.773-780
• Main Authors: Geretz, Aviva, Ehrenberg, Philip K., Bouckenooghe, Alain, Fernández Viña, Marcelo A., Michael, Nelson L., Chansinghakule, Danaya, Limkittikul, Kriengsak, Thomas, Rasmi
• Format: Article
• Language: English
• Subjects: Alleles; Computational Biology - methods; Dengue; Gene Frequency; Genes, MHC Class I; Genes, MHC Class II; Genotype; High-Throughput Nucleotide Sequencing; Histocompatibility Testing; HLA alleles; Humans; Illumina; Multilocus Sequence Typing; Next-generation sequencing; Quantitative Trait Loci; Thailand
• ISSN: 0198-8859; 1879-1166
• DOI: 10.1016/j.humimm.2018.09.005

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.