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

Aviva Geretz; Philip K Ehrenberg; Alain Bouckenooghe; Marcelo A Fernández Viña; Nelson L Michael; Danaya Chansinghakule; Kriengsak Limkittikul; Rasmi Thomas

doi:10.1016/j.humimm.2018.09.005

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

Hum Immunol. 2018 Nov;79(11):773-780. doi: 10.1016/j.humimm.2018.09.005. Epub 2018 Sep 19.

Authors

Aviva Geretz¹, Philip K Ehrenberg², Alain Bouckenooghe³, Marcelo A Fernández Viña⁴, Nelson L Michael², Danaya Chansinghakule⁵, Kriengsak Limkittikul⁶, Rasmi Thomas⁷

Affiliations

¹ U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
² U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
³ Asia-Pacific Clinical Development, Sanofi Pasteur, Singapore.
⁴ Stanford Blood Center, Stanford University School of Medicine, Palo Alto, CA, USA.
⁵ Asia-Pacific Clinical Development, Sanofi Pasteur, Thailand.
⁶ Department of Tropical Pediatrics, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
⁷ U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA. Electronic address: rthomas@hivresearch.org.

PMID: 30243890
DOI: 10.1016/j.humimm.2018.09.005

Abstract

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.

Keywords: Dengue; HLA alleles; Illumina; Next-generation sequencing; Thailand.

MeSH terms

Alleles
Computational Biology / methods
Gene Frequency
Genes, MHC Class I*
Genes, MHC Class II*
Genotype
High-Throughput Nucleotide Sequencing*
Histocompatibility Testing
Humans
Multilocus Sequence Typing
Quantitative Trait Loci
Thailand