Full-length next-generation sequencing of HLA class I and II genes in a cohort from Thailand |
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Authors: | Aviva Geretz Philip K. Ehrenberg Alain Bouckenooghe Marcelo A. Fernández Viña Nelson L. Michael Danaya Chansinghakule Kriengsak Limkittikul Rasmi Thomas |
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Affiliation: | 1. U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA;2. Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, 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 |
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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 A111:01:01, A133:03:01, A124:02:01, B146:01:01, C107:02:01, C101:02:01, C108:01:01, DPB1105:01:01, DPB1113:01:01, DPB1104:01:01, DPB1102:01:02, DQB1103:01:01, DQB1105:02:01, DQB1103:03:02, DRB1112:02:01, DRB1109:01:02, and DRB1115:02:01. A novel HLA allele, B115:450, 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. |
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Keywords: | HLA alleles Next-generation sequencing Dengue Thailand Illumina |
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