Allelic and haplotypic HLA diversity in indigenous Malaysian populations explored using Next Generation Sequencing

Timothy A Jinam; Kazuyoshi Hosomichi; Hirofumi Nakaoka; Maude E Phipps; Naruya Saitou; Ituro Inoue

doi:10.1016/j.humimm.2021.09.005

Allelic and haplotypic HLA diversity in indigenous Malaysian populations explored using Next Generation Sequencing

Hum Immunol. 2022 Jan;83(1):17-26. doi: 10.1016/j.humimm.2021.09.005. Epub 2021 Oct 4.

Authors

Timothy A Jinam¹, Kazuyoshi Hosomichi², Hirofumi Nakaoka³, Maude E Phipps⁴, Naruya Saitou⁵, Ituro Inoue⁶

Affiliations

¹ Population Genetics Laboratory, National Institute of Genetics, Mishima, Japan; Department of Genetics, The Graduate University for Advanced Studies, SOKENDAI, Mishima, Shizuoka, Japan. Electronic address: [email protected].
² Department of Bioinformatics and Genomics, Graduate School of Advanced Preventive Medical Sciences, Kanazawa University, Kanazawa, Japan.
³ Department of Cancer Genome Research, Sasaki Institute, Sasaki Foundation, Chiyoda-ku, Tokyo, Japan.
⁴ Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Jalan Lagoon Selatan, 47500 Bandar Sunway, Selangor Darul Ehsan, Malaysia.
⁵ Population Genetics Laboratory, National Institute of Genetics, Mishima, Japan; Department of Genetics, The Graduate University for Advanced Studies, SOKENDAI, Mishima, Shizuoka, Japan.
⁶ Human Genetics Laboratory, Department of Genomics and Evolutionary Biology, National Institute of Genetics, Mishima, Japan.

PMID: 34615609
DOI: 10.1016/j.humimm.2021.09.005

Abstract

The heterogenous population of Malaysia includes more than 50 indigenous groups, and characterizing their HLA diversity would not only provide insights to their ancestry, but also on the effects of natural selection on their genome. We utilized hybridization-based sequence capture and short-read sequencing on the HLA region of 172 individuals representing seven indigenous groups in Malaysia (Jehai, Kintaq, Temiar, Mah Meri, Seletar, Temuan, Bidayuh). Allele and haplotype frequencies of HLA-A, -B, -C, -DRB1, -DQA1, -DQB1, -DPA1, and -DPB1 revealed several ancestry-informative markers. Using SNP-based heterozygosity and pairwise Fst, we observed signals of natural selection, particularly in HLA-A, -C and -DPB1 genes. Consequently, we showed the impact of natural selection on phylogenetic inference using HLA and non-HLA SNPs. We demonstrate the utility of Next Generation Sequencing for generating unambiguous, high-throughput, high-resolution HLA data that adds to our knowledge of HLA diversity and natural selection in indigenous minority groups.

Keywords: Balancing selection; HLA; Malaysia; NGS.

MeSH terms

Alleles
Gene Frequency
HLA-DRB1 Chains / genetics
Haplotypes
High-Throughput Nucleotide Sequencing*
Histocompatibility Antigens Class II* / genetics
Humans
Phylogeny

Substances

HLA-DRB1 Chains
Histocompatibility Antigens Class II