Using high‑resolution human leukocyte antigen typing of 11,423 randomized unrelated individuals to determine allelic varieties, deduce probable human leukocyte antigen haplotypes, and observe linkage disequilibria between human leukocyte antigen‑B and‑C a

Kuo‑Liang Yang^a,b*, Hsee‑Bin Chen^a

^aLaboratory of Immunogenetics, Tzu Chi Cord Blood Bank and Buddhist Tzu Chi Marrow Donor Registry, Buddhist Tzu Chi Stem Cells Centre, Hualien Tzu Chi Hospital, Hualien, Taiwan, ^bDepartment of Laboratory Medicine, Buddhist Tzu Chi University, Hualien, Taiwan

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Open Access funded by Buddhist Compassion Relief Tzu Chi Foundation

Abstract

Objective: We report here the human leukocyte antigen (HLA) allelic variety and haplotype composition in a cohort of the Taiwanese Chinese population and their patterns of linkage disequilibria on HLA‑B: HLA‑C alleles and HLA‑DRB1: HLA‑DQB1 alleles at a high‑resolution level. Materials and Methods: Peripheral whole blood from 11,423 Taiwanese Chinese unrelated individuals was collected in acid citrate dextrose. Genomic DNA was extracted using the QIAamp DNA Blood Mini Kit. The DNA material was subjected to HLA genotyping for HLA‑A,‑B,‑C,‑DRB1, and‑DQB1 loci using a commercial polymerase chain reaction‑sequence‑based typing (PCR‑SBT) kit, the SeCore® A/B/C/DRB1/DQB1 Locus Sequencing kit. High‑resolution allelic sequencing was performed as previously described. Results: The number of individual HLA‑B alleles detected was greater than the number of alleles recognized in the both the HLA‑A and‑DRB1 loci. Several novel alleles were discovered as a result of employing the SBT method and the high number of donors tested. In addition, we observed a genetic polymorphic feature of association between HLA‑A and‑B, HLA‑B and‑C, and HLA‑DRB1 and‑DQB1 alleles. Further, the homozygous haplotype frequencies of HLA‑A and‑B; HLA‑A,‑C, and‑B; HLA‑A,‑C,‑B, and‑DRB1; and HLA‑A,‑C,‑B,‑DRB1, and‑DQB1 in Taiwanese Chinese population are presented. Conclusion: As increasing number of HLA alleles are being discovered, periodic HLA profile investigation in a given population is essential to recognize the HLA complexity in that population. Population study can also provide an up‑to‑date strategic plan for future needs in terms of compatibility measurement for HLA matching between transplant donors and patients.

Keywords: Alleles, Haplotypes, Human leukocyte antigen, Induced pluripotent stem cells, Linkage disequilibria, Taiwanese