Allele and haplotype frequencies of human leukocyte antigen-A, -B, -C, -DRB1, -DRB3/4/5, -DQA1, -DQB1, -DPA1, and -DPB1 by next generation sequencing-based typing in Koreans in South Korea

Abstract

Allele frequencies and haplotype frequencies of HLA-A, -B, -C, -DRB1, -DRB3/4/5, -DQA1, -DQB1, -DPA1, and -DPB1 have been rarely reported in South Koreans using unambiguous, phase-resolved next generation DNA sequencing. In this study, HLA typing of 11 loci in 173 healthy South Koreans were performed using next generation DNA sequencing with long-range PCR, TruSight® HLA v2 kit, Illumina MiSeqDx platform system, and Assign™ for TruSight™ HLA software. Haplotype frequencies were calculated using the PyPop software. Direct counting methods were used to investigate the association with DRB1 for samples with only one copy of a particular secondary DRB locus. We compared these allele types with the ambiguous allele combinations of the IPD-IMGT/HLA database. We identified 20, 40, 26, 31, 19, 16, 4, and 16 alleles of HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQA1, HLA-DQB1, HLA-DPA1, and HLA-DPB1, respectively. The number of HLA-DRB3/4/5 alleles was 4, 5, and 3, respectively. The haplotype frequencies of most common haplotypes were as follows: A*33:03:01-B*44:03:01-C*14:03-DRB1*13:02:01-DQB1*06:04:01-DPB1*04:01:01 (2.89%), A*33:03:01-B*44:03:01-C*14:03 (4.91%), DRB1*08:03:02-DQA1*01:03:01-DQB1*06:01:01-DPA1*02:02:02-DPB1*05:01:01 (5.41%), DRB1*04:05:01-DRB4*01:03:01 (12.72%), DQA1*01:03:01-DQB1*06:01:01 (13.01%), and DPA1*02:02:02-DPB1*05:01:01 (30.83%). In samples with only one copy of a specific secondary DRB locus, we examined its association with DRB1. We, thus, resolved 10 allele ambiguities in HLA-B, -C (each exon 2+3), -DRB1, -DQB1, -DQA1, and -DPB1 (each exon 2) of the IPD-IMGT/HLA database. Korean population was geographically close to Japanese and Han Chinese populations in the genetic distances by multidimensional scaling (MDS) plots. The information obtained by HLA typing of the 11 extended loci by next generation sequencing may be useful for more exact diagnostic tests on various transplantations and the genetic population relationship studies in South Koreans.

Comprehensive Analysis of CD4+ T Cell Response Cross-Reactive to SARS-CoV-2 Antigens at the Single Allele Level of HLA Class II

“…The genomic DNA was isolated from the red blood cells and granulocytes (Tiangen Biotech Corporation). The HLA was then genotyped using polymerase chain reaction sequencing-based typing and next-generation sequencing ( Table 1 ) (NCBI BioProject Accession: PRJNA721949) (MiSeqDx, Illumina), as previously described ( 24 , 25 ). The resolution of the HLA types was converted to 4-digits from 6-digits to analyze the HLA molecules at the protein level.…”

Frequency and distribution of HLA‐DQB1 alleles from 2076 cord blood samples of the Vietnamese cohort

“…HLA typing was performed from June 2015 to December 2020. Briefly, medium resolution HLA typing‐2F of locus HLA‐DQB1 was conducted by polymerase chain reaction sequence‐specific oligonucleotide (SSO) using the LIFECODES HLA SSO kit (Luminex, Austin, TX, USA) on a Luminex 200 system and analysed with Xponent 3.1 software connected to the International ImMunoGeneTics database version 3.43 library to provide us with the well‐documented allele (Baek et al., 2021; Do et al., 2020; Hoa et al., 2008; Huh et al., 2013; Park et al., 2016). Blind external controls supplied by UK External Quality Assessment Services were used to confirm the accuracy of the HLA‐DQB1 locus identified.…”

Allele and Haplotype Frequencies of HLA-A, -B, -C, and -DRB1 Genes in 3,750 Cord Blood Units From a Kinh Vietnamese Population

“…The polymorphic HLA-DRB1 (62) was higher than HLA-A and HLA-C but lower than HLA-B. Other studies have also reported that HLA-A and HLA-C have a very similar amount of information, and HLA-B is the most polymorphic locus in not only three loci of HLA class I but in all six HLA loci for both HLA class I and HLA class II (19)(20)(21)(22)(23). Although the number of highfrequency (occurring frequency >5%) alleles in HLA-A, -B, -C, and -DRB1 were the same (six alleles for each), the number of rare alleles (occurring frequency <0.1%) in HLA-B was approximately 3-, 1.6-, and 1.3-fold higher than those in HLA-A, -C, and -DRB1, respectively.…”

“…These results suggest that Asian populations have different HLA allele frequencies than the American and European populations. Moreover, the diversity in the frequencies of individual alleles of HLA loci creates large differences in frequencies and distributions of two-, three-, or four-loci haplotypes among various populations (19)(20)(21)(22)(23)(24)(25)(26)(27). This suggests that transplantations between different populations are quite challenging, and therefore, establishing a bank to store cord blood samples for transplantation programs is important.…”