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HLA‐A , ‐B, ‐C, ‐ DRB1 allele and haplotype frequencies of the Korean population and performance characteristics of HLA typing by next‐generation sequencing
Author(s) -
Jekarl Dong Wook,
Lee Gun Dong,
Yoo Jae Bin,
Kim Jung Rok,
Yu Haein,
Yoo Jaeeun,
Lim Jihyang,
Kim Myungshin,
Kim Yonggoo
Publication year - 2021
Publication title -
hla
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.347
H-Index - 99
eISSN - 2059-2310
pISSN - 2059-2302
DOI - 10.1111/tan.14167
Subject(s) - human leukocyte antigen , typing , allele , biology , haplotype , genetics , hla a , linkage disequilibrium , allele frequency , concordance , antigen , gene
Human leukocyte antigen (HLA) identification at the allelic level is important for haematopoietic stem cell transplantation (HSCT). Next‐generation sequencing (NGS) resolves ambiguous alleles by determining the phase of the polymorphisms. The aim of this study was to validate the software for HLA‐SBT (sequence‐based typing), assess Korean allele frequency, and characterise the performance of NGS‐HLA typing. Methods From the 2009 to 2016 registry, 1293 unrelated healthy donors with a complete dataset of previously characterised HLA‐A, ‐B, ‐C, and ‐DRB1 loci were selected and assessed for frequency, haplotype inference, and relative linkage disequilibrium. For performance characteristics of NGS‐HLA, alleles included in 1293 cases and ambiguous or alleles assigned as new by SBT‐HLA software, or unassigned alleles were included. A total of 91 and 41 quality control samples resulted in 1056 alleles (132 samples × 4 loci × 2 diploid) for analysis. The GenDx NGSgo kit was used for NGS‐HLA typing using the Illumina MiSeq platform. Results A panel of 132 samples covered 231 alleles, including 53 HLA‐A, 80 HLA‐B, 43 HLA‐C, and 55 HLA‐DRB1 by HLA‐SBT typing. Comparison of SBT‐HLA and NGS‐HLA typing showed 99.7% (1053/1056) concordance and discrepant cases were resolved by manual evaluation. Typing by NGS resulted in 67 HLA‐A, 112 HLA‐B, 71 HLA‐C, and 72 HLA‐DRB1 alleles. A total of 132 ambiguous, 4 new, and 1 unassigned alleles by HLA‐SBT were resolved by NGS‐HLA typing. Conclusions NGS‐HLA typing provided robust and conclusive results without ambiguities, and its implementation could support HSCT in clinical settings.