Allele and haplotype frequencies of 11 HLA loci in Koreans by next‐generation sequencing

Data on HLA genotype distribution, including DQA1 and DPA1, in the Korean population are limited. We aimed to investigate the allele and haplotype frequencies of 11 HLA loci in 339 Korean subjects using next‐generation sequencing (NGS)‐based HLA typing. A total of 339 samples from unrelated healthy subjects were genotyped for HLA‐A, ‐B, ‐C, ‐DRB1, ‐DRB3, ‐DRB4, ‐DRB5, ‐DQB1, ‐DQA1, ‐DPB1, and ‐DPA1 using two different NGS‐based HLA typing kits (166 tested using the NGSgo‐MX11‐3 kit [GenDx, Netherlands] and 173 by the AllType NGS 11 Loci Amplification kit [One Lambda, USA]). PyPop software was used to estimate allele and haplotype frequencies and linkage disequilibrium between the loci. Additionally, a principal component analysis was performed to compare the allele distribution of Koreans with that of other populations. A total of 214 HLA alleles (97 class I and 117 class II alleles) were assigned. The most frequent alleles for each locus were A*24:02:01 (24.78%), B*15:01:01 (10.18%), C*01:02:01 (18.44%), DRB1*04:05:01 (9.59%), DRB3*02:02:01 (13.72%), DRB4*01:03:01 (25.81%), DRB5*01:01:01 (9.0%), DQA1*01:02:01 (16.96%), DQB1*03:01:01 (14.31%), DPA1*01:03:01 (44.4%), and DPB1*05:01:01 (35.1%), respectively. The most frequent haplotypes were A*33:03:01‐C*03:02:02‐B*58:01:01 for HLA class I (5.01%) and DRB1*04:05:01‐DQA1*03:03:01‐DQB1*04:01:01‐DPA1*02:02:02‐DPB1*05:01:01 for HLA class II (6.23%). The total allelic ambiguities by NGS were estimated to be minimal and considerably decreased compared with those by Sanger sequencing. The Japanese population had the most similar allele distribution to Koreans, followed by the Chinese population. Frequency data of 11 HLA loci in Koreans can provide essential data for population genetics and disease association studies.

[1]  Tai-Gyu Kim,et al.  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 , 2021, PloS one.

[2]  J. Yang,et al.  Identification of 8-Digit HLA-A, -B, -C, and -DRB1 Allele and Haplotype Frequencies in Koreans Using the One Lambda AllType Next-Generation Sequencing Kit , 2021, Annals of laboratory medicine.

[3]  N. Chitnis,et al.  New challenges, new opportunities: Next generation sequencing and its place in the advancement of HLA typing. , 2021, Human immunology.

[4]  K. Park,et al.  Evaluation of LabType-SSO HLA Typing for HLA-A, -B, -C, -DRB1, and -DQB1 loci. , 2021, Clinical Laboratory.

[5]  Yonggoo Kim,et al.  HLA‐A, ‐B, ‐C, ‐DRB1 allele and haplotype frequencies of the Korean population and performance characteristics of HLA typing by next‐generation sequencing , 2020, HLA.

[6]  A. Hajeer,et al.  HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 Allele and Haplotype Frequencies of 28,927 Saudi Stem Cell Donors Typed by Next-Generation Sequencing , 2020, Frontiers in Immunology.

[7]  S. Worawichawong,et al.  Antibody-Mediated Rejection Due to Donor-Specific HLA-DQB1 and DQA1 Antibodies After Kidney Transplantation: A Case Report. , 2020, Transplantation proceedings.

[8]  L. G. Le,et al.  High-Resolution HLA Typing of HLA-A, -B, -C, -DRB1, and -DQB1 in Kinh Vietnamese by Using Next-Generation Sequencing , 2020, Frontiers in Genetics.

[9]  A. Hajeer,et al.  Common, intermediate and well‐documented HLA alleles in world populations: CIWD version 3.0.0 , 2020, HLA.

[10]  M. Kowalski,et al.  High-resolution allele frequencies for NGS based HLA-A, B, C, DQB1 and DRB1 typing of 23 595 bone marrow donors recruited for the polish central potential unrelated bone marrow donor registry. , 2020, Human Immunology.

[11]  Paul Flicek,et al.  IPD-IMGT/HLA Database , 2019, Nucleic Acids Res..

[12]  M. Kanai,et al.  Genetic and phenotypic landscape of the major histocompatibilty complex region in the Japanese population , 2019, Nature Genetics.

[13]  N. Michael,et al.  Full-length next-generation sequencing of HLA class I and II genes in a cohort from Thailand. , 2018, Human immunology.

[14]  Y. Xie,et al.  HLA common and well‐documented alleles in China , 2018, HLA.

[15]  J. Goudet,et al.  The Effect of Balancing Selection on Population Differentiation: A Study with HLA Genes , 2018, G3: Genes, Genomes, Genetics.

[16]  M. Halagan,et al.  Next generation sequencing characterizes the extent of HLA diversity in an Argentinian registry population , 2018, HLA.

[17]  Idan Alter,et al.  HLA class I haplotype diversity is consistent with selection for frequent existing haplotypes , 2017, PLoS Comput. Biol..

[18]  H. Yang,et al.  Typing and copy number determination for HLA‐DRB3, ‐DRB4 and ‐DRB5 from next‐generation sequencing data , 2017, HLA.

[19]  E. Weimer,et al.  Performance Characteristics and Validation of Next-Generation Sequencing for Human Leucocyte Antigen Typing. , 2016, The Journal of molecular diagnostics : JMD.

[20]  H. Yamada,et al.  Subclinical antibody‐mediated rejection due to anti‐human‐leukocyte‐antigen‐DR53 antibody accompanied by plasma cell‐rich acute rejection in a patient with cadaveric kidney transplantation , 2016, Nephrology.

[21]  P. Schroder,et al.  Early acute antibody-mediated rejection of a negative flow crossmatch 3rd kidney transplant with exclusive disparity at HLA-DP. , 2014, Human immunology.

[22]  J. Friedewald,et al.  Epitope Analysis of HLA-DQ Antigens: What Does the Antibody See? , 2014, Transplantation.

[23]  G. Ghiggeri,et al.  DQ molecules are the principal stimulators of de novo donor‐specific antibodies in nonsensitized pediatric recipients receiving a first kidney transplant , 2014, Transplant international : official journal of the European Society for Organ Transplantation.

[24]  A. Sanchez‐Mazas,et al.  HLA variation reveals genetic continuity rather than population group structure in East Asia , 2014, Immunogenetics.

[25]  Jennifer R. Zitzner,et al.  HLA-DQ Barrier: Effects on cPRA Calculations , 2013, Transplantation.

[26]  M. H. Park,et al.  HLA‐A, ‐B and ‐DRB1 polymorphism in Koreans defined by sequence‐based typing of 4128 cord blood units , 2013, International journal of immunogenetics.

[27]  Loren Gragert,et al.  Six-locus high resolution HLA haplotype frequencies derived from mixed-resolution DNA typing for the entire US donor registry. , 2013, Human immunology.

[28]  Jerzy K. Kulski,et al.  Distinct HLA allele and haplotype distributions in four ethnic groups of China. , 2012, Tissue antigens.

[29]  B. Zhu,et al.  Allelic diversity and haplotype structure of HLA loci in the Chinese Han population living in the Guanzhong region of the Shaanxi province. , 2010, Human immunology.

[30]  D. Segev,et al.  Subclinical Rejection in Stable Positive Crossmatch Kidney Transplant Patients: Incidence and Correlations , 2009, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[31]  Steven J Mack,et al.  Balancing selection and heterogeneity across the classical human leukocyte antigen loci: a meta-analytic review of 497 population studies. , 2008, Human immunology.

[32]  G Thomson,et al.  PyPop update--a software pipeline for large-scale multilocus population genomics. , 2007, Tissue antigens.

[33]  D. Charlesworth.  Balancing Selection and Its Effects on Sequences in Nearby Genome Regions , 2006, PLoS genetics.

[34]  S. Adams,et al.  Ambiguous allele combinations in HLA Class I and Class II sequence-based typing: when precise nucleotide sequencing leads to imprecise allele identification , 2004, Journal of Translational Medicine.

[35]  M. Remberger,et al.  Roles of HLA-B, HLA-C and HLA-DPA1 incompatibilities in the outcome of unrelated stem-cell transplantation. , 2003, Tissue antigens.

[36]  K. Tokunaga,et al.  HLA class II allele and haplotype frequencies in Koreans based on 107 families. , 2002, Tissue antigens.

[37]  H. Hattemer,et al.  Genetic distance between populations , 1982, Theoretical and Applied Genetics.

[38]  R. Lewontin.  The Interaction of Selection and Linkage. I. General Considerations; Heterotic Models. , 1964, Genetics.

[39]  Yoshio Tateno,et al.  Accuracy of estimated phylogenetic trees from molecular data , 2005, Journal of Molecular Evolution.