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Establishment of NGS‐based HLA 9‐locus haplotypes in the Eastern Han Chinese population highlights the role of HLA‐DP in donor selection for transplantation

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We collected HLA typing data from 653 families in the Eastern Han Chinese population. HLA‐A, B, C, DRB1, DRB3, DRB4, DRB5, DQA1, DQB1, DPA1, and DPB1 (HLA‐11 loci) typing of… Click to show full abstract

We collected HLA typing data from 653 families in the Eastern Han Chinese population. HLA‐A, B, C, DRB1, DRB3, DRB4, DRB5, DQA1, DQB1, DPA1, and DPB1 (HLA‐11 loci) typing of 1781 subjects was performed using a commercial next‐generation sequencing (NGS) method in our laboratory. The phasing of haplotypes in each family was determined by Mendelian segregation. Haplotype analysis revealed 1634 different haplotypes among a total of 2230 haplotypes. The predominant haplotype was A*30:01‐C*06:02‐B*13:02‐DRB1*07:01‐DRB4*01:03‐DQA1*02:01‐DQB1*02:02‐DPA1*02:01‐DPB1*17:01 (HF = 4.04%), followed by A*02:07‐C*01:02‐B*46:01‐DRB1*09:01‐DRB4*01:03‐DQA1*03:02‐DQB1*03:03‐DPA1*02:02‐DPB1*05:01 (HF = 1.84%) and A*33:03‐C*03:02‐B*58:01‐DRB1*03:01‐DRB3*02:02‐DQA1*05:01‐DQB1*02:01‐DPA1*01:03‐DPB1*04:01 (HF = 1.48%), accounting for 7.35% of the total. Meanwhile 76.41% of all haplotypes were observed only once or twice (HF < 0.1%). Different from HLA‐DRB3/4/5 and DQA1 loci, DP linkage markedly increased haplotype variation by 34.82% based on the 5‐locus haplotype. The much weaker linkage disequilibrium (LD) of DQB1‐DPB1 indicated the reason. We observed 10 analyzable recombination events, most of which occurred at DP loci. Even with the same common 5‐locus haplotype, HLA‐DP linkage alters the haplotype diversity and frequency. Analysis of related haplotype assignment and unrelated recipient‐donor pairs matching at the 9‐locus haplotype revealed that HLA‐DP affects the donor selection strategy. Haplotype study of a large sample size using NGS identified linkage haplotypes beyond the 5 loci. LD, recombination events, and haplotype variation caused by DP loci emphasized that HLA 9‐locus haplotype matching should be considered in donor selection, particularly the effect of DP loci. The finding lays the foundation for further studies on the effect of HLA‐DP mismatch on transplantation.

Keywords: dqa1; locus; hla; donor selection; haplotype; dqb1

Journal Title: HLA
Year Published: 2022

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