Oxford Nanopore Sequencing‐Based Phasing of Full‐Length HLA ‐G Alleles Reveals Tight Allele‐ UTR Linkage in Chinese Kidney Transplant Recipients

HLA-G is a nonclassical class I gene with immunoregulatory functions and limited polymorphism. Its expression is strongly influenced by genetic variations in the promoter and 3' untranslated region (3'UTR). However, comprehensive data on full-length phased alleles remain poorly characterised, particularly in Asian populations. In this study, we applied long-range PCR combined with nanopore sequencing to obtain complete HLA-G sequences, including the promoter, exons, introns, and 3'UTR, from 205 Chinese kidney transplant recipients. A total of 19 alleles were resolved at 4-field resolution, including five novel variants comprising changes in two different exons and three different introns. Each allele exhibited a strict allele-specific UTR linkage with a unique 3'UTR variant, demonstrating complete coding-UTR concordance. Several non-coding SNPs exhibited sub-allele specificity, and population differences were observed. A recombinant allele, G*01:01:22:01, was identified, carrying the promoter of G*01:01:01:01 and G*01:01:02:01. These findings expand the known HLA-G allele repertoire and highlight the utility of long-read sequencing for resolving full-length alleles, offering valuable insights for immunogenetics and population studies.