关键词: 人类白细胞抗原, HLA多态性, 点突变, 基因转换, 新等位基因

Abstract: Objective This study aims to analyze the characteristics of 46 new HLA alleles identified in the Chinese indivivduals and provide insights into selecting HLA-matched donors for hematopoietic stem cell transplantation patients. Methods Based on the sequences of the new alleles obtained by PCR-SBT and group-specific allele amplification sequencing methods, we analyzed the types and positions of nucleotide mutations, amino acid substitutions and their property changes, and constructed three-dimensional structural models of the protein molecules. Results The 46 new HLA alleles include 11 HLA-A, 13 HLA-B, 13 HLA-C, 3 HLA-DRB1 and 6 HLA-DQB1 loci. There are 57 base mutations, of which 53 are point mutations,3 are nucleotide deletions, and 1 is a nucleotide insertion. The amino acid mutations include both synonymous mutations (12) and missense mutations (40), as well as frameshift mutations (4). Of the amino acid substitutions, 22 did not alter the nature of the amino acids, while the remaining 30 resulted in different changes in amino acid properties. Mutations in HLA class Ⅰ molecules mostly occurred in the extracellular regions, including the α1 domain (13), α2 domain (11), and α3 domain (15), with a few in the transmembrane region (4), cytoplasmic region (1), and 1 in the leader sequence. All mutations in HLA class Ⅱ molecules occurred in the extracellular regions, including the β1 domain (9) and β2 domain (2). The three new alleles with deletion mutations resulted in premature termination of protein translation.The nucleotide sequences of the four new alleles with multiple base mutations were searched and aligned in the EMBL-EBI database to analyze whether the mutations might have been generated through gene conversion. Conclusion Our analysis of these new alleles demonstrates the different mechanisms that may contribute to the evolution of HLA polymorphism. These findings will help clinicians identify HLA-matched donors for hematopoietic stem cell transplantation patients and improve the success rate of matching.

Key words: Human Leukocyte Antigen, HLA polymorphism, Point mutation, Gene conversion, New alleles