The molecular mechanism analysis of 64 new HLA alleles discovered in Beijing HLA Typing Laboratory

Human leukocyte antigen (HLA) genes rank among the most polymorphic genes in the human genome, with an extensive variation in HLA alleles. To elucidate the mechanisms underlying the generation of novel HLA alleles and to establish a reference for future HLA genotyping and allele discovery, we analyzed a total of 64 newly identified HLA alleles from the Beijing HLA Typing Laboratory of Beijing Red Cross Blood Center. The novel alleles were analyzed against their most closely related sequence homologs. This study indicates that point mutations constitute the primary molecular mechanism driving the emergence of new gene, with missense mutations being the predominant type. Among the 124 base mutations identified in this study, cytosine C exhibited the highest mutational propensity, while thymine T showed the lowest propensity to mutate. Additionally, we identified 10 mutagenic positions at the HLA-B locus, specifically at positions 379, 412, 419, 527, 538, 539, 603, 605, 610, and 618. This study provides critical insights into the origin and evolution of HLA genes and reveals the molecular basis of immune response diversity.