国内北方汉族人群HLA-A、-B、-C基因序列多态性与进化分析OA

Objective To characterize the sequence polymorphism of HLA-A,-B,and-C loci in the northern Han Chi-nese population and to evaluate their selection signals and phylogenetic patterns based on long-read sequencing data.Meth-ods A total of 408 unrelated healthy blood donors were enrolled.Long-read sequencing of HLA-A,-B,and-C loci was per-formed using the PacBio Sequel Ⅱ platform.The Ewens-Watterson neutrality test,sliding-window nucleotide diversity(π)and Tajima's D analyses were conducted,together with genetic distance heatmaps,principal coordinates analysis(PCoA),and maximum likelihood phylogenetic analysis to assess polymorphism distribution,selection signals,and phylogenetic structure across the three loci.Results The analyzed sequence lengths for the HLA-A,-B,and-C loci were 3 257 bp,3 794 bp,and 3 831 bp,respectively;the numbers of locus-specific sequence types were 44,82,and 56,with correspond-ing locus-specific sequence type diversities of 0.905 2,0.964 9,and 0.939 8,respectively.The Ewens-Watterson test showed no significant deviation from neutrality(P>0.05).Sliding-window analysis revealed elevated π and Tajima's D val-ues in exons 2 and 3 as well as in certain intronic regions of HLA-A and HLA-B,whereas HLA-C exhibited relatively lower o-verall diversity.Genetic distance heatmaps,PCoA,and phylogenetic analysis consistently showed clear clustering in HLA-A and HLA-C,while HLA-B displayed the highest phylogenetic heterogeneity.Conclusion HLA-A,-B,and-C gene se-quences in the northern Chinese Han population exhibit high levels of polymorphism and marked regional heterogeneity.HLA-B shows greater diversity,stronger signals of selection,and more complex phylogenetic structure compared with HLA-A and HLA-C.