AbstractIn this study, we investigated the five polymorphic Alu loci located within human major histocompatibility complex (MHC) class I region in 445 individuals from four distinct Chinese populations: Hunan Han, Inner Mongolia Han, Inner Mongolia Mongol and Guangdong Han populations, with an emphasis on the linkage disequilibrium (LD) between Alu insertions and human leukocyte antigen (HLA)‐A, Cw and B loci in a southern (Hunan Province) and a northern (Inner Mongolia Autonomous Region) Chinese Han population. Our data showed that (a) the allele and haplotype frequencies of Alu and HLA‐A loci did not differ significantly between the two southern Chinese Han populations and showed remarkable homogeneity in the two northern Chinese populations; (b) AluyHG had the highest insertion rate and HLA‐A*02 harboring the single AluyHG insertion was most frequent among Alu insertion‐bearing haplotypes in all four populations; (c) haplotypes AluyHF insertion–HLA‐A*26, AluyHG insertion–HLA‐A*02 and AluyHJ insertion–HLA‐A*24 were in significant LD across the four groups and (d) haplotype AluyMICB insertion–HLA‐Cw*06 was in significant LD in both populations, while significant LD of haplotypes AluyMICB insertion–HLA‐B*54 and AluyMICB insertion–HLA‐B*48 was only observed in the Hunan Han population and the Inner Mongolia Han population, respectively. Haplotype HLA‐B*48‐MICA gene deletion–AluyMICB insertion was observed at a frequency of about 3.85% in the latter population. Our data, together with previous reports on several Asian‐Oceanian populations suggest the identity by descent of several common HLA‐A allelic lineages in these modern human populations. The novel population‐specific LD patterns uncovered in this study also shed new insight into HLA evolution and haplotype origin.