LARGE-SCALE COMPARATIVE MAPPING OF THE MHC CLASS-I REGION OF PREDOMINANT HAPLOTYPES IN JAPANESE

In order to further our understanding of major histocompatibility comp lex (MHC) class I gene organization, we began a comparative analysis o f the large scale organization of the class I region in diverse haplot ypes. For these studies, the MHC in healthy Japanese donors who have t he predominant MHC haplotypes and/or HLA-A or -B alleles was examined by pulsed field gel electrophoresis and Southern analysis using probes spanning the class I region. Hybridization with probes from the HLA-A to HLA-G region revealed that individuals expressing HLA-A30, -A31, o r -A33 have an approximately 70 kilobase (kb) insertion near the HLA-A gene as compared with haplotypes containing the HLA-AII or -A26 allel e. Conversely HLA-A24-containing haplotypes appear to have an approxim ately 50 kb deletion from the same region. Further, it appears that ch romosomes carrying closely related alleles are similar to each other i n this region, consistent with their presumed evolutionary relationshi p. While little is known about the gene content between the HLA-A and HLA-G region, it will be interesting to examine the prospect that func tional genes do in fact reside within the inserted or deleted portions , thereby raising the possibility that distinct functional differences are conferred by different haplotypes. Overall, the results reported here should contribute to furthering our understanding of the associat ion between diseases and HLA as well as provide new insights into the evolution of the MHC.