An HLA-A null haplotype was observed in a Japanese family by serological typing. The individual with HLAA31/blank were typed as HLA-A*3101 homozygote by both PCR-SSP and PCR-SBT methods. The PCR amplification of genomic DNA using an HLA-A locus-specific primer set designed with 3'- and 5'-untranslated regions produced only an approximately 3 kb fragment, which was expected from full length HLA-A. An approximately 10 kb fragment shorter than that of wild-type HLA-A was detected by pulse field electrophoresis analysis of Mlu I-digested DNA fragment. The nearest gene of HLA-A, HCGIX, was found to be 30 kb away from HLA-A on the side of the centromere. Therefore, the HLA-A null haplotype seemed to lack 10 kb including only HLA-A.

We have investigated the distribution of HLA-A, -B, -DRB1, -DQB1 genes and haplotypes in 228 families with a total of 680 members living in Ehime Prefecture, Japan. HLA-A and -B antigens were typed by standard microlymphocytotoxity assay, and high resolution typing of HLA-DRB 1 and -DQB1 alleles were performed by PCR-RFLP method. A total of 8 HLA-A antigens, 23 HLA-B antigens, 26 HLA-DRB 1 alleles and 13 HLA-DQB1 alleles, including two rare alleles, were detected. The rare alleles were HLA-DRB1*0809 and DRB1*1402. Most of HLA-DRB1 alleles were strongly associated with single HLA-DQB1 alleles. In contrast, DRB1*0802, *1201 and *1401 were associated with two different DQB1I alleles. The frequencies of HLADRB1*0803 (p<0.001), and -DQB1*0601 (p<0.01) were significantly increased in our family sample, whereas the frequencies of HLA-A33(p<0.01), -B44(p<0.05), -B48(p<0.01), -DRB1*1405(p<0.05), -DRB1*1501(p<0.01) and DQB1*0602(p<0.001) were decreased, when compared to the population living in the Kanto area, Japan. The six most common HLA-A-B-DRB1-DQB1 hplotypes of frequencies>2% were HLA-A24B52-DRB1*1502-DQB1*0601 (7.7%), HLA-A24-B7-DRB1*0101-DQB 1 *0501 (3.3%), HLA-A24-B54DRB1*0405-DQB1*0401(3.2%), HLA-A2-B46-DRB1*0803-DQB1*0601(3.0%), HLA-A33-B44-DRB1*1302-DQB1*0604/09(2.6%), and HLA-A2-B61-DRB1*0901-DQB1*0303(2.5%). It was shown that the HLA-A-BDRB1-DQB1 haplotypes of DRB1*0809 and *1402 were A24-B62-DRB1 *0809-DQB1*0402 (n=2), A24-B54-DRB1*0809-DQB1*0402 (n=1) and A26-B62-DRB1*1402-QB1*0301 (n=1).