POLYMORPHISM IN THE UPSTREAM REGULATORY REGION OF DQA1 GENES AND DRB1, QAP, DQA1, AND DQB1 HAPLOTYPES IN THE GERMAN POPULATION

Polymorphism in the URR of the MHC class II DQA1 gene defines ten diff erent alleles named QAP. Oligotyping for the alleles of DRB1, QAP, DQA 1, and DQB1 have been performed in 210 unrelated healthy controls from Germany. Moreover, 83 HTCs from the Tenth IHWS have been tested. Four point loci haplotypes (DRB1, QAP, DQA1, and DQB1) have been analyzed in the unrelated healthy population sample. Computer analysis of the l inkage disequilibria leads to the conclusion that QAP alleles are in s trong linkage disequilibrium with alleles either the DQA1 or the DRB1 locus. One typical (''common'') haplotype was found to be associated w ith each DRB1 allele in the majority (86%) of the tested persons. Apar t from that, 25 other less frequent (''unusual'') haplotypes, with an overall frequency of 14% have been defined. Some of these ''unusual'' MHC class II haplotypes were found to differ only in the regulatory al leles of DQA1 (QAP alleles) while they are identical for the alleles c oding for structural elements (DRB1, DQA1, and DQB1). Most of the ''un usual'' haplotypes were found to carry HLA-DQ6. Assuming that ''unusua l'' (= rare) haplotypes have arisen from ''common'' (= frequent) haplo types by point mutation and recombination, we propose the existence of three recombination sites in the MHC DR-DO region: one between DRB1 a nd QAP, the second between QAP and DQA1, and the third between DQA1 an d DQB1.