Molecular analysis of DQ beta 3.1 genes.

HLA class II genes have been implicated in susceptibility to a number of diseases. We have previously identified two allelic variants of DQw3 and have shown that DR4-DQ beta 3.2 haplotypes are associated with increased risk of IDDM whereas DR4-DQ beta 3.1 haplotypes are not. DR5 and DR8 DQw3+ individuals are exclusively DQ beta 3.1 and share numerous restriction sites within the DQ beta genes with DR4-DQ beta 3.1 individuals. In order to compare the DQ beta 3.1 genes associated with different haplotypes, we have sequenced coding and noncoding regions of the DQ beta genes from a DR4-DQ beta 3.1 HTC (ER) and a DR8-DQ beta 3.1 HTC (LUY). LUY and ER DQ beta genes share nucleotide substitutions in both the beta 1 and beta 2 exons, yielding six amino acid replacements distinguishing them from DQ beta 3.2. In the noncoding regions as well, LUY and ER share nucleotide substitutions distinguishing their DQ beta 3.1 genes from DQ beta 3.2. These data support the concept that the DQ beta 3.1 allele was introduced onto different backgrounds via homologous recombination.