Application of synthetic oligonucleotides to detect DQ beta genes transmission within insulin-dependent diabetes families.

Class II antigen genes encoded by the major histocompatibility complex region (HLA-D region) in man play an important role in susceptibility to insulin dependent diabetes mellitus (IDDM). Evidence suggests that the DQ subregion within the HLA-D region is more directly responsible for susceptibility to IDDM. Therefore, we designed a synthetic oligonucleotide specific for the DQ beta gene to further the understanding of the disease association with HLA-D region genes at the molecular level. Restriction fragment length polymorphism (RFLP) analysis was carried out using DNA isolated from nine families, each including at least two affected siblings (a total of 37 siblings). The segregation pattern of hybridizing fragments showed that: (1) for each of the DR2, DR3, and DR4 specificities, two different alleles can be identified by the DQ beta probe; (2) a 1.9 kb-Taq 1 fragment with the DR4 specificity and a 6.0 kb-Taq-1 fragment within the DR2 specificity tend to cosegregate with IDDM; (3) there was no preferential segregation of the two alleles detected within the DR3 specificity (one allele identified by a 4.7 kb-Taq 1 fragment is quite common among individuals with the DR3 specificity). The results from this study add to the evidence that certain DQ alleles appear to be more directly associated with the diabetogenic gene (or genes) in certain DR specificities.