Science Summary

Many autoimmune diseases occur only in individuals expressing one of a few predisposing histocompatibility alleles.  For example, all cases of type I diabetes in humans are associated with only two of the many class II histocompatibility alleles.  Consequently, if the frequencies of these few alleles were reduced by half, the incidence of diabetes would be reduced by half.  Here we propose to characterize histocompatibility susceptibility alleles for three major, heritable canine autoimmune diseases - diabetes, immune-mediated thyroiditis and immune-mediated hemolytic anemia.  If any of these three debilitating (or lethal) autoimmune diseases have a restricted number of susceptibility alleles it will allow: (1) development of diagnostic tests for identifying individuals at risk for prophylactic therapy and research and (2) reducing the incidence of the disease by reducing the breeding of individuals carrying the predisposing histocompatibility alleles.  For each of the three autoimmune diseases, we propose to collect DNA samples from approximately 100 purebred dogs diagnosed with the disease.  Polymorphic class II (DR_β, DQ_α and DQ_β) and class I (DLA-88) histocompatibility genes will be cloned and sequenced for the affected dogs.  Histocompatibility alleles will be tested for significant associations with each of the autoimmune diseases.