- Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences
The domestic dog, with its unique genetic structure formed by domestication and recent breed creation, has been proven to be an excellent model for mapping disease genes. In this thesis, we use the dog as a model to investigate the prevalence and genetic background of canine lymphocytic thyroiditis (CLT), one of the most common immune related diseases in dogs. The canine phenotype has been carefully characterized and suggests a strong comparative value to human Hashimoto’s disease because of similar etiology, clinical signs and disease progression. Therefore, our aim was to gain increased knowledge about CLT and its relevance to human autoimmune thyroid disease, to benefit both dogs and humans. In our first study (paper I) we screened two birth cohorts (3-4 and 6-7 years old, respectively) for elevated serum levels of autoantibodies to thyroglobulin (TgAA) and thyroid stimulating hormone (TSH) and could estimate a very high prevalence of CLT in the giant schnauzer and the hovawart breeds. Next, we aimed at unraveling the genetic background of CLT in the same breeds, using two different approaches; a candidate gene approach followed by a genome-wide association analysis. Using the first approach we obtained evidence that DLA class II polymorphisms can function both as a genetic risk factor predisposing for the disease as well as a protective factor against the disease. Using genome wide association we identified two additional strong susceptibility loci located on chromosome 11 and X. Both regions harbour genes with known immune-regulatory functions and implicates three genes involved in NF-κB pathway. Given the reported role of NF-κB in many human autoimmune diseases, our results suggest CLT as an excellent genetic model for human thyroiditis.
Dog; Canine lymphocytic thyroiditis; Hypothyroidism; Genome wide association ; Autoimmune; model organism; MHC; DLA; Hashimoto's
Acta Universitatis Agriculturae Sueciae
2012, number: 2012:31
Publisher: Institutionen för husdjursgenetik, Sveriges lantbruksuniversitet
Future Animal Health and Welfare (until Jan 2017)
Animal and Dairy Science