University of Helsinki

Dogs may provide an excellent model for understanding human complex diseases

The recent Swedish-Finnish study, published in Nature Genetics, indicates that the homogeneity of strong genetic risk factors within dog breeds makes dogs an excellent model to identify pathways involved in human complex diseases.

The unique canine breed structure makes dogs an excellent model for studying genetic diseases. Incidences of specific diseases are elevated in different breeds, indicating that a few genetic risk factors might have accumulated through drift or selective breeding.

In the new Swedish-Finnish study with 81 affected dogs and 57 controls from the Nova Scotia duck tolling retriever breed the researchers identified five loci associated with a canine systemic lupus erythematosus (SLE) -related disease complex. Fine mapping with twice as many dogs validated these loci.

— Our results indicate that the homogeneity of strong genetic risk factors within dog breeds allows multigenic disorders to be mapped with fewer than 100 cases and 100 controls, making dogs an excellent model in which to identify pathways involved in human complex diseases, says Professor Hannes Lohi from the University of Helsinki and Folkhälsan Research Center.

Nova Scotia duck tolling retrievers (NSDTRs) are strongly predisposed to many immune-mediated diseases, including a systemic lupus erythematosus (SLE) -related disease complex comprising an immune-mediated rheumatic disease (IMRD) and steroid-responsive meningitis-arteritis (SRMA). Pedigree analysis of the SLE disease complex in NSDTRs has indicated that it involves multi-genetic inheritance, like most autoimmune diseases in humans.

Some types of genetic risk factor will be more easily traced in dogs than in humans, and the dog studies might be a valuable complement to human study for identifying new genes and pathways that are important in disease pathogenesis.

— Although we plan to identify and characterize the functions of the canine mutations, this study opens the door for further studies of specific T-cell activation pathways in human populations, Lohi says.

In the more long term, the development of clinical treatment regimens based on a dog’s particular risk genotype might be possible. For instance, the effect of calcineurin inhibitors could be studied in dogs as a complement or alternative to traditional corticosteroid therapy. Such studies might also lead to better treatment options for human rheumatic diseases and SLE.

Text: Päivi Lehtinen
Photo: Wikipedia