A complex immune disease partly deciphered using dog

To find genes for human common complex diseases, thousands of blood samples are needed from both patients and healthy controls. The structure of dog breeds provided by selective breeding practices makes it much easier to find pathogenic genes with a smaller number of samples. This is the primary goal of the LUPA project and has elegantly been demonstrated recently by a group of Scandinavian and American scientists.

The Nova Scotia duck tolling retriever is often affected by an autoimmune disease where the dog develops joint complaints and inflammatory symptoms in various inner organs. Many of the clinical features are similar to the human Systemic Lupus Erythematosus (SLE). Among these, dogs affected frequently display antibodies against the nuclei of the body’s own cells and always showed arthritis. The Nova Scotia breed was decimated by canine distemper virus in the early 20th century. The dogs that survived may have been the dogs with the strongest immune system, and this strong immune response is now also resulting in an autoimmune disorder.  The researchers sifted through the DNA of 81 diseased dogs and 57 healthy dogs and identified five regions in the genome that each, greatly increase the risk of developing the disease. SLE in humans is caused by many genes and therefore scientists were not surprised to find several risk factors that contribute to the disease in dogs. It’s worth pointing out that the canine risk factors are very strong. The risk factors that have been found thus far in humans with SLE may double the risk, but in dogs, each disease gene increases the risk about five times. The scientists have examined what the genes are in the risk regions and note that several of them govern the activation of T cells, the white blood cells that deal with viruses in our immune system. The genes that have thus far been found in humans with SLE do not primarily regulate T cells, but a major share of the genetic risk factors is still unknown in humans. This study opens the door for further studies of specific T-cell activation pathways in human populations. Such studies might lead to better treatment options for human rheumatic diseases and SLE.

Original article:
M Wilbe et al. Genome-wide association mapping identifies multiple loci for a canine SLE-related disease complex.
Nature Genetics, 2010. DOI : 10.1038/ng.525

Vulgarisation article:
Dogs May Provide an Excellent Model for Understanding Human Complex Diseases
ScienceDaily (Feb. 2, 2010)