Researchers at Uppsala University and the Swedish University of Agricultural Sciences (SLU) have found several genes that lead to increased risk for an SLE-like autoimmune disorder in dogs. This is the first time scientists have found genes behind such a complex disease.
The study is being published in the journal Nature Genetics.
"It's extremely interesting and feels fantastic that we can so readily find genes even for complex diseases in dogs. The study also provides entirely new avenues for studying SLE in humans," says Professor Kerstin Lindblad-Toh, who directed the study, which was carried out in collaboration with scientists at SLU and colleagues in Finland and the US.
To find genes for human common diseases, thousands of blood samples are needed from both patients and healthy controls. The structure provided by dog breeding, and the refinement of various properties within the breeds, make it much easier to find pathogenic genes with a smaller number of samples.
Veterinarian Helene Hamlin at SLU has previously described an autoimmune disease complex in the breed Nova Scotia duck tolling retriever, which is characterized by a rheumatic SLE-like disorder (Systemic Lupus Erythematosus), where the dog develops joint complaints and inflammatory symptoms in various inner organs. In these, the body has often formed antibodies against the nuclei of the body's own cells, a characteristic found in SLE in humans as well. The other variant of the disease complex is non-bacterial meningitis, so-called steroid-responsive meningitis-arthritis (SRMA).
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. Three of the regions greatly increase the risk of developing the SLE-like variant of the disease, while the other two regions increase the risk for both SLE and meningitis.
"We know that SLE in humans is caused by many genes and were therefore not surprised to find several risk factors that contribute to the disease in dogs," says Maria Wilbe, a doctoral candidate at SLU and lead author of the article.
"It's worth pointing out that the canine risk factors are very strong," says Kerstin Lindblad-Toh. "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."
One can even hypothesize as to why Nova Scotia duck tolling retrievers develop this disorder to such a great extent. The 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 scientists have examined what the genes are in the risk regions and note that several of these genes 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 are still unknown in humans. It will therefore be interesting to move on and look at various subtypes of SLE and see whether genes that regulate T cells cause any of them," says Kerstin Lindblad-Toh.
- Maria Wilbe, Pδivi Jokinen, Katarina Truvι, Eija H Seppala, Elinor K Karlsson, Tara Biagi, Angela Hughes, Danika Bannasch, Gφran Andersson, Helene Hansson-Hamlin, Hannes Lohi & Kerstin Lindblad-Toh. Genome-wide association mapping identifies multiple loci for a canine SLE-related disease complex. Nature Genetics, 2010; DOI: 10.1038/ng.525
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