Researchers at Uppsala University and the SwedishUniversity of Agricultural Sciences (SLU) havefound several genes that lead to increased riskfor an SLE-like autoimmune disorder in dogs. Thisis the first time scientists have found genesbehind such a complex disease. The study is beingpublished today in the Web edition of Nature Genetics.
"It's extremely interesting and feels fantasticthat we can so readily find genes even forcomplex diseases in dogs. The study also providesentirely new avenues for studying SLE in humans,"says Professor Kerstin Lindblad-Toh, who directed the study, which was carried out incollaboration 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 bothpatients and healthy controls. The structureprovided by dog breeding, and the refinement ofvarious properties within the breeds, make itmuch easier to find pathogenic genes with a smaller number of samples.
Veterinarian Helene Hamlin at SLU has previouslydescribed an autoimmune disease complex in thebreed Nova Scotia duck tolling retriever, whichis characterized by a rheumatic SLE-like disorder(Systemic Lupus Erythematosus), where the dogdevelops joint complaints and inflammatorysymptoms in various inner organs. In these, thebody has often formed antibodies against thenuclei of the body's own cells, a characteristicfound in SLE in humans as well. The othervariant of the disease complex is non-bacterialmeningitis, so-called steroid-responsive meningitis-arthritis (SRMA).
The researchers sifted through the DNA of 81diseased dogs and 57 healthy dogs and identifiedfive regions in the genome that each , greatlyincrease the risk of developing the disease.Three of theregions greatly increase the risk ofdeveloping 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 causedby many genes and were therefore not surprised tofind several risk factors that contribute to thedisease in dogs," says Maria Wilbe, a doctoralcandidate 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 inhumans with SLE may double the risk, but indogs, each disease gene increases the risk about five times."
One can even hypothesize as to why NovaScotia duck tolling retrievers develop thisdisorder to such a great extent. The breed wasdecimated by canine distemper virus in the early 20thcentury. The dogs that survived may have been the dogs with thestrongest immune system, and this strong immuneresponse is now also resulting in an autoimmunedisorder. The scientists have examined what the genes are in the riskregions and notethat several of these genes govern the activationof T cells, the white blood cells that dealwith viruses in our immune system.
"The genes that have thus far been found inhumans with SLE do not primarily regulate Tcells, but a major share of the genetic riskfactors are still unknown in humans. It will therefore beinteresting to move on and look at varioussubtypes of SLE and see whether genes thatregulate T cells cause any of them," says Kerstin Lindblad-Toh.
Source: Uppsala University