After years of comparing a large group of Labrador retrievers and teasing apart their genome, researchers at the University of Wisconsin-Madison have come up with the first genetic test that can tell owners, breeders, and prospective owners if their dog is at risk for cruciate ligament rupture (CLR), a debilitating – and expensive – disease. And they can do it with 98 percent certainty.
It wasn’t too long ago that scientists made the connection between genetics and CLR; for decades, veterinarians assumed that it was caused by traumatic injury. But as genetic science advanced and allowed veterinarians to look more closely at the DNA strands, they have been able to see this disease, like many of the diseases dog owners deal with regularly, is, in fact, inherited.
While many of the genetic tests now available target “simple diseases” – think exercise-induced collapse, degenerative myelopathy, or progressive retinal atrophy – which involve a specific DNA mutation on a specific gene, UW-M’s test is one of the first for a complex disease, where thousands and thousands of genetic variants across the entire DNA contribute to its risk. That, as you can imagine, took a while to sort through. And they needed a large reference pool.
“While some other breeds have a higher incidence of cruciate ligament rupture, the Labrador is the most common purebred dog in the U.S. In the end, we studied the Labrador retriever because there’s more Labradors with cruciate rupture out there than any other breed,” said Dr. Peter Muir, the Melita Grunow Family Professor of Companion Animal Health at the University of Wisconsin-Madison School of Veterinary Medicine. According to Muir, rottweilers and Newfoundlands have twice the incidence rate of Labradors (between 5-10 percent of Labradors rupture their cruciate ligaments within their lifetime), but there are just a lot more Labs out there. The study’s reference group included more than 1,000 dogs.
“Our research in the Labradors suggests that… 62 percent of the risk of the disease is genetic, therefore 38 percent of the risk of the disease is environmental. In dogs with bad genetic risk, it doesn’t necessarily mean that they’re going to get cruciate ligament rupture, but it certainly means that they are more vulnerable,” said Dr. Muir, adding that environmental risk factors likely include neutering and weight gain.
A test returned as “predicted to be a case” gives the owner an opportunity to work with their veterinarian to reduce the environmental risks and, therefore, the possibility of CLR. Keeping in mind that dogs that develop a rupture on one side have a 50 percent chance of rupture on the other side, reducing those risk factors is even more vital. Not to mention the cost involved – UW-M estimates “gold standard” treatments for CLR to run between $4,000 and $7,000.
Likewise, those testing as “predicted to be a control” are not given a complete clean bill of health, and while they may be unlikely to rupture their cruciate ligament, there are still environmental factors that can contribute to development of the disease.
But it does give breeders, especially, a new look at the Labrador’s genetics and can help them with breeding decisions that can only improve the health of the breed.
“We know this is a complex disease that is highly polygenic, so there are thousands and thousands of risk variants across the genome,” said Dr. Muir. “When breeding decisions are made, it would be best to breed dogs that have low genetic risk. Parents with low genetic risk would likely produce puppies with low genetic risk. Whereas parents that have high genetic risk, it’s more likely that the puppies are going to have high genetic risk.”
He cautions, however, that the genetic risk of the puppies can be variable. So breeding high-risk CLR parents doesn’t mean that the puppies are all going to be affected, and breeding non-CLR parents doesn’t mean that the puppies aren’t going to get the disease. But the testing can tilt the odds in the breeder’s favor that they will have healthy puppies.
“From a breed improvement point of view at the level of selection of dogs, the idea would be to preferentially breed dogs with low genetic risk,” he said.
Labs, by virtue of their sheer numbers, are the first to benefit from this research, but Dr. Muir says rottweilers, Newfoundlands, and golden retrievers are probably not far behind. Right now, researchers are studying whether or not the thousands of pertinent pieces of the Lab genome are in the same places on the golden retriever genome, for instance. And they’ll be working to find large enough reference populations to make the testing more accurate.
Given that the only thing necessary for the analysis is the dog’s sex and the genetic markers, the testing can be done at any time – from birth to very old age. The cost of the test is estimated to be around $250 because of the genetically complex nature of the disease.
