By Caroline Coile
In a landmark study, scientists have developed one of the first DNA tests for a complex disease in dogs, meaning one that arises from the interplay of many genes as well as environment. So far, virtually all DNA tests for disorders have detected one or possibly two gene variables. This DNA test, for canine cruciate ligament rupture in Labrador Retrievers, relies on values at thousands of genetic loci to predict if a dog is likely to develop a ruptured cruciate ligament. Perhaps even more importantly, it could herald in more DNA tests for complex disorders.
Cruciate ligament rupture is one of the most common injuries in large dogs, with some breeds having a disproportionately high number of dogs affected. For example, between 5% and 10% of Labrador Retrievers rupture their cruciate ligament in their lifetime. At least half of the dogs that rupture the ligament in one hind leg go on to rupture the ligament in the other.
The cruciate ligaments are two ligaments within the stifle (knee) joint that prevent the joint from wobbling side to side. These two ligaments are termed the cranial and the caudal anterior ligaments, with the cranial cruciate ligament the same as the anterior cruciate ligament (ACL) in people. It’s not uncommon for people to injure their ACL, and that’s also the case with dogs. When we speak of cruciate ligament ruptures, we are almost always speaking of the cranial cruciate ligament, although sometimes the caudal one tears secondarily. The ligament frays over time, and the dog may become noticeably lame when the tear is partial, or only when it snaps all the way, and the tear is complete. It usually occurs in middle-aged or older dogs. It is more common in heavy dogs such as Labrador Retrievers, Rottweilers and Newfoundlands.
The injury is painful, and treatment is expensive (“gold-standard” treatment runs $4000 to $7000 per knee); and it requires long post-operative care and rest, and is often not totally successful. Many dogs are left untreated and remain lame for the rest of their life.
Veterinarians have long suspected the condition is at least partly inherited, due to its over-representation in some breeds, and the fact that dogs tend to develop it in both legs.
With a grant from the AKC Canine Health Foundation, researchers at the University of Wisconsin compared DNA from more than 1,000 Labrador Retrievers with and without cruciate ligament rupture in an effort to find the responsible genes. This proved to be a difficult task, as no single gene appeared as the culprit. Instead, they found that the genetic risk of having a cruciate ligament rupture depends on the thousands of genetic variants that together account for a 62% influence on whether a Lab will develop the injury in its lifetime. The other 38% of risk depends on environmental influences such as the dog’s body weight, conditioning, and as yet unidentified factors.
Based on these results, a DNA test using either cheek swabs or blood samples is now available that can tell you if a Labrador Retriever is at risk for cruciate ligament rupture. It’s not a definite yes/no prediction but using the test on the 1,000 Labs already tested yielded a 98% prediction accuracy.
The test is valuable to owners who may wish to take measures to protect their at-risk dog, for example by being careful to keep its weight down. It is also valuable to breeders as an aid to guide them towards breeding away from the condition. Note that because the condition is caused by thousands of genes, and because it is so widespread in the breed, removing affected or at-risk dogs from the breeding pool would be disastrous for overall breed heath. Also, because it results from the complex interaction between so many genes, it doesn’t act as a simple dominant or recessive.
The test is currently only available for Labrador Retrievers, although the same group of researchers is now working on validating it or a similar test for Rottweilers and Newfoundlands. It is expensive ($250) compared to most other single-condition DNA tests (but cheap compared to treating the condition). That’s because unlike most tests, it’s testing not one gene location but thousands of them. The test will be available through the School of Veterinary Medicine, University of Wisconsin-Madison. For more information contact firstname.lastname@example.org.
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