Dr Joan Coates & Dr Gary Johnson & associates (University of Missouri) in collaboration with Drs Claire Wade & Kirsten Lindblad-Toh & associates (Broad Institute at MIT) identified a mutation that is the primary risk factor for Degenerative Myelopathy (DM) in many breeds of dogs. A DNA test for this disorder has been available since May 2008. DM is a disease which causes spinal cord deterioration and progressive loss of function. Clinical signs begin to appear in older dogs – most are 8-10 yrs old or older, but onset at age 7 and as late as 15 yrs has been documented. Onset and progression of clinical signs is subtle, and the dog is not painful. The first clinical signs typically observed are dragging of the hind toes and hind limb weakness, progressing over several months to muscle wasting and a complete loss of control of hind limbs, at which point most owners opt for euthanasia for their dog. The mutation found to be responsible for DM in dogs is the equivalent of the most common inherited form of ALS (amyotrophic lateral sclerosis), or Lou Gehrig’s disease, in humans. The research team is collaborating with researchers from the ALS Foundation to try to develop a treatment that may be brought to clinical trial in dogs, and eventually could hold promise for humans as well.
The mutation was originally discovered in Boxers and Pembroke Welsh Corgis, and has now been shown to be present in over 110 breeds, from toy to giant breeds and representing all variety groups, and in mixed breed dogs as well. Post-mortem examination of spinal cord sections have been recruited from dogs with clinical signs of DM, and the microscopic changes in the spinal cord which are typical of DM have been documented in over 25 breeds and mixed breed dogs. While some breeds have a much higher prevalence of this disease than others, it appears that DM can appear in any breed or mix.
The DNA test is available through the Orthopedic Foundation for Animals (OFA), and can be ordered online using their secure Online Store. The test clearly shows dogs who do not have the mutation (normal), dogs who have one normal copy of the gene and one mutated copy of the gene (carrier), and those dogs with 2 mutated copies of the gene (affected/at risk). It is important to understand that not all dogs testing “at risk” will develop clinical signs of DM within their lifetime. Because of the wide variation of age of onset, there are genetically “at risk” dogs that may die from other causes before clinical signs of DM appear. Additional research is underway to develop a method for determining more precisely which dogs with the “at risk” genetic profile will develop symptoms relatively early (8-10 yrs) and which will remain symptom-free until a more advanced age (14-16 yrs+), and could potentially die earlier from other causes with no clinical signs of DM observed.
Thru the end of 2011, we have DNA-tested 46 Jack Russell Terriers for the DM mutation. Some of these were chosen randomly from our existing DNA collection as part of a screen of all breeds for this mutation, some were sent by veterinarians or neurologists with a client dog suspected of having DM signs, and some were from owners choosing to test their dogs. Of these 46 dogs, 25 tested NORMAL, 9 tested CARRIER, and 12 tested AFFECTED/AT RISK. This is a higher frequency of the mutation than we had expected to see in JRTs. The sample pool may be somewhat biased towards affected dogs due to the clinical cases being sent in by vets and neurologists, but the fact that clinical cases are appearing shows quite clearly that DM does exist as a real disease in this breed. While not reason for panic, it would be wise to test all dogs being considered or used for breeding, so that the DM test results can be included as breeding choices are being made. Certainly the dogs making a major genetic contribution to the breed (widely used stud dogs, and bitches producing multiple litters) should be tested so that the prevalence of the mutation in the overall population does not inadvertently increase. With careful and wise use of the test, overall risk of DM can be reduced while retaining the essential good qualities of the breed. Dogs testing carrier, and even affected/at risk CAN be used in a breeding program to keep all their other positive traits in the breed – if bred to a mate that has been DNA-tested normal, resulting pups can be no worse than carrier. Using the test wisely, genetic diversity and positive breed traits can be retained while reducing the incidence of the DM mutation in the breed. With this information, breeders can make informed choices and avoid producing puppies destined to be at risk for DM.
For additional information on the disease, discovery, research, and recommendations, please see the information on our website – go to www.CanineGeneticDiseases.net, in the DEGENERATIVE MYELOPATHY section. Testing information is found in the SAMPLE SUBMISSION portion of the website. We are interested in blood samples from dogs that show clinical signs of DM. A file with instructions and submission form is found in this section of the website. For general screening of any dog, including breeding stock and other young, healthy dogs, as well as dogs with clinical signs if the owner prefers to use this method, testing kits can be ordered through OFA – go to www.OFFA.org, look to the left side for the “OFA/MU DNA TESTS” link, and then follow the links to order an OFA DNA test. OFA will send instructions and a kit to collect DNA by cheek swab, the test is run in the University of Missouri lab, and results reported to owners by OFA.
If there are additional questions not answered by the website, contact information is listed below. We hope that this news will be shared with the entire JRT community, and that availability of this test will be seen as an opportunity toward improved overall health for the breed.
Animal Molecular Genetics Laboratory
University of Missouri – College of Veterinary Medicine
321 Connaway Hall
Columbia, MO 65211