Degenerative Myelopathy Research approved by AkC/CHF. September 2006
Phenotypic Characterization and Mapping Genes Associated with Canine Degenerative Myelopathy in the boxer dog
Joan R. Coates, DVM, MS, Diplomate ACVIM-Neurology, Associate Professor Veterinary Neurology/Neurosurgery, College of Veterinary Medicine, University of Missouri
Degenerative myelopathy (DM) is a disease of the spinal cord causing progressive paraparesis most commonly in the German Shepherd Dog. A high disease prevalence also exists in other breeds, such as Cardigan and Pembroke Welsh Corgis, Rhodesian Ridgebacks, and Boxer dogs. The increased risk in specific breeds suggests a significant genetic predisposition and adds power to mapping the genetic risk factor. The purpose of this proposal is to map genes associated with DM in the Boxer dog. We propose to characterize the phenotype in the Boxer dog using sequential antemortem neurodiagnostic testing, and neuropathology. A network of board-certified veterinary neurologists has been established to help diagnose dogs across the country. A small subset of 10 boxer dogs will be further characterized directly by the principal investigator, to determine if the phenotype is identical to that seen in Welsh Corgi.
Genome-wide association mapping will be performed to identify a genomic locus associated with DM in 50-100 affected and 50-100 old healthy boxers using the ~20,000 SNP array. If the same phenotype is seen in boxers as in Corgi and Rhodesian Ridgebacks as expected, disease haplotypes are likely to be shared between these breeds. We will thus fine map using boxers as well as smaller numbers of affected and control dogs from Welsh Corgi and Rhodesian Ridgebacks. We expect to narrow the region to contain only 1-2 genes. This project will allow for more rapid development of genetic tests for carrier and affected dogs of DM, which will enable the distinction of DM from other neurological disease enabling accurate choices of treatment.
Degenerative myelopathy (DM) is a degenerative spinal cord disease affecting, most commonly the older German Shepherd dog. Affected dogs show progressive rear limb weakness and eventually paralysis. A particularly high prevalence also exists in certain breeds, such as boxer, Cardigan and Pembroke Welsh Corgis and Rhodesian Ridgebacks, to suggest a genetic predisposition. Specifically, this study will characterize DM in the Boxer dog. Our goal is to identify the mutation for DM so that we can devise DNA tests that will detect carrier and affected dogs. We will use a new approach to identify genes that contribute to the increased risk for DM in Boxer dogs and disease-related breeds. This mapping strategy will determine the location of DM mutation on the dog chromosome and permit more rapid development of genetic tests for DM predisposition. We will then examine the genes at that chromosomal location to identify the DM mutation. We expect the results of this study to permit development of a genetic test, that can help determine carrier status and give a definitive diagnosis for dogs from neurological signs similar to DM. We expect this research to be applicable to several breeds.
The Rhodesian Ridgeback Club of the United States is a proud sponsor of this research.
Dr. Coates is accepting blood samples for DNA now on Rhodesian Ridgebacks presumptively diagnosed with degenerative myelopathy. While conformation of degenerative myelopathy via necropsy is desired, DNA on dogs presumptively diagnosed based on family history is also extremely valuable. For more information on sample collection and shipping go to: http://www.cvm.missouri.edu/neurology/dm/forms.html or contact Susan Ralston, H&G Senior Chair.
For those people who voluntarily collected DNA via cheek swabs on dogs with presumptive degenerative myelopathy in the past, we will be in contact with you soon as Dr. Coates will be able to use those samples in the later stages of the research.
To better understand the prevalence of degenerative myelopathy in our breed, in 2005 and part of 2006 the Rhodesian Ridgeback Club of the United States subsidized necropsy and pathology costs for owners and breeders who wanted a conclusive diagnosis on their Ridgeback presumptively diagnosed with the disease. The four cases subsidized were all confirmed for degenerative myelopathy.
Up until that point, our health survey had reflected a low incidence of degenerative myelopathy in Rhodesian Ridgebacks, with nine cases reported between 1986 and 1991. This relatively low number is attributed to most people not following through to confirm the diagnosis because of the necropsy procedure is not only complex and expensive, but also emotionally taxing. However, the additional cases subsidized by RRCUS raised the total incidence by 44 percent, suggesting a higher prevalence of the disease than previously thought.
Research in degenerative myelopathy is arduous primarily because of the late onset of the disease and the fact that usable DNA samples are often not available. Usable DNA would be samples from affected dogs (confirmed via necropsy) as well as immediately family members such as sire, dam, siblings, grandparents and offspring. Because the disease most often strikes in a dog’s twilight years, many of these family members are often already deceased when symptoms occur. Researchers predict it will take 10 years before decisive research can be done in this area -- and that is only if they get the appropriate DNA.
For this reason, the RRCUS Health & Genetics Committee has undertaken a Degenerative Myelopathy Initiative to bank as much DNA as possible on individual dogs as well as extended families. Here is how you can help:
For owners: If your veterinarian feel your Ridgeback may have degenerative myelopathy, please contact Senior H&G Chair Susan Ralston for DNA swabs and more information about this program. DNA collection requires you to simply roll a small swab inside the dog’s cheek, and is quick and non-invasive. The DNA you collect could be very useful for future research.
For breeders: If you have produced degenerative myelopathy (presumed or confirmed) or if you know of an occurrence in your line’s ancestry (presumed or confirmed), we strongly encourage you start collecting DNA now on all dogs from that line and continue to collect DNA on subsequent generations. The only way we can collect meaningful samples on large family groups where DM has occurred is before the DM manifests. The goal of this program is to have the DNA available if and when a case of DM appears, at which point we can assist you in having the diagnosis confirmed.
You can start this process easily by entering all your dogs and subsequent generations in the Rhodesian Ridgeback Comprehensive Health Survey and elect to participate in DNAah. If you prefer, you can contact the Senior Chair of the H&G Committee, Susan Ralston.