A literature review of current published studies.
We comissioned this review, done by Ashley Smith, MS, LCGC
Licensed Certified Genetic Counselor
Genetic Test results are easy to misinterpret.
Blue House Cavaliers breeding dogs are genetically tested for a variety of diseases. When it comes to Degenerative Myelopathy, a test result of TWO copies of the SOD1 gene is often called “AFFECTED” by the companies who sell DNA tests to consumers.
We disagree with that label, which causes unnecessary fear. We asked a genetic counselor to research all available information about DM and Cavaliers. Our 4 questions were:
- How often are Cavaliers actually diagnosed with Degenerative Myelopathy?
- Does a test result of two copies of the mutation mean that my Cavalier will get Degenerative Myelopathy?
- Is the presence of the mutation a risk factor or a diagnosis?
- What are the implications for Cavalier King Charles Spaniel breeders?
Here is what she found!
How many King Charles Cavalier Spaniels are diagnosed with DM?
- Overall frequency of DM and approximate age of disease onset in King Charles Cavalier Spaniels are unreported/unknown. Generally, it appears to be at a lower prevalence than other dog breeds
- DM appears to be more common in German Shepherd dogs, Rhodesian Ridgebacks, Pembroke and Cardigan Welsh Corgis, Boxers, and Chesapeake Bay Retrievers.
- Across all 432,467 dogs that presented to veterinary teaching hospitals that contributed to the Veterinary Medical Databases between January 1, 1990 – December 31, 1999, the overall prevalence of DM was 0.19%.
- The dog breed with the highest prevalence of DM was German Shepherd, with a prevalence of 2.01%
- Cavalier King Charles Spaniels were not listed in the study
Does having two A mutations in the SOD1 gene mean my King Charles Cavalier Spaniel will get DM? Are there specific risk numbers?
- No. Current research suggests that the A/A genotype (homozygous for the A mutation in the SOD1 gene) is a genetic risk factor for DM, but does not guarantee that the dog will develop DM. More research needs to be done to determine how this specific gene mutation affects King Charles Cavalier Spaniels specifically.
- More research studies with a bigger sample size of King Charles Cavalier Spaniels are needed to determine more definitive risk numbers. Unfortunately, there are not any DM risk numbers available specific to King Charles Cavalier Spaniels based on SOD1 gene mutations.
- Right now, having the SOD1 A mutations can only be interpreted as being at risk of developing DM within the dog’s life.
Are the SOD1 A gene mutations a risk factor or diagnosis?
- At this point in time, it seems more like a genetic risk factor for DM. Current research suggests that having two A mutations in SOD1 may increase the risk for DM in King Charles Cavalier Spaniels, but we don’t know by how much and there are likely other factors at play such as different gene mutations, lifestyle factors, and environmental factors which can all vary from breed to breed.
- A definitive diagnosis of DM is made by examination of the spinal cord after the dog passes away. A clinical diagnosis of DM can be made based on symptoms, imaging tests, and by ruling out other causes
- For dogs showing clinical signs with a presumptive diagnosis of DM, genetic testing for the SOD1 mutations can be used as an additional tool to aid in the diagnosis of DM
What are the breeding implications?
- “We recommend that breeders take into consideration the DM test results as they plan their breeding programs; however, they should not over-emphasize the test results. Instead, the test result should be one factor among many in a balanced breeding program.” – presented at the 2009 Annual Forum of the American College of Veterinary Internal Medicine in Montreal Canada June 3-6, 2009.
Want More?
That’s only page one of her NINE-page document. If you’d like to read the literature review in its entirety, please CONTACT ME, and I will send it to you.
Click this little triangle to read all the references.
Coates, J. R., March, P. A., Oglesbee, M., Ruaux, C. G., Olby, N. J., Berghaus, R. D., O’Brien, D. P., Keating, J. H., Johnson, G. S., & Williams, D. A. (2007). Clinical characterization of a familial degenerative myelopathy in Pembroke Welsh Corgi dogs. Journal of veterinary internal medicine, 21(6), 1323–1331. https://doi.org/10.1892/07-059.1
Awano, T., Johnson, G. S., Wade, C. M., Katz, M. L., Johnson, G. C., Taylor, J. F., Perloski, M., Biagi, T., Baranowska, I., Long, S., March, P. A., Olby, N. J., Shelton, G. D., Khan, S., O’Brien, D. P., Lindblad-Toh, K., & Coates, J. R. (2009). Genome-wide association analysis reveals a SOD1 mutation in canine degenerative myelopathy that resembles amyotrophic lateral sclerosis. Proceedings of the National Academy of Sciences of the United States of America, 106(8), 2794–2799. https://doi.org/10.1073/pnas.0812297106
Zeng, R., Coates, J. R., Johnson, G. C., Hansen, L., Awano, T., Kolicheski, A., Ivansson, E., Perloski, M., Lindblad-Toh, K., O’Brien, D. P., Guo, J., Katz, M. L., & Johnson, G. S. (2014). Breed distribution of SOD1 alleles previously associated with canine degenerative myelopathy. Journal of veterinary internal medicine, 28(2), 515–521. https://doi.org/10.1111/jvim.12317
AND NOW, TWO BIG PLAYERS HAVE SPOKEN UP.
FIRST: About two weeks after I built this webpage, GenSol Diagnostics made this statement on November 4th, 2024.
“Some mutations have a straightforward effect in that any dog within the affected breed that inherits the mutation is known to progress to the disease. An example of this type of mutation would be Neonatal Encephalopathy in Poodles. Other mutations are not as simple to predict disease progression due to either the genetic background or environmental factors. By genetic background, we are referring to the fact that different breeds may carry the same mutation but the rest of their DNA is different enough to prevent disease progression. An example of this type of mutation would be Degenerative Myelopathy. Many breeds test positive for this mutation but only certain breeds (German Shepherds, Boxers, Bernese Mountain Dogs, etc.) routinely succumb to the disease while other breeds that have the mutation never show symptoms.” –Genetic Tests are not always Disease Tests, Nov 4, 2024, https://www.gensoldx.com/genetic-tests-are-not-always-disease-tests/?utm_source=blog&utm_medium=email&utm_campaign=genetictestsarenotalwaysdiseasetests_11.4.24&mc_cid=60828dee8a&mc_eid=b5c25bb51b
SECOND: The American Kennel Club published this article on Nov 15, 2024.
Understanding Incomplete Penetrance in Canine Genetics: What Breeders Need to Know