Degenerative Myelopathy DNA Test

Report by the ASSA Research Advisory Committee, March 2015
Degenerative myelopathy (DM)* is an adult-onset degenerative neurological disease affecting the spinal cord of many breeds of dogs. Early clinical signs include incoordination (or clumsiness) and abnormal reflexes of the hind legs. The condition gradually increases in severity leading to paralysis and eventually to euthanasia. A genetic mutation has been found that is strongly associated with DM in dogs, and a DNA test is commercially available. (A similar genetic mutation has been found in humans with amyotrophic lateral sclerosis, Lou Gehrig’s disease.) An explanation of the test results can be found on the Orthopedic Foundation for Animals (OFA) website [1]. Basically, a dog that is tested as normal (G/G) or heterozygous carrier (G/A) is much less likely to develop the condition than homozygous mutant dogs (A/A) [2]. Degenerative myelopathy “appears to be an incompletely penetrant autosomal recessive disease.” [3]. From the OFA website, a dog that is “…homozygous A/A, with two mutated copies of the gene, is at risk for developing Degenerative Myelopathy (DM). Although almost all dogs in the research study with confirmed DM have had A/A DNA test results, recent evidence suggests that there are other causes of DM in some breeds” [1]. For example, an affected Bernese Mountain Dog was found to have a different mutation in the same gene [2]. “In addition, not all dogs testing as A/A have shown clinical signs of DM. DM is typically a late onset disease, and dogs testing as A/A that are clinically normal may still begin to show signs of the disease as they age. Some dogs testing A/A did not begin to show clinical signs of DM until they were 15 years of age. Research is ongoing to estimate what percentage of dogs testing as A/A will develop DM within their lifespan. At this point, the mutation can only be interpreted as being at risk of developing DM within the animal's life. For dogs showing clinical signs with a presumptive diagnosis of DM, affected (A/A) test results can be used as an additional tool to aid in the diagnosis of DM. Dogs testing At-Risk (A/A) can only pass the mutated gene on to their offspring” [1].

“Although any dog can be tested for (the mutation associated with) DM, it is possible that the genetic background that predominates in some breeds prevents the development of symptoms even in dogs testing affected (at risk). At this time, we are reluctant to recommend (DNA) testing for members of breeds where the University of Missouri has not yet proven susceptibility to DM through microscopic examination of spinal cords from deceased dogs that exhibited symptoms of the disease. At this time the required evidence of association between the genetic mutation and actual spinal cord evaluations has only been proven in the breeds listed” [1]. Shelties and 16 other breeds are on that list.

Degenerative myelopathy DNA test results submitted to OFA through December, 2014 include only 21 Shelties. Approximately 66% were normal (G/G), 28% were carriers (G/A), and 5% were homozygous (A/A) for the mutation. In the 2014 publication, 58 Shelties were tested with 41 (71%) being normal, 10 (17%) heterozygous and 7 (12%) homozygous. The frequency of the allele was 0.21. [2] It is likely that some of the dogs included in the OFA database were also included in the research report. At this time, too few Shelties have been tested to know what the true frequency of the mutation is, and more testing would help determine this. In spite of the apparent frequency of the mutation, there have not been many reports of DM in Shelties, so it is possible that the onset of symptoms in most Shelties occurs so late that most at-risk dogs do not live long enough for the disease to be manifested. It is good that more breeders and veterinarians are now aware that DM can occur in Shelties and that a DNA test can be done to help confirm the diagnosis in Shelties with signs suggestive of DM.

A good discussion on how to use the test is found on the University of Missouri-Columbia, College of Veterinary Medicine website concerning DM and specifically the section “Using the DNA Test” where it is stated “We recommend that dog breeders take into consideration the DM test results as they plan their breeding programs; however, they should not over-emphasize this test result. Instead, the test result is one factor among many in a balanced breeding program.” [4]

* In the past, the abbreviation “DM” was used by Sheltie owners to refer to Dermatomyositis. Since the same abbreviation has since been used to refer to Degenerative Myelopathy, “DMS” is now used to refer to Dermatomyositis. The two conditions are not related.

[1] https://www.ofa.org/diseases/dna-tested-diseases/dm

[2] Zeng R, Coates JR, Johnson CG, et al: Breed Distribution of SOD1 Alleles Previously Associated with Canine Degenerative Myelopathy. JVIM, vol.28, pp. 515–521, 2014. http://onlinelibrary.wiley.com/doi/10.1111/jvim.12317/full

[3] Awano T, Johnson GS, Wade CE, et al: Genome-wide association analysis reveals a SOD1 mutation in canine degenerative myelopathy that resembles amyotrophic lateral sclerosis. PNAS, vol. 108, pp 2797-2799, 2009. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2634802/

[4] http://www.caninegeneticdiseases.net/DM/testDM.htm

Patellar Luxation Database

The patella, or kneecap, is part of the stifle joint (knee). In patellar luxation, the kneecap luxates, or pops out of place, either in a medial or lateral position and may cause lameness. Patellar luxation is not common in Shelties, but can occur. Of dog breeds having 50 or more patellar luxation evaluations submitted to OFA, Shetland Sheepdogs rank 40th of 122 breeds. As of December, 2015, 162 Shelties have been evaluated with 96% being normal.

More information about patellar luxation, how to have a dog tested for it and register the results see: https://www.ofa.org/diseases/other-diseases/patellar-luxation.

Progressive Retinal Atrophy

Progressive retinal atrophy (PRA) is progressive retinal degeneration that causes visual impairment and eventual blindness. There are many different forms of PRA. It has been diagnosed in over 100 breeds, and at least 22 mutations have been found in 50 or more breeds. The age of onset and rate of progression varies. Night blindness is often the first sign of PRA noticed by owners.

Norwegian researchers have identified a mutation that causes early PRA in Shetland Sheepdogs in which the average age of onset is 5 years [1]. A DNA test, CNGA1-PRA, for this disease is offered by OptiGen.

At least one other form of PRA, Slow Progressing Retinopathy (SPR), has been diagnosed in Shelties in Norway [2]. The progression of this form is much slower and some vision is preserved even in older Shelties. The genetic mutation for the SPR form has not been identified. The mode of inheritance for both forms is likely to be autosomal recessive. OptiGen is supporting research to find genetic mutations on other forms of PRA and has a “Free DNA” testing program.

PRA appears to be uncommon in American Shelties, but breeders should be vigilant and continue having ophthalmic examinations done on older dogs.

[1] Wiik AC, Ropstad EO, Ekesten B, et al. : Progressive retinal atrophy in Shetland sheepdog is associated with a mutation in the CNGA1 gene. Animal Genetics; 46, 515-541, 2015. http://onlinelibrary.wiley.com/doi/10.1111/age.12323/full[2] Karlstam L, Hertil E, Zeiss C, et al.: A slowly progressive retinopathy in the Shetland Sheepdog. Veterinary Ophthalmology; 14, 227–38, 2011. http://onlinelibrary.wiley.com/doi/10.1111/j.1463-5224.2010.00866.x/abstract