Canine Degenerative Myelopathy DM Test Code 355
For Breeds*: American Eskimo Dog, Bernese Mountain Dog**, Borzoi, Boxer, Cardigan Welsh Corgi, Chesapeake Bay Retriever, German Shepherd dog, Golden Retriever, Great Pyrenees, Kerry Blue Terrier, Pembroke Welsh Corgi, Poodle (all varieties), Pug, Rhodesian Ridgeback, Shetland Sheepdog, Soft Coated Wheaten Terrier, Wire Fox Terrier
*These are breeds for which there is evidence of a strong correlation between the SOD1 mutation and clinical symptoms of Degenerative Myelopathy (DM). Upon request from the owner, OptiGen will perform the DM test for any breed NOT listed here.
**Two different mutations in the SOD1 gene can cause Degenerative Myelopathy in Bernese Mountain Dogs (BMD). A test for the second mutation, called DM-BMD, is expected to be available at OptiGen for BMDs in the near future.
Clinical signs/Disease Description:Canine Degenerative Myelopathy (DM) has been recognized for more than 35 years as a spontaneously occurring spinal cord disorder in older dogs, with age of onset ranging between 8 and 14 years. Initially thought to be specific to German Shepherds, DM has been diagnosed in many other breeds, being most prevalent in Pembroke Welsh Corgis, Boxers, Rhodesian Ridgebacks and Chesapeake Bay Retrievers.
Degenerative Myelopathy is characterized by a gradual degeneration of spinal reflexes and muscle weakness. The initial signs of DM typically include loss of coordination (asymmetric ataxia) in the hind limbs. The symptoms worsen with time when the affected dog can no longer support its weight in the hind limbs. The age of onset and the speed of disease progression is variable. Affected small breed dogs often develop DM at an older age and deteriorate more slowly than affected dogs of large breeds. Affected medium to large breed dogs can be difficult to manage and owners often elect euthanasia when their dog can no longer support weight in the hind limbs.
For owners and veterinarians it is important to make a distinction between progressive Degenerative Myelopathy and a variety of acquired compressive spinal cord diseases and injuries because the initial symptoms are similar but the outcome and the approach for treatment is very different.
DM Mutation Test:
A genetic test for DM was developed based on a mutation in the SOD1 gene that has been identified as a major genetic factor contributing to the development of DM in Pembroke Welsh Corgi, Boxer, Rhodesian Ridgeback, German Shepherd, and Chesapeake Bay Retriever . The mutation is widespread and has been detected in at least 124 dog breeds with the frequency of the mutation ranging from as high as 0.94 in the Wire Fox Terrier to as low as 0.01 in the Rat Terrier . There is strong evidence that homozygosity for the SOD1 mutation is highly associated with the development of DM: out of 115 dogs of various breeds with histologically confirmed DM 105 were homozygotes for the mutation, 8 were heterozygotes and only 2 were free of the mutation.
The DNA-based DM test allows to determine the genotype of a tested dog with respect to the SOD1 mutation as being:
Homozygous Normal - this dog has two copies of the normal gene and is likely to be free of the DM disease.
Carrier - this dog has one copy of the mutation and one copy of the normal gene. The chances that the dog will develop the disease are low.
Homozygous Affected - this dog has two copies of the mutated SOD1 gene and has a high risk of developing the disease during its lifetime.
The identified mutation in the SOD1 gene is a major factor contributing to the development of DM in many breeds. The DM test is effective for estimating relative risk of developing the disease by a given dog but it does not account for unknown genetic factors that influence the trait. There were instances of dogs with two copies of the SOD1 mutation that did not develop the disease, as there were cases when dogs clear of the mutation were diagnosed with DM (2).
The mode of inheritance of the SOD1 mutation is best described as autosomal recessive, meaning that dogs of both sexes have a much higher risk of developing the disease when they receive two copies of the mutated gene, one from each parent. For detailed recommendations on breeding strategies using results of OptiGen testing, please, refer to the Breeding Strategy Chart below.
Expected results for breeding strategies using the|
|Parent 2 Genotype|
|Normal/Clear||All = Normal/Clear||1/2 = Normal/Clear|
1/2 = Carrier
|All = Carrier|
|Carrier||1/2 = Normal|
1/2 = Carrier
|1/4 = Normal/Clear |
1/2 = Carrier
1/4 = Affected
|1/2 = Carrier|
1/2 = Affected
|Affected ||All = Carrier|
|1/2 = Carrier|
1/2 = Affected
|All = Affected|
This table highlights in yellow the breedings that will NOT produce DM-affected pups due to the presence of the SOD1 mutation, which is the major risk factor associated with the disease. These breedings include at least one parent proven "Normal/Clear" by the OptiGen DM test. All other combinations are at risk of producing DM-affected pups.
- Awano T, Johnson GS, Wade CM, Katz ML, Johnson GC, Taylor JF, Perloski M, Biagi T, Baranowska I, Long S, March PA, Olby NJ, Shelton GD, Khan S, O'Brien DP, Lindblad-Toh K, Coates JR. Genome-wide association analysis reveals a SOD1 mutation in canine degenerative myelopathy that resembles amyotrophic lateral sclerosis. Proc Natl Acad Sci U S A. 2009 106(8):2794-9.
- Zeng R, Coates JR, Johnson GC, Hansen L, Awano T, Kolicheski A, Ivansson E, Perloski M, Lindblad-Toh K, O'Brien DP, Guo J, Katz ML, Johnson GS. Breed Distribution of SOD1 Alleles Previously Associated with Canine Degenerative Myelopathy. J Vet Intern Med. 2014 Feb 13. doi: 10.1111/jvim.12317.