Explanation of Optional Tests

Report by the ASSA Research Advisory Committee, Fall 2020
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].  The required evidence of association between the genetic mutation and actual spinal cord evaluations has been proven in Shelties and at least 16 other breeds [1].

Degenerative myelopathy DNA test results submitted to OFA through 2019 include 251 Shelties. Approximately 86% were normal (G/G), 12% were carriers (G/A), and 2% were homozygous (A/A) for the mutation. In a 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. 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, or it wasn’t recognized as DM. 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 symptoms suggestive of DM. The symptoms are not in themselves diagnostic, and dogs exhibiting them may alternatively be suffering from treatable ailments, including hip dysplasia and intervertebral disc disease [4]

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.” [4,5]

Two videos of the same Sheltie with DM can be seen at the following links: https://youtu.be/2hfFJtCZNJA and https://youtu.be/mc4pt3cxz5Y.  As noted above the symptoms exhibited by this dog, are not in themselves definitive for DM.  Additional testing and evaluation by a veterinarian are required to determine the cause of such symptoms.

* 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://ofa.org/degenerative-myelopathy/

[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] Fiszdon K,  Gruszczyńska J, Siewruk K: Canine Degenerative Myelopathy – pathogenesis, current diagnostics possibilities and breeding implications regarding genetic testing.  Acta Sci. Pol. Zootechnica, vol 19, pp. 3‒10, 2020.  https://asp.zut.edu.pl/2020/19_1/asp-2020-19-1-01.pdf

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

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 several DNA testing laboratories.

British researchers have identified a mutation that causes a different form of PRA in Shetland Sheepdogs in the UK called BBS2-PRA [2,3].  Along with PRA, affected dogs have physical characteristics that include an upturned nose, an unusual coat texture which is wavy, and dental defects (Figure 1).  The condition is comparable to a syndrome in humans called Bardet Biedl syndrome.

Figure 1 - Sheltie with Bardet Biedl syndrome.  Image from reference #3.

At least one other form of PRA, Slow Progressing Retinopathy (SPR), has been diagnosed in Shelties in Norway [4]. 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.

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] UK’s largest canine genome bank leads to breakthrough for Shetland Sheepdogs, Vet Practice, 2020. https://veterinary-practice.com/news/2020/uks-largest-canine-genome-bank-leads-to-breakthrough-for-shetland-sheepdogs

[3] Hitti-Malin RJ, Burmeister LM, Lingaas F, et.al.: A Missense Variant in the Bardet-Biedl Syndrome 2 Gene (BBS2) Leads to a Novel Syndromic Retinal Degeneration in the Shetland Sheepdog. Genes 2021, 12, 1771. https://doi.org/10.3390/genes12111771

[4] 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

A lance upper canine tooth (also known as maxillary canine tooth mesioversion (MCM) or rostrally-displaced maxillary canine tooth) is a condition in which an upper canine tooth points forward toward the nose instead of downward.  Mutations of two genes that are associated with the inheritance of lance canine teeth and smaller size have been identified [1].  On average, Shelties with lance canine teeth were 1 inch shorter and 6 pounds lighter than those with normal canine teeth.  In the study, 88% of the dogs with 2 copies of the risk alleles of both genes had lance canine teeth.

One of the variant genes, FTSJ3, had a larger effect on lance canine teeth and a DNA test for that is available.*

To learn more about lance canine teeth, the test and how to use it, go to the following links: Lance canine teeth description  and Lance canine tooth research & breeder advice.

[1] Abrams S, Hawks A, Evans J,: Variants in FtsJ RNA 2′-O-Methyltransferase 3 and Growth Hormone 1 are associated with small body size and a dental anomaly in dogs.  PNAS: 117, 40 24929-24935, 2020. https://www.pnas.org/content/117/40/24929

*As of November, 2020, the DNA test (MCM - lance canine tooth susceptibility) is offered by VetGen.  Other DNA testing laboratories may eventually offer the test.

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.

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.

Many congenital cardiac defects have a genetic component, and nearly all common ones produce audible murmurs that can be detected by a veterinarian using a stethoscope. Although not common in Shelties, such defects have been found in the breed. OFA certification for the cardiac database is primarily based on examination by a veterinarian using a stethoscope. Because some veterinarians are more experienced at detecting subtle murmurs than other veterinarians, the ASSA Research Advisory Committee stipulated that the examination must be performed by a board certified veterinary cardiologist or internal medicine specialist. Dogs must be 12 mos. of age to receive a certification number. More information can be obtained at the following link: https://www.ofa.org/diseases/other-diseases/cardiac-disease.

Dental exam by licensed veterinarian to certify full dentition. https://www.ofa.org/diseases/other-diseases/dentition-database

Disease Database Reports for the above can be found on the OFA website at: https://www.ofa.org/diseases/breed-statistics