Understanding the Limitations of DNA Testing in Detecting Canine Degenerative Myelopathy (DM) – Abhai Kaul.

Introduction
Canine Degenerative Myelopathy (DM) is a neurodegenerative disease with implications for many dog breeds. While DNA tests targeting the SOD1 mutation identify genetic predisposition, studies show these tests fall short as standalone diagnostic tools. The following article delves into the numbers and research to find evidence, challenges, and practical implications surrounding the use of DNA tests for DM detection.
Why DNA Tests Are Not Definitive
Incomplete Penetrance and Variability
Genetic predisposition does not equate to disease manifestation. For instance:
- A study in the UK showed 16% of young GSDs (<6 years) were homozygous for the SOD1:c.118A mutation but exhibited no clinical signs, (Genome-wide DM analysis reveals a SOD1 mutation in Canine Degenerative Myelopathy resembles Amyotrophic Lateral Sclerosis.)
- In older GSDs (>8 years) showing ataxia, 42% (21/50) were homozygous for the mutation. However, among senior dogs with non-neurological issues, 0% (0/50) showed the A/A genotype.
These findings highlight the incomplete penetrance of the SOD1 mutation, making DNA tests insufficient to determine if a dog will develop clinical DM.
Confounding Factors and Overlap with Other Conditions
DM shares overlapping clinical signs with other conditions, such as Degenerative Lumbosacral Stenosis or Intervertebral Disc Disease. Dogs may carry the mutation without presenting symptoms, or symptoms might stem from unrelated disorders.
Additionally, other factors like co-morbidities or environmental influences likely interact with the genetic predisposition, complicating interpretation of results.
Lack of Definitive Ante-Mortem Testing
DM diagnosis typically relies on exclusion of other conditions and post-mortem histopathology to confirm axonal degeneration patterns in the spinal cord. DNA tests alone cannot fulfill this diagnostic criterion.
Geographic and Breeding Considerations
Mutation frequencies and penetrance rates vary across studies:
- North America: In an earlier cohort, 96% of DM-affected dogs across five breeds were A/A homozygous, but in GSDs specifically, this ranged from 4/5 in affected individuals to 7/120 in controls.
- UK: In another study, allele frequency for SOD1:c.118A was 0.38 overall, with 16% homozygous (A/A), and mutation prevalence in older, healthy dogs reveals a SOD1 mutation in canine degenerative myelopathy that resembles amyotrophic lateral sclerosis
Breeding programs face challenges balancing the need to reduce mutation prevalence while avoiding loss of genetic diversity. In breeds like the Pembroke Welsh Corgi or Boxer, where the mutation frequency exceeds 70%, restrictive breeding could harm the breed’s overall genetic health.
Here are the visualizations based on the data:Â

Bar Chart: Genotype Frequency Across Populations
– This chart illustrates the frequency of A/A, G/A, and G/G genotypes in different GSD populations:
– Young dogs (<6 years)
– Older, ataxic dogs (>8 years)
– Older, neurologically healthy dogs (>8 years)
Pie Chart: Allele Frequency of SOD1 Mutation
– This pie chart shows the overall proportions of the G and A alleles in the UK GSD population (SOD1:G at 62% and SOD1:A at 38%).
These visual aids emphasize the variability in genotypic expression and allele distribution, further supporting the discussion of incomplete penetrance and inconclusiveness of genetic testing for definitive DM prediction.
Recent research on Degenerative Myelopathy (DM) in dogs and its connection to oxidative stress provides limited but significant findings.
Degenerative myelopathy is believed to involve complex mechanisms, including genetic predispositions (such as mutations in the SOD1 gene) and potential contributions from oxidative stress. Superoxide dismutase (SOD) enzymes play a key role in neutralizing reactive oxygen species (ROS), and mutations in the SOD1 gene might disrupt this process. However, the exact relationship between oxidative stress and DM remains unclear.
Some studies suggest that while oxidative damage is a component of other neurodegenerative disorders, there is currently insufficient evidence supporting its direct role in DM. For instance, researchers have found no significant alterations in vitamin E levels (a known antioxidant) in dogs with DM, nor any therapeutic effect from vitamin E supplementation. Other indicators of oxidative stress, such as F2-isoprostanes (markers of lipid peroxidation), have shown varying relevance in spinal cord-related oxidative damage but are not consistently elevated in dogs with Degenerative Myelopathy (DM).
Oxidative stress pathways remain an area of ongoing research, and future studies might reveal stronger links or uncover potential treatments involving antioxidants. For now, therapeutic strategies for DM mostly focus on supportive care rather than addressing oxidative stress.
Practical Implications for Diagnosis
Diagnostic Reliability
DNA testing should be viewed as part of a larger diagnostic strategy. While homozygosity for the SOD1 mutation raises the suspicion for DM, confirmatory diagnostics like MRIs or post-mortem spinal histopathology are necessary to exclude similar conditions.
Tailored Breeding Practices
Careful genetic screening is advised to reduce mutation prevalence without compromising genetic diversity. Breeding carriers to outcross dogs instead of eliminating them altogether offers a balanced approach.
Potential Nutritional Interventions to Support SOD1 Function
Emerging research highlights specific nutritional compounds with antioxidant properties as promising tools to mitigate oxidative damage. While evidence remains preliminary, these compounds have shown potential efficacy in maintaining cellular health in neurodegenerative conditions.
Exploring the Promise of Nutritional Support for SOD1 Dysfunction in Degenerative Myelopathy
SOD1’s Role in Oxidative Stress and Its Link to Canine DM
The SOD1 gene codes for superoxide dismutase, a vital enzyme responsible for neutralizing harmful reactive oxygen species (ROS). In dogs with DM, mutations in the SOD1 gene disrupt this process, leading to oxidative stress—a mechanism similarly implicated in amyotrophic lateral sclerosis (ALS) in humans. As scientific understanding of DM grows, parallels to ALS treatment strategies open avenues for potential interventions targeting oxidative damage.
1. Acai Extract
Rich in polyphenols, Acai has demonstrated antioxidant properties that combat oxidative stress. In contexts like ALS research, antioxidants have been linked to slowed disease progression in experimental models. Though canine-specific studies are needed, its role in reducing oxidative damage presents a compelling adjunctive approach.
2. Resveratrol
Resveratrol enhances mitochondrial function and may activate SOD1 enzyme activity, potentially offsetting the effects of a mutation. Studies on ALS models have shown this compound to have neuroprotective effects, offering a promising parallel for its application in DM.
3. Copper and Zinc
As essential cofactors for SOD1 activity, these trace minerals are crucial in supporting enzyme functionality. Their supplementation, however, requires careful monitoring to avoid toxicity. In canine diets, evidence suggests that balanced mineral levels can influence overall antioxidant capacity, laying the foundation for further exploration in Degenerative Myelopathy (DM)-specific management.
4. Taurine
Studies reveal that taurine can boost antioxidant systems by directly scavenging ROS. While this has not been directly linked to SOD1 mutations, taurine’s antioxidative and neuroprotective effects suggest a potential benefit for dogs with Degenerative Myelopathy (DM).
Implications: Perceived and Unperceived
Further, restrictive breeding within the German Shepherd Dog (GSD) population poses significant challenges in a breed already governed by numerous regulations related to appearance, health, and working abilities. While such regulations aim to ensure standardization and quality, excessive restriction, especially genetic limitations like only allowing breeding of dogs with specific genetic markers or results, can create broader complications. Below are the key adverse issues such breeding restrictions might exacerbate:
1. Reduced Genetic Diversity
Restrictive breeding narrows the gene pool by excluding dogs based on certain physical traits, genetic markers, or performance criteria. For an already regulated breed like the GSD, this could lead to several long-term consequences:
- Increased Inbreeding: Restrictive policies force breeders to reuse limited breeding stock, increasing the inbreeding coefficient and elevating the risk of recessive genetic disorders becoming more prevalent.
- Loss of Vitality: A smaller gene pool limits the natural resilience of a population to disease, environmental pressures, and mutations, potentially resulting in a weaker breed overall.
A landmark study in dogs linked the narrowing of genetic diversity in several breeds to heightened predisposition to diseases such as cancer, autoimmune diseases, and cardiac issues.
2. Overemphasis on Visual or Genotypic “Perfection”
- Phenotypic Standards and Overbreeding Specific Lines: German Shepherds are already affected by controversies surrounding show and working line splits. For example, an overemphasis on a sloped back or angulation may further exclude healthy dogs from breeding, forcing breeders to compromise health for a visual standard.
- The False Promise of Genetic Markers: For diseases like Degenerative Myelopathy (DM), Club and Veterinarian pushed testing may inadvertently label carriers as “unfit” for breeding despite unclear penetrance rates of the SOD1 mutation. As a result, dogs excluded solely based on a genetic test could lead to breeding stock depletion without addressing overall breed health.
3. Behavioral & Functional Deterioration
Restrictive breeding policies risk prioritizing specific health or physical traits over temperament and working capabilities. German Shepherds are prized for their intelligence, trainability, and roles as working dogs. A narrowed breeding scope has already led to:
- Behavioral Issues: Over-reliance on a limited pool of breeders may perpetuate heritable aggression, timidity, or stress-reactivity traits, which can emerge from breeding programs focused too narrowly.
- Functional Decline: Excessive regulation risks straying from the breed’s original purpose as a versatile working dog. Similar declines have been seen in other breeds such as, Bulldogs and Boxers, where stringent appearance standards compromised functionality.
4. Increased Ethical and Economic Pressures on Breeders
- Economic Viability: For small-scale breeders, stringent restrictions can make compliance financially and logistically unsustainable. This favors larger breeders, who sacrifice ethical breeding for volume production.
- Ethical Breeding Dilemmas: Mandatory elimination of dogs for minor imperfections, or exclusion based on unproven genetic conditions, could create pressure for breeders to shy away from potentially great breeding partners.
5. Unintended Global Impact: Diverging Standards
Restrictive self imposed policies by breeders at a national or international level risk fragmenting the GSD community internationally. With already differing approaches to show lines, working lines, and health prioritization between regions (e.g., Germany, the United States, South Asia), new genetic mandates could deepen these divides, threatening global breeding collaboration and further separation of populations.
Proposed Solutions to Counteract Restrictive Breeding
- Balanced Breeding Programs: Instead of outright phasing out of carriers for certain mutations, e.g., SOD1 for Degenerative Myelopathy (DM), responsible pairing of carriers with non-carriers can preserve genetic diversity while lowering the risk of producing affected offspring.
- Emphasis on Phenotype and Health: Regulatory bodies must emphasize overall health, longevity and functional fitness rather than rigid adherence to arbitrary visual or genetic traits.
- Cross-Collaboration Among Breeders Globally: Shared knowledge and genetic resources among international GSD communities through various bloodlines can help prevent over-reliance on restricted gene pools within certain familial types in breeding populations.
Conclusions
Although DNA tests targeting the SOD1 mutation offer an insight into Degenerative Myelopathy (DM) risk, they are not definitive in detecting or predicting the disease due to incomplete penetrance and confounding variables. These tools are best utilized in conjunction with clinical evaluations and careful breeding strategies to ensure informed decision-making without jeopardizing canine genetic diversity.
The natural compounds and trace minerals outlined above offer exciting possibilities for complementing conventional DM management strategies. While current research underscores their antioxidative and neuroprotective properties, further studies—particularly in canine-specific models of DM—are necessary to confirm their efficacy. These approaches, coupled with advancements in gene therapy and understanding of the SOD1 pathway, provide a beacon of hope for dogs and their owners battling this progressive disease.
Restrictive breeding practices pose serious threats to the health, temperament, and future of the German Shepherd Dog. It is critical for policymakers, breeders, and breed enthusiasts to strike a balance between standardization, genetic health, and preserving the genetic diversity of this iconic breed.
References:
https://www.ncbi.nlm.nih.gov/m/pubmed/20732599/?i=2&from=/19188595/related
https://cgejournal.biomedcentral.com/articles/10.1186/2052-6687-1-10
http://www.pnas.org/content/106/8/2794.full.pdfi
https://pmc.ncbi.nlm.nih.gov/articles/PMC5510473
Stress in the Spinal Cord of Dogs and Cats | Veterian Key https://veteriankey.com/stress-in-the-spinal-cord-of-dogs-and-cats/
Oxidative stress, antioxidants, and assessment of oxidative stress in dogs and cats in: Journal of the American Veterinary Medical Association Volume 231 Issue 5 https://avmajournals.avma.org/view/journals/javma/231/5/javma.231.5.714.xml
Stress in the Spinal Cord of Dogs and Cats | Veterian Key https://veteriankey.com/stress-in-the-spinal-cord-of-dogs-and-cats/
Oxidative stress, antioxidants, and assessment of oxidative stress in dogs and cats in: Journal of the American Veterinary Medical Association Volume 231 Issue 5 https://avmajournals.avma.org/view/journals/javma/231/5/javma.231.5.714.xml
1. PubMed: SOD1 Gene and ALS
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3. Zinc and Copper’s role in oxidative stress mitigation