Understanding DM Test Results Through Bayes’ Theorem: Addendum – Abhai Kaul.

While DNA testing for Degenerative Myelopathy (DM) is a diagnostic tool in partially identifying genetic predisposition, it does not provide a definitive diagnosis. A dog testing “At Risk” (homozygous for the SOD1 mutation) means it carries two copies of the gene associated with DM, but it does not guarantee the dog will ever develop the disease.

Using Bayes’ Theorem, we can better understand the actual probability of a dog developing DM given a positive test result. The theorem is expressed as:

Baye's Theorem

Where:

  • P(A|B)  is the probability that a dog will develop DM given a positive test result.
  • P(B|A)  is the sensitivity of the test—how likely it is to detect the mutation in dogs that actually develop DM.
  • P(A)  is the prior probability of a dog developing DM in the population.
  • P(B)  is the overall probability of a positive test in the population.

Expanding Bayes’ Theorem for DM Testing

Since a positive test result ( B ) can occur whether or not a dog actually develops DM, we refine Bayes’ Theorem to account for both true positives and false positives:

Where:

  • P(B ~ A)  is the probability that a dog tests positive despite never developing DM (false positive rate).
  • P( ~ A)  is the probability that a dog will not develop DM.
Baye's Theorem

Applying This to DM Testing

From available data and anecdotal evidence, let’s assume:

  • P(A)  (Prior Probability of DM): Only a portion of “At Risk” dogs develop DM. If 20% actually show clinical symptoms, then  P(A) = 0.2 .
  • P(B|A)  (Test Sensitivity): The test is highly sensitive, detecting nearly all cases with the mutation. Assume  P(B|A) = 0.99 .
  • P(B|\sim A)  (False Positive Rate): Many dogs test “At Risk” but never develop DM. If 30% of those who never develop DM still test positive, then  P(B ~ A) = 0.3 .
  • P(B)  (Overall Test Positivity Rate): If 40% of German Shepherds test positive for the mutation, then  P(B) = 0.4 .
Baye's Theorem

While applying Bayes’ Theorem to DM test results provides valuable insight, there are several potential weaknesses in this approach due to the nature of the test:  

1. Assumptions About Prior Probability P(A)

Bayes’ Theorem relies on the prior probability of a dog developing DM P(A), which we estimated under 20% based on anecdotal and limited statistical data. However, the true prevalence of DM in “At Risk” dogs is not well-documented. Studies clearly suggest that many never develop symptoms, but there is no universally accepted figure. If this probability were significantly lower or higher, the final result would change drastically.  

2. Incomplete Understanding of False Positives P(B ~ A) 

We estimated that 30% of dogs who never develop DM still test positive P(B ~ A), but the exact false positive rate is difficult to determine. This is because:  

– The test doesn’t predict disease, only genetic predisposition.  

– Some dogs with the mutation might develop DM later in life, even if they initially seem unaffected.  

– Other health factors (e.g., spinal issues, arthritis) can mask or mimic DM symptoms, complicating diagnosis.  

If the actual false positive rate is higher or lower than assumed, the calculated probability of a dog developing DM after a positive test would change significantly.  

3. The Role of Environmental and Genetic Modifiers

Bayes’ Theorem assumes independent probabilities, but in reality, DM expression is influenced by multiple genetic and environmental factors.

– The SOD1 mutation is necessary for DM but not sufficient on its own. Other genetic modifiers may prevent or accelerate disease onset.  

– Environmental factors like exercise, diet, and medical care may alter the probability of disease manifestation.  

Longevity in family lines is a better predictor of health outcomes than a single genetic test.  

By focusing on a binary risk assessment, the test metric, with which we can base the Bayes’ Theorem off, oversimplifies the complexity of disease expression.  

4. No Direct Clinical Correlation  

The DM test:

– Does not diagnose DM, only limited genetic predisposition.  

– Lacks a clear window for when or if symptoms will appear.  

– Cannot account for non-genetic cases of paralysis or mobility loss, which could confound real-world interpretations of test results.  

A Limited Diagnostic Tool

As we have already discussed, While DNA testing for degenerative myelopathy (DM) has found a wide used as a diagnostic tool, its predictive value remains uncertain. The test identifies the presence of the SOD1 Mutation, but it Does Not diagnose the disease itself, nor does it guarantee that an “At Risk” dog will ever develop symptoms. This lack of clinical certainty creates several key issues that limit the test’s practical usefulness.  

1. No Clear Correlation Between the Mutation and Disease Onset

The presence of two copies of the SOD1 mutation is considered a risk factor for DM, yet many dogs that test “At Risk” never develop the disease. This raises questions about the actual role of the mutation in disease progression and whether additional genetic or environmental factors are necessary for DM to manifest.  

2. High Rate of False Positives

Since the test only identifies genetic predisposition, not disease, many dogs that test positive will never experience DM symptoms. Without long-term clinical tracking of affected and unaffected dogs, it is impossible to determine how frequently the test misidentifies “At Risk” dogs who will remain healthy.  

3. Ignores Other Genetic and Environmental Influences

The test assumes that the SOD1 mutation is the sole determinant of DM, yet emerging research suggests that other genetic modifiers and environmental factors may play a significant role. Factors such as diet, exercise, and overall health history could influence whether a dog with the mutation actually develops the disease. The test provides no insight into these external influences.  

4. Lack of Longitudinal Data on Longevity and Health Outcomes  

A more reliable predictor of health is family longevity—dogs from long-lived lines with no history of DM are statistically more likely to remain unaffected, regardless of their genetic test results. The DM test does not account for this crucial factor, making it an incomplete tool for assessing a dog’s actual health risks.  

The DM genetic test should be viewed as a peripheral risk indicator, not a diagnosis. While it identifies a mutation associated with DM, it does not determine whether a dog will ever develop symptoms. Given the high rate of false positives and the lack of consideration for other genetic and environmental factors, test results should not be used in isolation to make breeding or health decisions. Instead, real-world longevity and family health history remain far more reliable measures of a dog’s true health outlook.

What This Means for Owners

Even if a German Shepherd tests “At Risk,” the likelihood of actually developing DM is far from guaranteed—many dogs with the mutation live their full, natural lifespan without ever showing symptoms. In fact, for every 10 dogs that test “At Risk,” the majority will never experience the disease.  

This statistical perspective highlights why genetic testing alone should not dictate a dog’s future. Owners shouldn’t let a test result deter them from a broader health strategy—one that includes veterinary evaluations, monitoring for clinical signs, and, most importantly, an understanding of longevity within the dog’s lineage. The ultimate proof of health in any population is not a single genetic marker but the real-world outcomes observed over generations. A long-lived, active family line speaks louder than any test result.

Ethical Considerations of DM Genetic Testing  

The widespread use of genetic testing for degenerative myelopathy (DM) has sparked ethical debates about how these results should be interpreted and applied. While DNA testing offers valuable insights, its limitations raise questions about responsible breeding practices, owner decision-making, and the potential consequences of over-reliance on genetic markers.  

  1. Should Breeding Decisions Be Made Solely on this Genetic Test?

Many breeders use DM test results to determine breeding eligibility, often avoiding dogs that test “At Risk.” However, given the high number of false positives and the uncertain correlation between the mutation and disease expression, is it ethical to eliminate otherwise healthy dogs from breeding programs based on an inconclusive test?

Arguments for exclusion: Avoiding “At Risk” dogs could theoretically reduce the overall presence of the SOD1 mutation in future generations.  

Arguments against exclusion: Rigid selection based on a single genetic marker could reduce genetic diversity, leading to unintended health consequences (such as increased risk of other hereditary diseases). Moreover, many “At Risk” dogs never develop DM, making exclusion potentially unnecessary.  

  1. Are Owners Being Given the Full Picture?  

A positive DM test result can cause unnecessary distress for dog owners, leading them to believe their pet is doomed to a painful fate. Veterinarians and genetic testing companies have an ethical responsibility to provide context—including the reality that many “At Risk” dogs live full, healthy lives.  

  • If an owner receives a positive test result without understanding its limitations, they may make extreme decisions, such as prematurely euthanizing a dog at the first sign of mobility issues, even when those symptoms may not be related to DM at all.  
  • Ethical veterinary practice should emphasize A holistic approach to canine health, where genetic testing is only one piece of the puzzle, alongside clinical evaluations and family health history.  
  1. Profit Motives and the Responsibility of Genetic Testing Companies.

The commercial availability of DM genetic tests raises concerns about profit-driven narratives that may exaggerate the test’s predictive power. Should companies be held accountable for how they market these tests?  

  • Some companies fail to clarify the distinction between genetic predisposition and actual disease risk, leading to misconceptions about the test’s reliability.  
  • Ethical responsibility dictates that test providers should present probability-based interpretations rather than absolute statements. A more responsible approach would involve direct collaboration with veterinarians to ensure test results are correctly explained to owners.  
  1. Do We Owe Breeding Programs a More Comprehensive Approach to Health instead of a catch all? 

If a dog has an “At Risk” genetic status but comes from a lineage of long-lived, DM-free ancestors, should genetic results outweigh real-world evidence?  

  • Ethical dog ownership means considering long-term health trends over generations, rather than making reactive decisions based on a single test.  
  • Over-reliance on genetic tests could lead to unjustified breeding restrictions, potentially harming the breed by narrowing the gene pool without actually improving health outcomes.  

Conclusion: The Ethics of Balanced Decision-Making

While DM genetic testing provides valuable data, it is not a crystal ball for a dog’s health future. The ethical approach is one of Balance—where test results are considered but not overemphasized, breeding decisions are made with genetic diversity in mind, and owners are given accurate, science-based information to make informed choices.  

Ultimately, the responsibility falls on breeders, veterinarians, and testing companies to ensure that a test like this serves as just another tool to be considered for better decision-making, rather than a source of unnecessary fear or misguided exclusion in the shape of ill perceived dogma.

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