Some Info
EIC is a gene mutation test.
We are testing for a single DNA base pair change in a specific gene, the DNM1 gene; therefore this can be referred to as a gene mutation test. This situation is different from other types of genetic tests that describe only the identification of a DNA marker that could be very far away from the EIC gene, and not be as highly predictive of the true gene and mutation as desired. The results for this EIC mutation test will always be the same for samples provided from the same dog.
Why say "highly associated" and not causes:
Scientists are always cautious in reporting conclusions regarding data to other scientists and to the public, and in so doing usually try not to state anything has a 100% certainty of being correct. However, the chances that the DNM1 mutation is not associated with EIC are less than 1 in a trillion as reported in our Nature Genetics article. Nature Genetics is one of the most respected and prestigious scientific journals.
The role of DNM1 in nerve and muscle function clearly supports it being an extremely plausible EIC gene. A description of the precise effect of the DNM1 mutation on the function of the dynamin 1 protein remains before we can even more confidently state that the DNM1 mutation (i.e., E form of the this gene) is the causative EIC mutation.
Being a carrier of the EIC mutation is very common in field and bench line Labradors. We have tested more than 6,000 Labradors and the carrier rate in our sample population (which is not random, but is large) is >30%. It is estimated that 3-5% of the population is EIC affected. Any disease with a greater than 1% affected frequency in the population is considered to be a major health issue within the breed.
Lastly, greater than 80% of genetically affected dogs have experienced episodes of collapse by three years of age. Others may not show signs of collapse until later in life. Confirmed first collapse has occurred in dogs as old as age 10yrs. However, even genetically affected dogs that never show signs of collapse do frequently produce collapsing affected offspring. So, while not every dog with the affected genotype will collapse, all dogs with EIC are homozygous for the DNM1 mutation. This is referred to as incomplete penetrance. The variation in the severity of symptoms is referred to as expressivity.
Opitgen also discuss these terms in their glossary:
Expressivity - Some diseases are very predictable in terms of age of onset and severity of symptoms. Such a disease is typically “expressed” in the same way in each affected individual. But some conditions, for example Toller PRA, don’t fit this description. They might have very different ages of onset, different degrees of severity, and/or different rates of progression even within the same line, the same pedigree, or even the same litter. One confusing result of reduced or variable expressivity is that a dog can be affected according to a DNA test, yet show no clinical signs of disease until much later, or show only mild and slowly progressing clinical signs of the disease. This dog must not be confused with a case of false positive.
Penetrance - The extreme case of reduced expressivity is incomplete penetrance. An inherited disease has incomplete penetrance in cases where the individual is known to have the affected genotype, but never shows the clinical disease. Even so, the clinical disease shows up again in its offspring. Clearly, the affected genes were present in the parent but the disease didn’t “penetrate” to a recognizable state. Again, this case must not be confused with a case of false positive. Incomplete penetrance has been documented in some PRA-affected Toller pedigrees.
I hope this helps.