THE VALUES AND PITFALLS OF DNA TESTS
written by Dick Koster
Recently I had our Gina checked for CEA and PLL. But by saying that, I might have added to the confusion which might exist in some people’s mind. Let me explain that.
I can’t imagine, that we, who love the breed so much, are willingly harming its health. So why not do a puppy eye test? Why not do a clinical eye test before breeding? Why not do DNA tests? Do owners/breeders think that one makes the other superfluous? Lack of knowledge? Or a bit of both? Let me explain the situation for CEA and PLL, and also about other, non-validated DNA tests.
Collie Eye Anomaly (CEA)
CEA is not a condition as such, it is an umbrella term for several conditions. At least two different and important conditions can be differentiated, but there are more.
Choroid hypoplasia: the blood vessel network under the retina, called choroid, is underdeveloped. This leads to poor retina function. Although this can lead to poor vision or even blindness, mild cases usually do not lead to significant loss of vision. The diagnosis should be made at a young age (6-7 weeks) during the ECVO puppy test. Later in life, pigment in the retina can camouflage CH.
Coloboma: a coloboma is a hole in the structure in the eye, usually near the optic nerve. It can lead to significant loss of vision. Other eye conditions like microphthalmia (small eye ball) have been associated with coloboma.
Both conditions are inherited and the mode of inheritance is autosomal recessive. It means several things:
An affected puppy carries 2 copies of the mutation.
If a puppy is affected, both parents are (at least) carrier.
Breeding later with an affected dog produces 100% carriers (if the other parent is free) and 50% affected/50% carriers if the other parent is a carrier.
Having said that, the conclusions are that one shouldn’t breed with an affected dog. That causes dissemination of the causative mutation within the population.
However, there is a DNA test for the CH component. This will irrevocably make clear what the genotype of a dog is. Breeding with two dogs DNA tested free for CH will produce only CH free dogs, or in laboratory terms: only the N/N wild type. A carrier should only be mated to a free dog, but will then produce carriers with a chance of 50%. NOTE: chance! It is not a certainty that in a litter of 4, there will be 2 carriers and 2 free dogs. It can also be 1-3, or even 0-4. Therefore it is only ethical to test the puppies from such a combination for CH before they go to their new owners.
But there is NO DNA-test for coloboma, as the CH test doesn’t cover that mutation. It means that the puppy test (the ECVO, BVA or ACVO test) is extremely important to detect this anomaly. If the puppy test is not performed, a new owner can easily be rocked to sleep thinking that “CEA DNA free” means that everything is okay and that no eye testing is necessary anymore. On the contrary: the clinical eye tests stay an extremely important instrument to keep the breed healthy.
Primary Lens Luxation (PLL)
The situation for PLL is slightly different, but some issues create that false feeling of safety also in this context. PLL was an immense threat to the breed, until the causative mutation was found: ADAMTS17. We were able to eradicate the mutation almost completely. But still we can’t lean back because the mutation still goes around in the population. There is nothing wrong with that: if you test, you can use carriers. If you don’t test, well, then you take an enormous risk.
However, despite testing we found dogs that showed an early sign of lens luxation, namely vitreous leakage. This must however be a different mutation, because it is seen in dogs that were tested free or carrier with the DNA test. Furthermore, this condition, that I started to call mutation X, emerges significantly later in age that the ADAMTS17 variant, and progresses slower. Often it is also only seen in one eye. In the end, the lens can luxate, but that is not necessarily the end stage in all cases.
To detect these cases of mutation X, a clinical eye test is so far the only option! So again, a PLL DNA test doesn’t give a 100% certainty, an eye test is still strongly recommended, at least during the breedable age. As soon as the mutation X symptoms are found, the dog should absolutely not be bred from anymore.
But a complicating factor is, that the leakage (and sometimes I also see the term vitreous prolapse) is usually found at a later age, and the dog might have produced puppies already. Then it becomes extremely important that the diagnosis is registered, and that the genotype of those puppies is set on “carrier mutation X”. If we can identify affected dogs and carriers, we can try to keep the risks as low as possible to avoid new cases.
A completely different story are the unvalidated tests. Companies like Gensol and Embark offer panel tests. They test all the mutations for which they have a test available. That can lead to very strange, frightening or even ridiculous results. For example, a Lancashire Heeler tested “Carrier for Bald Thigh Syndrome”, a phenomenon which is exclusively seen in sighthounds. Frightening was the result “Carrier for prcd-PRA”. It made me do the prcd-PRA test for one of my own dogs. I received a phone call from Laboklin, that that specific test was not validated for the Lancashire Heeler, therefore the result, whatever it would be, would be worthless. Later research made me believe strongly that prcd-PRA is not an issue (yet) in the Lancashire Heeler. By the way, my dog tested free of that mutation.
Are all returned results apart from CH and PLL test results worthless? Maybe not. There are a few tests that are universal. One of them is the SOD-1 test for degenerative myelopathy, a progressive and aggressive neurological disease. But it appears that for its expression, it needs another mutation, and that mutation might not be present in the Lancashire Heeler. A similar situation could be true for Craniomandibular Osteopathy (CMO), an uncontrolled, but self-limiting, growth of the bones in the jaws in young dogs. Both conditions have never been diagnosed yet in the Lancashire Heeler.
DNA tests for CH or PLL never safeguard us from other related or similar problems. Clinical eye tests, at puppy age and at least before each mating, with a validity of only one year, but preferably regularly, are even more important because they can detect more and different problems then we can prevent with DNA tests. Therefore DNA tests never make clinical eye tests superfluous, nor can clinical eye tests take away the need for DNA tests. A puppy eye test should be mandatory, but eye tests at later ages, before breeding, also.
But, DNA tests should have been validated for the breed, or should at least have some clinical relevance. Using panel tests can only lead to confusion, unnecessary limitation of the gene pool and more expenses than necessary.