Let’s yap about PRA health in Lowchen
For years I have been told that Lowchen have “no markers” for health conditions, that DNA testing is “useless”, and there are so many “false positives” that the test has no meaning.
Here’s the problem. Every PRA symptomatic dog which has been DNA tested has been homogenous for crd4/cord1 PRA. This was announced in 2024. This marker was initially discovered in the breed in 2014. We’ve had a marker for over a decade, we just haven’t been using it.
“But Devon” I hear you say “many labs have st
opped testing for it because it’s inaccurate!”. Well my friends, that is a half truth.
This type of PRA is a tricky beast, I will grant you that. Onset can be from 10 weeks to 15 years, and some dogs with test as homogenous for crd4 and never become symptomatic. Wild right? The answer is equally as migraine inducing. This PRA has 2 modifiers which impact the onset of PRA. The MAP9 deletion activates the PRA, allowing symptoms to present in a dog, and the L3 modifier accelerates those symptoms into aggressive deterioration. The earliest onset is seen in dogs homogenous for crd4, MAP9 and L3.
L3 research is in its infancy. MAP
9 has been detected in both related and unrelated breeds, it is believed to be an ancient gene which predates modern dog breeds. And yes, “modern” is relative here and includes medieval and renaissance breeds.
There is a theory that there are 2 types of PRA in Lowchen, and this could still be true. However, we currently have no shared and verified information which supports this claim. It’s a bit of an urban legend. The behaviour of crd4/cord1 and its modifiers explains the drastic range of onset and speed of deterioration which was previously believed to be caused by 2 different variants of PRA in Lowchen.
After reviewing the new research on crd4 and MAP9 (none of which names Lowchen in published research due to our tiny sample size) my hypothesis is this;
Crd4 is the only PRA in Lowchen. Dogs present symptoms differently because of the presence or absence of MAP9. Dogs who are both homogenous for crd4 and MAP9 will become symptomatic earlier than those with a single copy MAP9. L3 could be entirely absent from the breed due to the lack of infant/juvenile onset and blindness.
The new information and research around crd4/cord1 PRA provides an explanation for the diversity of PRA presentation in Lowchen. It also explains why PRA “sleeps” for so many generations, making it challenging to track. While a 2021 study did not find MAP9 in Lowchen, out of the 95 Lowchen only one was symptomatic.
The first thing is quite simple, DNA testing identifies the dogs risk of developing PRA through the crd4/cord1 PRA (RPGRIP1) and is not a guarantee that they will become symptomatic. Therefore, DNA testing for crd4 will reduce the risk of producing a Lowchen who is at risk of developing PRA, however, it is not a predictor of PRA.
Here it is imperative to note that there are lines which are clear of crd4 PRA. DNA testing and intentionally breeding to clear dogs will reduce the risk of crd4 PRA as generations progress. This can allow breeders to move forward with confidence, as well as allowing breeders to keep at risk and carriers in the gene pool and continue to breed from them safely. The absence of crd4/cord1 renders MAP9 (or other modifiers) neutralised.
Plenty of people have come forward and given me the DNA results for many of their dogs, clear, carrier, at risk and affected. This has allowed me to map the disease more thoroughly in Lowchen, and has led to identifying potentially safe dogs (possibly clear) and potential carriers or at risk dogs). What I can tell you is that those who are DNA testing for crd4 PRA are successfully reducing the number of carriers they breed. It is also allowing them space to focus on other things in their breeding program because they are no longer doing (what I call) “PRA Math”.
I am not one of these breeders. I ignored the initial discovery of crd4 and did not act with prudence, largely due to the nay-saying and uncertainty coming from others. I was pleasantly surprised when by first dog came back as n/n (clear). This partly reflected the good choices I had made, selecting lines with strong linebreeding and eye exam results, the other part was pure, dumb luck.
I have spent 12 years doing “PRA Math”, sometimes holding my breath at eye exams and questioning every clumsy behaviour of my dogs. The stress of “PRA Math” has spread to my husband, who without knowing much about PRA or being a breed expert, has become a helicopter dog parent regarding our dogs sight (and grass seeds). One affected dog changes your whole behaviour towards your dogs and breeding. This is a game changer.
So how do we move forward as breeders?
The first thing is, we still need physical eye exams. But having DNA knowledge changes how we move forward with these exams, so they must be used in conjunction with DNA testing.
DNA test potential breeding stock for crd4/cord1, prcd is an optional test. |
If breeding from an affected dog or carrier, all puppies should be tested for good measure unless the outcomes are known. |
The only known outcomes are Clear to Clear (= all CLEAR) and At Risk/Affected to Clear (= all CARRIERS). |
I am not going to tell you what to retain as there are other things to consider outside of eye health which may impact your decision.
Knowing the crd4/cord1 PRA genetics of a dog changes the way we can conduct physical eye exams.
This table outlines my suggestion for physical eye exams, some tests are mandatory for all dogs as they are in a window which looks for other abnormalities.
Age | Clear (n/n) | Carrier (n/crd4) | At Risk/Affected (crd4/crd4) MAP9 unknown |
8-10 weeks |
|
| ERG Test |
6 months |
|
| ERG Test |
12-18 months | ERG Test | ERG Test | ERG Test |
2-3 years |
|
| ERG Test Annually |
3 years (approx.) | ERG & Gonioscopy Exam | ERG & Gonioscopy Exam | ERG & Gonioscopy Exam |
6 Years | ERG & Gonioscopy Exam | ERG & Gonioscopy Exam | ERG & Gonioscopy Exam |
9 Years | ERG & Gonioscopy Exam | ERG & Gonioscopy Exam | ERG & Gonioscopy Exam |
12 years | ERG & Gonioscopy Exam | ERG & Gonioscopy Exam | ERG & Gonioscopy Exam |
15 Years | ERG & Gonioscopy Exam | ERG & Gonioscopy Exam | ERG & Gonioscopy Exam |
At risk dogs must be tested annually. Some ophthalmologists will recommend more frequent testing if atrophy is noted.
Gonioscopy is for the detection of glaucoma, and as there has been cases of glaucoma in Lowchen 3 yearly testing is recommended.
It is essential that any eye abnormalities detected or suspected by you are checked in a timely manner.
What if my dog is clear of crd4 and has a positive physical exam for PRA?
Usually in these cases your ophthalmologist will have a more senior team member verify the findings. PRA is distinctive, however a second opinion is essential.
Once the second opinion confirms that this is in fact PRA, get in touch with myself or Angela Stevenson as we are heading up the Lowchen PRA Project. Firm, clinical evidence of a second type of PRA will need to be documented properly.
Then we will run broad DNA tests for other kinds of PRA markers. As there are over 20 markers for PRA, this would at least eliminate some variations of PRA which are known.
The future with DNA…
DNA is an excellent tool which breeders can use to determine how breeding stock can impact future generations of Lowchen. The next year is going to be exciting as we solidify our knowledge, in both what we know and what we do not know about our own dogs and other Lowchen.
The research around crd4 and MAP9 are evolving at a rapid pace, so it is essential we keep an open mind as to what the future of health testing can look like for our breed.
Pettinen, I.-T., Donner, J., Turunen, J. A., Kaukonen, M., & Lohi, H. (2021). Gene Panel Screening Across Canine Eye Disorders Highlights Genetic Heterogeneity and the Need for Molecular Discoveries. Springer Science and Business Media LLC. https://doi.org/10.21203/rs.3.rs-417922/v1
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