Thursday, December 8, 2011

DM & ARVC: A Tale of Two Tests

Because I was the secretary of both the ABC Health & Research Committee (HRC) and the American Boxer Charitable Foundation (ABCF) when Drs Joan Coates and Kate Meurs announced their gene discoveries and DNA tests in 2008 and 2009, respectively, I followed the research closely and published updates regularly as editor of the ABCF Messenger (www.abcfoundation.org).  Although I resigned from both the HRC and the ABCF Board of Trustees earlier this year, I have continued to research and write about Boxer health issues for this blog over the last six months, and have recently made an interesting observation: Even though there are still big holes in our knowledge of how DM “works” (e.g., no one knows what percentage of At Risk dogs will actually develop the disease), the DM test is being increasingly considered by North American Boxer breeders when they make breeding decisions; while the ARVC test seems to have fallen into a PR black hole. How did this situation come about? How did the DNA test that was going to enable Boxer breeders to breed away from ARVC instead become a lightning rod for controversy and disagreement among both breeders and researchers?    

In my opinion, the most important reason for the broad acceptance of the DM test is that even though we can’t predict which or what percentage of At Risk dogs will develop DM, we can be certain that a DM Clear or Carrier Boxer will never develop the disease. (Dr Coates says “highly unlikely to develop DM,” rather than “will never develop DM”; but In the 3+ years since the DM test became publicly available, there hasn’t been a single report of a DM Carrier or Clear dog that has developed DM.)  Furthermore, there have been no reports of Boxers that developed clinical symptoms of DM, without having tested genetically At Risk.** In other words, regarding the most important aspect of a DNA test – the ability to identify both the presence and the absence of the mutated gene that causes the disease – what you see seems to be what you get when it comes to the DM DNA test.


Unfortunately, the same can’t be said of the ARVC test. When the test was first offered to the attendees at the 2009 ABC, breeders and owners rushed to snap up the available test kits, and used the detailed list of breeding recommendations almost as a catechism.

As test results began to trickle in, many breeders in all corners of the globe were horrified to discover that their beautiful new litter – bred before the test was available – was full of Homozygous Positive puppies (two copies of the ARVC gene) that were going to be impossible to sell as show and breeding prospects and presented an ethical dilemma even when placed as pets. Outstanding stud dogs became pariahs overnight, and breeding arrangements that had been in place for months and even years were canceled. But no one questioned the need to adhere to those stringent breeding recommendations; after all, this was a dominant gene, which meant that even dogs with only one copy of the “bad” gene had the potential to develop ARVC, and would pass it on to an average of 50% of their offspring.

Only a few months later, there were reports of ARVC Negative dogs that had been diagnosed with ARVC by board-certified cardiologists; and a noted UK geneticist announced that the test results on the 22 DNA samples he had submitted to WSU were not consistent with the disease status of the dogs whose samples he had submitted. (A subsequent test of DNA samples from 84 UK Boxers, submitted to WSU by several leading UK cardiologists and prepared to Dr Meurs’ specifications, produced the same inconsistent results.)  In the face of growing evidence that WSU’s announcement had been premature, unquestioning belief turned to skepticism, and ultimately, to disbelief.
    
Fast forward through the next two years: In the January 13, 2010 issue of the ABCF Messenger, Dr Kerstin Lindblad-Toh wrote “…the current testing [for ARVC] is not comprehensive…but we are working to make it better.”

In the May 2010 issue of the Purina Boxer Update (Vol. 9, No. 1), Dr Meurs wrote, “…While our test is a valuable tool, it is clearly not predictive in all Boxer populations.”

In the November 22, 2010 issue of the UK “Veterinary Times,” leading UK researchers in genetics and cardiology published an informal paper in which they concluded: “From the UK results, it can be seen that cases of boxer cardiomyopathy occur in dogs without having the striatin [ARVC-1] genetic mutation. Conversely, some genotype-positive dogs lead a normal life without ever manifesting the disease. Both the UK and USA data indicate that the search for genes implicated in boxer cardiomyopathy should continue.” [Emphasis mine]

Finally, in the September 2011 issue of the ABCF Messenger, Dr Meurs was quoted as saying that she stands by her findings and believes the ARVC-1 gene she discovered is the major cause of ARVC; but because of the current controversy over the test, she is working on other aspects of canine cardiology and has discontinued her study of ARVC, at least for the present. [Emphasis mine]

At this point, I think it’s obvious that the ARVC test is not a reliable means of breeding away from this truly horrible hereditary heart disease that is so widespread in our breed. And though my opinion can be easily discounted because I have no scientific or medical qualifications, I haven’t heard any endorsements of the test from prominent NA board-certified cardiologists, either.

What really distresses me about this situation, though, is not that a definitive test wasn’t produced right out of the gate – given the complexity of present day genetics and this disease, that is perfectly understandable. No, what I find most frustrating is that ARVC research – at least in the United States – hangs in limbo while we ignore the clear evidence that there is still much more research to be done before conscientious Boxer breeders have a way to breed away from ARVC. 

Surely we can do better than this?


** Correction: Jennifer Walker just pointed out to me that the DM DNA test site now states, "of those cords submitted for evaluation, and where the cellular changes have been consistent with a diagnosis of DM, the dogs have had a DNA test result of A/A in all but 2 individuals." 
The quoted test is in the 4th paragraph under "Understanding the DNA Test for Degenerative Myelopathy."

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  2. I am trying to determine if it's possible to find a genetically sound and healthy boxer in regards to heart and cancer , eye issues and health guarantee that reflects that

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    1. Sadly, boxers are a very flawed breed when it comes to heart disease and, especially, cancer, but I don't of ANY breeder of ANY breed that would issue that kind of guarantee. If someone tells you s/he will, run in the other direction.

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    2. You won't get that kind of guarantee, but choosing Boxers from fully health tested working German bloodlines gives you a much better chance of having a Boxer be healthy and live a long life. DM is pretty much non-existent in these lines, and no other health problems are nearly as common as in U.S. bloodlines.

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  8. The DM test is definitely not 100% reliable, although unfortunately most Boxer breeders believe it to be so, and claim clear or carrier dogs can never get DM. I had a Boxer who was a DM carrier, had him tested as a puppy right away and was so happy that I thought we would never have to deal with this devastating disease only to have him develop it at the age of 10, euthanized 23 months later when he could no longer even drag himself around or use his wheels and was having trouble eating and drinking. Clearly other factors are involved besides that genetic test.

    I will never buy another Boxer from U.S. bloodlines because they are so sickly. European, especially German, working bloodlines pretty much never get DM, hips and hearts are also much better.

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