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."

5 comments:

  1. This comment has been removed by a blog administrator.

    ReplyDelete
  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

    ReplyDelete
    Replies
    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.

      Delete
  3. Hiv disease for the last 3 years and had pain hard to eat and cough are nightmares,especially the first year At this stage, the immune system is severely weakened, and the risk of contracting opportunistic infections is much greater. However, not everyone with HIV will go on to develop AIDS. The earlier you receive treatment, the better your outcome will be.I started taking ARV to avoid early death but I had faith in God that i would be healed someday.As a Hiv patent we are advise to be taking antiretroviral treatments to reduce our chance of transmitting the virus to others , few weeks ago i came on search on the internet if i could get any information on Hiv treatment with herbal medicine, on my search i saw a testimony of someone who has been healed from Hiv her name was Achima Abelard and other Herpes Virus patent Tasha Moore also giving testimony about this same man,Called Dr Itua Herbal Center.I was moved by the testimony and i contacted him by his Email.drituaherbalcenter@gmail.com We chatted and he send me a bottle of herbal medicine I drank it as he instructed me to.After drinking it he ask me to go for a test that how i ended my suffering life of Hiv patent,I'm cured and free of Arv Pills.I'm forever grateful to him Drituaherbalcenter.Here his contact Number +2348149277967...He assure me he can cure the following disease..Hiv,Cancer,Herpes Virus,Lyme Disease,Epilepsy, ,Bladder Cancer,Colorectal Cancer,Breast Cancer,Kidney Cancer,Leukemia,Lung Cancer,Non Hodgkin Lymphoma,Skin Cancer,Lupus,Uterine Cancer,Prostate Cancer, fibromyalgia ,ALS,Hepatitis,Copd,Parkinson disease.Genetic disease,Fibrodysplasia disease,Fibrodysplasia Ossificans Progressiva,Fluoroquinolone Toxicity Syndrome,Liver/Kidney Inflammatory,Men/Woman infertility, bowel disease ,Huntington's disease ,Diabetes,Fibroid...

    ReplyDelete
  4. I am 29 years old and I was diagnosis of Breast cancer, easy well and have a similar story except my first acceptance as a Herbal medicine denials. I wasn’t into the movement Perseid and didn’t establish connections with any of them really, just had faith in believing how they work. I say this because it was during using Dr Itua herbal medicine i now then testify herbal medicine is real, Dr Itua herbal medicine cure my breast cancer I was suffering from for 2 years. Dr Itua herbal medicine is made of natural herbs which has no side effect and is easy to drink as well. Contact Dr Itua herbal Center if you are suffering from the same Breast Cancer or any kind of human Diseases including....HIV/AIDS, HERPES COLORECTAL CANCER, BLADDER CANCER, PROSTATE CANCER, KIDNEY CANCER, LUNG CANCER, SKIN CANCER, UTERINE CANCER, LEUKEMIA, VIRUS, HEPATITIS, WOMEN/MEN INFERTILITY, LOVE SPELL,LOTTERY SPELL. HIS CONTACT EMAIL/WHATSAPP: drituaherbalcenter@gmail.com/+2348149277967

    ReplyDelete