Thursday, August 25, 2011

The DM DNA Test + a Personal Question for Breeders


Sunday before last, we published a blog entitled, "When Is It Time?"  Two days later, it was time for me to take my DM-affected boxer Bobby on his last trip to my vet's office. Unlike his sire Max, who was affected later in his life than Bobby but maintained his cheerful, animated demeanor to the end, Bobby seemed far less resilient in the face of the rapid loss of his mobility. Perhaps because Bobby also had cardiomyopathy and was exhausted by the effort of going through what used to be the routine motions of living in this oppressive Florida heat?  I don't know, but Bobby was very subdued – uninterested in even his favorite foods -- for the last week or so of his life.

Although I thought I had resigned myself to the inevitable, when I got to the vet's office I found I wasn't such a tough cookie after all, and neither was my vet or her staff. I drove home vowing that I would never again breed a litter that might contain an at risk puppy. I suspect that everyone who has just lost a dog to DM says the same thing.

And of course, it’s an easy thing for me to say: I’ve been breeding and showing boxers since 1973, and at this point will probably breed only one or two more litters in my lifetime. But how easy is it going to be for the next generation of breeders to avoid breeding At-Risk puppies while trying to consider ARVC, SAS and myriad other health concerns, along with temperament, head type, conformation and movement? Not easy at all when you consider this update from Dr Joan Coates (taken from the October 2010 ABCF Messenger at www.abcfoundation.org):

Results on genetic testing for the Boxer breed so far…
As of 10/1/2010, we have tested 1987 Boxers.  The genotype total includes 251 clears (12.6%), 608 carriers (30.6%), and 1128 (57%) AT-RISK. The allelic frequency takes into account the number of chromosomes with the mutation. The allelic frequency is 72% in the population of Boxers tested.” 

I also took a look at the information sheet that was included with the OFA DM certificate I just received for one of my dogs, and under Explanation of results this was the explanation for At-Risk:

AT-RISK (A/A): This dog is homozygous A/A, with two mutated copies of the gene, and is at risk for developing Degenerative Myelopathy (DM). The research has shown that all dogs in the research study with confirmed DM have had A/A DNA test results; however, not all dogs testing as A/A have shown clinical signs of DM. DM is typically a late onset disease and dogs testing as A/A that are clinically normal may still begin to show signs of the disease as they age…Research is ongoing to estimate what percentage of dogs testing as A/A will develop DM within their lifespan. At this point, the mutation can only be interpreted as being at risk of developing DM within the animal’s life. [Emphasis mine.]

Then under Guidelines for Breeding, Dr Coates wrote:
“…The “A” (mutated) allele appears to be very common in some breeds [over 70% of boxers have the allele].  In these breeds, an overly aggressive breeding program to eliminate dogs testing A/A or A/N might be devastating to the breed as a whole because it would eliminate a large fraction of the high quality dogs that would otherwise contribute desirable qualities to the breed....A realistic approach when considering which dogs to select for breeding would be to treat the test results as one would treat any other undesirable trait or fault. Dogs testing At-Risk (A/A) should be considered to have a more serious fault than those testing as Carriers (A/N)….the test result should be one factor among many in a   balanced breeding program.”  Good, conservative advice: Don’t throw the baby out with the bathwater.

Now go back up to Dr Coates’ explanation of At-Risk and reread the parts in bold print. While I was writing this blog, I was emailing back and forth with geneticist and boxer breeder Dr Bruce Cattanach. Due to my own personal experience with DM – so far, 100% of my At-Risk dogs and their At-Risk close relatives have developed DM – I have always been of the opinion that if an At-Risk boxer lived long enough, he or she was going to develop DM. But after reading the following in one of Dr Cattanach’s emails, I had a “light bulb” moment, and finally understood what Dr Coates has been saying about At-Risk, and why her breeding guidelines are so cautious and conservative.

Here’s what Dr Cattanach wrote: 
OK, here is something factual.  57% of the breed is homozygous At Risk.  But does over half the breed die of DM – no they die of cancer or ARVC, etc, as well. But of those that don’t die of these other things, do more than half get DM?  I am fairly sure this will not be true.  Hence, as Joan Coates says, there is a question of penetrance.  Only a proportion of these gets DM. Do 80% get the disease? Or, say, only 20%?  This would make a big difference to me about how I thought about breeding from or producing DM homozygotes.”

 I hope Dr Coates’ research will give us the answer to the question of penetrance one day, but in the meantime, I’d be very interested to hear your answers to this question:  How many of the breeders and owners who are reading this have DM At-Risk boxers that are 10 years old or older, but have not yet developed DM?  Unfortunately, I know what the penetrance rate is for my own dogs so far, but I would be very curious to know if my dogs are typical. This is not a formal survey, so names of dogs and owners are not important. Just email me privately at vzboxers@gmail.com, or if you prefer, comment on the blog.  I will publish the results of the survey in a couple of weeks’ time. Thanks in advance for your responses.    

11 comments:

  1. Thank you for this blog Virginia! I hope this will help breeders realize that it will take many, many years to get to the point where there are less "At Risk" Boxers and that one should not eliminate using "At Risk" dogs in a breeding program. It would be detrimental to the breed.

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  2. I have one over 10 year old dog that is A/A and has not produced symptoms yet, she still runs agility and all things are fine, I am convinced in examing her pedigree and knowing how the dogs died in pedigree whe will in fact die of cancer, time will see if I'm right

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  3. Thank you for reading the blog, Cindy. :-) I agree completely that DM cannot be the be-all and end-all of our breeding programs, but that makes for some very tough decisions.
    VZ

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  4. Jill, That's the kind of information I was hoping to get. Good luck, and please keep me posted on your bitch.
    Thanks again!
    VZ

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  5. >> Unfortunately, I know what the penetrance rate
    >> is for my own dogs so far

    And I think this is the key for making breeding decisions with dogs that carry the DM gene, in one or two copies. For an At Risk dog with a history of DM in the pedigree, reducing the incidence of that gene is going to be a higher priority than it might for someone with an At Risk dog with no history of DM in the pedigree (even among long-lived dogs).

    Personally, I've come to treat At Risk dogs just as I treated them before there was a test -- there's a chance they'll develop DM, and family history will give a clue as to how high that chance is; looking at the family history of potential mates will tell me whether to breed those two dogs together. (A high incidence of DM on both sides of the pedigree? Nope.) The test gives me some added information -- I know I can avoid doubling up on that gene if I need to.

    Think about this, though -- since there is clearly another factor at play with DM, and if it is a genetic one, those Clear (or even Carrier) dogs from lines with a high incidence of DM may be passing on that "factor X" to their get, and down the line an At Risk puppy could be born that will then have that "trigger" to lead to DM. We can't look at the gene test results and stop, as far as DM is concerned -- family history is important, even in the Clear and Carrier dogs. I believe -- or at least, I like to think ;) -- that's what Dr. Bell meant when he said not to use the DM test as a screening tool. He didn't mean don't use it at all -- he meant don't use it as a sole means to remove or include dogs in breeding programs.

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  6. Actually, what Dr Bell *said* was don't bother to *test* unless your dog has close relatives that were affected. That was the statement I took issue with, for two reasons: 1) there's a 5-7 year turnover rate in breeders/exhibitors, and many breeders are not forthcoming about DM, ARVC and many other health issues. Thus, in many cases, a relative newbie doesn't know that his dog has close relatives that were affected. 2) I can name 4 VERY popular sires in just the last 20 years that were affected. And their descendants' name is Legion.

    So far, I've heard from only 3 breeders with 10+ year-old At-Risk dogs with no sign of the disease. Two of them died ( at 10 and 12) of something else; only one - a 10 y/o -is still alive and symptom-free.

    IMO, Dr Bell also made some very questionable statements about the ARVC-1 test, but that'll be the subject of another blog. :-)

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  7. I don't recall Dr. Bell saying that, Virginia, but I'll check my notes. :) If he did, then yes, I disagree with that statement (and as you know, I disagree with the ARVC-1 statement, too!).

    I've only been fortunate enough to have one Boxer live past 10 years of age (by four months), and she died before the test was developed, so I can't be much help there. Clearly, my personal experience leads me to focus more on getting them to live to 10 than on what might happen after they turn 10.

    I know of a dog who was almost assuredly At Risk who died at 10.5 and never showed any signs, but he wasn't tested. My own At Risk dogs are 6 and 2; I'll let you know several years from now how they're doing! (Based on family history, I expect one will never show signs of it and -- knock wood and barring accident -- should live well past 10, and the other has a small chance of doing so and should -- knock wood and barring accident, again -- make to at least 10 or 11.)

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  8. I took notes, too, Jen, and was so shocked by Dr Bell's statement that I wrote to the ABC Health Committee (HRC), of which I was still a member at that time, and pointed out that his professional "advice" was in direct opposition to the testing recommendations on which the committee was planning to base a new ABC health brochure.

    A friend of mine, also an HRC member, had lost five bitches in quick succession to DM over the past 5 years or so and was speechless with disbelief when she heard Dr Bell say that.

    My first blog here was a review of Dr Bell's seminar, taken from my (copious) notes. Here is the part I quoted, almost verbatim:

    "His recommendation re the DM test was even more puzzling: Dr Bell said that, in general, DM is seen only in "show lines," and that we shouldn't bother to test for it "unless close relatives of our dog have been affected"! This, despite that DM is a late-onset disease, so one often wouldn’t know a close relative had been affected till the relative was 10 or 11 years old (if he or she didn't die of something else in the meantime); and despite evidence from breeders all over North America that DM *is* currently a big problem in the breed, probably due to the Popular Sire Syndrome, which we see in action every year in the ABC Catalog."

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  9. I've checked my notes, and they differ slightly from yours. :) I wrote down:

    "'You will decimate your gene pool and destroy your breed' if you use this as a breed-wide screening test. Use as a screening test only for those dogs with close relatives affected."

    Which explains why I wasn't as appalled as you were by that portion of the talk. ;) He probably said "use it only for dogs with close relatives affected" and we heard "it" as two different things. Regardless, I think we both agree that using the test as a sole breed-wide screening tool is just as foolish as not testing at all, regardless of family history.

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  10. Jen,
    Breed-wide screening for DM won't decimate the breed; making the DM test the sole criterion for breeding decisions WILL decimate the breed. Most serious breeders understand that. Dr Coates has repeated that over and over again. But many breeders have no way of knowing which, if any, close relatives of their breeding stock were or, more to the point, *will be affected* by DM.

    I certainly didn't know that back in 1989 when I bred what would turn out to be my first DM affected boxer. And I didn't know back in 1994 when I bred that bitch at the age of five to a five y/o stud dog that both of them would end up being affected; and that therefore my whole litter of 4 was going to be affected.

    I don't know what Dr Bell meant, I only know what he said; and IMO, what he said about both DM and ARVC has the potential to put our breed right back where it was in 1994 vis a vis those two often fatal diseases, if present-day breeders heed his advice.

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  11. >> Breed-wide screening for DM won't decimate the breed

    I guess we're getting into semantics, now. I've always been taught that a "screening test" is used to "screen out" affected dogs. (Like a screen window keeps bugs out.) In that sense of the term then yes, breed-wide screening for DM (which means removing all At Risk dogs, and most Carriers) will, in fact, decimate the breed.

    Breed-wide *testing* for DM won't, of course; it's the use of the test as a screening tool to remove most or all dogs that possess the DM gene that becomes problematic.

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