Replies to This Discussion

Permalink Reply by Beth on January 6, 2012 at 6:30pm

Here is my understanding about what we know of DM.

It is a straight recessive on a gene not prone to mutation.  What that means is a dog needs two copies of the gene to be at risk, but as has been mentioned the vast majority of At Risk dogs never develop DM.   "At Risk" is the accepted term to refer to a dog with two copies of the gene. 

Let's call the "good" gene A and the "bad gene" B.

A dog can be AA, AB, or BB.    AA is "clear" and cannot get DM nor pass it on to offspring.  AB is "carrier" and cannot get the disease but can pass on either the good gene or the bad gene to offspring.  BB is "At Risk" and may get the disease and is guaranteed to pass the bad gene on to offspring.

An AA bred to an AA will give all AA's (clears)

An AA bred to an AB will give 50% AA's (clear) and 50% AB (carriers)

An AA bred to a BB will give 100% AB (carriers)

An AB bred to an AB will give 25% AA (clear), 25 % BB (At Risk) and 50% AB (carriers).

An AB bred to a BB will give 50% AB (carrier) and 50% BB (At Risk)

A BB bred to a BB will give 100% BB (At Risk)

These statistics hold for large numbers of breedings, and not for individual litters.  Someone might breed an AB to an AB and get 5 At Risk (BB) puppies.  

The problem is that something like 8% of all Pems are clear, as mentioned.  It would be irresponsible to breed rapidly away from the disease.  The breed would be ruined.  

Moreover, I believe the researchers consider it a polygenic disease, and they are still looking for modifier genes.  They know dogs MUST have two copies of the bad gene to get DM, but they think other genes influence whether the dog gets symptoms, and at what age symptoms begin (for example, in German Shepherds age of onset is much younger than in Corgis).  

The guidelines I have seen by geneticists are this:

For breeders who do not have a history of dogs with DM in their lines, they should test but not give too much weight to the results.  If a dog was of breeding quality before you knew the test results, then the dog is still of breeding quality after you know the results.  For this reason, I think many breeders are either not testing, or testing for the researchers but not going public with results.

For breeders who have a history of dogs with DM in their lines (these are dogs who actually got the illness, NOT dogs who test positive), breeders should slowly, over several generations, breed away from the disease.  What that might look like is this:

Josette Corgi Breeder has a nice quality bitch who had a litter.  Her aim was to keep one bitch from the litter for breeding and place one dog as a possible breeding dog with her kennel partner, and place the rest in pet/performance homes.

She has a litter of 8.  She assesses them for quality, decides 4 MIGHT be show quality (three bitch puppies and a dog puppy), and tests them.  She finds the dog puppy is At Risk and sends him to her kennel partner, with the idea that they will watch him carefully to determine if his good points outweigh the risk of breeding him when he is At Risk and the line has DM.  She finds two of the bitch puppies are At Risk and one is a Carrier.   What does she do?

She keeps the Carrier and puts the two At Risk puppies in pet homes.  She then tries to breed her bitch puppy in a few years to another carrier, hoping to get some more carriers or maybe even a clear.  

What does that mean to you, the puppy buyer?

It means that many responsible breeders without DM in their lines are not testing, or testing and not sharing the results.

It means that responsible breeders with DM in their lines are keeping their quality Carrier pups and PLACING the AT Risk pups in pet homes.  

And that all boils down to putting yourself in their shoes.   Would you want to try to explain to a pet puppy buyer that you are really and truly doing the right thing by sending the At Risk pups off to pet homes, and keeping the Carriers (who won't get the disease but might still pass it on)?

For myself, when we got Maddie (as an adult) I did not even ask if she'd been tested.  I know her von Wildebrand's status (carrier), her fluff status (carrier), her eyes and hips but did not ask about DM.   I really don't want to know.  If my dogs stay symptom free into old age and they are stilling looking for DNA samples for research, I may send them in.  If I were looking for a pup, I would not ask about DM status.

And I would worry about a breeder who was only breeding Clears at this point because it is against the advice of the geneticists. 

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Permalink Reply by John Wolff on January 9, 2012 at 1:02pm

That's a good analysis.   Excruciatingly technical detail: 

The "bad" allele is "A", stands for Adenine, one of the 4 DNA nucleotides.

The "good" allele is "G", stands for Guanine.

Labeled this way, GG is clear, AA is at-risk.

The high incidence of the A allele may be chance inbreeding, or it might be because the A allele is "tightly linked" (close to) some valuable corgi trait that breeders have selected for.  In this case, we'll have to wait for a lucky crossover (natural DNA recombination) that separates the two.

The breeding strategy you describe looks quite sound to me.

http://www.akcchf.org/research/

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Permalink Reply by Beth on January 6, 2012 at 7:44pm

Here's a study that's open that's looking for modifier genes:

http://www.akcchf.org/research/funded-research/1271.html

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Permalink Reply by John Wolff on January 6, 2012 at 11:58pm

Punnett squares

Offspring of two DM carriers have a PROBABILITY of:

25% AA  at-risk (only AAs develop DM, but many AAs never do)

50% AG  carriers (no symptoms of disease)

25% GG clear

From two carrier parents, it would be possible to have an 8-puppy litter of 8 AAs, or 8 GGs, or 8 AGs, but this would be unlikely.

If only one parent is "clear", no pups will develop DM.

I doubt that any breeders would be testing puppies; they'd be testing prospective parents.  If they are testing at all, I doubt they'd be breeding AA at-risk parents.  Breeders who ARE testing do not necessarily publicize the results, understandably.

In the trade, this is called a "point mutation".  The DNA has either an A (adenine) or G (guanine) at that place in the code, and this changes the amino acid in the protein that this gene codes for.  AA individuals MIGHT develop DM, but often do not, so we say the "penetrance" is less than 100%.  AA is necessary, but not sufficient.  Other "modifier" genes, or circumstances, are possibly involved.

I'm a tech in a medical genetics research lab.  We work on hereditary neurologic diseases.  This is right up our alley.  Joan Coates' DM paper caused a stir among human neurologists because the DM gene is SOD1 (superoxide dismutase, if you must know), which is mutated in ALS, Amyotrophic Lateral Sclerosis, Lou Gehrig's Disease.  (Sorry)    

This stuff is still in its infancy.  I would caution against making DM a deal-breaker if a breeder is otherwise good.  There are very sound reasons for not excluding all dogs who carry the "A" allele from the breeding stock:  most Pembrokes carry the "A" allele, so if you breed only GG clears at this point, you'll squeeze the breed through a narrow genetic bottleneck, inbreed the stock, and create other problems (I believe Chesapeake Bay retrievers, who have a high DM incidence, passed through such a bottleneck, the offspring of Newfoundland net-hauling dogs who washed ashore from shipwrecks -- this is called a "founder effect").  It could be that this A allele is "tightly linked" (close to) some desirable corgi gene, and thus inadvertently selected for.  You don't want to throw the baby out with the bathwater.  

That said, I think if a breeder is testing their stock for DM, that's a good sign.  

I attended Dr. Coates' presentation to the Cascade Pembroke Welsh Corgi Club.  REALLY interesting.  Some of the microscope slides she showed reminded me of some of my boss's stuff.  Turns out, the AG carriers DO shows some signs of pathology in the spinal cord under the microscope;  it may be that the age-of-onset for AG carriers is older than life expectancy (if they lived long enough, the carriers might get sick).  Compared to Western human pedigrees, dog pedigrees looked like a drunken electrician's wiring diagrams...

Bottom line:  if at least one parent is GG clear, no pups should develop DM.  But elimination of DM might be considered something for the future, not the present.  This stuff is in its infancy.  We do not know the whole story yet , I think.

BTW, Dr. Coates empahsized that they need OLDER, HEALTHY corgis for controls.  This is really important.  Big commitment, autopsy specimens at an emotional time.   So if you have an older corgi with no signs of DM and want to contribute to this research (at least, this was a coupla years ago):

DM research healthy older corgis

The original linkage of ALS (Lou Gehrig's Disease)  to mutations in the SOD1 gene was kind of a surprise, because this is a "housekeeping gene" which every cell requires to decompose superoxide, O3, a toxic form of oxygen.  Apparently, one good copy of the gene is not enough to protect motor neurons over a lifetime.  Just remember:  this science is in its infancy.

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Permalink Reply by Patti on January 8, 2012 at 7:20pm

Emily, I read with interest - a biased interest, no less - of your inquiry.  I posted a while back that IMO it would be best to ask breeders if they tested for DM and my reasons were personal, I presently have a "heart dog" who was diagnosed with DM in August of 2011. I was succinctly flamed and told that my opinion would be the downfall of the breed. That, of course to a reasonable person, was not my intent. My intent, as I stated - was in purchasing a dog, one should be educated and informed to make the best decision possible for the dog and the owner.  Yes, DM is/can be rare - but it is happening - and the cases seem to be occurring more frequently.

So, be educated.

I had spent approx. $800 in vet bills trying to figure out what was wrong with Kai prior to his being sent to the University of Florida for MRI's/Myelograms and further testing - which cost upwards of $3000. Since then, his vet bills, neurologist, physical therapist and medicines are around $2000.  His cart cost $400.  The ramps in the house so he can get around cost $100.  My dr bills to get my back fixed from picking him up am/pm are around $500 so far.  That is the financial cost.

The emotional cost is devastating.  My "heart dog" is generally in one place all day. I am fortunate that he can still pee/poop on his own, but he is now having accidents. Soon, I will have to "express" him - in order for him to "do his business", as well as to avoid the subsequent infections that may arise from his not being able to do so himself. We will be lucky if he survives 2012. He is 8 yrs old, soon to be 9.

Don;t get me wrong - I LOVE this dog and will do anything and everything for him.  

But in choosing a dog - we ask potential owners to check for PRA/Hip clearances etc - as a precursor to make sure that they are getting a "healthy" dog - a healthy dog means a healthy/happy home.  I personally don't want to see the end of a corgi breed - but I also do NOT want to see DM dogs dropped off at kill shelters/or euthanized early because their owners can't take care of them. As for the breeders - when I contacted my breeder - she was devastated at my dog's illness, and now tests her pup's and advertises that fact.

So I applaud in wholeheartedness your ability to plan a good home for your dog - and I wish you and your puppy a happy future!

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Permalink Reply by Beth on January 8, 2012 at 7:46pm

Patti, I am sorry you feel you were flamed.   I posted responses in the other thread very similar to what I posted in this thread (I even just went back and read them to be sure), and I expressed then, and will again now, my heartfelt sympathy for your DM dog.   I believe you mentioned your Corgi also has IVDD, which would continue to cause some Corgis to need wheels even if DM were eradicated tomorrow.  

You have Cardis I believe and there are much, much higher numbers of clear Cardis than clear Pems.  With Cardi breeders, there are certainly more options out there. 

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Permalink Reply by Emily & Scout on January 9, 2012 at 7:36am

Thanks for everyone's responses.  I've been away from home so haven't been able to get on this site until this morning.  I'm glad to know more now when I am ready to make a decision. I took a genetics class but wasn't sure if DM applied to normal genetics.  This isn't going to be my only deciding factor in what puppy to choose, just making sure that there are responsible breeders that don't necessarily test for genetic disorders.  It's hard trying to sort out which ones are truly responsible from the ones who just want to sell puppies.  I'm still going to be on the lookout at shelters around here (within a day's driving distance) to see if there are any rescues that show up, but will most likely get a puppy later in this year or in 2013.  Again thanks to all on this site. I'm glad to have come across it as I do believe everyone on here gives the best advice / info possible.

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Permalink Reply by Jane on January 9, 2012 at 9:32am

In regards to the breeder saying it hasn't come up in their lines, keep in mind that DM generally only affects senior dogs. So if the people have only been breeding say, 5 or 6 years, they wouldn't have had a chance to see DM in their dogs.

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Permalink Reply by Beth on January 9, 2012 at 10:17am

I read some overviews of the older studies, and they were pretty sure it was familial BEFORE the DNA test was discovered.   I think that frankly the researchers were stunned by the frequency of the gene in some breeds.   The next study is trying to find the "modifier" genes that may exist; they might either help turn on or off the causative gene, OR impact the age of onset.  So for instance if one line does not get symptoms til a hypothetical age 20, and the average lifespan is around 13, obviously you would not see the disease in the dog's lifetime.

 

Or, to make a long story short:  My (limited) understanding is that it does show up in some lines and not in others, and they are looking further to find out why that is.

 

It's also impossible to diagnose DM without autopsy; some dogs with severe IVDD or another neuro condition might present similarly to DM dogs.   The researchers were doing necropsy/ spinal cord assessment to ensure proper diagnosis when they were looking for the causative genes.   I believe they are still doing that now.

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Permalink Reply by Jane on January 9, 2012 at 11:04am

I'm not saying it's not genetic or doesn't run in certain lines of dogs. I just want people to be careful interpreting the response from the breeder, especially if you're not sure the breeder is reputable or not (like the OP). Kind of like the "there's no hip dysplasia in my lines, my dogs run and walk just fine!" excuse. If a breeder isn't testing or isn't in touch with the person they originally got their dogs from, it could be many years (and many generations of dogs produced) before their senior dog shows symptoms of DM.

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Permalink Reply by Megan C on January 9, 2012 at 9:46pm

In horses Arabians are known for SCID which is less tragic than DM because the foal dies quickly as opposed to after someone has bonded with the animal (although still sad).  It is also a recessive disease.  The breed has done a good job breeding away from the disease by only breeding clear to carrier.  Yes it eliminated quite a few breeding prospects (a SCID carrier stallion will rarely be used.) but if you are breeding for a sound animal than fatal genetic diseases need to be at the top of the list for things to not breed for.  And if they do breed carrier to carrier or at-risk to carrier then they certainly should disclose the fact that a buyers pet puppy may get a slow paralysis and die after the dogs health guarantee expires.  

If being a fluff, having ears that are a not quite right, or having a little too much white are enough to eliminate a Corgi as a breeding prospect then having 2 copies DM should eliminate it as a breeding prospect as well.  Carriers are a much smaller fault than at risk.  If carriers were only bred to clear then within one generation the breed would be over 50% clear.   

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Permalink Reply by Beth on January 9, 2012 at 10:29pm

I feel like a broken record, but I will say this again:  9% of Pembrokes at thus point are clear.

9%

That would put 9% of the current population in the first generation of every Corgi born in this country, and then a significant percent of those would have to be bred back again to the same 9%.

It would be a travesty if that were to happen.  You would not eliminate "quite a few" breeding prospects.  You would eliminate almost all of them.  

Not one single geneticist suggests this is a good course to follow, but in every DM thread we always get a cluster of posters who suggest it's the best option.  We could introduce a whole slew of diseases as a result that we don't even know about.  Would we want to trade a tiny percent of dogs who get sick in old age (as is the case with DM's in Pems) for a whole lot of dogs who get cancer at a young age (as do Goldens?).

Or are riddled with heart problems (like Cavs)?

Or Fanconi syndrome (like Basenji's)?

Or cancer again (like Boxers)?

You are not working with a clean genetic slate.  Every line of every dog represents some possible health problem.  Breeding down to 9% of dogs in one generation would have unforeseen consequences.  At the very least, the loss of genetic diversity would tend to weaken immune response (the reason why people and most animals instinctively avoid close relatives as potential mates is to ensure the widest diversity for immune protection).   At worst, we have implanted a time bomb in the breed and end up with something like Cavalier King Charles Spaniels, where most have heart problems and the breed is considered beyond saving without outcrosses by many.  

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