genetic testing

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by amysue on 27 August 2008 - 19:08

The recent discussions on DM testing raised a question for myself. What, and when, could one test young dogs that do not display outward signs for?

1. DM: If the DNA test is accurate, which there has been much debate on this board about, then you should be able to find out at any age which dogs are affected and which are carriers. If the DM Flash test is only accurate for those likely to be affected, what age is the earliest you can screen for it?

2. vWD: In an interesting article it is stated that something like 70-180% of the vWD factor would be clear for it, 50-70% of the vWD factor indicates the dog is likely to be a carrier, and below that the dog is affected. (Note: my numbers may be off as I could not locate the article.) If so, at what age could one get reliable numbers on their dog? Or do you have to wait for the disease to progress?

3. EPI has a test that I believe only identifies those affected. Can this be done at any age or do you need to wait for the dog to become symptomatic?

Just throwing some thoughts out there as I would use the above as screening tools as early as possible if there was proof to back it up. Unfortunately most dogs enter the breeding pool before they show signs. I'm excited what DNA research will offer in years to come!

by marjorie on 28 August 2008 - 00:08

Hmmm- I answered this question, but the answer appears to have been lost somewhere in cyberspace, so, I will answer again....

[quote] If the DM Flash test is only accurate for those likely to be affected[/quote]

?????? Who said that??? Where did you get that impression? Perhaps you misunderstood what you read? The Flash Test is accurate in affected dogs, yes, but it is also accurate in determining which dogs have the DNA marker for DM. However, neither the gene test or the Flash Test can tell which dogs will actually develop DM, and that is because there is more to developing DM than just having the marker, or the one gene! The marker/gene has to be triggered, for the dog to develop DM,and at this stage of research, we have no idea what the trigger is. It is probably somewhere in the Dark DNA. However, the Flash Test does sucessfully identify the dogs which have the DM markers.

Marjorie
http://www.gsdbbr.org --> The German Shepherd Dog Breed Betterment Registry (including frozen/chilled semen database)
Please utilize this registry to ensure a healthy future for our breed!
Be PROACTIVE!
http://mzjf.com --> The Degenerative Myelopathy Support Group

by marjorie on 29 August 2008 - 01:08

That being said, for breeding purposes:

They should not do either our test or the Gene test for screening of normal patients. Here is why:

A screening test has to meet 3 basic criteria:

must be cheap
1. in that case, the tests are good since they are relatively cheap
must correctly identify the affected individual
1. both tests have a 10% positive predictive value (or less) since so many that are positive in either test never get the disease
2. even in ALS or PPMS only a limited few who have the gene get the disease and many who do not have the gene get the disease

by marjorie on 29 August 2008 - 01:08

i. the DM Flash test is better, since 91% of the reason for getting the disease is genetic

ii. however, still only 10% who carry the gene will become affected

c. we do not believe that “test and slaughter” is good, since you will remove 9 or more dogs for every affected one

3. the affected individual must benefit from being identified

c. we do not know that we can alter the likelihood of finding the potentially affected dog will change the overall risk for that dog

by marjorie on 29 August 2008 - 01:08

d. the disease does not have a treatment (particularly for Boxers or Corgis) which we know can reliably affect outcome even though we have made strides in helping many GSDM patients

So, with those things in mind, I do not recommend testing normal dogs. In affected dogs who show clinical signs, it can confirm the presence of GSDM (even without all the other tests [probably in the GSD, at least]). So it is a great diagnostic test, just a lousy screening test.

Dr Clemmons

by amysue on 29 August 2008 - 02:08

Thank you for clearing things up for me. I understand that if everyone were to screen for it that we could do the breed a disservice by going overboard and causing extra cautious buyers and breeders to select only dogs that are cleared... thus greatly limiting the gene pool. My concern would be the same for EPI and vWD. One source claims that vWD can be found in 15 to 80% of the GSD population. That is quite a large margin of error. However, if everyone tested for it so that we had a better idea of what the real percentage is, than that can help us decide how to tackle the issue. If it is only around 15% then steps can easily be taken to decrease the number of those affected... however, if the percentage is high (as it sounds so the genes for DM) then carriers cannot logically be eliminated anytime soon... but determined breeders can decrease the number of carriers over time. It's not something one breeder can do alone, but screening your breeding stock does help fund research that one day may really contribute to the breed. I appreciate everyone who does put in their efforts.

by marjorie on 29 August 2008 - 05:08

-- > That is quite a large margin of error.

Well, I dont know that I would call it a margin of error. The dogs could be carrying the marker, but again, its not the marker, but what triggers the marker, be it DM, VW or EPI. I guess had people been more open, before these problems became so ingrained in the breed, we would not be where we are today. I, personally, would still do my best not to breed 2 dogs together that carry the marker. However, with approximately 75 % of the population carrying the marker, that could be difficult to find one that doesnt carry the marker. Joss, my male, tested clear, but I got sick of the show world and all the politics that went along with it, so I altered him. Had I known then what I know now, I probaby wouldnt have altered him.

At any rate, you are correct in saying that testing helps research. Only through research and testing will we eventually find the trigger that turns on these markers, or genes. I wish more people would embrace that concept, so research will be able to move in a forward direction. Having a marker or a gene is simply not enough. Its a great start, but that is all it is- a start. Its certainly not an end, unless people dont particpate in future research.

by Blitzen on 29 August 2008 - 16:08

When I read of the DNA test for DM I was very excited to be able to participate in the study of a serious disease like this one. Blitz is neutered, not breeding quality, but his pedigree is a good one and contains many well known and heavily bred dogs in Germany. I had him DNA tested because I think that it is important to know which GSD's may carry that gene recessively, which are likely to develop it in the future, and which are probably free of the gene. I also look at this test as a way to do something positive for the breed.

Some day we may have a cure for DM and/or a way to prevent at risk dogs from developing it because of the DNA and Flash tests. IMO that's a good enough reason to have every single GSD DNA tested for the presence of this gene. No one is suggesting carriers or at risk dogs should be withheld from breeding, it's really not about that at this stage of the game. It's about setting a baseline to try to understand why some dogs that test at risk never develop the disease while others do. It's also about identifying normal carriers and learning how to best use them in a breeding program. Statistically a carrier x carrier will produce 25% clear and if puppies can be DNA identified it would be very important information for breeders to use when planning a future breeding. This is assuming it proves to be a simple recessive mode of inheritance.

Blitz tested positive as a carrier and as a dog that will probably not develop DM in the future. That is of course great news for me. However, he probably inherited that gene from one or both of his parents, so it's something that those with related dogs should know about IMO. I don't think his breeder is still active in the breed, but I'm sure there are some here with dogs from that breeder or related dogs; maybe they too will want to have their dogs tested so they can help with the research. It's the right thing to do.

by marjorie on 30 August 2008 - 00:08

You couldnt have said that better, or more eloquently. If we are to move forward, we all need to particpate in research. if we do not, we will never be able to rid the breed of this horrid disease :(

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