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polygenic disease
POLYGENIC DISEASE SUCH AS HIP DYSPLASIA

Dale Malony: I’m curious how we should be calculating the probabilities of transmission of polygenic diseases, such as Hip Dysplasia. A dog might produce one puppy that has an extremely bad case and another that has a mild case, because of either the number of genes passed, or however that functions. Isn’t there someway that we could track the likelihood that a dog is going to transmit Hip Dysplasia and maybe use that number in our calculations? Say that one dog tends to throw to Hip Dysplasia 30% of his offspring, but another tends to throw it to only 10%. Can we assume the dog with the lower production carries or passes fewer of the genes?

Dr. Padgett: Absolutely. That’s exactly what you do. That is what your target is. We call that "progeny testing," and that progeny, or that dog that throws 10% of his progeny abnormal is better genetically than that dog that throws 30% of his progeny abnormally.

Dale Malony: We’ve talked about how to do calculations on our internet group. We’ve looked at and said this dog is affected, so if he’s bred he is going to produce 50 percent carriers if bred to a non-carrier. Would you consider it 50/50 that the pups might turn out carriers? Or could we say that we know from this dog’s other litters that we should only be counting this at a 10 percent?

Dr. Padgett: Yes, that is your target. The problem is that you need enough data to make that real. And the problem that we have in dogs is we don’t x-ray all our dogs. So we cannot really evaluate sires the way we handle our dogs. Here’s the general rule - we radiograph the dogs that we consider breeders. Those are the dogs that we radiograph. And if we don’t think they are breeders, we don’t radiograph unless we’re really dedicated, and some people are.

I can show you breeders that do x-ray, or try to x-ray all of their dogs. And I can show you one of them at least that really reduced the frequency of Hip Dysplasia by doing that. But it’s a very expensive process.

So where does that leave us? If your statement is true, and I think it is true, I think we need to understand that some dogs are going to be better than other dogs, even if they do bring some Hip Dysplasia. Where do we get enough data? Who do we get enough data from? Well, we’re keeping track of it all, and our matadors - our very best dogs, the ones that we breed a lot - will give us data on Hip Dysplasia if we follow those dogs. And the reason they’re matadors is that they produce winners. They also produce a lot of dogs that we radiograph.

Dale Malony: Now what about the whole concept of incomplete, or stronger or weaker genes? What could make something that’s distinguished by one gene express itself in varying degrees?

Dr. Padgett: There are what they call modifying genes, or if it’s a polygenic trait, genes that are stronger, or that are more severe. For example, one of the arguments about Hip Dysplasia is that the more severe dogs either have more genes for Hip Dysplasia, more total genes for Hip Dysplasia, or they have one gene or two genes that cause more severe disease than the other ones. And we don’t know which of those arguments is true. We don’t know.

But we do know a lot of genes modify traits so that one individual expression of the disease will be much more severe than it is in others. You see that a lot in diabetics. You see people end up with severe diabetes by the time they’re 50, and other people won’t become severely diabetic until they’re 65. I took pills for diabetes for about six years, but eventually that ran out and I’ve been on insulin for 10 or 12 years now.

And what causes that variation they say, are modifying genes that make a trait less severe or more severe. And you get into the same arguments about one-sided diseases. For example, Hip Dysplasia can occur in one leg or both legs. Most of the time it’s in both legs, but sometimes it’s in one leg. In some breeds they will tell you it will be either the right leg or the left leg, and it varies by breed. Labrador’s tend to have it on the left. If they’re going to have a unilateral Hip Dysplasia, it tends to be in the left leg.

Usually you won’t get it in severe dogs, but you will get it in relatively mild dogs. Unilateral also occurs in Legges Perthes in the small breeds, which is kind of "small dog’s Hip Dysplasia."

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Debbie Martin:
It seems that each breed of dog has been developed for physical traits that are aborations or deformities of the blueprint of the proto-typical dog. In our breed, some select for sloping top-line. Could this trait would be one of the contributing factors for diseases like Cauda Equina?

Dr. Padgett: Cauda Equina could be. Certainly, I think it influences Hip Dysplasia. You could probably really find that out if you went to Shepherds produced in some of the eastern European countries, which have really quite a different looking Shepherd than the Shepherds in this country. A lot of European Shepherds are different than ours. They don’t go for that sloping rear that we tend to go for. I bet you could compare them and come up with an answer regarding a relationship to Cauda Equina. I mean, that answer is pure speculation. You have to understand that it’s not scientific at all.

Debbie Martin: If the physical characteristics that identify our breed are part of the cause or of the health problems our dogs are experiencing, then how can we breed dogs that can still be identified as a separate breed but not exhibit the health problems associated with their appearance?

Dr. Padgett: There are breeds that you could give a clear-cut answer for. For example, bloodhounds used to have a really drooping lower lid…really drooping. In England they went through the standards of like 150 breeds and made them correct…things that induce disease, like drooping eyelids is the easiest example to understand. And now they don’t have that. Eventually that moved to America so now we seldom see Bloodhounds the way we used to see them with that big, kind of red dip under the eyes where the eyelid hung out. That clearly was a disease-enhancing feature.

In German Shepherds, as far as I can think of German Shepherds, I don’t think you have anything in your standard except that acceptance of the sloping rear end that really is disease enhancing. Some breeds have things that are disease enhancing and others don’t. And you guys really don’t.

Dale Malony: When you say the sloping rear end do, do you mean from the pelvis bone back to the tail, the croup?

Dr. Padgett: It is where most of that slant that you see when you set your dogs up comes from, and then when the dog stands up they still kind of slope to the back.

Debbie Martin Question: I want to go back to phenotype in our dogs. For as long as I have known Shepherds working in the animal hospital 30 years, it has always been believed that what you’re going to see in an old Shepherd is it’s hind end is going to go, and you’re going to put it down for arthritis or dysfunction of the rear-end. So it’s always been part of the history of this breed to have a weak rear end. Do you think part of our problem is that we’ve accepted this as part and parcel of being a Shepherd and possibly we should breed away from this?

Dr. Padgett: I think you can’t do anything unless you change the way Shepherds are judged.

Others’ Remarks: Some White Shepherds are not sloping and we do have a lot of…. I can remember back a lot of my old dogs had rear ends that were not sloping. Now they are getting weak in their rear end and finally we end up having to put them down and you never…

Debbie Martin: They’re finding now that there are varying degrees. There are degrees of Spinal Stenosis that are traumatic, like Judy’s, but there are also degrees where it may cause intermittent pain, but never gets to the point of loss of bowel or bladder control. And they said this was also new information that they hadn’t realized before. Some of it wouldn’t have been diagnosed or labeled as Cauda Equina’s disease. So, I guess all those old dogs with bad backs are going to be a mystery until we start seeing…

Dr. Padgett: You guys will be the ones that classify it. The more accurate you can be in your diagnosis and observations, the better off you will be, because you’re going to look at more dogs than any vet or any vet school.