Padgett: Is it genetic?

Is It Genetic?

(An excerpt from Control of Canine Genetic Diseases by Dr. George A. Padgett, DVM)

The thrust of this book is the control of canine genetic diseases by breeders and breed clubs. But one of the first things a breeder asks when confronted with a defect that apparently appears suddenly among the progeny they produce is “Is this disorder genetic?”

Sometimes it is easy to tell whether a condition is genetic, but at other times, especially if there are only one or two cases, it is very difficult to determine whether it is or not, and in the final analysis, you may not be able to state with certainty that a trait is genetic in origin.

For traits that repeatedly occur within a breed, the first question to ask is “Is it familial?” While there are many situations in which a disorder occurs in multiple members of a litter, in most instances, the disorder will not recur in spaced litters unless it is genetic. Genetic traits must follow family lines, and they do occur in multiple, widely spaced litters.

So if a defect occurs among the dogs in your kennel or in your breeding line, you must be sure the diagnosis is accurate. If it is, there are questions you can ask to determine whether a trait is likely to be inherited

In your breed
In other breeds
In other species

If the defect is inherited in dogs or in other species, then the chances that it is inherited in the affected dog(s) in your kennel are good. There are, of course, phenocopies – traits that are known to be genetic, but that can also be produced by something in the environment – that tend to confuse the situation. Cleft palate, a defect that occurs in nearly all breeds of dogs, is an example of a trait in which phenocopies occur. There are twenty-two compounds known to cause cleft palate in dogs. One of these is vitamin A. However, for vitamin A to cause cleft palate, a bitch would have to consume or receive 100,000 units of the vitamin on days 18 through 21 of her pregnancy (the critical period for cleft palate in dogs). That means the bitch would have to have access to the full-strength vitamin A additive or eat a couple of hundred pounds of dog food on days 18 to 21 of her pregnancy. Neither of these things is likely to occur in the normal course of events. Other examples are the anti-inflammatory drugs like prednisone or prednisolone. If these drugs are given on days 18 through 21 or are carried over in the body from a slightly earlier treatment, they can cause cleft palate. The point here is that these compounds are not generally available in the environment. They have to be prescribed and given exogenously to the bitch. She cannot just pick them up on the street. The end result is that most cleft palates in dogs are inherited, despite the fact that phenocopies are known to occur.

My view is that a trait that is known to be inherited in your breed, in other breeds or in other species should be considered to be inherited in your dog unless proven otherwise. Ask yourself whether the mode of inheritance of the trait is known

In your breed
In other breeds
In other species

If the mode of inheritance of a trait that occurs in your kennel or line is known in your breed, your problem is straightforward. You may not like this simple fact, but if you follow the principles in this book, you can control the trait.

If the mode of inheritance of a trait is not known in your breed but is known in another breed, it is less straightforward. For the most part, the mode of inheritance of a trait in one breed is likely to be the same in another breed, even though there are good examples where that is not true. It is still the most reasonable course to follow in attempting to adjust to the situation. The best, of course, is to urge your breed club to determine the mode of inheritance of the trait in your breed.

If the mode of inheritance in dogs is not known, but it is known in other species, you are left even more uncertain of the way in which to proceed. Nevertheless, the mode of inheritance for a given trait is most often the same even between species. Here it is even more important that a breed club play a role in generating accurate information about the trait of dogs in general and in their breed in particular.

The most difficult situation to encounter is when a trait is not known to be inherited in any species. Even so, the first thing to do is the same as for a trait that is known to be inherited: MAKE SURE THE DIAGNOSIS IS ACCURATE.

If the diagnosis is accurate, the following factors must be considered:

Is it due to trauma?
Is it due to infection?
Is it due to diet?
Is it due to a teratogen?
Is it due to a toxin?
Is it due to a birth injury?
Is it due to a chromosomal aberration?

If you can prove that any of these etiologies caused the trait, you are home free, because you do not have to consider the trait in regard to your breeding program, although you may very well have to worry about it in regard to kennel management.

When you cannot prove that any of the above etiologies caused the trait, problems begin to arise. Here is where a veterinarian’s “famous” advice to breeders comes into play. “Don’t worry about it; outcross, and even if it is genetic, it will go away.” It is this “famous” advice that has messed up breeds of dogs from time immemorial. Instead of controlling a trait when there are one or two dogs or one or two families involved, we outcross the dogs and spread the trait throughout the breed. Many breed clubs also play a role here. They have guidelines, rules, suggestions or advice for their members that say you don’t have to worry about a trait being genetic unless the dog or bitch produces at least two or three cases. In this situation, even the proverbial village idiot knows what to do – outcross the dogs. The breed club often gives this advice even if a trait is known to be genetic in other breeds, and of course, you end up spreading the disease. If the trait is new or very rare in a breed (one case per 5,000 dogs) and you outcross, you may breed that dog or bitch until their ears fall off, and they will never produce another case, because there are very few or no carriers of the trait in the general population of the breed. But you can be sure that you are spreading the gene(s) for the trait throughout the breed.

It is this “famous” advice that is currently causing breeders and owners of purebred dogs to spend $500 million annually to diagnose and correct genetic diseases in their breeds.

For situations in which you do not know the cause of a trait, and that trait has a severe detrimental effect on an animal, such as pain or permanent disability, you should determine that the trait is not genetic before you continue to mate dogs that produce it. Further, you should determine the cause of a trait if it is likely to cause severe monetary distress to any person who buys an affected puppy. This seems to me to be only good sense as well as fair play.

You should determine whether or not a severe trait is genetic before you proceed to spread it throughout a breed. This is discussed more in Chapter 8, “Test-Mating,” but succinctly, you repeat the mating or, if possible, breed the affected dog back to the appropriate parent to determine whether the trait is genetic.

When all is said and done, if you want to find out whether a trait is genetic, you can. In my opinion, you should.

My intention is to make this a straightforward text, so we will not get into deep discussions about Mendel or the Lyon Hypothesis or intricate breeding schemes. Many who read this text will say that the author didn’t discuss this or he didn’t discuss that. They will clearly point out all the exceptions to the rule, and there will be some, I can assure you. To cover every contingency for every disease and to meet everyone’s objections, I would need a book of several thousand pages, if not an encyclopedia, and I fear my hand would fall off before I was done compiling such a weighty tome.

For example, mitochondrial inheritance is important, but to my knowledge, it has not been clearly documented in any important way in dogs. Gene frequencies play a major role in the control of genetic disease, but with the exception of four breeds for which some data is available (Cairn and Scottish Terriers, Bichons Frises, and Newfoundlands), these frequencies are not well-established in dogs. Of equal importance are mutation rates, and these may well plague us even when DNA analysis allows us to identify specific genes in the various breeds. Since little information is available on these points, they will not be emphasized in this book

My goal is to help prevent serious genetic diseases in dogs, both in breeds and in kennels. If you learn the material presented here, follow the guidelines, and apply this information to your breed or your kennel, you will reduce the frequency of disease and it will not take you twenty-five years to do it.

You need three things to accomplish this task: knowledge, information, and honesty. All three are within your control.

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