GDC EXCHANGE: From your perspective as a veterinarian and genetic counselor, how serious is canine genetic disease?

Dr. Jerold Bell: There is no simple answer as to where we stand now with genetic disease. Some breeds have serious problems with one or more genetic disorders, and others have more minor problems. Every breed and every disorder in the breed is different, based on the frequency of affected individuals and carriers in the population and on the seriousness of the disorder itself. All breeds have several disorders to try to deal with, and there are no simple formulas or fixes that apply across the board. We have learned, for example, that focusing our efforts on controlling just one defective gene can have the unanticipated effect of increasing the frequency of another defective gene in the breed. Each breed group has to look at the overall picture and design a program that will work best.

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GDC EXCHANGE: What is your concern about breeders focusing on the elimination of a single defective gene?

Dr. Jerold Bell: If we are selecting against one gene out of the estimated 100,000 genes in the canine genome without considering what desirable genes we may also be selecting against, we are doing a disservice to the breed. If breeders eliminate most of the carriers of a particular defective gene they can be eliminating entire families along with their desirable genes.

When tests for carriers exist, we advise breeding carrier individuals to non-carrier individuals in many cases so that we don't lose the good genes in that breeding program. But then the next critical step is replacing carrier parents with normal testing offspring. We need to select against carrier offspring, and to select individuals whom we know are not carrying the gene and have the positive characteristics we want to preserve in the breed.

A major problem is that it is almost never just one trait you are selecting for or against. There may be a couple of other genetic disorders you want to control--maybe hip dysplasia, or a problem in certain families in the breed with epilepsy. And that is just the negative selection pressure you want to apply.

You also need to put positive pressure on traits like conformation, behavior, personality, or performance characteristics like hunting or coursing. The more things that you want to select for, the smaller the group that you are selecting among becomes. And eliminating the families of carriers entirely can profoundly reduce genetic diversity in your breed.

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GDC EXCHANGE: What are the key principles or tools that breeders can work with?

Dr. Jerold Bell: With the exception of genetic tests, for many years we've actually had most of the tools we need to control genetic disorders, but I don't feel we have gotten the word out to breeders on how to use them.

They are relatively simple tools--diagnostic tests such as radiographs or blood tests to tell us whether a dog is affected or not; test matings to try to identify carriers, open disclosure of information so we know which dogs are affected and which are not, and genetic pedigree analysis and relative risk assessment.

In many instances these are the tools we have to use even now when we don't know a mode of inheritance, or don't have genetic or other tests for an apparent carrier.

One of the most important things we do is to try to understand the epidemiology of a defective gene. How old is that gene in the population? How far back does it go? Does it have a widespread pedigree base? Do all affecteds trace back many, many generations to where that gene originated, and so does the entire breed then have a high liability factor for carrying that gene?

A breed health survey is extremely important as a first step in starting a program for controlling a genetic disorder. The AKC Canine Health Foundation has worked on standardizing breed health surveys to help breed clubs get valid information about the whole breed, identifying the most common problems. The breed has to be open about which dogs are affected and which are not. Having an open registry is absolutely essential, whether it is run by the breed, a genetics researcher or by an outside organization like GDC.

For example, if we know that a disorder is produced by an autosomal recessive gene, then we know that both parents of the affected dog are carriers. We know that full siblings of carrier parents have a 50 percent chance of being carriers. And we know that offspring of carriers have a 50 percent chance of being carriers when bred to dogs with an unknown background. And if they are bred to dogs with a known background, we can actually calculate the relative risk of producing carrier offspring.

The bottom line is that we don't want to multiply the carrier frequency in the gene pool. Many people might say, "Well, I am producing carriers, but I know I can breed to normals and not produce an affected, so I don't care." We don't want to replace carrier parents with three or four carrier offspring, thereby increasing the frequency of the gene in the population.

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GDC EXCHANGE: So the real bottleneck in controlling genetic disease is people's attitudes rather than the technology?

Dr. Jerold Bell: Yes. No one really wants to breed carriers, or produce affected dogs, or propagate a genetic defect. But everyone is doing it, whether we know it or not. Some detrimental genes are in every litter. The major reason people are afraid to be open is that they don't want to be attacked; they don't want to be blamed. People have to recognize that breeders did not create defective genes. We need to put emotions and accusations behind us and deal with the problem of control.

When we start to do genetic counseling with a breed group, we say, "OK, we all need to work together for the betterment of the breed you love. We need to have everybody willing to talk to each other. We need for people to be open about which dogs are and are not affected.

For the vast majority of genetic disorders, maintaining open registries such as those at GDC is the only way we can get the selection potential we need to control those diseases. If we are dealing with polygenic disorders, or single gene disorders that we don't have extremely accurate tests for, we need to have pedigree breadth and depth. We need to look at the close relatives of a dog (the siblings, half-siblings, parents and their siblings) like GDC does with their KinReports™. You need to know not just who is normal, but who is affected, who are the carriers, and be able to utilize that information in making breeding decisions.

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