Longlease Bernese Mountain Dogs Cancer Information

The Bernese Mountain Dog and Malignant Histiocytosis:

A Challenge in Selection

By Elaine Gunn Lawrence


Why do Berners get MH more often than other Breeds?


It is well known among Berner owners that our breed is more susceptible than average to Malignant Histiocytosis. What isn’t often discussed is why this breed is more susceptible to this deadly disease than the vast majority of other breeds. The simple answer to why so many of our Berners are affected by MH is that the deleterious gene or genes responsible for susceptibility occur at much higher frequencies in the population of the Bernese Mountain Dog compared to the population of canines at large. The number of genes involved in conferring susceptibility for MH is unknown; however, it is believed to be polygenic (i.e. controlled by multiple genes), making it particularly difficult to predict.

Understanding Gene Frequencies

Why would a deleterious gene occur at a higher frequency in one breed compared to another? First, the deleterious gene would have been present in at least one of the breed’s “founders” when the breed was standardized — when we began registering Bernese Mountain Dogs as “pure bred”. This effectively closes the gene pool from the rest of the canine species, since interbreeding with other breeds is not permitted. We have no way of knowing if only one or more than one founder carried the deleterious gene(s), but from that point, the frequency of the gene(s) in question could have a) increased in frequency, b) decreased in frequency or c) remained at a constant frequency. Frequency of a gene increases when dogs carrying a particular gene are used in breeding more often than dogs not carrying the gene in question. The gene frequency will decrease in a population if dogs not carrying the gene are bred more often than dogs that are carrying the gene. The gene frequency will remain the same if dogs that carry the gene are bred in equal amount to dogs not carrying the gene. It may be that one or more of the popular sires that exercised profound influence upon the breed carried the gene(s) controlling susceptibility, which would have certainly increased the frequencies of these genes —consequently; we would see a corresponding increase in the number of dogs affected by the disease.

Can we reduce the incidence of this disease in our population by our breeding practices?

What can we do to reduce the frequencies of the gene(s) causing this disease when we can’t (yet) test for a genetic risk factor or factors? We have a hard time removing affected dogs from the gene pool because by the time we find they are affected, they’ve already been bred! …And there are also dogs that may simply carry the deleterious gene(s) without ever becoming affected by the disease.

Possible Solutions: Pros and Cons

Possible Solution #1: Pedigree research and risk analysis. The way most breeders look to minimize risk in the pups they breed is by looking at pedigrees 3 or 4 generations back and trying not to “double” closely on known affected dogs. This is certainly better than nothing, but it is pretty weak selection. Imagine trying to control hip dysplasia if you couldn’t know the status of the hips of the dogs actually being bred—only the status of the ancestors behind those dogs. An improvement would be to know the percentage of affected littermates for each dog in the pedigree; the problem being that many owners do not want the expense or emotional distress of necropsy. Also, there seems to be a propensity for some veterinary professionals to jump to the conclusion that any tumor found in a Bernese must certainly be Malignant Histiocytosis, so it is important for pet owners to know where to send tissue for proper diagnosis.

Possible Solution #2: Breeding with frozen semen of dogs known to be not affected. This would be a way to exercise direct selection by removing affected sires from the gene pool, and would certainly work to reduce frequencies of the gene(s) in question. However, there has been limited success with frozen semen breeding in BMD’s, and of course it is substantially expensive. Would puppy buyers be willing to pay more for puppies so breeders don’t go broke trying to breed using the 20/20 vision of hindsight?

Possible Solution #3: Dilute the frequency of the gene in the population by attempting a “Backcross” project. This was effective in the Dalmatian to address the genetic defect causing problems with uric acid metabolism. In Europe, a backcross between the Boxer and Corgi produced a natural bob tail in the Boxer to preserve the look of the breed when docking was banned. Note though, that the healthy progeny of the Dalmatian backcross project were not allowed to be registered with the AKC. The vote in the national club was lost by a single vote. An obvious drawback to this possible solution is that it is certainly controversial—particularly with “doodle” breeders often using “hybridization” as a marketing ploy. On the other hand, there are several FCI breed clubs that allow other breeds to be brought in at the breed club’s discretion. The dogs are given a special registration number for 3 generations, and after the fourth backcross to the original breed, they may be granted full registration privileges—provided that the dogs can pass the club’s breeding evaluation. (AKC’s new “Conditional Registration” works in much the same way, in that a dog of unknown parentage may be used in breeding on a conditional basis if it appears to be purebred. Conditional status is so noted on the pedigree until 3 generations of known parentage is established.)

Possible Solution #4: Use of math-based “predictor” software to objectively assess the risk of a potential mating. In large animal agriculture, the use of BLUP (Best Linear Unbiased Predictor) and BLUE (Best Linear Unbiased Estimator) can be used to improve the probability of producing desirable traits—such as to improve milk production in the dairy industry, for example. These predictors are only accurate if there is data on a large portion of the population and that data is accurate. Again the problems with litter data and diagnosis come into play. Some European breed clubs have begun using these tools.

Other Possible Solutions for the Future: We can hope that a genetic test will be developed for at least one genetic risk factor. However, this may not be sufficient to eliminate all cases of MH. Note that in humans 95% of breast cancer cases occur in individuals that test negative for the known genetic risk factors for the disease. There is also the possibility that a knee-jerk reaction in the breed to this new genetic test might cause decimation of the genetic diversity in the breed or the gene frequency of another deleterious gene to increase significantly, if the disease proves to be wide spread. Other solutions might involve treatments or gene therapy that will at least make this disease manageable instead of the death sentence it currently means for our dogs.

Other Factors

There are some factors which we can control that may help limit the susceptibility of our individual dogs, if not that of our breed — such as diet, exercise and environment. Certainly these factors are important and should not be overlooked. I give them only a brief mention here because these factors don’t account for the increased susceptibility of our specific breed. All the other breeds live in the same world Berners do, after all.

One other factor worth a mention is the effect of inbreeding upon longevity and upon the immune system as a whole. Inbreeding has been shown to decrease the breadth of immune response. It is possible that keeping inbreeding to a minimum might serve to decrease the susceptibility of the individual by maximizing the efficacy of the immune system. But, again, this does not account for our breed’s increased susceptibility as there are other breeds with similar levels of inbreeding not affected with this particular disease to the degree that Berners are.

Conclusion

The state of our gene pool is not a result of fate or the will of God. It is simply a direct result of the cumulative decisions made by breeders since the inception of the breed. Breeding is a trade off, and the gene pool will directly reflect our priorities as breeders. If we are given the tools to exercise selection with respect to MH, what trade offs are we willing to make?




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