There is a major concern regarding breeding and the genetics of epilepsy and how the epileptic pups got that way. This is a major concern to us, to the Standard Schnauzer people, and to all dog owners in general.

We have been doing some research regarding breeding and our Korie, the Standard Schnauzer with epilepsy. We have researched 1. Line Breeding, 2. Cross Breeding, 3. Inheritance, and 4. Mathematics of gene pairs.

Any breeder will tell you that breeding is a "crap shoot." You have the back yard breeders, and you have the professional breeders. The back yard breeder is doing breeding for the "bucks", but the object of the professional breeder is to preserve the established standards of the breed while at the same time attempt to eliminate the defective traits. That is, you want "go for the gold" and produce the canine that best matches the defined standard for the breed.

Through the study of pedigrees, the competent breeder studies the bloodlines and ascertains the relationships between the dogs in that pedigree. A dog or a bitch with a championship gives the canine some credibility to quality, however, you must look beyond what is on the piece of paper that says "Champion". It is the irresponsible breeder that assumes that their breeding stock is free of any defective genes or attempts to dismiss a genetic anomaly that is a problem of little or no concern. The breeder that attempts to hide any problems in their breeding program is just allowing water to build up behind the dam. The dam will eventually fail and the fanciers of the breed and the breed itself suffers. Professional breeders generally are in agreement that you want to eliminate or breed around any deleterious genes, but their methods may not be beneficial to the breed nor genetically healthy. The genetic defect can be anything from coloration to primary inherited epilepsy. To avoid, or reduce, and possibly eliminate genetic defects, the breeder must do their homework, that is, set up a program to:

• breed for the good of the breed, and not the kennel name
• study the scientific literature for the adverse condition(s) in other breeds
• collect the pedigrees and search for dogs that show a similar condition
• accumulate litter data to establish any pattern(s) in the lineage
• design test mattings (if necessary)

1. Line Breeding.

With line breeding, you breed a dam or sire to a 3rd or 4th cousin, or to a 3rd or 4th generation aunt or uncle. The breeder performs line breeding to increase the dominant gene pairs (NN) or homozygosity and fix desirable traits i.e., top line, square body, tail set, etc. The expression (the physical attribute or "what you see") of the desired traits is more predictable and more uniform in the dog. A side effect of line breeding is that it permits the "greater expression of recessive genes" according to Jerold S. Bell, DVM. In other words, it increases the chances of a recessive gene being paired up to become a phenotype, a physical trait, and be more predictable. Say, for example, that back in the 4th or 5th generation of a pedigree, a dog was brought in with a particular recessive gene on the bitch’s side of the line. Now assume that some of the offspring carries that recessive gene. Also assume that at some point, that same bitch was brought in on the sire’s side. As the line breeding continues, you eventually will have a mating of 2 carriers and suddenly where there were no problems, a deleterious recessive gene, like skabosis, becomes homozygous dominant and you have one or more affected dogs. At this point, the water that was building up behind the proverbial dam has caused it to fail.

Computer programs are available that calculate inbreeding coefficients They show that inbreedings from 5th and 6th and 7th generation have "more influence on the total inbreeding coefficient than the first-cousin mating" according to Dr. Jerold S. Bell (Getting What You Want From Your Breeding Program). This tells us that the genes from the dog’s common ancestors have a higher probability of appearing in the dog than those genes from a dog that only appear once.

2. Cross Breeding.

The next type of breeding is cross breeding where there are no common ancestors in the first 4 generations or any generations for that matter. The breeder brings in a dog from a different kennel to introduce new genes into their breeding pool. You are breeding a dog and bitch of mixed ancestry.

3. Inheritance.

When dealing with a simple recessive trait, you base your expected results on an initial assumption (we assume that primary inherited epilepsy is a simple autosomal recessive gene). The "results" here would be the affected pups of the litter. In this case we also assume that both dog and bitch are carriers of the recessive trait, that is, they are ’Ne’ (N = dominant normal and e = recessive epileptic). Then by use of the Punnett square diagram we have:

where NN is a normal dog, Ne is a carrier, and ee is an affected dog. This analysis gives the following status of a litter of 4 puppies as: NN, Ne, Ne, ee, or 25% are normal, 50% are carriers and 25% are affected, that is, we have a ratio of 3:1, 3 "normal" and 1 affected. The word normal is placed in quotes to emphasize the fact that 3 of the 4 dogs are not affected but 2 of those 3 "not affected dogs" are carriers. After removing the affected dogs from a breeding program, the dogs that remain have a 66% chance of being carriers.

4. Mathematics of Gene Pairs.

For a litter of 9 pups, this says that there should be 2 affected pups. However, this technique is not quite proper in that the data needs to be corrected. Using an a priori expectation and pre-supposing an expected ratio of 3:1, we use the "correcting equation" to better quantify the expected results:


c = p / ( 1 - q ) ** n

where:
    c = corrected value or corrected expectation
    p = proportion of affected offspring - .250 in this example
    q = proportion of "normal" offspring - .750 in this example
    n = number of puppies in the litter

For values of n ranging from 2 to 12, we have constructed the following table. The first column is the number of pups in a litter and the second column is the probability or corrected expectation based on the number of pups. The number of pups in a litter multiplied by the corrected expectation yields the decimal value in column 3. Rounding this value down gives a more realistic count of the number of affected pups. With regard to Korie’s litter that consisted of 9 pups, we know that there are 2 affected pups in her litter. Therefore, from the probabilistic standpoint, we have an exact match of the number of expected with the exact number of affected.

If no pups in the litter are affected, the status of the dog in question is still an uncertainty. In any litter, the actual ratio of "normal" and affected may be different from what is expected. A mating can produce normal offspring, carrier offspring, or affected offspring. In a posting on the EPIL-K9 Internet List in December 1996, a person stated that she had 3 epileptics in one litter of 5 and 2 in a second litter of 5. The table shows what to expect, and not what you may actually get.

In the October 1966 AKC Gazette, there is an informative article by Mark Roland titled "Finding the Genetic Link". It briefly describes how researchers at the University of Michigan determined the genetic marker for copper toxicosis, an autosomal recessive disorder that effects the livers in Bedlington Terriers. Please note, that the mode of inheritance is known. A 16 month old Bedlington Terrier male was diagnosed with the disorder. However, the parents did not have the disorder and so they were both carriers (Nt). The breeding was repeated. We emphasize repeated here because the breeding was a test breeding. It was part of a test program to verify a procedure to determine copper toxicosis -- it was part of university research! Their repeat test breeding produced 5 puppies. At 6 weeks of age, DNA samples (cheek swabs) were taken from each pup. From the DNA analysis, the researchers verified that one pup was affected with copper toxicosis. From the derived chart above, the mathematics infers that you should expect to have 1 affected pup from a litter of 5.

If there are no affected dogs in a repeat litter, the breeder still cannot claim that the sire and the dam are not at fault. There is a 5% chance that the recessive anomaly - primary inherited epilepsy in this example - is still present. A test mating would have to produce 11 normal pups and no affected pups to obtain a confidence level of .950 and 16 normal pups would need to survive to obtain a confidence level of .990 that a dog is not a carrier. A problem with this type of test case is that it may produce 11 carriers or 16 carriers.

Epilogue.
In March 1998 we were notified by Korie's breeders that there are 3 pups in the repeat breeding of Korie's sire and dam that are seizuring. At that time they requested that we participate in a research study to help find the genetic marker(s) for epilepsy. We sent a substantial sample of Korie's blood to Dr. Gary Johnson, DVM, PhD at the University of Missouri at Columbia. Dr. Johnson also received 23 other blood samples from the familial line of Korie and her parents and grandparents. We are enthusiastic about this research and we hope that Dr. Johnson will find the genetic marker for epilepsy in our lifetime.
To our knowledge, this study and this data are unique in that it is not from one or 2 dogs, but a family.