Jana Carraway reports on the MCKC 2000 Education Seminar, featuring renowned canine geneticist George Padgett DVM.
Part 1 of 2
".there is no hope for control without knowledge."
The educational seminar held Friday of Montgomery County weekend, featured Dr. George Padgett, DVM, Professor of Pathology at Michigan State University. Dr. Padgett is one of the most well known researchers, writers, and lecturers on the subject of canine genetic diseases.
Many of us have attended Dr. Padgett's seminars previously, usually a two-day presentation. Although this was a one-day seminar, the material was well condensed and focused and Dr. Padgett completed the presentation with examples specific to current Wheaten health issues.
Due to the volume of material in his presentation, both in range of discussion and pedigree analysis, a supplement focusing more specifically on "controlling canine genetic disease" through Dr. Padgett's methods of risk analysis and use of genetic pedigrees (example by example and step by step explanations of the calculations) will be included with the March issue and in Part 2.
For now, I would like to cover Dr. Padgett's philosophy regarding the control of canine genetic diseases and the key points of his methods for controlling canine genetic diseases.
The quotation following the title, ".there is no hope for control without knowledge", embodies his philosophy. All actions and responsibilities, as outlined by Dr. Padgett, are aimed at gaining knowledge to be used for the control of genetic disease. The people responsible for controlling canine genetic disease are the breed clubs and the breeders.
The actions a breed club should take to support the ability of club members and other breeders to control genetic disease in a breed include:
- Assess the problems in the breed via a health survey.
- Establish on Open Registry.
- Provide literature outlining the diseases in the breed, including clinical signs, method of diagnosis and treatment.
- Provide literature discussing various systems that can be used to control genetic disease and how to evaluate or estimate potential risks.
- Support breeders and owners. "They should strongly support those breeders and owners with the honesty, courage and foresight to openly register dogs affected with genetic disease, because there is no hope for control without knowledge."
The Soft Coated Wheaten Terrier Club of America has undertaken many of these steps to support breeders in the control of genetic disease by conducting the recent health survey, establishing an Open Registry, and endeavoring to educate club members, breeders, and owners. And while many of these activities must be driven by the national club, breeders, as individuals, must: participate fully in the Open Registry, follow-up on all puppies, keep meticulous records, and openly share such information.
Breed surveys, such as the recent survey of Wheaten Terriers, are used to determine the frequency of occurrence (percent affected) of genetic diseases in a breed. There are always discussions of how good or accurate survey results are; regardless, they are an estimate and most breed clubs have no better source of data. That includes our national club and our recent survey.
From the percent affected within a breed, an estimation can be made as to the frequency of carriers in the gene pool. This is where things get difficult and controversial! The reason it gets difficult is that in order to talk about the frequency of carriers (% carriers) a formula is needed to calculate the number. There is a formula for calculating the carrier frequency for simple recessive or dominant traits and it is called the Hardy-Weinberg Law. If you haven't heard the name of this law bantered around, you will! This is the Hardy-Weinberg Law:
(p + q)2 = p2 + 2pq + q2
You see two variables, p and q, which represent the dominant and recessive genes A and a, respectively, and 2pq represents Aa. The significance is that this formula works for one gene at a time, not a combination of genes such as are involved in polygenic traits. Dr. Padgett stresses that there is no formula for calculating the carrier frequency of a polygenic trait. Therefore, Dr. Padgett, and others, use the Hardy-Weinberg Law to guesstimate the carrier frequency, and thereby guesstimate the frequency of genetically normal dogs. As Dr. Padgett says, as imperfect as a survey might be and as imperfect as the calculations might be, "such information is essential if you want to approach the control of genetic disease in a logical manner."
To apply this method of calculation to the Wheaten survey results which found 5% occurrence of PLE/PLN in the surveyed population we find:
|Disease Frequency||Guesstimate of
Genetically Normal Frequency
|5% (from survey)||34.6%||60.4%|
|10% (just for example)||43.2%||46.8%|
|15% (just for example)||44.4%||40.6%|
For a polygenic trait, the guesstimate will be lower, not higher, than actuality. Since the Hardy-Weinberg Law is accurate for one gene, this guesstimate will be accurate for one gene of the polygenic trait!
An Open Registry is one of the most important tools a breed club can have for the control of canine genetic disease. From Dr. Padgett's book: "Registries, of necessity, must be the backbone of control of genetic disease in dogs. Control of genetic disease is a complicated problem, revolving around the provision of and use of information about the genetic makeup of dogs. If a registry is to be effective in the control of disease, the starting point must be the dog affected with a given trait."
An Open Registry, such as our Open Registry for PLE/PLN and RD, tells us which sires and dams have produced affected puppies and are therefore carriers or are themselves affected. The value of the Open Registry is that we can use the "known affected" and "known carrier" data to Retrospectively Test Mate dogs.
Retrospective Test Mating (R-T-M) is a mating for which the genotype (the actual genes) of the dogs was not known at the time of the mating. Since PLE/PLN are late onset diseases, retrospective test mating using data from the Open Registry is a very valuable tool.
Dr. Padgett emphasizes that we have an opportunity in Wheatens to gather a great deal of information through R-T-M of the breedings of Ch. Carlinayer's Brendon Murdock, Dockers. The reason Dockers is of such value is not just that he has produced a large number of offspring (and some beautiful puppies), but that it gives information on every dam that was bred to him and subsequently every other sire to which that dam was bred! For example, since Dockers is a known affected, if a breeding produces an affected pup, the dam is now a known carrier. If no affected pups are produced, the dam may be a carrier or may be clear. If she has in turn been bred to another known producer of affected puppies and still not produced an affected pup, she begins to look more like a clear or genetically normal. Each breeding of a dam that has been bred to a known producer or affected dog can be used as a Retrospective Test Mating. This information allows breeders to begin to assign risks to individual dogs or litters and begin to find breedings that SIGNIFICANTLY LOWER THE RISK OF PRODUCING DISEASE, thereby diluting the gene(s) and thus, the frequency of the trait.
To begin R-T-M, we first need to learn to construct a genetic pedigree.
A genetic pedigree is more like a family tree in that the dog in question is listed, as well as littermates, the sire and dam with as much as is known of their littermates, etc. Do construct a genetic pedigree on all your dogs, not just those dams bred to Dockers or sires bred to dams bred to Dockers. Let's get this started on all our dogs and breeding lines! We can sit around and share our dog's circles and squares!
The symbols to use for a genetic pedigree are: males are shown as squares, females as circles, and sex unknown is a diamond.
If a dog is known affected with the trait in question, the symbol is filled in solid. If a dog is a known carrier, the symbol is half filled in. If a dog is deceased, the symbol used is a cross or a line through the symbol. More than one trait, cancer and PLE/PLN for example, can be tracked at a time by dividing the symbol into sections, such as partitioning a square or circle. A breeding is indicated by the horizontal line connecting the square and the circle. Here's an example:
This pedigree tells us that dog 1 is an affected male born in 1990. This means his sire (2) and dam (3) are now known carriers. The grandparents, dogs 5,6,7,8 have 50% chance of being carriers. In litter B, born in 1991, each puppy has a 50/50 chance of being a carrier. Each puppy in litter C and D has a 50/50 chance of being a carrier. If dam 4 had been bred to Dockers (R-T-V to known affected) and no affected puppies were produced, she has a significantly higher chance of being genetically normal!
The information is not only valuable to breeders when searching for breedings to reduce the risk of producing affected puppies, it will also be valuable to researchers in the future as they go forward with family studies and the search for the actual genes. This may, in fact, be the most important use of the data. So, start drawing your genetic pedigrees and we'll continue this discussion in March and in Part 2!
Your homework assignment in preparation for the March issue is to read:
- Control of Canine Genetic Diseases by Dr. Padgett, DVM, available through Amazon.com.
- Future Dog, Breeding for Genetic Soundness by Patricia J. Wilkie, available at the AKC bookstore.