This lack of specificity is difficult to reconcile with a desire to predict outcomes. Nearly everyone believes that German shepherd dogs are prone to hip dysplasia. We might say that the German shepherd dog has a breed predisposition or predilection for hip dysplasia. Yet, German shepherd dogs are not necessarily one of the breeds most commonly afflicted with the disorder, especially when their popularity is taken into account in terms of relative risk.
Whenever possible, risk should include a correction for a breed's prevalence in the population sampled. For example, if we were to run a hip dysplasia screening clinic and find that we had eight German shepherd dogs and four St Bernards with hip dysplasia, we might conclude that German shepherds have a higher prevalence of the problem. When these numbers are compared with the prevalence of each breed in our clinic population, however, the prevalence of hip dysplasia in St Bernards might turn out to be more than twice that in German shepherds. Because our hospital has many more German shepherd dogs, they would naturally account for a larger number of affected individuals. For many conditions, the prevalence might be high in mixed‐breed dogs (mutts) and cats (moggies), just because they represent the largest segment of a hospital population.
As a fictitious example, let's say we have a clinic population of 10 000 dogs, and when we review our medical records, we see that we have diagnosed 43 cases of follicular dysplasia over the past five years. Of these, 27 cases were seen in mutts, 11 in Chinese shar pei, and five in Irish water spaniels. In this hypothetical situation, which breed has the highest prevalence of follicular dysplasia? We cannot know until we see how the hospital population breaks down by breed. Of the dogs in the practice, 3723 are mutts, 89 are Chinese shar pei, and 12 are Irish water spaniels. According to our study, then, the condition is really seen in fewer than 1% of mutts, more than 12% of Chinese shar peis, and more than 40% of Irish water spaniels. The lesson is that, without accounting for breed numbers in a population, we could easily draw inaccurate conclusions (see 2.3 Prevalence and Incidence).
Relative risk, accounting for the prevalence of issues (events) in a specified population, is a reflection of probability. Also used is an odds ratio, wherein numbers greater than 1 represent increased risk and numbers lower than 1 represent decreased risk. Thus, a canine breed with an odds ratio of 4 has four times the risk of the general canine population of developing a specific condition. For the sake of accuracy, relative risk and odds ratios are not really synonymous. Relative risk is the ratio of two probabilities, the probability (risk) of an event in a select group over the probability (risk) of an event in the control group; the odds ratio is a ratio of two odds, the odds of an event in the select group over the odds of an event in the control group. Even with odds ratios and relative risk, breed predisposition is only a rough guide to disease prevalence. As long as individual breeders decide which qualities they wish to emphasize in their matings, overall breed statistics may not tell us much.
Finally, genetic and congenital abnormalities should be differentiated. The term congenital merely implies that a trait was present at birth. It does not mean that the disorder is heritable.
3.4.9 Hardy–Weinberg Law
Sometimes the magnitude of a heritable problem is not immediately obvious. It can be brought more sharply into focus with something called the Hardy–Weinberg law. This law helps to predict genotype frequencies with a simple algebraic formula, where p 2 is the frequency of the homozygous dominant gene pairing, 2pq is for heterozygotes, and q 2 is the frequency of the homozygous recessive gene pairing, with the individual gene frequencies, p + q, equaling 1. The Hardy–Weinberg law applies as long as no mutation (allelic changes), migration (“new blood”), or active selection for a trait occurs. Although the Hardy–Weinberg law is very useful in canine genetics, it must be remembered that dog breeding invalidates some of the basic tenets of the law because matings do not occur randomly or without selection, the way they might in nature. Also, the population is rarely in equilibrium because breeders often bring in breeding animals from outside the local population. As such, gene frequencies predicted by the Hardy–Weinberg law may not be completely accurate. Still, much useful information is provided.
Let's examine this with the American car‐chasing terrier (ACCT) and the prevalence of an autosomal recessive trait, von Willebrand disease, in this breed. Although the genetic mutation associated with von Willebrand disease has been determined in many breeds, it has not yet been characterized in the ACCT, but pedigree analysis suggests that it is autosomal recessive in nature. Because von Willebrand disease in the ACCT is autosomal recessive, it is difficult to distinguish between the homozygous dominant and the heterozygote; von Willebrand factor testing does not convincingly differentiate the two in this breed, and DNA mutation testing is not yet available. The only phenotype that can conclusively be demonstrated is the homozygous recessive, those affected with von Willebrand disease.
We did a survey with the local ACCT club and found that of 1000 dogs, 53 had von Willebrand disease. The ACCT club seemed happy that the prevalence of the disorder in the breed was of the order of only about 5%. Using the figures from the survey, the actual genotype frequency for homozygous recessive (q 2) is 0.053 and the gene frequency (q) is the square root of 0.053, or 0.23. We know the sum of p and q equals 1, and q equals 0.23, so p must equal 0.77, and p 2, the proportion with the homozygous dominant genotype, equals 0.59. On the basis of these numbers, 2pq, or 0.35 (35%), would be predicted to be the likely proportion of heterozygous carriers in the population.
What does this exercise in algebra tell us? Well, it tells us that although only 5.3% of ACCTs actually have von Willebrand disease, an incredible 35% of the ACCT population are carriers of the trait, which is not detectable by conventional means. The breed club has a potentially serious problem and would be best advised to invest money in a genetic test to detect heterozygotes. In the interim, however, the goal is to identify heterozygotes by other means so that animals that are homozygous normal can be discerned. We'll have to do the best we can with von Willebrand disease testing and progeny testing to differentiate normal homozygotes from normal‐appearing heterozygotes until that DNA test becomes available.
Identifying dogs that are homozygous recessive is not a problem. They are the ones with von Willebrand disease. We also know that both normal‐appearing parents of these affected animals are heterozygotes, carriers of the trait. Nevertheless, most of the other heterozygotes, which we would like to avoid breeding together, are clinically indistinguishable from the homozygous normal animals that we would like to use in our breeding program. For example, because we know that the parents of affected animals are carriers, it follows that at least one of each of their parents (grandparents of the affected animal) must also be a carrier. Inferring genotype from a family tree is known as pedigree analysis.
3.4.10 Preserving Genetic Diversity
Although establishing harsh criteria to rid breeds of genetic disorders by completely eliminating affected animals and carriers may seem reasonable, it is neither practical nor desirable. Because each animal carries nearly 20 000 different genes, ridding lines of all deleterious alleles is not possible. If carriers can be determined, however, breeding phenotypically normal dogs is a real possibility by never breeding two carriers together. If we are aware of heterozygotes, we can safely breed carriers with known normal individuals, and we will never see cases of the disorders we are trying to avoid. Is that not what genetic counseling is all about?
Trying to overcome polygenic traits takes longer and is more troublesome. Obviously, the higher the heritability of a trait and the more ruthless we are in selecting superior individuals for breeding, the more successful our selection process will be. This response to selection (R) can also be described as an algebraic function, R = h 2 S, where R is the
