Simple strategies to reduce genetic disorders in dogs

By Carol Beuchat PhD

Over the last few decades, the number of genetic disorders in dogs has been increasing at an alarming rate. This is despite the diligent efforts of breeders to breed healthy dogs. Why is this happening?

I have created a very basic flow chart to illustrate how a breeding strategy to reduce genetic disorders in a population will actually have the opposite effect. I will go through each of the steps in the process, and you can follow along on the picture.
1) Let's start with a population of dogs in a closed gene pool like the one in the left circle below. Because all the dogs in the population come from a small number of founders, they are all related. Breeding two together is likely to produce offspring that are homozygous for some loci; that is, they inherit two copies of an allele that originated in a common ancestor of both parents. In the flow chart, the inbreeding step results on average in an increase in homozygosity in the offspring.

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2) Every dog carries dozens or even hundreds of recessive mutations. For the most part, these cause no problems if there is only a single copy of the mutation and the other allele at the locus is normal. But if two copies of the mutation are inherited, there is no copy of the normal allele. This is why inbreeding, which results in homozygosity. increases the expression of these recessive mutations.

3) Homozygosity also has more general detrimental effects on function such as reduced fertility, smaller litters, higher puppy mortality, shorter lifespan, etc., which we collectively call "inbreeding depression". Inbreeding also increases the incidence of polygenic disorders such cancer, epilepsy, immune system disorders, heart and kidney issues, and others.
4) Dogs with genetic disorders are usually removed from the breeding population.

5) Removing dogs from the breeding population reduces the size of the gene pool.

6) Smaller gene pools have less genetic diversity.

7) With less genetic variation in the population, the genetic differences among individuals are reduced and their similarity and relatedness increases.

8) Breeding related animals is inbreeding, so once again this step results in an increase in homozygosity.
From here, we now have a negative feedback loop that goes back to the top of the list of steps. Again, the increased homozygosity increases inbreeding depression, the risk of cancer, epilepsy, and other polygenic disorders, and the expression of recessive mutations.

The result of this negative feedback loop is the steady deterioration in health of the population over the generations unless there is appropriate intervention.
Let's have a look at the cycle for the population of dogs in the circle on the right in the illustration.

a) Breeders are very selective about which dogs are used for breeding. In general, about 25% of the purebred puppies produced are bred, and typically this is only one or two puppies per litter.

b) Of course, this means that 75% of the puppies are not bred. Removing them and any unique genes they may carry from the breeding population reduces the size of the gene pool.

c) Smaller gene pools have less genetic diversity.

d) If there is less genetic diversity, the dogs in the population are more similar to each other genetically.

e) Breeding dogs that are similar genetically will produce homozygosity in the offspring.

f) Homozygosity increases the expression of deleterious mutations.

Ultimately, the path feeds into the steps we have already described that form a negative feedback loop that increases the incidence of genetic disease.
The goal of selective breeding is to produce quality dogs. The two breeding strategies we have just described, breeding of related dogs (inbreeding) and breeding "the best to the best", do not result in improvement except in the short term. In the long term, the loss of genetic diversity limits the possibility of genetic improvement because the population has lost the genetic variation needed for selection. Inbreeding depression and increased incidence of genetic disease reduce the quality of the breeding stock, and improvement - or just maintaining quality - becomes more and more difficult. Without intervention, animal populations bred this way will go extinct.
If you understand the downstream consequences of breeding decisions, which are depicted as steps in these flow charts, you can prevent this cycle of genetic deterioration. For example, the simplest action to take is to be less restrictive about which animals are bred. Breeding 50% instead of 25% of the puppies produced will reduced the depletion of the gene pool. Breeding dogs that are less closely related will reduce the risk of producing genetic disorders in the puppies, and it will also reduce inbreeding depression. Replacing genes lost from a population through outcrosses to another population (i.e., through a plan of rotation breeding) or introduction via a cross-breeding program will broaden the gene pool and mitigate the negative effects of selective breeding.

DNA testing is a valuable tool but not the holy grail. By itself, it will not result in healthy dogs. Ultimately, to improve the health of the purebred dog we need to understand basic population genetics and follow a sound strategy for genetic management. Solving the problem requires understanding the cause and how some simple changes in the way we breed can dramatically improve the quality of the dogs we produce.

Continue to read Part 2 of this article:
"MORE ON "Simple strategies to reduce genetic disorders in dogs"

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