FROM SINGLE GENE TESTS TO A GENOME-WIDE ANALYSIS – The Possibilities Canine Genetics Research has to offer

Canine genetic disease research has been going on actively for the past ten years and through this research, dozens of single gene tests have been developed.
Nevertheless, these single gene tests don’t provide us with a comprehensive overview on the genetic health and the genetic diversity in dogs.
The 1992 UN Convention on Biological Diversity set its objective to protect genetic diversity in animals. Now, over two decades later, the genome-wide DNA analysis of dogs finally makes it possible to simultaneously assess both the genetic diversity and inherited disorders and utilise the most comprehensive information available on the basis of breeding decisions as well as in health care.

Quick overview on canine genetics – Formation of dog breeds and the effects of bottlenecks on today’s canine genome

We all know that the origin of the domestic dog is in the Grey Wolf. Nonetheless, most people probably haven’t stopped to think about domestication of the dog as the starting point of possibly the biggest animal experiment made by man – selective breeding of dogs aiming to establish and maintain particular characteristics – the results of which can be seen in around 400 different dog breeds today.

The breeding of dogs for desired characteristics can cause so-called bottleneck phenomena that reduce genetic diversity. The variation of alleles (gene forms) is reduced if only a few individuals are allowed to transfer their genetic material to the next generation. A natural and historical example of the bottleneck phenomenon in humans is the founder effect that occurs when a new population is established by a very small number of individuals from a larger population (for example, the Amish or the French-speaking Canadians in Québec).

In dogs, as a result of breeding the genome has become more homogeneous, which also results in a favourable genetic structure for the identification of disease genes. Genomic homogeneity, resemblances in vital physiological functions between dogs and humans as well as the role of the dog in society (as the most popular pet that shares almost the same habitat) have turned the dog into an interesting and valuable model for medical research. Consequently, the information derived from canine genetics research has already been utilised in the identification of disease genes in humans.

What does breed disease heritage mean?

At the moment, approximately 600 inherited disorders or other heritable characteristics have been identified in dogs. At least half of them occur similarly in humans but the hereditary mechanisms behind the disorders have only been discovered for about one third of them.

Gene tests for inherited diseases are constantly developed as their underlying causes are identified. Mutation discoveries are often based on a few breeds included in the original study but further studies may indicate that the same mutation occurs in several breeds. Mutations are also thought to transfer from one breed to another as a result of crossbreeding.

Based on our current knowledge, one could rather talk about breed disease heritage instead of breed-specific mutations. A large proportion of the disease mutations were likely present already in the genome of the ancestors of today’s dogs. Therefore, not all mutations have arisen separately within each breed. As a consequence of the systematic breeding implemented by humans, certain mutations have become more frequent in certain breeds whereas other mutations occur more rarely or not at all in the same breeds. In principle, this leads to a situation where different breed groups and separate breeds have a characteristic breed disease heritage.

What is genetic diversity and why does it matter?

Genetic diversity indicates the extent of allele (gene form) variation as well as the degree of heterozygosity (inheritance of different versions of a gene from dam and sire) in an individual’s genome. As presented above, population bottlenecks may decrease the degree of heterozygosity, and lead to loss of allelic variation compared to the original population.

By maintaining and increasing genetic diversity it is possible to reduce the occurrence of inherited diseases. Genetic diversity prevents the recessively inherited diseases from being manifested, as carriers that carry only one mutated copy of a particular disease gene are usually unaffected by the disease or condition. In multifactorial (onset influenced by both genes and the environment) diseases genomic heterogeneity is likely to be the only way to reduce disease risks: diversity of genetic variants lowers the probability that an individual dog would simultaneously inherit all of the variants increasing the disease risk.

The concept of biological and genetic diversity is considered so important that there is an international convention for its protection. The Convention on Biological Diversity (UN, 1992) is an agreement covering the conservation of biodiversity, explicitly mentioning the protection of genetic diversity in all organisms, including the breeding of animals. When optimising genetic diversity in breeding, the offspring becomes more resilient to environmental change and has a greater capacity to adapt. Genetically diverse offspring is also more resistant to diseases, and litter sizes are also larger. On the contrary, selective breeding (e.g. systematic breeding of only one or two desired characters, or excessive use the same dogs for reproduction) increases inbreeding depression and consequently enhances the enrichment of recessive diseases.

So, let’s add some of that genetic diversity, please. But how?

Systematic development of genetic diversity helps conserve the genetic health and vitality of dog breeds.

This involves striving towards increased genetic variation. The following breeding strategies would help increase the diversity in dogs:

  1. Mating of genetically different dogs within the same breed
  2. Mating of dogs from different breeding lines (i.e. show dogs vs. working dogs, different coat colours)
  3. Mating dogs from different countries
  4. Controlled cross-breeding

The required genetic information can only be obtained by comprehensive assessment of the dog's DNA.

Systematic development of genetic diversity aims at improving and gaining long-term benefits for breed health. Nevertheless, many of its benefits are also direct: Use of one new genetically different sire in breeding already increases diversity within breed. The change can be instantaneous if several different individuals are introduced in breeding.

How will we assess the genetic health of dogs in the future?

As demonstrated in this article, a dog’s genetic health consists of its breed disease heritage and genetic diversity. The increase of genetic diversity offers a powerful means to reduce the occurrence of inherited disorders and to improve the genetic health of the future offspring within breed.

The modern dog DNA testing finally enables the simultaneous assessment of both the genetic diversity and a wide range of inherited disorders. This makes it possible to optimise breeding selections and to increase genetic diversity within all dog breeds. Carrier frequencies of single diseases should be taken into account, but in principle, it is recommended that healthy carriers (with a single copy of disease mutation) should be used in breeding to avoid unnecessary loss of genetic variation. In this context, the selection of a right kind of mating partner is essential.

Systematic development of the genetic diversity in a dog breed produces the best results when the diversity is measured genome-widely, and the outcome of breeding selections aiming at increasing genetic variation can be monitored from generation to generation. Single gene tests don’t provide us with sufficient information. Modern technology finally enables comprehensive genome-wide assessment of the genetic health of dogs allowing us simultaneously test both the inherited disorders and genetic diversity. Ergo, it is not justified anymore to base our breeding decisions only on the results of a single disease gene test as we would miss a significant amount of important information that a dog's DNA can tell us.

Let's Strive Together for Dog Health!