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Your dog is also a geneticist’s best friend

Dogs are man’s best friend, and this friendship goes back a long way. In fact, the dog Canis lupus familiaris, is the first animal species domesticated by man, long before cows or sheep. All dogs share a common ancestor with wolves. The first “wolf-dogs” were domesticated around 15,000 to 30,000 years ago, probably to help them hunt or defend against other animals, but also to benefit from the protection and food of men. But it’s only in the last two centuries that the modern breeds we know today were truly created, with today over 400 breeds listed worldwide.

A unique and natural study model for genetic research

Why is the dog a good model in genetics? The dog is close to the human species in terms of genetic similarities and it also shares its environment, its food, its stresses, and sometimes even its couch! The dog develops many genetic diseases similar to those of the human species, for example the ichthyosis of the Golden Retriever, whose genes and physiopathology are similar.

Read more: How humans shaped dog brains and why they give it back to us

Unlike other classic models used for genetic research, such as mice or fruit flies, we do not have dogs in the laboratory. We work closely with dog owners, breeders, breed clubs and of course veterinarians, who take samples as part of the care process for their dog patients and with the owner’s authorization. It is from these blood samples provided by veterinarians, from dogs with genetic diseases and from undamaged dogs that we carry out genetic analyses.

The dog is a “natural” model: we are working on specificities naturally present in dogs, and particularly frequent in certain breeds, indicating a genetic origin. Indeed, some breeds are, for example, predisposed to developing complex genetic diseases – such as hip dysplasia, cancers, immune diseases for example – or even more “simple” diseases, such as retinopathies, epilepsies, dermatological in particular. The mutations responsible for these diseases have indeed been involuntarily selected by humans during the creation of dog breeds.

Dogs can have genetic diseases similar to those of humans.
Nathalie Spehner/Unsplash, CC BY

We are therefore looking in the DNA of these dogs for genes and their alleles (maternal or paternal version of a gene) involved in these diseases. The objective is then to transfer our discoveries to the human species by collaborating in particular with teams working on the same diseases in human medicine, in order to bring reflections, knowledge and a medical benefit to both species.

To do this, we have, since the 2000s, built up a collection of DNA samples, from blood and tissue samples provided by veterinarians. Then, this collection was organized and structured and we now have a BRC: “biological resource center” comprising more than 32,000 dog DNA and 6,500 tissues – the Cani-DNA biological resource center. Led by Dr Catherine André, this center of biological resources, in a network with the four National Veterinary Schools, the Antagene company and the French association of practicing veterinarians, AFVAC, is national in scope, with international visibility.

The idea that the dog constitutes a unique and particularly interesting model in genetics was really concretized in 2005, following the sequencing of the DNA of a boxer at the Broad Institute, in the United States. Since then, a community of 200 researchers has been working on the genetics not only of diseases common to dogs and humans, but also on morphology, behavior and life expectancy.

A companion for basic research

What is striking when looking at the 350 dog breeds is the incredible diversity that exists in terms of size, color, coat, while it is one and the same species. Today we find very small breeds of dogs measuring about ten centimeters and weighing barely 2 kilograms such as the Chihuahua, but also giant breeds, such as the Great Danes, measuring more than 80 centimeters at the withers for a weight greater than 80 kilograms.

A mutation leading to wide variety of height in dogs has been identified. It dates from before the domestication of dogs by humans.
Hannah Lim/Unsplash, CC BY

This great morphological variability therefore underlies that many gene mutations have appeared in the DNA of these dogs, during the evolution of the species and the artificial selections applied to breeds by the human species. The search for these mutations therefore offers an opportunity to understand the genetic mechanisms that intervene in the development of an organism and define its morphology, could make it possible to understand certain human diseases, associated for example with malformations of the bones.

Unlike the human species, for which hundreds of genes are involved in the variations in height and weight observed between individuals, it has recently been shown that in dogs, only about fifteen genes are involved. Some of these genes are already known in the human species and others are not, which therefore offers new avenues of research to explore in order to understand how genes intervene during the development of an organism.

An unusual old story

It is generally accepted that for domesticated species, most of the morphological characters selected by the human species would result from mutations that appeared after their domestication. Thus for the dog, it was thought that the morphological differences resulted from mutations which would have appeared well after the period of domestication, that is to say, less than 15,000 years ago.

But for one of them, we discovered a whole different story. In a study that I conducted (Jocelyn Plassais) in the United States in the laboratory of Dr Elaine Ostrander, and recently published, I identified a mutation involving the IGF1 gene which allows the production of a growth hormone, and which would explain 15% of the height/weight variability observed between dog breeds. Unlike the other genes involved in size variations in dogs, this mutation is much older.

Read more: What did dogs look like in prehistoric times?

Indeed, by studying DNA from dog fossils between 1,000 and 53,000 years old, we have demonstrated that this mutation already existed in wolves more than 53,000 years ago, long before the first wolf-dogs be domesticated by the human species. The human species would therefore have used this mutation naturally present in the wolf tens of thousands of years ago to create the first small dogs, and would still continue today to play with this ancestral mutation present in certain canine breeds. to create new breeds.

The objective of our research is now to try to understand how these mutations work, that is to say, thanks to what genetic mechanisms do we actually go from an individual the size of a poodle, to that of a German Shepherd?

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