Dogs are man’s best friend, and this friendship has come a long way. In fact, the dog Canis lupus Familris, was the first animal to be domesticated by man, long before cows or sheep. All dogs share a common ancestor with wolves. The first “wolves” were domesticated between 15,000 and 30,000 years ago, possibly to help them hunt or defend themselves from other animals, but also benefit from protection and as food. man. But it was only in the last two centuries that the modern dog breeds we know today were truly created, with today more than 400 breeds listed worldwide.
A natural and unique research model for genetic research
Why is the dog a good role model in genetics? Dogs are close to humans in genetic similarities and they also share the same habitat, food, stressors and sometimes even sofas! Dogs develop many genetic diseases similar to those of humans, such as the Golden Retriever chromosomal disease, which have similar genes and pathophysiology.
Read more: How humans formed dog brains and why they gave it back to us
Unlike other classical models used to study genetics, such as mice or fruit flies, we don’t have dogs in the lab. We work closely with dog owners, breeders, breeders clubs and of course veterinarians who collect samples as part of their canine patient care routine and with permission of the owner. It is from these blood samples provided by veterinarians, from dogs with genetic disease and from undamaged dogs that we perform the genetic analysis.
The dog is a “natural” model: we are studying specific traits that are naturally present in dogs, and especially frequently in certain breeds, that suggest a genetic origin. Indeed, some dog breeds are predisposed to developing complex genetic diseases – such as hip dysplasia, cancer, immune diseases – or even more “simple” diseases, such as schizophrenia. conjunctivitis, epilepsy, and dermatology in particular. The mutations that cause these diseases were actually selected unintentionally by humans during the creation of dog breeds.
Therefore, we are looking at the DNA of these dogs to find the genes and their alleles (mother or father gene versions) that are associated with these diseases. The goal, then, is to transfer our discoveries to the human race by specifically collaborating with groups working on the same diseases in human medicine, to bring reflections, knowledge, and insights into the future. and medical benefits for both species.
To do this, since the 2000s we have built a collection of DNA samples, from blood and tissue samples provided by veterinarians. This collection was then organized and structured, and we now have a BRC: a “biological resource center” comprising more than 32,000 canine DNA and 6,500 tissues – the Cani-DNA bioresource center. Led by Dr. Catherine André, this biological resource center, in a network of four National Veterinary Schools, the company Antagene and the French association of practicing veterinarians, AFVAC, has its scope. national and international vision.
The idea that dogs make up a unique and particularly interesting pattern in genetics really materialized in 2005, after sequencing the DNA of a boxer at the Broad Institute, USA Ky. Since then, a community of 200 researchers has worked on the genetics of not only common diseases in dogs and humans, but also morphology, behavior, and lifespan.
A companion for basic research
What stands out when looking at 350 dog breeds is the amazing variety that exists in terms of size, color, coat, while it is one species and the same species. Today, we find very small breeds of dogs only about 10 cm and weighing less than 2 kg like Chihuahuas, but also huge breeds, such as Great Danes, more than 80 cm long at the shoulder with great weight. more than 80 kg.
This amazing morphological variation thus underlies that many genetic mutations have appeared in the DNA of these dogs, during the evolution of the species and the artificial selection applied to the breed of the species. People. Finding these mutations therefore offers the opportunity to understand the genetic mechanisms that interfere with an organism’s development and determine its morphology, which could help us understand some of the most common diseases. human characteristics, such as malformations of the bones.
Unlike in humans, where hundreds of genes involved in height and weight variation have been observed between individuals, it was recently shown that in dogs, only about 15 genes are involved. Some of these genes are known in humans and others are not, thus providing new avenues of exploration to understand how genes interfere in the development of an organism. .
An unusual old story
It is generally accepted that for domesticated species, most of the morphological traits selected by humans will be the result of mutations that emerge after they have been domesticated. So for dogs, it is thought that the morphological differences are the result of mutations that may well have emerged after domestication, less than 15,000 years ago.
But for one of them, we discovered a completely different story. In a study that I did (Jocelyn Plassais) in the United States in the lab of Dr. Elaine Ostrander and recently published, I identified a mutation associated with the IGF1 gene that allows the production of a growth hormone and this would account for 15% of the observed height/weight variation between dog breeds. Unlike other genes involved in size change in dogs, this mutation is much older.
Read more: What did prehistoric dogs look like?
Indeed, by studying DNA from canine fossils between 1,000 and 53,000 years old, we have shown that this mutation existed in wolves more than 53,000 years ago, long before the first wolves. domesticated by humans. Humans would therefore have used this naturally occurring mutation in wolves tens of thousands of years ago to create the first small dogs, and will continue to play with this ancestral mutation present in certain dog breeds to create new breeds.
The goal of our research now is to try to understand how these mutations work, that is, by what genetic mechanism we actually go from being the size of a dog. ruffled to an individual German Shepherd?