Dr. Grossi's Blog
I enjoyed watching the variety of dogs from Pekingese and Pomeranians to Great Dames and Mastiffs at the Westminster Dog Show the last few nights. I began to think of the important contribution that dog genetics is making and will make to understanding the genetic underpinning of human illnesses. The dozen most common illnesses in dogs are also commonly found in humans. Some examples are cancer, allergy, heart disease, and epilepsy. Furthermore, dogs are highly inbred for specific traits such as size, coat pattern, color, and behavior such as pointing, retrieving, herding and swimming. In addition, dogs have large families with clearly documented genealogies. The inbreeding is especially important because each dog breed in an isolated population that typically goes back only a few hundred years, which limits the chance of spontaneous mutations as well as mutations from outbreeding. Also, dogs live in the same environment as humans do and are thus exposed to the same risk factors. All of these features make dog genetics extremely valuable and powerful in illuminating human illnesses.
There was a lot of skepticism about this conclusion until 1998 when Emmanuel Mignot at Stanford found the gene that causes narcolepsy in dogs. His group found causative mutations in the Hcrtr 2 gene of Doberman pinschers, Labrador retrievers, and dachshunds. This opened up a whole new molecular pathway involving sleep and researchers minds were also opened to the importance of dog genetics. Indeed, this discovery was important in convincing the National Human Genome Research Institute to support the sequencing of the canine genome, which was published in December 2005.
The power of dog genetics comes largely from the inbreeding and this is especially evident in complex disorders. In a given human illness there may be many responsible genes, but in dogs of a particular breed you will find exactly the same mutation as the cause in a small animal sample size because they have descended from an isolated inbred population. This characteristic of dog genetics is very powerful. If you find the same illness in two different breeds, you can find another causative mutation which leads to additional insights into the molecular pathways involved in the causation of the illness in question. These techniques can also be used to sort out how different breeds are related. The more variants that are shared, the closer are the breeds. This has led to a project called PhyDo which has revealed that 150 or so breeds recognized by the American Kennel Club recognizes break down into five genetically defined groups that can be further subdivided.
Some non-psychiatric illnesses that are currently under investigation in dogs include bladder cancer, squamous cell carcinoma, skin or coat color, atopic dermatitis, and neural tube defects. Some efforts are now being made to track down genes related to behavioral characteristics such as pointing (lifting a paw and holding it in the direction of a quarry) or "cocker rage" which is sudden unprovoked episodes of rage and aggressive behavior in generally friendly docile animals. This occurs in English cocker spaniels and English springer spaniels, as well as some other breeds. The hope is that this will get the researchers close to the gene or genes involved and can shine a light on rages in those who have schizophrenia, bipolar disorder, anxiety disorders, or depressions.
Going to the dogs is acquiring a whole new meaning.