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Genetics and the Shape of Dogs

Studying the new sequence of the canine genome shows how tiny genetic changes can create enormous variation within a single species

Elaine A. Ostrander

Figure%201.%20Chihuahua-toy%20poodle%20mix%20and%20Scottish%20deerhoundClick to Enlarge ImageA pekingese weighs only a couple of pounds; a St. Bernard can weigh over 180. Both dogs, though vastly different in appearance, are members of the same genus and species, Canis familiaris. How dog breeds can exhibit such an enormous level of variation between breeds, and yet show strong conformity within a breed, is a question of interest to breeders and everyday dog lovers alike. In the past few years, it has also become a compelling question for mammalian geneticists.

The "dog genome project" was launched in the early 1990s, motivated by scientists' desire to find the genes that contributed to many of the ills suffered by purebred dogs. Most dog breeds have only been in existence for a few hundred years. Many exhibit limited genetic diversity, as dog breeds are typically descended from a small number of founders, created by crossing closely related individuals. Further, breeds often experience population bottlenecks as the popularity of the breed waxes and wanes. As a result of this population structure, genetic diseases are more common in purebred dogs than in mixed-breed dogs. Scientists have been motivated to use dog populations to find genes for diseases that affect both humans and dogs, including cancer, deafness, epilepsy, diabetes, cataracts and heart disease. In doing so we can simultaneously help man and man's best friend.

The initial stages of the dog genome project involved the building of maps that allowed scientists to navigate the dog genome. Quick to follow were the production of resources that facilitated the manipulation of large pieces of dog genome DNA and a numbering of the dogs' 38 pairs of autosomes (non-sex chromosomes) as well as the X and Y chromosomes. Finally, in 2003, a partial sequence of a standard poodle was produced that spanned nearly 80 percent of the 2.8 billion base pairs that make up the dog genome. This was followed quickly by a concerted effort to fully sequence the boxer genome, producing what is today the reference sequence for the dog.

How is this information being used by geneticists today? The availability of a high-quality draft sequence of the dog genome has quite literally changed the way geneticists do their work. Previously scientists used so-called "candidate gene" approaches to try and guess which genes were responsible for a particular disease or trait of interest. By knowing something about what a gene does or what family it belongs too, we can sometimes, but not always, develop excellent hypotheses as to what happens when a specific gene goes awry. However, candidate gene approaches are often characterized by frustration and great expense. Hence, companion-animal geneticists are turning increasingly to the more sophisticated genomic approaches made possible by the success of the dog genome project.

Central to our ability to use the newly available resources is an understanding of breed structure, the strengths and limitations of the current molecular resources, and consideration of the traits which are likely to lend themselves to mapping using available resources. In this article I highlight first our current understanding of what a dog breed really is and summarize the status of the canine genome sequencing project. I review some early work made possible by this project: studies of the Portuguese water dog, which have been critical to our understanding of how to map genes controlling body shape and size, along with studies aimed at understanding the genetics of muscle mass.

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