THE CANINE GENETIC SYSTEM
by Nathan B. Sutter and Elaine A. Ostrander
Purebred dogs are providing invaluable information about morphology, behaviour and complex diseases, both of themselves and humans, by supplying tractable populations in which to map genes that control those processes. The diversification of dog breeds has led to the development of breeds enriched for particular genetic disorders, the mapping and cloning of which have been facilitated by the availability of the canine genome map and sequence. These tools have aided our understanding of canine population genetics, linkage disequilibrium and haplotype sharing in the dog, and have informed ongoing efforts of the need to identify quantitative trait loci that are important in complex traits.
Almost 38 million households in the United States (36%) own at least one dog1,and it is estimated that 55% of these dogs are pure bred. The American Kennel Club(AKC), the most recognizable purebred registry in the United States, registers 154 breeds of dog, with the 20 most popular breeds making up over 70% of registrations (FIGS 1,2).The total health-care expenditure on dogs is nearly 20 billion US$ (REF.1); the level of medical surveillance and care that pet dogs receive is second only to that to which we treat ourselves2.Nearly half of genetic diseases reported in dogs occur predominantly or exclusively in one or a few breeds 2,3. Susceptibility of some breeds to particular diseases such as types of cancer, deafness, forms of blindness, cataracts or metabolic disorders, coupled with a near absence in other breeds indicates that a subset of dog breeds are strongly enriched for particular disease alleles (BOX 1). Such an enrichment can be caused by origination from a small group of founders, population bottlenecks and popular-sire effects4. But this enrichment will only occur when the number of risk alleles is small, and they are relatively rare in the overall population. Dog breeds are therefore similar to geographically isolated human populations, such as those from Finland or Iceland, except that the isolation is more extreme. This offers an enormous advantage in the search for genes associated with complex diseases, which, in theory, can be more easily mapped using dog families than human families.
Here we describe the growing role of modern dog genetics in improving human health through the use of purebred dogs to uncover genes that are important in development, behaviour and disease susceptibility. First, we summarize what is known about the domestication of the dog from the wolf. We then discuss the canine genome map and sequence, focusing on comparative aspects, and how our understanding of dog population genetics can inform the mapping of human disease genes, including COMPLEX TRAITS. Each of these advances is tied to recent and rapid progress by the research community in mapping, and ultimately sequencing, the canine genome. As information about dog health and biology grows, knowledge about our own species also advances. In the following discussion we describe work that, because of its timeliness or innovation, has moved dog genetics forwards and has contributed to the development of purebred dogs as a new and unique genetic system.
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