Almost 38 million households in the United States (36%) own at least one dog1, and it is estimated that 55% of these dogs are purebred. 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. The total health-care expenditure on dogs is nearly 20 billion US$, the level of medical surveillance and care that pet dogs receive is second only to that to which we treat ourselves. Nearly half of genetic diseases reported in dogs occur predominantly or exclusively in one or a few breeds.
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 . Such an enrichment can be caused by origination from a small group of founders, population bottlenecks and popular-sire effects. 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.
In ancient Egypt, the appearance of Sirius, the dog star, heralded the onset of the Nile flood that brought prosperity and life. The dog is the oldest domesticated species and has served man by herding flocks, guarding homes, hunting by sight and scent, retrieving wild animals, pulling sledges and simply by providing companionship. The dog was the only domesticated species populating both the Old and New World five centuries ago, when Europeans found the Americas. So, dogs either came to the Americas with humans from the Old World or they were domesticated independently in the Old and the New World.
The phenotype variation in dogs led Charles Darwin to argue that different breeds had been independently domesticated from wild CANID species on different continents, perhaps descending from wolf, coyote and several jackal species. Mitochondrial sequence data, however, show that dogs descend solely from wolves. In a key experiment, Vila et al.7 analysed 261 bp of mitochondrial sequence from dogs,wolves and other wild canids, and showed that dog and wolf mitochondrial HAPLOTYPES were similar. Indeed, the most dissimilar haplotypes between the two species differed by no more than 12 substitutions.
By contrast, the minimum number of differences between dog and other wild canid haplotypes was 20 substitutions. Subsequent phylogenetic analysis of mitochondrial haplotypes identified four canid CLADES, including one containing 19 of the 26 dog haplotypes, but no wolf haplotypes. The existence of a dog-specific clade with high haplotype diversity supports a relatively ancient time frame for the domestication of dogs, perhaps >100,000 years before the present.
Mitochondrial sequence data have also been used to refute the New World domestication hypothesis. Mitochondrial DNA was sequenced from archaeological dog specimens collected throughout the Americas and dating before the arrival of Europeans. The haplotypes fit with those from modern breeds, which are known to have come from Old World domestication. They also included a large number of haplotypes assigned to one of the dog-specific clades.
Therefore, the haplotypes do not provide any evidence for an independent domestication in the New World. Savolainen and colleagues refined this picture by examining mitochondrial haplotypes from 654 dogs representing main populations around the world. They report a similar phylogeny in every geographic region, suggesting a single domestication event in one geographic region. The greatest haplotype diversity occurs in East Asian dog populations, consistent with the notion that the key domestication event occurred in Asia.
Beyond the time and place of dog domestication, there is interest in how domestication occurred. In what ways do all domestic dogs differ from wolves? This has been addressed recently by Hare and colleagues, who studied how dogs and wolves differ in their ability to relate to humans9. They devised a study in which dogs were challenged to find a hidden food reward, aided by a human who stared and pointed at the treat’s hiding place.Adult dogs and puppies, even those raised with little human interaction, did significantly better than wolves. Dogs have therefore acquired a social-cognitive capability to ‘read’ humans, which is lacking in wolves. Identifying the genes that regulate such evolutionary events will be both challenging and exciting.
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