(better known as the dog) Canis familiaris First domesticated animal ~300 breeds Dog genome with 7x coverage published July 14, 2004 2.5 billion base pairs 600,000 SNPs also published On July 14, 2004, the fully assembled dog genome with 7x coverage was released to the public. The effort was led by Kerstin Lindblad-Toh and her colleagues at the Broad Institute and the Agencourt Bioscience Corporation. The first draft of the dog genome came from a boxer because it was determined that this breed had the least amount of genetic variability among the 60 breeds that were originally considered for sequencing. At 2.5 billion base pairs, the dog genome is about a billion base pairs smaller than the human genome. Along with the dog genome sequence, 600,000 SNPs were characterized by examining sequences from nine other breeds, as well as wolves and coyotes. Researchers hope that the dog genome will generate insights into what makes breeds unique as well as helping to understand diseases shared by canines and humans, such as epilepsy and cancer. Photograph by A. D. Protopapas Canis familiaris (better known as the dog) © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458

Genetic markers for breeds Used microsatellites Able to determine breed with 99% accuracy Deduced breed phylogeny Asian and African breeds are oldest Previous studies using mitochondrial DNA (mtDNA) indicated that all domestic dogs are descended from wolves. Unfortunately, mtDNA changes too slowly over time to determine phylogeny among contemporary breeds, most of which are less than 400 years old. A study by Elaine Ostrander and colleagues maneuvered around this problem by using microsatellite markers in the nuclear genomes of dogs. By collecting microsatellite data from 85 different breeds, they were able to devise a system that assigned dogs to their correct breed with 99% accuracy. Using the microsatellite data, they were also able to construct a phylogenetic tree (shown in the slide) that placed African (e.g. Basenji) and Asian breeds apart from all others, and closer to the base of the tree, indicating that these were the oldest breeds. The microsatellite marker study also showed that contemporary Egyptian sight hounds and the Norwegian Elkhound, which were previously thought to be of ancient origins, are actually recent creations. From Figure 2 in Parker, H. G. et al. (2004) “Genetic Structure of the Purebred Domestic Dog” Science 304: 1160-1164. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458

Applications of Canine Genomics Understanding genetic basis of breed distinctions Find human disease genes for diseases shared by dogs and humans Find gene in easily controlled dog population Search for human homolog Studies of complex traits facilitated by genetic homogeneity in purebred dogs The application of canine genomics to authenticating dog breeds was demonstrated in the previous slide, but the dog genome will have its greatest impact in basic biology and medicine. For example, sequence comparisons between breeds will make it possible to determine the genetic basis for different breed characteristics. The medical applications of canine genomics arise from the fact that many of the most common diseases found in purebred dogs, such as cancer, heart disease, and epilepsy, are also found in humans. Over 400 hereditary disorders have been characterized in dog breeds. Because dog breeds are genetically well defined and often display unusually high occurrences of even rare diseases, they make an excellent model system for studying disorders. For example, the cause of narcolepsy in a group of Doberman pinschers was tracked down to a mutation in the hypocretin 2 receptor gene. Subsequent human studies showed that deficiencies of hypocretin in humans are responsible for most cases of narcolepsy. Additional medical benefits from the dog genome are expected to come in the form of disease gene homology searches between canine and human sequences and gene therapy experiments in dogs. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458