Thursday, December 8, 2005

Canine Genetics Made Easy?



First we had artificial insemination, then we had artificial insemination with frozen sperm ("pupcicles"), and then we had dogs being cloned ("Clone, clone on the range, where the dogs and the puppies all play ..."

Now scientists have mapped almost the entire canine genome. The article below, from The Boston Globe, gives the details:


Team of Scientists Maps Out 99% of Dog Genome

Scientists have finished a sophisticated map of a dog's genes, providing new insights into the deep links between humans and one of their most treasured animals, as well as creating a unique tool for studying a range of diseases, from cancer to blindness, that affect people and their dogs.

The team of scientists, led by the Broad Institute of Harvard and MIT, determined virtually the entire genetic code, or genome, of the dog, making the achievement the canine equivalent of the completion two years ago of the Human Genome Project, the scientists said yesterday. Rough drafts of the dog genome have been released over the past several years, but the new work represents the first highly accurate version and also includes, for the first time, a detailed library of common genetic variations seen in dogs -- making possible a new generation of fast, accurate genetic studies of diseases and other traits.

Biologists have taken up the genetics of many animals, but the dog is uniquely interesting and useful, the scientists said, because of its history. The modern dog, including several hundred breeds, is the product of thousands of years of careful breeding, aimed at drawing out specific behaviors, such as the obsessive herding of the Border collie, or appearances, such as the hairless Chinese crested. By applying the modern tools of genetics to these breeds, it is now easy to find the small genetic variations responsible for the differences, with applications from dog breeding to human psychiatry. The genetic map of the dog announced yesterday should also accelerate the search for the genetic causes of diseases that plague certain breeds, perhaps leading to cures for dog and man alike.

''It is a historic day in the relationship between man and dog," said Eric S. Lander at a press conference yesterday, as a pug and an Akita tussled in the back of the room at the Bayside Exposition Center, where a dog show was being set up. Lander is the director of the Broad Institute and the owner of two golden retrievers.

Scientists said that the dog also stands as a testament to the power of evolution -- and its importance -- at a time when some are challenging its teaching in public schools. Looking for the genetic causes of human diseases in dogs makes sense only if humans and dogs are close evolutionary relatives that share a common ancestor -- a fact that is strongly supported by the genetic map Lander and his colleagues found.

''Biomedical research today depends on evolution," said Lander. ''It is hard to say that it is 'just a theory.' "

The research, which is reported today in the journal Nature, was led by Kerstin Lindblad-Toh, co-director of genome sequencing and analysis at the Broad Institute. Using a blood sample from a boxer named Tasha, the team determined about 99 percent of the sequence of DNA that makes up the dog genome.

The team, which included researchers across the United States as well as in France and the United Kingdom, also compiled a list of 2.5 million places in this sequence where there are common differences among dogs. This was done, according to the Nature paper, by comparing Tasha's DNA with DNA from a poodle and a number of other breeds -- enough, the scientists said, to record many of the most common variations in dogs.

Having this list of common differences will make it far easier for researchers to do genetic studies involving large numbers of dogs, because they can focus on the places in the genome where dogs are likely to have differences that might explain why one dog gets bone cancer and another does not. For example, scientists who are interested in why some greyhounds get bone cancer, and others do not, can look at these places to see if there is a pattern, without having to determine the entire genetic code of each dog -- about 2.4 billion molecules long. ''This is really the big thing," said Gregory M. Acland, a senior research associate at the Institute for Animal Health at Cornell University.

Many ailments -- including cancer, epilepsy, and heart disease -- are thought to be similar in dogs and humans, but it will be easier to identify the genes involved using dogs, said Acland, who studies genetic diseases that affect vision. In contrast to humans, dog breeds are highly in-bred, making two dogs in the same breed more similar genetically than two humans. Thus, for example, scientists could compare Dalmatians that are deaf with those that are not deaf, and there would be fewer random genetic differences between the dogs clouding the picture than if the same study were done in humans.

The work described yesterday, and follow-up work planned to study specific diseases, were made possible by the efforts of the American Kennel Club and dog owners who agreed to send in blood samples from their pets. (Owners of pure-breed dogs who are interested in participating can find more information at www.dogdna.org.) The research was funded by the National Human Genome Research Institute, part of the National Institutes of Health.

Dogs themselves are a human creation, thought to have begun when people domesticated the wolf in East Asia. The new analysis suggests that this happened about 30,000 years ago, said Lindblad-Toh.

The researchers also compared the DNA of dogs with completed genomes for humans and mice, and what they found challenges one idea about what makes humans special. When the human genome was first compared with that of the mouse, several years ago, scientists found evidence that the genes that are active in the cells of the brain seem to have evolved more quickly in humans than in mice, hinting that this might explain the intellect of humans. The new analysis casts doubt on this theory, because it shows that the brain-related genes in dogs have been evolving just as fast as those of humans, according to Tarjei S. Mikkelsen, a scientist at the Broad. The dog has about 19,300 genes, slightly fewer than humans, who have about 20,000 genes, according to Lindblad-Toh.

The researchers also identified a portion of the genome, about 5 percent, that is shared by dogs, humans, and mice -- meaning this portion is apparently essential to mammals. Yet less than half of that is devoted to genes. What the rest of the genetic material does is a mystery, but it is thought that some of this material may regulate when the genes turn off and on in particular cells. Still, the fact that the function of this crucial part of the genome is unknown underlines how much there is to learn.

For those who have been involved in dog genetics for years, there is hope that the new work will put the dog on the same footing as other favorite research organisms, such as the fruit fly and the mouse. In a way, it is a logical next step for the dog, which has done so much for humans -- guardian, hunter, companion. Yet there is also irony in discovering the scientific potential of dogs, noted Mark W. Neff, a scientist at the Center for Veterinary Genetics at the University of California, Davis. ''We are so close to our pet dogs, that we stop thinking of them as this incredible, unique species," Neff said.

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