Tasha, the boxer with the sequenced genome. Credit: National Institute of Health
This week marks the dog days of science, when the publication of a new book, The Dog and Its Genome, coincides with a series of dog genome articles in Genome Research and a high-quality draft sequence of the dog genome in Nature.
"It’s an exciting time to be working on the dog genome," said Ewen Kirkness, of The Institute for Genomic Research, via e-mail.
"Canine genetics has entered a period of unprecedented growth and discovery," as Elaine Ostrander and Francis Galibert wrote in their foreword to The Dog and Its Genome. "The dog is now set to take its rightful place as a valued system for genetic studies along with the mouse, rat, and several insect species."
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Gordon Lark's research uncovers the power of a single region of a chromosome to change several aspects of skeletal shape; Ewen Kirkness and Wei Wang found a type of variation that may be responsible for differences between breeds; and Chris Ponting and Caleb Webber identified genetic "hot spots" where chromosomes are likely to break. All of these were observed in dogs, but discoveries in our canine friends may have crucial implications for understanding the human genome.
Lark, of the University of Utah, was bribed into researching dog genetics. He had previously studied quantitative genetics in soy beans and only briefly thought about extending his results to the animal kingdom. Then, a Portuguese Water Dog breeder gave him a free dog, and dug up genealogical information on another 5,000, with the hope that he'd study dog genetics. It worked.
The principal investigator in two studies published in Genome Research, Lark exclusively studies Portuguese Water Dogs. He said they make for good subjects because the entire breed descends from a mere 30 ancestors.
In both of his studies, Lark compared DNA and skeletal structure to determine correspondences between regions of the genome and aspects of the skeleton. He then observed how changes in these regions alter a dog's shape and size.
The first paper concerns why female dogs are smaller than males. Through his comparison of genes and phenotype, Lark concluded that all dogs tend to get larger, but in females this process is inhibited. In males, the inhibition is, itself, inhibited, so males grow more than females.
In the second paper, Lark details 40 markers that are responsible for determining skeletal size. From this work, he concluded that single markers control multiple, related skeletal traits.
"It turns out that the shape of the head and the shape of the limb bones are connected by a single region of the chromosome, and this makes sort of functional sense," Lark said, noting that a fast dog, such as a greyhound, will want to have a small head, pointy nose and long legs, whereas a strong dog, such as a pit bull, will want to have a massive jaw and short, thick legs.
Lark said the greatest benefit of his technique lies in its medical applications. Dogs suffer from many diseases common to humans, including diabetes, hemophilia and autoimmune diseases. If we can take quantitative measurements that correspond to these diseases and compare those to genetic markers, we can find the genetic roots of the disorders.
"Initially, dog diseases were studied by waiting until the genetic cause of a human disease was discovered and seeing how that applied to dogs," he said. "But now, with the dog genome sequenced, it's really highly probable that we can discover the cause of a disease in a dogs and apply it to a human."