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Dog genome sequenced

Today a plethora of dog genome-related materials are published, including a new book entitled The Dog and Its Genome and a series of primary research articles in the journal Genome Research. These publications, concomitant with the publication by Nature of a high-quality draft sequence of the dog genome, are expected to provide both researchers and the public with informative resources about canine genomics and biology.

"Canine genetics has entered a period of unprecedented growth and discovery," explain Drs. Elaine Ostrander and Francis Galibert 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."

Phenotypic variation among dog breeds, whether it be in size, shape, or behavior, is greater than for any other animal. Because of this diversity, the dog has attracted enormous interest as a model organism for genome plasticity. In addition, dogs are susceptible to genetic diseases that are difficult to study in humans, including cancer, blindness, heart disease, deafness, autoimmune disorders, and neurological diseases, making the dog model system particularly useful in medical and pharmaceutical research.

The Dog and Its Genome puts these and other aspects of the dog into context and focus. In the book's 26 chapters, dog experts cover morphological and behavioral variation in dogs, their origins and domestication, and characteristics of their genome. Chapters are devoted to discussing the genetic basis of canine diseases, as well as health initiatives aimed at curing diseases in dogs by approaches that include genetic testing and gene therapy. The book also deals with the history of dog breeds, the American Kennel Club, dog shows, and dogs as helpers.

How canine chromosomes crumble

In a special dog genome section of the journal Genome Research , University of Oxford researchers Dr. Caleb Webber and Prof. Chris Ponting are publishing a manuscript describing their comparison of dog and human chromosomes. Since the evolutionary divergence of dogs and humans approximately 95 million years ago, canine chromosomes have undergone considerable breakage relative to other species. In contrast to the 46 chromosomes present in each human cell, dogs possess 78 chromosomes, but each set essentially encodes the same amount of information.

"We present a new model of chromosome evolution that accounts for the extensive breakage seen in the dog genome," explains Webber. "Our results demonstrate that dog chromosomes have not broken randomly, which is the commonly held view, but instead that they preferentially fracture within ancient 'hot spots.' These fragile 'hot spots' contain an unusual number of guanine and cytosine DNA bases and appear to suffer higher rates of mutation."

SINEs of genetic diversity

Another study appearing in the dog genome section of Genome Research highlights an important source of canine genomic variation: SINEs, or short interspersed elements. SINEs are abundant mobile DNA elements that are common in mammals and have contributed extensively to genome evolution. In their publication, Drs. Wei Wang and Ewen Kirkness, scientists at The Institute for Genomic Research, report the identification of more than 10,000 SINE insertions in the canine genome and describe the potential impact of these insertions on phenotypic diversity in dogs.

"These SINEs are bimorphic, which means that at a given locus, some dogs have the SINE sequence while others do not," explains Kirkness. "This may have a profound impact on gene expression differences and disease determination in dogs."

SINE-associated diseases have already been described in Doberman Pinchers and Labrador Retrievers. For example, centronuclear myopathy, a muscle-wasting disease, is associated with a SINE insertion in a gene called PLPTA. The discovery of highly variable patterns of SINE insertion between individual dogs suggests that SINEs may play a significant role in canine disease and diversity.

Sizing up skeletal variation

Portuguese Water Dogs (PWDs) were originally derived from two kennels that disagreed on an appropriate size standard for the breed. Although there were only a few animals in this initial gene pool, the considerable size differences among the founding individuals has made the PWD breed an excellent model for investigating the genetic basis of skeletal variation. Dr. Gordon Lark, Distinguished Professor Emeritus of Biology at the University of Utah, has been studying skeletal variation in the PWD breed and is the principal investigator on two papers appearing in the dog section of Genome Research.

In one of the publications, Lark's group reports forty QTL, or quantitative trait loci, that are responsible for determining skeletal size in dogs. A striking aspect of these loci is that they control functionally related skeletal traits. "For example," says Lark, "one of the QTL that we identified controls both pelvic size and metacarpal length, but the two traits are inversely correlated. This could represent a functional trade-off between high-speed, energy efficient running versus limb strength. Mammals specialized for running tend to exhibit large pelvic bones and relatively slender limbs."

In the second manuscript, Lark's team describes the genetic basis for sexual dimorphism, or size differences between male and female dogs. They attribute the differences to at least two interacting loci, one of which is located on the X chromosome. "Sexual dimorphism seems to have evolved as females became smaller than males due to natural selection for optimal size," Lark explains. "This is consistent with our finding that a variant on the X chromosome plays a role in skeletal size determination."


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Source:North Carolina State University


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