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PAG Presentation Describes Dog Model for OCD; Crowdsourcing Study of Dog Behavior Genetics

SAN DIEGO (GenomeWeb) – During a cat and dog workshop at the Plant and Animal Genomes conference held here Sunday, University of Massachusetts Medical School researcher Elinor Karlsson touched on ongoing efforts aimed at using dogs as a model organism for studies of obsessive compulsive disorder (OCD) and behavioral conditions.

In addition to highlighting findings from several past genetic studies of dogs with canine compulsive disorder, Karlsson introduced an effort known as Darwin's Dogs, which will pair genetic data generated with spit samples to behavioral information provided by the animals' owners, who can join the project free of charge and will be asked to fill out survey questions about their pets' habits.

Similar to OCD in humans, Karlsson explained, the most serious cases of canine compulsive disorder tend to start manifesting themselves in 'adolescent' dogs that are around nine months old.

The condition can be distressing, time consuming, and potentially injurious for affected animals. While some dogs with canine compulsive disorder might pace or chase their tails ceaselessly, for example, others groom excessively or suck their own flanks until the skin becomes injured or raw.

Both human and dog forms of the disease are thought to be highly heritable, though the nature of compulsive traits differ and the animal motivation for such behaviors are difficult to discern.

Whereas OCD affects an estimated 1 percent to 3 percent of the human population, Karlsson explained, canine compulsive disorder has been documented more frequently in certain breeds, including Doberman Pinschers.

In a study published in Molecular Psychiatry in 2010, Karlsson and her colleagues described a chromosome 7 region that appeared to coincide with risk of compulsive disorder in dogs, based on a genome-wide association study involving 92 genotyped and well-phenotyped Doberman Pinschers and 68 unaffected controls. That study implicated a cadherin-coding gene called CDH2, which is believed to have neuronal activity.

Subsequent analyses of mouse, dog, and human data are offering still further hints about the brain-related pathways at play in compulsive conditions, Karlsson said, pointing to a GWAS paper in Genome Biology in 2014 that again detected ties between compulsive behavior in Doberman Pinschers and other high-risk dog breeds at variants in CDH2.

Analyzing their data with the help of the MAGIC algorithm, Karlsson and her co-authors also uncovered three more genes in that study: the catenin alpha 2-coding gene CTNNA2; the ataxin-1 gene ATXN1; and PGCP, which codes for a plasma glutamate carboxypeptidase enzyme.

Such associations were not specific to Doberman Pinschers, though regions that have reached fixation in the genomes of dogs from that breed include sequences coding for brain-related genes — a pattern supported by findings from targeted sequencing studies.

Although GWAS of OCD done in humans have yet to yield strong genetic associations, Karlsson noted, there are hints that the same sorts of brain-related pathways contribute to OCD in humans.

With that in mind, Karlsson and her colleagues recently set out to garner much larger dog datasets that can be mined for future behavioral GWAS. The Darwin's Dogs effort, launched this past October, has signed up nearly 2,500 dogs — including mutts and representatives from various dog breeds.

Participating owners are asked to fill out surveys described their dogs' traits and behavior, including everything from front leg crossing to habits linked to impulsive or compulsive behavior.

So far, Karlsson said owners appear quite happy to provide information about their dogs' behavior, with tens of thousands of answers to survey questions rolling in so far. Data for each dog will be returned to the respective owner once it is available, she noted.

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