Unleashing the Power of Comparative Genomics
PUBLISHED ON November 15, 2024
Our bond with dogs may be the missing link to discovering the genetic basis of neuropsychiatric disorders.
Darwin’s Ark was founded on the idea that the better we understand our pets, the better we understand ourselves. We share so much with our pets—environments, behaviors, and even genetics. Humans share about 82 percent of our DNA with dogs, and recent research suggests that some of this shared genetic material may influence diseases that affect both species.
At Darwin’s Ark, scientists study dogs’ genomes—a dog’s complete set of genetic material. Our growing genetic database is a valuable resource for studies in comparative genomics, a field of research that compares the genomes of different species—such as dogs and humans— to uncover genetic and biological similarities. By identifying genes that influence similar biological processes in dogs and humans, researchers could develop treatments that target those genes and benefit patients in both species.
Comparative genomics can help researchers learn more about human health conditions that are difficult to study through traditional research methods. Neuropsychiatric disorders, or disorders that affect the brain and behavior, are challenging to study because of their diverse symptoms and scientists’ limited understanding of their genetic causes. About two to three percent of adults in the United States have obsessive-compulsive disorder (OCD), a neuropsychiatric disorder classified by repetitive behaviors and/or persistent obsessive thoughts that disrupt daily life. Dogs can develop a similar condition known as canine compulsive disorder (canine CD), where they get stuck in repetitive behaviors like tail chasing or flank-sucking. Dogs with canine CD cannot stop these behaviors even when they have harmful consequences.
The similarities between OCD and canine CD are striking. Both conditions exhibit similar behavioral traits and affected individuals often have family members with neuropsychiatric disorders, suggesting a genetic link. Humans with OCD and dogs with canine CD are even prescribed the same types of medications. However, these medications only work for about 50 percent of patients in both species, suggesting that compulsive disorders may arise from multiple biological mechanisms. By exploring more ways that genetics influences these behaviors, researchers hope to find more genes that can be targeted with drugs to help treat compulsive disorders.
Scientists need to study large numbers of genomes to identify genetic variants that give rise to complex traits like OCD. That’s where Darwin’s Ark comes in. By partnering with thousands of community scientists, Darwin’s Dogs has built a large database of dog genomes. A dataset at the scale of Darwin’s Dogs would be impossible to amass through traditional research methods, which makes it a powerful tool in comparative disease research.
Darwin’s Ark Scientists Find Four Genes Linked to OCD
In a 2017 study published in Nature Communications, scientists from Darwin’s Ark and other organizations used genetic data from mice, dogs, and humans to identify four genes linked to OCD. The study was also featured in an October 2017 National Institutes of Health (NIH) Director’s Blog post. Even seven years later, these four genes remain among the most significant genetic associations with the disorder.
Two of these four genes were identified because of previous research on canine CD, and helped to demonstrate that OCD and canine CD are influenced by the same class of genes. These crucial genetic links in humans might have gone undiscovered if dogs were not included in this research.
So, what do these four genes do? They’re all active in the cortico-striatal pathway, a brain circuit involved in movement and habit formation. Hyperactivity in the cortico-striatal pathway is known to play a role in many neuropsychiatric disorders, including OCD. Two of the four genes—one of which is similar to a gene involved in canine CD—make proteins that help maintain connections between brain cells. Some scientists speculate that mutations in these genes might muddle communication between brain cells, potentially explaining why OCD causes symptoms like getting “stuck” in repetitive thoughts or behaviors.
The Path Forward
Currently, Darwin’s Ark scientists are pursuing research that builds off of the 2017 Nature Communications study. Together with scientists from Dr. Kerstin Lindblad-Toh’s group at Uppsala University, they are analyzing genomic data from Darwin’s Dogs to expand this research.
Scientists in the Karlsson Lab at UMass Chan Medical School, one of Darwin’s Ark’s institutional partners, are also part of the Psychiatric Genetics Consortium, a global collaboration of researchers who study the genetics of psychiatric disorders.
While we still have much to learn about the genetic causes of OCD, studies like this one suggest that the path forward could be marked with pawprints. The large canine genetics datasets that helped power this research are only possible with contributions from dog owners. Through community science projects like Darwin’s Dogs, pet owners contribute to a growing body of scientific knowledge that can lead to breakthroughs in both veterinary and human medicine.
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