Darwin’s Dogs project
“The team, led by Elinor Karlsson, a professor in the bioinformatics and integrative biology program, hopes that studying a large number of diverse breeds and mixed-breed dogs will yield more insight into the genetic underpinnings of certain traits and illnesses in dogs, and one day lead to improved medical treatments for humans. Humans and canines share almost all the same genes and suffer from many of the same diseases..
— Shirley S. Wang – WALL STREET JOURNAL, Dec. 2, 2015
THERE IS NO COST TO PARTICIPATE. EVERY DOG – PUREBRED OR PURE MUTT – WILL HELP!
Darwin’s Dogs is an exciting new research project being run through the University of Massachusetts Medical School in collaboration with the International Association of Animal Behavior Consultants (IAABC). This project needs the input of literally thousands of dog owners nationwide in order to gain a real understanding of how genetics influence behavior and to learn insights into certain illnesses.
YOU CAN HELP! Through a series of short surveys on the Darwin’s Dogs website (http://darwinsdogs.org), dog owners are asked about their dog’s personality and behavior. After filling out the surveys, owners will receive an easy-to-use kit to collect a small saliva sample we can use for DNA analysis.
WHAT and WHY? Darwin’s Dogs is bringing together geneticists, animal behavior specialists, and pet owners to learn how genetic changes may lead to behavior differences — even in normal behaviors. This project is looking to gain new insights into various traits, including psychiatric diseases shared by canines and humans, to develop new ways to help both people and dogs.
Please help by visiting http://darwinsdogs.org and joining this important research today.
DOGS DEVELOP MANY OF THE SAME DISEASES HUMANS DO, MAKING THEM GOOD SUBJECTS FOR RESEARCH
Humans and canines share almost all the same genes and suffer from many of the same diseases.PHOTO: GETTY IMAGES
By SHIRLEY S. WANG
Dec. 2, 2015 1:29 p.m. ET
The DNA of dogs may offer clues about human conditions, such as obsessive-compulsive disorder and autism, according to researchers at the University of Massachusetts Medical School, who have launched a major study of canine genetics, behavior and personality.
The team, led by Elinor Karlsson, a professor in the bioinformatics and integrative biology program, hopes that studying a large number of diverse breeds and mixed-breed dogs will yield more insight into the genetic underpinnings of certain traits and illnesses in dogs, and one day lead to improved medical treatments for humans. Humans and canines share almost all the same genes and suffer from many of the same diseases.
Other scientists, including Brian Hare at Duke University, are focusing on pets and pet owners, investigating canine cognition to learn more about how both dogs and humans think and learn.
Dogs are a better natural model for some human diseases than mice or even primates because they live with people, Dr. Karlsson says. “Compared to lab mice, with dogs they’re getting diseases within their natural life span, they’re exposed to the same pollutants in the environment” as humans, she says.
Dr. Elinor Karlsson of the University of Massachusetts Medical School, with her sister’s dog, Beskow. PHOTO: MICHAEL J. BUTTS
Previous canine studies conducted by other scientists have shed light on human diseases like osteosarcoma, a type of bone cancer, as well as the sleep disorder narcolepsy and a neurological condition, epilepsy.
With osteosarcoma, the most common type of bone cancer in children and one that frequently strikes certain dog breeds, researchers have discovered that tumors in dogs and children are virtually indistinguishable. The tumors share similarities in their location, development of chemotherapy-resistant growths and altered functioning of certain proteins, making dogs a good animal model of the disease. Collecting more specimens from dogs could lead to progress in identifying tumor targets and new cancer drugs in dogs as well as in children, some scientists say.
Dr. Karlsson and her team at the University of Massachusetts, in collaboration with the International Association of Animal Behavior Consultants, hope to expand canine genetic discoveries with their project, launched in October and dubbed Darwin’s Dogs. Rather than focus on specific breeds and on DNA collected by scientists, the researchers are asking pet owners to share observations about their pets’ behaviors and personalities and to collect DNA at home via mouth swabs, similar to the way consumer genetics companies collect DNA.
Dr. Karlsson hopes the collective genetic and behavioral canine data will help elucidate psychiatric conditions.
She began her work on dog genes as a graduate student, when she helped map out which genes were responsible for coat color in boxers and bull terriers. The classic genetics research, published in Nature Genetics in 2007, showed that a technique called genome-wide association mapping, often known as GWAS, could be used within dog breeds to look broadly across genes for links with a condition or characteristic of interest.
Later, as a post-doctoral researcher, Dr. Karlsson worked with a team studying Dobermans and their high rates of a condition known as canine compulsive disorder. It is similar to humans’ obsessive-compulsive disorder, or OCD, which is defined as doing an otherwise normal behavior much too frequently. In the case of Dobermans, the behavior was chewing on their sides or on blankets.
Canine compulsive disorder starts in around early- to mid-adolescence—at about the same age as in humans and likely with similar neurological processes. Humans and dogs with compulsive disorders are treated with the same drugs, and among those treated with the drugs only 50% respond, Dr. Karlsson says.
The team studied genes of hundreds of Dobermans with and without canine compulsive disorder and initially identified one gene associated with the compulsive condition in the breed—called CDH2, the gene is thought to be important in human OCD—and later identified genetic mutations near CDH2.
Then the researchers looked at other dog breeds and found more genes linked to OCD and all tied into the same pathway in the brain, in a study published last year in Genome Biology. The team aims to look more closely at the genetics of compulsive behaviors and expand to other psychiatric conditions, which could lead to new targets for treatment.
Dr. Hare, a professor in the department of evolutionary anthropology at the Duke University Institute for Brain Sciences, is taking a similar approach with canine cognition.
Drawing on some methods used to test human infants, such as having babies complete various tasks while researchers observe and draw conclusions from the behavior, Dr. Hare began thinking about the millions of U.S. dog owners and all the data that could be collected if they were recruited to help with research. In 2013, he founded a company, Dognition, which tells pet owners they can be “citizen scientists” by getting their dogs to complete games, or experimental tasks.
In an exercise called the “memory vs. pointing task,” the owner shows the dog where a treat is hidden, then points in the opposite direction. The owner sees whether the dog goes to the treat, relying on his own memory, or if he heads in the direction where the owner pointed, suggesting he is more reliant on people than on independent problem solving.
Dr. Hare and his team have tested the validity of data collected from owners at home compared with that of data collected in the lab and found they were comparable—suggesting citizen-scientist data is useful and reliable, according to a paper they published in September in the journal Plos One.
The data tends to be interesting for pet owners, who often want to know how their dog’s results compare with other dogs’, says Dr. Hare. But as with any behavioral research, it can be difficult to know if behaviors and the motivation for behaviors are interpreted correctly, says Marji Alonso, executive director of the International Association of Animal Behavior Consultants, who is collaborating with the Massachusetts group.
Unpublished data from Dognition suggests that dogs experience cognitive decline, a phenomenon that hasn’t previously been established, Dr. Hare says. If the corresponding owner also develops cognitive decline, questions arise about whether there are environmental or behavioral factors affecting both human and canine, Dr. Hare says—an inquiry that is central to the idea of “one health,” or how animal research can help human health and vice versa. “One health is this fantastic opportunity,” Dr. Hare says. “By helping animals, you’re actually helping us.”
What clues does your dog’s spit hold for human mental health?
Dogs were the first animals people domesticated, long before the earliest human civilizations appeared. Today, tens of thousands of years later, dogs have an unusually close relationship with us. They share our homes and steal our hearts – and have even evolved to love us back. Sadly, they also suffer from many of the same difficult-to-treat psychiatric and neurological diseases we do.
Beskow, in fine spirits.
Elinor Karlsson, CC BY-ND
I learned this firsthand about six years ago, when my sister Adria adopted Beskow, a beautiful, boisterous, black and white mutt. Beskow became my constant companion on my morning runs along the Charles River. Her joy in running was obvious to everyone we passed, and she kept me going mile after mile.
When not running, though, Beskow suffered from constant anxiety that left her stressed and unhappy – on edge around other dogs and prone to aggressive behavior.
When not running, though, Beskow suffered from constant anxiety that left her stressed and unhappy – on edge around other dogs and prone to aggressive behavior. Beskow had trouble even playing outdoors, since she was compelled to attend to every sound and movement. Working one-on-one with skilled behaviorists and trainers helped immensely, but poor Beskow still never seemed able to relax. Eventually, Adria combined the intensive training with medication, which finally seemed to give Beskow some relief.
Beskow’s personality – her intelligence, her focus and her anxiety – was shaped not only by her own life experiences, but by thousands of years of evolution. Have you ever known a dog who would retrieve the same ball over and over again, for hours on end? Or just wouldn’t stay out of the water? Or wasn’t interested in balls, or water, but just wanted to follow her nose? These dogs are the result of hundreds of generations of artificial selection by human beings. By favoring useful behaviors when breeding dogs, we made the genetic changes responsible more common in their gene pool.
When a particular genetic change rapidly rises in prevalence in a population, it leaves a “signature of selection” that we can detect by sequencing the DNA of many individuals from the population. Essentially, around a selected gene, we find a region of the genome where one particular pattern of DNA – the variant linked to the favored version of the gene – is far more common than any of the alternative patterns. The stronger the selection, the bigger this region, and the easier it is to detect this signature of selection.
In dogs, genes shaping behaviors purposely bred by humans are marked with large signatures of selection. It’s a bit like evolution is shining a spotlight on parts of the dog genome and saying, “Look here for interesting stuff!” To figure out exactly how a particular gene influences a dog’s behavior or health, though, we need lots more information.
To try to unravel these connections, my colleagues and I are launching a new citizen science research project we’re calling Darwin’s Dogs. Together with animal behavior experts, we’ve put together a series of short surveys about everything from diet (does your dog eat grass?) to behavior (is your dog a foot sitter?) to personality (is your dog aloof or friendly?).
Any dog can participate in Darwin’s Dogs, including purebred dogs, mixed breed dogs, and mutts of no particular breed – our study’s participants will be very genetically diverse. We’re combining new DNA sequencing technology, which can give us much more genetic information from each dog, with powerful new analysis methods that can control for diverse ancestry. By including all dogs, we hope to be able to do much larger studies, and home in quickly on the important genes and genetic variants.
A beagle considers making the saliva donation.
Stephen Schaffner, CC BY-ND
Once an owner has filled out the survey, there’s a second, crucial step. We send an easy-to-use kit to collect a small dog saliva sample we can use for DNA analysis. There’s no cost, and we’ll share any information we find.
Our plan is to combine the genetic data from many dogs and look for changes in DNA that correlate with particular behaviors. It won’t be easy to match up DNA with an obsession with tennis balls, for instance. Behavior is a complex trait that relies on many genes. Simple Mendelian traits, like Beskow’s black and white coat, are controlled by a single gene which determines the observable characteristic. This kind of inherited trait is comparatively easy to map. Complex traits, on the other hand, may be shaped by tens or even hundreds of different genetic changes, each of which on its own only slightly alters the individual carrying it.
Adding to the complexity, environment often plays a big role. For example, Beskow may not have been as anxious if she’d lived with Adria from puppyhood, even though her genetics would be unchanged.
Darwin’s Dogs team member Jesse McClure extracts DNA from a sample.
Elinor Karlsson, CC BY-ND
To succeed, we need a lot of dogs to sign up. Initially, we’re aiming to enroll 5,000 dogs. If successful, we’ll keep growing. With bigger sample sizes, we’ll be able to tackle even more complex biological puzzles.
This is a huge effort, but could offer huge rewards. By figuring out how a genetic change leads to a change in behavior, we can decipher neural pathways involved in psychiatric and neurological diseases shared between people and dogs. We already know these include not just anxiety, but also PTSD, OCD, autism spectrum disorders, phobias, narcolepsia, epilepsy, dementia and Alzheimer’s disease.
Understanding the biology underlying a disease is the first step in developing more effective treatments – of both the canine and human variety. For example, genetic studies of narcolepsy in Doberman pinschers found the gene mutation causing the disease – but only in this one dog population. Researching the gene’s function, though, led to critical new insights into the molecular biology of sleep, and, eventually, to new treatment options for people suffering from this debilitating disease.
Darwin’s Dogs is investigating normal canine behaviors as well as diseases. We hypothesize that finding the small genetic changes that led to complex behaviors, like retrieving, or even personality characteristics, like playfulness, will help us figure out how brains work. We need this mechanistic understanding to design new, safe and more effective therapies for psychiatric diseases.
Beskow with one of her loving family members.
Adria Karlsson, CC BY-ND
And Beskow? Six years later, she is as wonderful as ever. While still anxious some of the time, the medication and training have paid off, and she enjoys her daily walks, training and playtime. She still gets very nervous around other dogs, but is a gentle, playful companion for my sister’s three young children.
We are now sequencing her genome. In the next few months, we should have our first glimpse into Beskow’s ancestry. We know she is a natural herder, so we’re curious to find out how much her genome matches up to herding breeds, and which genes are in that part of the genome.
OF COURSE, WE CAN’T FIGURE OUT MUCH FROM JUST ONE DOG – IF YOU ARE A DOG OWNER, PLEASE ENROLL YOUR DOG TODAY!