Is There a Genetic Link to Being an Extremely Good Boy? | WIRED

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Dec 7, 2021 8:31 AM

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Raphael Thys

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Sabrina Weiss

Science

12.06.2021 07:00 AM

Is There a Genetic Link to Being an Extremely Good Boy?

Guide dogs need the right personality, health, and training. Scientists are studying the genetics behind the traits that make a dog suited to working.

Photograph: Getty Images

Flash isn’t your average puppy. A yellow Labrador, named after one of the first British guide dogs from 1931, she is playful, affectionate, and loves learning new commands. Flash is enrolled in an elaborate program herself, one that takes two years and nearly $50,000 to train her to become a guide dog for the blind and visually impaired. Her temporary caregiver Melanie will make sure she maintains a healthy routine: twice-daily walks in different environments, a train ride here, a trip to a mall there to get used to other people. But Melanie has already accomplished one of her most important tasks: When Flash was five months old, she swabbed the puppy’s cheek and mailed the saliva away to a team of researchers that is trying to decipher the link between dog genetics, health, and behavior.

Around half of the dogs that are bred for guiding don’t end up doing that work because of health or behavioral problems. Modern dogs suffer from many genetic diseases, a side effect of keeping breeds separate and selecting them for desirable traits. Some of these purebreds might have the right looks, but not the right temperament, to become a working dog. But what if breeders could predict what makes a good guide dog and select against undesired traits, ensuring they aren’t passed on to the next generation?

More than 500 traits analogous to human genetic conditions have been described in dogs—both species can suffer from cancer, eye disease, or dysplasia of the hip, to name a few. Cheap DNA tests for canines can screen for changes, known as mutations, in a single gene. The causes of many other conditions, however, are more complex. They can be linked to multiple genes or to environmental factors like exercise, food, dust, or mold spores. “We definitely want to get a handle on complex traits,” says Tom Lewis, head of canine genetics at Guide Dogs. The charity breeds around 1,000 puppies a year, which spend their first year in the homes of volunteers before entering formal training.

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Before joining Guide Dogs in January, Lewis worked at the Animal Health Trust and the Kennel Club in the United Kingdom, where he studied the genetic risk of hip dysplasia in breeds registered with the club. Dysplasia is one of the hereditary conditions that can be difficult to diagnose and treat. It is a malformation of the hip joint that develops during growth, though traumatic injury, being overweight, or lacking muscle strength can worsen the condition. For example, puppies raised in homes with hardwood flooring may build less muscle mass in their legs—they can’t get traction on the floor, and slip and slide around, which is hard on their little joints. The constant pain can eventually turn into lameness and arthritis in grown dogs, making them unsuitable for guiding or assisting people with disabilities.

Good health is key for guide dogs, but temperament is just as important. They need to lead their owners around obstacles and other people while staying calm and obedient. They need to resist chasing after squirrels or getting too excited when meeting other dogs. Not every breed has what it takes. For example, the typical cocker spaniel is intelligent, affectionate, and a great option for families, but it is also too excitable. “Even if you give them the same training, you would never expect a spaniel to be a guide dog. They're far too temperamentally unsuited, and that's probably a genetic thing,” says Lewis.

Sixty years of breeding and research at the charity has shown that German shepherds, golden retrievers, and Labradors—especially golden retrievers crossed with Labradors—are best suited to guide blind or visually impaired people. These breeds are confident, intelligent, and eager to please; they are large enough for the harness that wraps around their torso and includes a sturdy handle for the owner; they are strong enough to pull their owners away from dangerous obstacles, and yet small enough to lie comfortably under a bus seat.

In 2019, researchers at four universities in the United States analyzed genetic information and behavior logs for more than 14,000 dogs from 101 breeds. They found some genes that contributed to 60 to 70 percent of variation among breeds for traits such as aggressiveness toward strangers or trainability, but no gene turned out to be solely responsible for any of them. This suggests that the behavioral patterns seen in dogs are an interplay of many genes and environmental influences.

This study, however, was based on existing genetic data sets and surveys with dog owners. That’s not ideal, because the genetic and behavioral data were from separate sample groups, and not from the same dogs. “The only reason we took the breed-average approach was to compile massive amounts of behavioral and genetic data from the existing literature,” says lead author Evan MacLean, director of the Arizona Canine Cognition Center at the University of Arizona, whose ongoing research involves DNA sampling and behavioral experiments with dogs.

The new Guide Dogs project aims to bridge this gap by collecting full genome sequences from 3,000 of their bred dogs, including puppies and their parents, and correlating that with their internal data to identify genes that determine patterns of disease and behavior. So far, staff and volunteers have collected DNA samples from 400 dogs, and sequencing will begin next year. But the project will take many years to complete; a team of researchers will study the guide dogs until their retirement, to watch for diseases that develop late in life.

The DNA data will be matched up with the extremely detailed and standardized information collected from guide dogs in training. “We monitor our dogs throughout their entire lives, right from the moment they’re born. Actually, we monitor them from conception,” says Helen Vaterlaws-Whiteside, head of research at Guide Dogs. The file of a newborn puppy details the mating behavior of its parents, its birth weight, and order in the litter. Records of diet, exercise routines, and veterinary visits will then follow. Training staff and volunteer caregivers also assess the puppy’s behavior at 5, 8, and 12 months to look out for signs of distraction, anxiety, or excitability. This information is typically used to single out dogs who are not suitable for work, before they enter the costly, months-long formal training.

An international team led by the Broad Institute of Harvard and MIT sequenced the genome of the domestic dog in 2004, meaning it determined the order of the 2.8 billion base pairs that make up the species’ DNA. (Despite looking so different from one another, the 354 breeds that are recognized today all belong to the same species. There is genetic variation within breeds, and even more among breeds.) The sample came from a 12-year-old purebred boxer named Tasha, which would serve as a reference for future sequencing. It was a slow process, assembling a few hundred base pairs at a time, and costly. At the time, the US National Human Genome Research Institute (NHGRI) provided about $30 million so that the team could publish the first complete analysis of the genome a year later.

But sequencing technology has come a long way. The price varies depending on where the sampling is done, but it now costs around £1,000 in the UK, and only $700 in the US, to process dog DNA. And researchers can obtain results within a day. However, the analysis of a canine genome takes much longer and costs more than that of a human genome, because there are fewer dog samples available for reference and comparison. The NHGRI has gathered genome sequences from nearly 4,200 dogs since then.

Given that guide-dogs-to-be are regularly checked by veterinarians and follow set routines when spending the first 12 months of their lives with the caregivers, the research team at Guide Dogs will be able to tweeze apart the genetics and environment, to some extent. “Getting the insights into the genetics of behavior, that will be really exciting because it's something that is quite difficult to measure in a controlled way,” says Cathryn Mellersh, who leads the Kennel Club Genetics Centre at the University of Cambridge. “They'll probably be some of the best examples of dogs that you could study behavior in.” Of course, the researchers cannot completely rule out external influences, and pinning down the exact DNA sequences of polygenic traits such as distractibility will be difficult, if not impossible.

The researchers at Guide Dogs want to get to the bottom of what makes their dogs tick—or sick—in order to breed dogs that are more likely to pass the formal training. But it will also be about finding dogs who best fit their future owners’ needs: Some people have allergies, some have trouble balancing and need a larger dog for support, some travel or socialize often and want a confident, outgoing dog. It’s not just about screening out unwanted traits, Lewis says, but maintaining a variety of desirable ones, “because not every guide dog owner is going to be exactly the same.”