The Canine Genome Project: how dog DNA can help humans

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The Canine Genome Project: how dog DNA can help humans

The Canine Genome Project — an initiative that maps dog DNA — has implications for understanding issues in both dogs and humans.

There’s a new class of mapmakers out there. They’re not plotting territories or any sort of topography; they’re mapping dog DNA. This historical map, called the Canine Genome, can trace a dog’s evolution from an ancient wolf to a modern Labrador Retriever. It can also show us the locations of genes that trigger inherited canine diseases, and even find the source of particular behavioural tendencies.

The Canine Genome Project is an expensive, labour-intensive project that continues to grow in size. So you might ask why researchers are expending so much effort to understand the humble domestic dog.

The answer is actually easy. After a period of skepticism and decades of research, scientists now recognize that dogs are a geneticist’s dream. Purebred breeds are highly interbred for specific traits, so that means that there is a remarkable degree of genetic similarity among individuals of the same breed. Purebred dogs also have well documented genealogies. This greatly simplifies the task of tracking down the genes responsible for the size, shape, or coat colour of the dogs, as well as mutations that cause disease.

Imagine it like this: you want to find a mutated gene responsible for some inherited disorder. If you use groups of test subjects with very similar genetic makeup — except for the fact that one group has the disease and another does not — then the one different gene will stand out much more clearly.

 

Dog DNA

The genetic material of dogs is stored in 39 pairs of chromosomes, each made up of tangled strands of DNA. The DNA molecule is shaped like a twisted ladder and each rung represents a pair of base chemicals. Think of these “rungs” as the letters in an alphabet that spell out the genetic makeup of a dog.

In order to interpret the message in the canine DNA, over two dozen laboratories have measured the genetic makeup of more than 1,700 dogs from over 160 breeds. The labs then transcribe the pattern of occurrence of those 2.8 billion genetic “letters”, and organize them into sequences that make up the roughly 19,000 genes in the dog. In simple terms, think of these as a series of genetic letters that spell out words and sentences. These “written” instructions tell the body which proteins to produce and ultimately determine the dog’s development and behaviour.

Implications for humans

Researchers now believe this work on the canine genome might have implications for understanding humans better. Dogs and humans share 95% of their DNA, and also share some of their species’ most common diseases, such as cancer, epilepsy, diabetes, heart disease, and even psychological and neurological problems such as Alzheimer’s, phobias, and obsessive-compulsive disorder. The Canine Genome may ultimately lead to solutions for issues in both our species!

What the Canine Genome tells us about dogs

Apart from the potential benefits to humans, the Canine Genome allows us to trace the history of dogs, their evolution, and the effects that domestication and selective breeding have had on them. That means we can construct a timeline showing when particular dog breeds were created, as well as study the relationship among the various breeds. It can even help us understand how dogs migrated around the world.

For example, the data seems to show that nearly all the dog breeds that were native to the Americas originally came from Asia, brought by migrants who travelled over a land bridge that existed across the Bering Strait. These original breeds were then virtually wiped out by the later influx of Europeans who arrived with their own breeds of dogs.

How breeds developed

The Canine Genome research shows that there are at least 23 clades (groups of dogs based on their physical and behavioural characteristics). We also now know that dog breeds evolved in two separate historical stages:

  1. The early stage started when dogs were first domesticated and humans engaged in what could be termed “seat of the pants”-applied genetics. Historically, if a person had a dog that showed a particular desirable trait, such as the ability to herd sheep, he would mate that dog with another who had somewhat similar characteristics in the hope he would get a better type of herding dog. This is how the early breeds of herding, hunting, and guarding dogs came to be. Although there were clear differences among the various lines of dogs, the concept of “breed” was much more loosely defined at that time.
  2. The world of dogs changed abruptly, and forever, in the 1800s — the Victorian era. With a better understanding of breeding, designing dogs became a hobby of the middle and upper classes in England. Kennel clubs were established to keep records of the breeding of particular lines of dogs and to oversee dog shows that displayed and evaluated these selectively-bred specimens. This led to an explosion of new breeds, with many of the most popular Retrievers, Spaniels, and companion dogs emerging during this era.

Milestones in the Canine Genome Project

It all started with plants in the late 1980s

The Canine Genome Project got its start thanks to plant geneticist Jasper Rine, at the University of California at Berkeley. Rine recognized that dogs were bred for specific behaviours, and that these behaviours most likely had a strong and perhaps easily identifiable genetic basis.

As a sideline to his plant research, he crossbred a Newfoundland (friendly dogs that love water and know nothing about herding) with a Border Collie (which are somewhat standoffish, dislike water, and have a suite of built-in herding behaviours). After two generations of study, it became clear that a number of key behaviours were genetically determined. However, Rine also realized that he lacked a vital tool. He conceived the idea of creating a map of genetic markers made up of known stretches of DNA, so he could figure out which genetic material was passed on to make specific traits, such as strong swimmers or good herding dogs. This map would become the Canine Genome.

Enter Elaine Ostrander, circa 1990

Researcher Elaine Ostrander arrived at Berkeley in 1990 to do some postdoctoral work in plant genetics. While waiting on her fellowship funding, she took a temporary job with Rine and started building the map he needed of dog DNA. She never did make it to the plant genetics lab. When she left Berkeley three years later, she was committed to the Canine  Genome Project.

To continue her research, Ostrander needed lots of samples of genetic material from many different individual dogs and breeds. She haunted dog shows, collecting as much dog DNA as she could. Progress was slow until she found Gustavo Aguirre and Gregory Acland at the University of Pennsylvania’s School of Veterinary Medicine, who had been studying an inherited form of blindness common in Collies. They had carefully collected, stored, and documented a huge bank of blood samples from breeds that didn’t have the disease, but they knew they could never find the gene causing the blindness without that map of the Canine Genome that Rine envisioned.

With the combination of samples and research data from these two labs, it took only a year to produce a preliminary map showing the positions of 150 markers on the dog genome. This allowed these scientists to determine that the gene causing the form of inherited blindness commonly seen in Collies was on chromosome 9. A few years later they isolated the specific gene itself.

Waking up the skeptics – 1990 to 1999

The scientific community finally accepted the Canine Genome Project after Emmanuel Mignot’s research team at Stanford University isolated the gene that causes narcolepsy in dogs. Narcolepsy is a sleep disorder that causes an individual to fall into an uncontrollable, involuntary state of sleep. Based on genetic samples taken from affected Doberman Pinschers, researchers determined the nature and location of the narcolepsy gene, which led to an understanding of a new molecular pathway involved in sleep.

The results also garnered increased interest from scientists studying human genetics. With the realization that the Canine Genome Project could further understanding of human genetic problems, research funding finally started to flow in.

Tasha the Boxer — 2005

Ultimately, a nearly complete canine genome was recorded, starting with the genetic material from a highly inbred Boxer named Tasha. With a complete map of canine DNA, comparisons can now be made to determine the differences among breeds of dogs, and between dogs and wild canines, such as contemporary wolves, and even their ancient ancestors.

What’s happening today?

Researchers, including Elaine Ostrander (who is currently at the National Human Genome Research Institute) and her associates, continue to look for relatively rare breeds of dogs whose DNA are not adequately represented in the Canine Genome Project. She still requests samples of genetic material, which can now be obtained by simply swabbing the dog’s mouth. In this way, our understanding of the genetic map of dogs continues to evolve and become more precise.

Thanks to the Canine Genome Project, ongoing research into canine and human genetics will continue to shed light on the past, and hopefully result in improved health for both the canine and human species in the future.

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