Mapping Your Dog's Behavior, Health, and Heritage
It was a pair of plant geneticists who started to map the DNA of dogs.
Posted Nov 21, 2018
Imagine that there are a group of scientists who are trying to construct a treasure map from the clues that are available to them. However, quite differently from the typical adventure stories, for certain scientists it is not the treasure that is important, but rather the map itself. This new class of mapmakers are geneticists, who are not mapping territories or any sort of geography, but who are mapping your dog. The map that they are making is a historical map which can trace a dog's evolution from an ancestral ancient wolf to a modern Labrador retriever. It is also a map of the
locations of genes that trigger inherited canine diseases. This map can even find the source of particular behavioral tendencies. In addition, as a special bonus, this map may help to heal humans. It is a map of dog's DNA, and that map is called the "canine genome."
The Canine Genome Project is a massive undertaking which continues to grow in size. The dog's genetic material is stored in 39 pairs of chromosomes, each made up of tangled strands of DNA. The DNA molecule is shaped like a ladder, with each rung of the ladder being a pair of base chemicals. It is sensible to think of these "rungs" as if they were the letters in an alphabet that spell out the genetic makeup of a dog. The attempt to interpret the message in the canine DNA has already involved more than two dozen laboratories, which have measured the genetic makeup of more than 1,700 dogs coming from more than 160 dog breeds. For each of these, the idea is to transcribe the pattern of occurrence of those 2.8 billion genetic "letters," and to organize them into sequences which make up the roughly 19,000 genes in the dog. It makes sense to imagine that these genes are a series of genetic words that spell out sentences. These "written" instructions tell the body which proteins to produce and ultimately determine the dog's development and behavior.
Obviously this is an expensive, labor-intensive project. So you might ask: Why would so much effort be expended to understand the humble domestic dog? To understand this, we have to go back to the start of the project.
Starting to Draw a Map of the Dog
Strangely enough, the canine genome project got its start through the activity of a plant geneticist at the University of California at Berkeley. Jasper Rine recognized that dogs were bred for specific behaviors, and that these behaviors most likely had a strong, and perhaps easily identifiable, genetic basis. As a sideline to his plant research, he crossbred a Newfoundland (which are 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 behaviors). After two generations of study, it became clear that a number of key behaviors were genetically determined. However, it also became clear to Rine that he lacked a vital tool, namely a map of genetic markers made up of known stretches of DNA, which could be used to figure out which genetic material was passed on to make strong swimmers or good herding dogs. Thus he conceived the idea of creating such a map, and this map would be the canine genome.
It was 1990, and Elaine Ostrander had just arrived at Berkeley to do some postdoctoral research in plant genetics. Unfortunately, there was going to be a wait before her fellowship funding would start, so she took a temporary job with Rine. He assigned her the task to start building the map he needed of dog DNA. She never did make it to the plant genetics lab, but when she left Berkeley three years later, she was committed to the dog genome project. This was extremely important, because Rine eventually had to close down his canine behavior studies due to lack of funding, and because he was being harassed by animal rights activists.
Gathering the Data
What Ostrander needed to continue her research was lots of samples of genetic material from as many different individual dogs and dog breeds as she could lay her hands on. So this dedicated researcher haunted dog shows to ask breeders and owners to allow her to gather such genetic material. Progress was slow, until she discovered that a pair of investigators at the University of Pennsylvania's School of Veterinary Medicine, Gustavo Aguirre and Gregory Acland, had been studying an inherited form of blindness which was common in collies. They had been breeding affected and unaffected individuals in order to trace the patterns of inheritance, and also had been collecting blood samples from breeds which did not have the disease. Unfortunately, like Rine, they knew that they could never find the gene which caused the blindness until there was a proper canine genome map. However, in the hopes that such a map would eventually become available, they carefully stored and documented the huge bank of blood samples that they had collected.
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.
By this time, some other scientists began to recognize that dogs just might be a geneticist's dream. Purebred breeds are highly interbred for specific traits. Purebred dogs have extended family histories and well-documented genealogies, which greatly simplifies the task of tracking down things like mutations that cause disease, or genes responsible for the size, shape, or coat color of the dogs. However, within each breed, there is a remarkable degree of genetic similarity among individuals.
Why is the similarity among members of the same breed important for geneticists? Well, imagine that you are trying to find a mutated gene responsible for some inherited disorder. If you use groups of test subjects with very similar genomes — except for the fact that one group has the disease and another does not — then the one different gene is going to stand out clearly. Compare this to using groups of test subjects who, in addition to differing in disease susceptibility, also differ on a whole lot of other factors. All of those extraneous genetic differences are going to make up a noisy kind of static and make it difficult to find the one important gene which is causing the sought for difference.
Why the Canine Genome Is Important to Humans
What was also becoming clear is that this work on the canine genome might have implications for understanding humans better. Dogs and humans share 95 percent of their DNA, and also share some of their species' most common diseases, such as cancer, epilepsy, allergy, heart disease, and even psychological disorders, such as Alzheimer's disease, phobias, and obsessive-compulsive disorders. However there was still resistance from the scientific community as to whether dog genetics would tell us anything useful.
This skepticism disappeared quickly after Emmanuel Mignot's research team at Stanford University isolated the gene that causes narcolepsy in dogs, starting with genetic samples taken from affected Doberman pinschers. Narcolepsy is a sleep disorder that causes an individual to fall into an uncontrollable, involuntary state of sleep regardless of what they happen to be doing at the time. Based on their canine research, these researchers isolated the narcolepsy gene, and this led to an understanding of a new molecular pathway involved in sleep. These results also led to increased interest coming from scientists who were interested in human genetics, and furthermore, and because it was now clear that these results might help in our understanding of human genetic problems, more research funding became available for this kind of work.
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 also comparisons can be made with wild canines, such as contemporary wolves, and even their ancient ancestors.
Discovering the History of Dogs
This basic canine genome allows us to trace the history of dogs, their evolution, and the effects that domestication and selective breeding have had on them. To see how this would work, imagine that we presume (as most scientists do) that the original ancestors of all of our dogs were wolves. If a breed of dog evolved directly from the wolf in the distant past, then its DNA would be very wolf-like. If however, many generations and a long time period have passed since a particular breed was created, then we would expect many mutations and differences between that more modern breed and that of the ancient wolf. This means that we can construct a timeframe for when particular dog breeds were created. This also allows us to study the relationship among various dog breeds.
Using research that looks at the different mutations found in various dog breeds it has become clear that there are at least 23 clades (or groups of dogs based upon their physical and behavioral characteristics). Furthermore it is now clear that dog breeds evolved in two separate historical stages. The early stage started when dogs were first domesticated and humans were engaging in a sort of seat-of-the-pants applied genetics. Historically, if a person had a dog that showed a particularly desirable trait, such as the ability to herd sheep, then he would mate that dog with another who had somewhat similar characteristics in the hope that he would get a better type of herding dog. This is the way that the early breeds of herding, hunting, and guarding dogs came to be. However, although there were clear differences among the various lines of dogs the concept of "breed" was much more loosely defined.
The world of dogs changed abruptly, and forever, in the Victorian era. With a better understanding of dog breeding, designing dogs became a hobby of the middle and upper classes in England. In effect dogs were now something to be moulded and shaped by humans, often more for the physical characteristics which determined how the dog looked rather than for particular inborn skills and behaviors. Kennel clubs were established to keep records of the breeding of particular lines of dogs and to oversee dog shows, which 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.
The canine genome map has also allowed us to understand how dogs have migrated around the world. For example it provides data that seems to show that nearly all of the dog breeds that were native to the Americas originally came from Asia, brought by migrants who traveled over a land bridge which existed across the Bering Strait. These original breeds were then virtually wiped out by the later influx of Europeans who brought along their own breeds of dogs.
Where We Are Now
Today many scientists recognize the research value provided by the genetic similarity between dogs and humans. Because of this, the dog is becoming a popular "model" that investigators can use to gain an understanding of human disorders, including psychological disorders, such as Alzheimer's disease and obsessive-compulsive disorders.
However, even after all of these years and this huge research effort, Elaine Ostrander (who is now at the National Institutes of Health in Bethesda, Maryland) and her associates can still be found wandering through dog shows, looking for relatively rare breeds of dogs whose DNA are not adequately represented in the canine genome project. She is still requesting 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.
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