Tag Archives: genome

The evolution of dog breeds

When people migrate, Canis familiaris travels with them. Piecing together the details of those migrations has proved difficult because the clues are scattered across the genomes of hundreds of dog breeds. However, in a study published April 25, 2017 in Cell Reports, researchers have used gene sequences from 161 modern breeds to assemble an evolutionary tree of dogs.

The map of dog breeds, which is the largest to date, unearths new evidence that dogs traveled with humans across the Bering land bridge, and will likely help researchers identify disease-causing genes in both dogs and humans.

Cladogram of 161 Domestic Dog Breeds

Cladogram of 161 Domestic Dog Breeds

The study highlights how the oldest dog breeds evolved or were bred to fill certain roles. “First, there was selection for a type, like herders or pointers, and then there was admixture to get certain physical traits,” says study co-author and dog geneticist Heidi Parker of the National Institutes of Health (NIH). “I think that understanding that types go back a lot longer than breeds or just physical appearances do is something to really think about.”

Most popular breeds in America are of European descent, but in the study, researchers found evidence that some breeds from Central and South America — such as the Peruvian Hairless Dog and the Xoloitzcuintli– are likely descended from the “New World Dog,” an ancient canine sub-species that migrated across the Bering Strait with the ancestors of Native Americans. Scientists have previously reported archaeological evidence that the New World Dog existed, but this study marks the first living evidence of them in modern breeds.

“What we noticed is that there are groups of American dogs that separated somewhat from the European breeds,” says study co-author Heidi Parker of the NIH. “We’ve been looking for some kind of signature of the New World Dog, and these dogs have New World Dogs hidden in their genome.” It’s unclear precisely which genes in modern hairless dogs are from Europe and which are from their New World ancestors, but the researchers hope to explore that in future studies.

Other results were more expected. For instance, many breeds of “gun dogs,” such as Golden Retrievers and Irish Setters, can trace their origins to Victorian England, when new technologies, such as guns, opened up new roles on hunting expeditions. Those dogs clustered closely together on the phylogenetic tree, as did the spaniel breeds. Breeds from the Middle East, such as the Saluki, and from Asia, such as Chow Chows and Akitas, seem to have diverged well before the “Victorian Explosion” in Europe and the United States.

Herding breeds, though largely European in origin, proved to be surprisingly diverse. “When we were looking at herding breeds, we saw much more diversity, where there was a particular group of herding breeds that seemed to come out of the United Kingdom, a particular group that came out of northern Europe, and a different group that came out of southern Europe,” says Parker, “which shows herding is not a recent thing. People were using dogs as workers thousands of years ago, not just hundreds of years ago.”

Different herding dogs use very different strategies to bring their flocks to heel, so in some ways, the phylogenetic data confirmed what many dog experts had previously suspected, the researchers noted. “What that also tells us is that herding dogs were developed not from a singular founder but in several different places and probably different times,” says the study’s senior co-author and dog geneticist Elaine Ostrander, also of the NIH.

Ostrander and her colleagues have spent years sequencing dog genomes but can also frequently be found out in the field at dog shows, recruiting dog owners to participate in the study. “If we see a breed that we haven’t had a good sample of to sequence, we definitely make a beeline for that owner,” says Ostrander. “And say, ‘Gosh, we don’t have the sequence of the Otterhound yet, and your dog is a beautiful Otterhound. Wouldn’t you like it to represent your breed in the dog genome sequence database?’ And of course, people are always very flattered to say, “Yes. I want my dog to represent Otterhound-ness.” All of the dog sequences in the study are from dogs whose owners volunteered, Ostrander says. Over half the dog breeds in the world today still have not been sequenced and the researchers intend to keep collecting dog genomes to fill in the gaps.

Understanding dogs’ genetic backstory also has practical applications. Our canine compatriots fall victim to many of the same diseases that humans do — including epilepsy, diabetes, kidney disease, and cancer — but disease prevalence varies widely and predictably between breeds, while it is more difficult to compartmentalize at-risk human populations. “Using all this data, you can follow the migration of disease alleles and predict where they are likely to pop up next, and that’s just so empowering for our field because a dog is such a great model for many human diseases,” says Ostrander. “Every time there’s a disease gene found in dogs it turns out to be important in people, too.”

Source:  ScienceDaily

Full journal article available here

Canine compulsive disorder genetics

Research led by investigators in veterinary and human medicine has identified genetic pathways that exacerbate severity of canine compulsive disorder in Doberman Pinschers, a discovery that could lead to better therapies for obsessive compulsive disorder (OCD) in people.  The discovery appears in the International Journal of Applied Research in Veterinary Medicine.

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A Doberman pinscher flank sucking, an example of canine compulsive behavior

“Dogs naturally suffer complex diseases, including mental disorders that are similar to those in humans. Among those is canine compulsive disorder (CCD), the counterpart to human obsessive compulsive disorder (OCD),” says the study’s first and corresponding author Nicholas Dodman, BVMS, DACVA, DACVB, professor in clinical sciences and section head and program director of animal behavior at Cummings School of Veterinary Medicine at Tufts University.

OCD is one of the world’s most common neuropsychiatric disorders, affecting an estimated 1 to 3 percent of people and listed by the World Health Organization as among the 20 most disabling diseases. OCD is often characterized by distressing thoughts and time-consuming, repetitive behaviors, while canine compulsions may include repetitive tail chasing, excessive grooming and flank and blanket sucking. Current OCD therapies are not as effective as they could be; medicinal treatment benefits only about half of all human patients.

No previously recorded study in humans or dogs has addressed the factors that drive severity in OCD and CCD.

“Genomic research on human neuropsychiatric disorders can be challenging due to the genetic heterogeneity of disease in humans,” says neurologist Edward Ginns, MD, PhD, professor of psychiatry, neurology, pediatrics and clinical pathology, and director, program in medical genetics at the University of Massachusetts Medical School and a co-author on the new study. “Canine compulsive disorder shares behavioral hallmarks, pharmacological responsiveness, and brain structural homology with human OCD, and thus is expected to be an important animal model.”

The research team compared whole genome sequencing of 70 Doberman pinschers to search for inherited factors that exacerbate CCD. Researchers identified two loci on chromosomes that were strongly correlated with severe CCD, as well as a third locus that showed evidence of association.

The locus most strongly associated with severe CCD was found on chromosome 34 – a region containing three serotonin receptor genes.

“This is particularly significant because drugs that work on the serotonin system are the mainstay treatment for OCD in humans, which demonstrates further correlation between the human and animal models,” says Dodman.

The second locus significantly correlated with severe CCD was on chromosome 11, the same chromosome that contains a gene thought to increase the risk of schizophrenia in humans. This discovery, along with suggestive evidence found on chromosome 16 linking CCD to stress tolerance, may also be relevant to the pathophysiology of OCD, according to the study authors. “Comparative genomics is a particularly attractive approach to reveal the molecular underpinnings of disease in inbred animals with the hope of gaining new insights into these diseases in dogs and humans,” says Ginns.

“If the canine construct is fully accepted by other OCD researchers, this spontaneously-occurring model of the condition in humans, right down to the biological pathways involved, could help point the way to novel and more effective treatments for such a debilitating condition,” Dodman says.

Source:  Tufts Now media release

A bond that goes way back

The special relationship between humans and dogs may go back 27,000 to 40,000 years, according to genomic analysis of an ancient Taimyr wolf bone reported in the Cell Press journal Current Biology on May 21. Earlier genome-based estimates have suggested that the ancestors of modern-day dogs diverged from wolves no more than 16,000 years ago, after the last Ice Age.

The genome from this ancient specimen, which has been radiocarbon dated to 35,000 years ago, reveals that the Taimyr wolf represents the most recent common ancestor of modern wolves and dogs.

his image compares an ancient Taimyr Wolf bone from the lower jaw to a modern pipette.  Photo by Love Dalén

This image compares an ancient Taimyr Wolf bone from the lower jaw to a modern pipette. Photo by Love Dalén

“Dogs may have been domesticated much earlier than is generally believed,” says Love Dalén of the Swedish Museum of Natural History. “The only other explanation is that there was a major divergence between two wolf populations at that time, and one of these populations subsequently gave rise to all modern wolves.” Dalén considers this second explanation less likely, since it would require that the second wolf population subsequently became extinct in the wild.

“It is [still] possible that a population of wolves remained relatively untamed but tracked human groups to a large degree, for a long time,” adds first author of the study Pontus Skoglund of Harvard Medical School and the Broad Institute.

The researchers made these discoveries based on a small piece of bone picked up during an expedition to the Taimyr Peninsula in Siberia. Initially, they didn’t realize the bone fragment came from a wolf at all; this was only determined using a genetic test back in the laboratory. But wolves are common on the Taimyr Peninsula, and the bone could have easily belonged to a modern-day wolf. On a hunch, the researchers decided to radiocarbon date the bone anyway. It was only then that they realized what they had: a 35,000-year-old bone from an ancient Taimyr wolf.

The DNA evidence also shows that modern-day Siberian Huskies and Greenland sled dogs share an unusually large number of genes with the ancient Taimyr wolf.

“The power of DNA can provide direct evidence that a Siberian Husky you see walking down the street shares ancestry with a wolf that roamed Northern Siberia 35,000 years ago,” Skoglund says. To put that in perspective, “this wolf lived just a few thousand years after Neandertals disappeared from Europe and modern humans started populating Europe and Asia.”

Source:  EurekAlert! media statement

A dog cancer that is 11,000 years old

Scientists have sequenced the genome of the world’s oldest continuously surviving cancer, a transmissible genital cancer that affects dogs.

Credit: © Melinda Nagy / Fotolia

Credit: © Melinda Nagy / Fotolia

The cancer, which causes grotesque genital tumours in dogs around the world, first arose in a single dog that lived about 11,000 years ago. The cancer survived after the death of this dog by the transfer of its cancer cells to other dogs during mating.

Analysis of the genetic variants in the genome revealed that the dog may have resembled an Alaskan Malamute or Husky. It probably had a short, straight coat that was coloured either grey/brown or black. Its genetic sequence could not determine if this dog was a male or a female, but did indicate that it was a relatively inbred individual.

The genome has over 2 million mutations; the research team used one type of mutation, known to accumulate steadily over time, as a ‘molecular clock.’  This led to the estimate that the cancer first arose 11,000 years ago.

“The genome of this remarkable long-lived cancer has demonstrated that, given the right conditions, cancers can continue to survive for more than 10,000 years despite the accumulation of millions of mutations”, says Dr Elizabeth Murchison, first author from the Wellcome Trust Sanger Institute and the University of Cambridge.

Transmissible cancers are very rare in nature.  Apart from the dog transmissible cancer, the only other known naturally occurring transmissible cancer is an aggressive transmissible facial cancer in Tasmanian devils that is spread by biting.

Source:  Wellcome Trust media statement

Getting your head around dog genetics

Another public release of research this week.  This one from the Genetics Society of America about an article entitled ‘The Genetics of Canine Skull Shape Variation.’  Published in the February issue of Genetics, researchers review progress in defining genes and pathways that determine dog skull shape and development.

The researchers believe that the results are useful to humans because of the genetic expression of the features is likely to be similar process in humans as in dogs.

Skull shape is a complex trait, involving multiple genes and their interactions. Thanks to standardized canine breeding, which documents more than 400 breeds worldwide, and their distinct morphological features, researchers can disentangle traits such as skull shape, which in many breeds is a breed-defining variation.

Researchers are beginning to identify which genes cause a Bulldog or a Pug to have short pushed-in faces, or brachycephaly, and those that cause Salukis or collies to have narrow, elongated snouts, or dolichocephaly.

Source:  Genetics Society of America media release