Tag Archives: DNA

Why huskies have blue eyes

DNA testing of more than 6,000 dogs has revealed that a duplication on canine chromosome 18 is strongly associated with blue eyes in Siberian Huskies, according to a study published October 4, 2018, in the open-access journal PLOS Genetics by Adam Boyko and Aaron Sams of Embark Veterinary, Inc., and colleagues.

Embark is a dog DNA startup company headquartered in Boston, MA, and Ithaca, NY, and research partner of the Cornell University College of Veterinary Medicine. According to the authors, this represents the first consumer genomics study ever conducted in a non-human model and the largest canine genome-wide association study to date.

Lakota

Embark dog, Lakota, shows off bright blue eyes. Credit: Jamie Leszczak CCAL

Consumer genomics enables genetic discovery on an unprecedented scale by linking very large databases of genomic data with phenotype information voluntarily submitted via web-based surveys. But the promise of consumer genomic data is not limited to human research. Genomic tools for dogs are readily available but the genetic underpinnings of many important traits remain undiscovered. Although two genetic variants are known to underlie blue eye color in some dogs, these do not explain the trait in some other dogs, like Siberian Huskies.

To address this gap in knowledge, Boyko, Sams and colleagues used a diverse panel of 6,070 genetically tested dogs with owners that contributed phenotype data via web-based surveys and photo uploads. They found that a 98.6-kilobase duplication on chromosome 18 near the ALX4 gene, which plays an important role in mammalian eye development, was strongly associated with variation in blue eye color, primarily in Siberian Huskies but also in non-merle Australian Shepherds. One copy of the variant was enough to cause blue eyes or heterochromia (blue and brown eyes), although some dogs with the variant did not have blue eyes, so other genetic or environmental factors are still involved.

Future studies of the functional mechanism underlying this association may lead to the discovery of a novel pathway by which blue eyes develop in mammals. From a broader perspective, the results underscore the power of consumer data-driven discovery in non-human species, especially dogs, where there is intense owner interest in the personal genomic information of their pets, a high level of engagement with web-based surveys, and an underlying genetic architecture ideal for mapping studies.

Aaron J. Sams adds: “Using genetic data from the pets of our customers, combined with eye colors reported by customers for those same animals, we have discovered a genetic duplication that is strongly associated with blue eye color. This study demonstrates the power of the approach that Embark is taking towards improving canine health. In a single year, we collected enough data to conduct the largest canine study of its kind. Embark is currently pursuing similar research projects in a range of morphological and health-related traits and we hope to continue to use our platform to move canine genetics and health forward in a very real way.”

Source:  Science Daily and PLOS Genetics

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Researchers identify a common underlying genetic basis for social behavior in dogs and humans

Dogs’ ability to communicate and interact with humans is one the most astonishing differences between them and their wild cousins, wolves. A new study published in the journal Science Advances identifies genetic changes that are linked to dogs’ human-directed social behaviors and suggests there is a common underlying genetic basis for hyper-social behavior in both dogs and humans.

An interdisciplinary team of researchers, including those from Princeton University, sequenced a region of chromosome 6 in dogs and found multiple sections of canine DNA that were associated with differences in social behavior. In many cases, unique genetic insertions called transposons on the Williams-Beuren syndrome critical region (WBSCR) were strongly associated with the tendency to seek out humans for physical contact, assistance and information.

In contrast, in humans, it is the deletion of genes from the counterpart of this region on the human genome, rather than insertions, that causes Williams-Beuren syndrome, a congenital disorder characterized by hyper-social traits such as exceptional gregariousness.

“It was the remarkable similarity between the behavioral presentation of Williams-Beuren syndrome and the friendliness of domesticated dogs that suggested to us that there may be similarities in the genetic architecture of the two phenotypes,” said Bridgett vonHoldt, an assistant professor in ecology and evolutionary biology at Princeton and the study’s lead co-author.

Dogs ability to communicate

Dogs’ ability to communicate and interact with humans is one of the most astonishing differences between them and their wild cousins, wolves. Shown here, Lauren Brubaker, a graduate research assistant in the Department of Animal and Rangeland Sciences at Oregon State University and one of the study’s authors, interacts with a gray wolf. Photo by Monty Sloan

VonHoldt had identified the canine analog of the WBSCR in her publication in Nature in 2010. But it was Emily Shuldiner, a 2016 Princeton alumna and the study’s other lead co-author, who, as part of her senior thesis, pinpointed the commonalities in the genetic architecture of Williams-Beuren syndrome and canine tameness.

By analyzing behavioral and genetic data from dogs and gray wolves, vonHoldt, Shuldiner and their colleagues reported a strong genetic aspect to human-directed social behavior by dogs. Monique Udell, an assistant professor of animal and rangeland sciences at Oregon State University and the paper’s senior author, collected and analyzed the behavioral data for 18 domesticated dogs and 10 captive human-socialized wolves, as well as the biological samples used to sequence their genomes.

First, Udell quantified human-directed sociability traits in canines, such as to what extent they turned to a human in the room to seek assistance in trying to lift a puzzle box lid in order to get a sausage treat below or the degree to which they sought out social interactions with familiar and unfamiliar humans. Then, vonHoldt and Shuldiner sequenced the genome in vonHoldt’s lab and correlated their findings.

Consistent with their hypothesis, the researchers confirmed that the domesticated dogs displayed more human-directed behavior and spent more time in proximity to humans than the wolves. The also discovered that some of these transposons on the WBSCR were only found in domestic dogs, and not in wolves at all.

VonHoldt’s findings suggest that only a few transposons on this region likely govern a complex set of social behaviors. “We haven’t found a ‘social gene,’ but rather an important [genetic] component that shapes animal personality and assisted the process of domesticating a wild wolf into a tame dog,” she said.

Anna Kukekova, an assistant professor in the Department of Animal Sciences at the University of Illinois at Urbana-Champaign who is familiar with the research but had no role in it, said that the paper points to these genes as being evolutionarily conserved, or essentially unchanged throughout evolution. “The research provides evidence that there exist certain evolutionary conservative mechanisms that contribute to sociability across species,” she said. “That they have found that this region contributes to sociability in dogs is exciting.”

The researchers’ evidence also calls into question the role of domestication in the evolution of canine behavior. Most experts agree that the first domesticated dogs were wolves that ventured into early human settlements. These proto-dogs evolved not only in their looks, but also their behavior, a process likely influenced by the species’ cohabitation, according to vonHoldt.

However, unlike previous research which suggests that, during the process of domestication, dogs were selected for a set of cognitive abilities, particularly an ability to discern gesture and voice, vonHoldt and Shuldiner’s research posits that dogs were instead selected for their tendency to seek human companionship.

“If early humans came into contact with a wolf that had a personality of being interested in them, and only lived with and bred those ‘primitive dogs,’ they would have exaggerated the trait of being social,” vonHoldt said.

Source:  Princeton University media statement

The history of canine transmissible venereal cancer

Researchers at the University of Cambridge have produced this interesting YouTube video about how canine transmissible venereal cancer has spread over time.  If you are interested in evolution, genetics or DNA research – this video is for you.

See also my previous posts:

A dog cancer that is 11,000 years old

Global snapshot of infectious canine cancer

Kathleen Crisley, specialist in dog massage, rehabilitation and nutrition/food therapy, The Balanced Dog, Christchurch, New Zealand

 

Dogs were domesticated not once, but twice

The question, ‘Where do domestic dogs come from?’, has vexed scholars for a very long time. Some argue that humans first domesticated wolves in Europe, while others claim this happened in Central Asia or China. A new paper, published in Science, suggests that all these claims may be right. Supported by funding from the European Research Council and the Natural Environment Research Council, a large international team of scientists compared genetic data with existing archaeological evidence and show that man’s best friend may have emerged independently from two separate (possibly now extinct) wolf populations that lived on opposite sides of the Eurasian continent.

Domestication photo

Man’s best friend. Dogs were domesticated not once, but twice… in different parts of the world. Credit: © lenaivanova2311 / Fotolia

This means that dogs may have been domesticated not once, as widely believed, but twice.

A major international research project on dog domestication, led by the University of Oxford, has reconstructed the evolutionary history of dogs by first sequencing the genome (at Trinity College Dublin) of a 4,800-year old medium-sized dog from bone excavated at the Neolithic Passage Tomb of Newgrange, Ireland. The team (including French researchers based in Lyon and at the National Museum of Natural History in Paris) also obtained mitochondrial DNA from 59 ancient dogs living between 14,000 to 3,000 years ago and then compared them with the genetic signatures of more than 2,500 previously studied modern dogs.

The results of their analyses demonstrate a genetic separation between modern dog populations currently living in East Asia and Europe. Curiously, this population split seems to have taken place after the earliest archaeological evidence for dogs in Europe. The new genetic evidence also shows a population turnover in Europe that appears to have mostly replaced the earliest domestic dog population there, which supports the evidence that there was a later arrival of dogs from elsewhere. Lastly, a review of the archaeological record shows that early dogs appear in both the East and West more than 12,000 years ago, but in Central Asia no earlier than 8,000 years ago.

Combined, these new findings suggest that dogs were first domesticated from geographically separated wolf populations on opposite sides of the Eurasian continent. At some point after their domestication, the eastern dogs dispersed with migrating humans into Europe where they mixed with and mostly replaced the earliest European dogs. Most dogs today are a mixture of both Eastern and Western dogs — one reason why previous genetic studies have been difficult to interpret.

The international project (which is combining ancient and modern genetic data with detailed morphological and archaeological research) is currently analysing thousands of ancient dogs and wolves to test this new perspective, and to establish the timing and location of the origins of our oldest pet.

Senior author and Director of Palaeo-BARN (the Wellcome Trust Palaeogenomics & Bio-Archaeology Research Network) at Oxford University, Professor Greger Larson, said: ‘Animal domestication is a rare thing and a lot of evidence is required to overturn the assumption that it happened just once in any species. Our ancient DNA evidence, combined with the archaeological record of early dogs, suggests that we need to reconsider the number of times dogs were domesticated independently. Maybe the reason there hasn’t yet been a consensus about where dogs were domesticated is because everyone has been a little bit right.’

Lead author Dr Laurent Frantz, from the Palaeo-BARN, commented: ‘Reconstructing the past from modern DNA is a bit like looking into the history books: you never know whether crucial parts have been erased. Ancient DNA, on the other hand, is like a time machine, and allows us to observe the past directly.’

Senior author Professor Dan Bradley, from Trinity College Dublin, commented: ‘The Newgrange dog bone had the best preserved ancient DNA we have ever encountered, giving us prehistoric genome of rare high quality. It is not just a postcard from the past, rather a full package special delivery.’

Professor Keith Dobney, co-author and co-director of the dog domestication project from Liverpool University’s Department of Archaeology, Classics and Egyptology, is heartened by these first significant results. ‘With the generous collaboration of many colleagues from across the world-sharing ideas, key specimens and their own data — the genetic and archaeological evidence are now beginning to tell a new coherent story. With so much new and exciting data to come, we will finally be able to uncover the true history of man’s best friend.’

Source:  Science Daily

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.

OLYMPUS DIGITAL CAMERA

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

The mis-labelling of pit bulls

DNA results show that shelter workers are often mistaken when they label a dog as a pit bull, with potentially devastating consequences for the dogs, a new University of Florida study has found.

DNA pit bull study

Dr. Julie Levy holds a dog currently up for adoption at the Alachua County Animal Services facility in Gainesville, Florida

“Animal shelter staff and veterinarians are frequently expected to guess the breed of dogs based on appearance alone,” said Julie Levy, D.V.M., Ph.D., a professor of shelter medicine at the UF College of Veterinary Medicine and the lead author of a study published recently in The Veterinary Journal.

“Unlike many other things people can’t quite define but ‘know when they see it,’ identification of dogs as pit bulls can trigger an array of negative consequences, from the loss of housing, to being seized by animal control, to the taking of the dog’s life,” she said. “In the high-stakes world of animal shelters, a dog’s life might depend on a potential adopter’s momentary glimpse and assumptions about its suitability as a pet. If the shelter staff has labeled the dog as a pit bull, its chances for adoption automatically go down in many shelters.”

The past few decades have brought an increase in ownership restrictions on breeds including pit bulls and dogs that resemble them. The restrictions are based on assumptions that certain breeds are inherently dangerous, that such dogs can be reliably identified and that the restrictions will improve public safety, the study states.

The study focused on how accurately shelter staff identified dogs believed to be pit bulls. ‘Pit bull’ is not a recognized breed, but a term applied to dogs derived from the heritage breeds American Staffordshire terrier or Staffordshire bull terrier. The purebred American pit bull terrier is also derived from these breeds and is often included in the loose definition of ‘pit bull.’

The research team evaluated breed assessments of 120 dogs made by 16 shelter staff members, including four veterinarians, at four shelters. These staff members all had at least three years of experience working in a shelter environment. The researchers then took blood samples from the dogs, developed DNA profiles for each animal and compared the DNA findings against the staff’s initial assessments.

“We found that different shelter staffers who evaluated the same dogs at the same time had only a moderate level of agreement among themselves,” Levy said. Results of the study also showed that while limitations in available DNA profiles make absolute breed identification problematic, when visual identification was compared with DNA test results, the assessors in the study fared even worse.

Dogs with pit bull heritage breed DNA were identified only 33 to 75 percent of the time, depending on which of the staff members was judging them. Conversely, dogs lacking any genetic evidence of relevant breeds were labeled as pit bull-type dogs from 0 to 48 percent of the time, the researchers reported.

“Essentially we found that the marked lack of agreement observed among shelter staff members in categorizing the breeds of shelter dogs illustrates that reliable inclusion or exclusion of dogs as ‘pit bulls’ is not possible, even by experts,” Levy said. “These results raise difficult questions because shelter workers and veterinarians are expected to determine the breeds of dogs in their facilities on a daily basis.

Additionally, they are often called on as experts as to whether a dog’s breed will trigger confiscation or regulatory action. The stakes for these dogs and their owners are in many cases very high.”

Dog breeds contain many genetic traits and variants, and the behavior of any individual dog is impossible to predict based on possible combinations.

“A dog’s physical appearance cannot tell observers anything about its behavior. Even dogs of similar appearance and the same breed often have diverse behavioral traits in the same way that human siblings often have very different personalities,”Levy said.

Even though most pet dogs are of unknown mixed breeds, there is a natural inclination among pet owners to speculate on what their dog’s breed heritage might be, the authors said.

“This has fueled an entire industry of pet dog DNA analysis,” Levy said. “These tests are fun, but they won’t help predict behavior or health traits. Shelters and veterinary clinics are better off entering ‘mixed breed’ or ‘unknown’ in their records unless the actual pedigrees are available.”

As for legal restrictions on dogs based on their appearance, Levy said public safety would be better served by reducing risk factors for dog bites, such as supervising children, recognizing canine body language, avoiding an unfamiliar dog in its territory, neutering dogs and raising puppies to be social companions.

Source:  University of Florida media release

See also my 2013 post on Visual identification of breed – one reason why BSL doesn’t work

New twist in tale of dogs’ origins

The origin of dogs has inspired a lingering controversy in academia. Where and when did dogs first split off from wolves? One of the top dogs in this dispute, population genetics expert Peter Savolainen of Sweden’s KTH Royal Institute of Technology, isn’t about to roll over. He hopes his latest research will finally settle the matter.

Some researchers say canines first split off from wolves in the Middle East; others say it happened in Europe. But Savolainen has long held that dogs originated in South East Asia alone, and he says his team has compiled new evidence that confirms his earlier findings.

The study concludes that the split with wolves occurred about 33,000 years ago.

Savolainen’s earlier studies were based on analysis of mitochondrial DNA. But recently other researchers have used data from nuclear DNA to refute those findings, arguing that dogs originated in the Middle East, Central Asia or Europe.

But apparently, those researchers were thrown off the scent, according to Savolainen. The data they relied on did not include samples from South East Asia, he says. So if, as Savolainen says, dogs did indeed come from South East Asia, these studies would not have been able to detect it.

Photo by IStock

Photo by IStock

“Which is why we analysed the entire nuclear genome of a global sample collection from 46 dogs, which includes samples from southern China and South East Asia,” he says. “We then found out that dogs from South East Asia stand out from all other dog populations, because they have the highest genetic diversity and are genetically closest to the wolf.”

Savolainen says this provides strong evidence that the dog originated in South East Asia, which confirms his earlier studies of Mitochondrial DNA.

“We also found that the global dog population is based on two important events: the dog and wolf populations first began to split off about 33,000 years ago in South East Asia. The global spread of dogs followed about 18,000 years later.

He says one explanation for the split between dogs and wolves 33,000 years ago could be that the wolf population became divided and the south Chinese wolf developed into dogs. In that case, it is possible the global spread of dogs out of South East Asia is associated with domestication.

“The dog’s story thus appears to have begun 33,000 years ago, but the exact path to the fully-domesticated dogs that spread throughout the world 15,000 years ago is not yet clear,”

Savolainen, along with 14 other scientists, recently published the scientific article “Out of Southern East Asia: The Natural History of domestic dogs across the world.

Source:  AlphaGalileo media release