Chromosomal 'breakpoints' linked to canine cancer

ScienceDaily (Nov. 3, 2011) — North Carolina State University researchers have uncovered evidence that evolutionary "breakpoints" on canine chromosomes are also associated with canine cancer. Mapping these "fragile" regions in dogs may also have implications for the discovery and treatment of human cancers.

When new species evolve, they leave genetic evidence behind in the form of "breakpoint regions." These regions are sites on the genome where chromosomes broke during speciation (when new species of dogs developed). Dr. Matthew Breen, professor of genomics at NC State, and graduate student Shannon Becker looked at the breakpoint regions that occurred when the canid (dog) species differentiated during evolution. They compared the genomes of several wild canine species with those of the domestic dog. By overlaying the genomes, they found shared breakpoints among 11 different canid species -- the so-called evolutionary breakpoints.

"The interesting thing about the breakpoint areas in the canid chromosome is that they are the same regions that we have shown to be associated with chromosome breaks in spontaneously occurring cancers," Breen says. "It is possible that the re-arrangement of chromosomes that occurred when these species diverged from one another created unstable regions on the chromosome, and that is why these regions are associated with cancer."

The researchers' results appear in Chromosome Research.

"As species evolve, genetic information encoded on chromosomes can be restructured -- resulting in closely related species having differently organized genomes," says Becker. "In some cases, species acquire extra chromosomes, called B chromosomes. We looked at these extra B chromosomes in three canid species and found that they harbor several cancer-associated genes. Our work adds to the growing evidence that there is an association between cancer-associated genomic instability and genomic rearrangement during speciation."

"The presence of clusters of cancer- associated genes on canid B chromosomes suggests that while previously though to be inert, these chromosomes may have played a role in sequestering excess copies of such genes that were generated during speciation," adds Breen. "We now need to determine whether these stored genes are active or inert -- that information could give us new tools in cancer detection and treatment."

The research was funded by the Morris Animal Foundation. The Department of Molecular Biomedical Sciences is part of NC State's College of Veterinary Medicine.

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Shannon E. Duke Becker, Rachael Thomas, Vladimir A. Trifonov, Robert K. Wayne, Alexander S. Graphodatsky, Matthew Breen. Anchoring the dog to its relatives reveals new evolutionary breakpoints across 11 species of the Canidae and provides new clues for the role of B chromosomes. Chromosome Research, 2011; 19 (6): 685 DOI: 10.1007/s10577-011-9233-4

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Medical research using dogs as models

ScienceDaily (May 9, 2012) — Dogs are among the best animals when it comes to providing models for better medical treatments in humans, and with more than 77 million dogs in the United States alone, it's another way the human-animal bond has become closer than anyone had ever dreamed. Researchers at the Texas A&M College of Veterinary Medicine & Biomedical Sciences are looking into ways how dogs -- and several other animal types -- can provide a variety of medical benefits to people, ranging from bone cancer studies to spinal cord injuries and others.

"Dogs can be ideal models to study," says Theresa Fossum, director of the Texas A&M Institute for Preclinical Studies.

"This is especially true when it comes to certain types of cancer. Cancers in dogs, such as bone cancer, lymphoma and many other types of tumors, are almost identical to those same kinds found in humans and they tend to develop faster and run their course quicker, so it's an ideal way to see if a certain therapy will work. Dogs also tend to be better predictors of how new cancer drugs and medical devices can work. By studying cancer treatments in dogs, we can come up with better and more improved ways to treat cancer in humans and animals."

Bone cancer in dogs, Fossum explains, is almost identical to human bone cancer. To get a big picture of just how the disease forms and progresses in dogs, Fossum has helped to create the Texas Veterinary Cancer Registry, a database of treatment information.

"We want to get the word out to dog owners that this service is available and it can help their pet and quite possibly, their next door neighbor one day," she adds. "There is no charge to register your dog and we encourage pet owners to do this. The information we get can be very useful in canine treatments.

"People may not know it, but it costs $3 billion and up for a drug to be created and tested in many trials before it is offered to the public. With more information, we believe it's possible to cut those drug development costs way down."

Cancer is no stranger to dogs -- in fact, about 1 in every 4 dogs will eventually get it, and breeds such as Boxers and Golden Retrievers are especially prone to bone cancer, she adds. "Larger dogs are more likely to develop certain cancers, but any dog -- or cat -- can suffer from the disease," she notes.

Treatments, as in humans, can be very expensive, with costs easily ranging from $5,000-$10,000 and up, "but it's possible some cases can be paid for if they are eligible for study in a clinical trial. Also, by getting more information on dogs who suffer from cancer, we can learn better ways to fight the disease and hopefully one day the costs will go down dramatically," Fossum says.

Fossum adds that eventually, she would like to develop a similar program to find treatments for other diseases that dogs and humans share such as diabetes and heart and kidney disease.

Pet owners -- and even other veterinarians -- are encouraged to go to http://texasvetcancerregistry.com/ to register their dogs in the program.

Jonathan Levine, an assistant professor in the Small Animal Clinic who specializes in spinal cord injuries, agrees that dogs with naturally occurring diseases may offer promise in advancing human therapies. He has received a $900,000 Department of Defense grant to develop non-invasive treatments and therapies for spinal cord injuries in dogs.

"We hope the results will translate into successful therapies and treatments for humans -- that's our goal," he says.

"Since most of these injuries happen naturally, they are more diverse," he notes "The affected dogs are out in the environment, they're not all the same breed, and the injuries don't happen the same way. So the diversity probably gives a little advantage exploring theories into the possible treatment of dogs and humans with similar spinal cord injuries."

He adds that the Defense Department was particularly interested in this type of research because of the possible implications it may have on troops with spinal cord injuries. Such injuries in humans can be physically debilitating, and also incredibly expensive. Studies show that a person who has sustained a spinal cord injury at age 25 may face medical expenses of $729,000 to $3.2 million over a lifetime.

Levine says clinical trials will be performed on young dogs who suffer from a severe disk problem called canine thoracolumbar intervertebral disk herniation, a disease that is very similar to spinal cord injuries in humans. Dachsunds appear to suffer from the disease most often, and this breed will represent about half of the cases.

Other veterinarians, such as oncology specialist Heather Wilson-Robles, are conducting similar research with human-animal connections. Her work involves lymphoma, melanoma, mammary and other types of cancer and canine tumors, and it has been funded several times by the American Kennel Club and the National Institutes for Health.

"In many cases, the cancers we see in dogs are almost identical to those in humans, so dogs are a great predictor for us," she explains. "For example, bone cancer in children and dogs is very similar -- it results in about a 90 percent chance of death in a dog, and about 60 percent in children.

"Melanoma in dogs is usually not caused by sunshine, but the behavior of the cancer is similar in both humans and dogs," she adds. "With mammary cancer, women get breast cancer, dogs get mammary cancer and the two are very alike. We know that not having children increases the risk in both species."

She and Levine have created a website at http://vetmed.tamu.edu/clinical-trials detailing clinical trials they have conducted.

Levine says that the type of research "we do involves a lot of trial and error, many times over," he notes.

"It's like Thomas Edison and the thousands of attempts he made before he got the light bulb to work. With dogs, spinal cord injuries are much like those in people -- the damage is the same, the MRIs we do on both look pretty much the same, and on and on.

"In the last 10 to 15 years, there has been very limited success in treating these types of injuries. But we think a major breakthrough is possible in the years to come, and again, our ultimate goal is to see if what we do is successful in dogs, it can also be successful in humans."

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Dog-associated house dust protects against respiratory infection linked to asthma

ScienceDaily (June 19, 2012) — House dust from homes with dogs appears to protect against infection with a common respiratory virus that is associated with the development of asthma in children.

Researchers from the University of California, San Francisco, recenlty presented their findings at the 2012 General Meeting of the American Society for Microbiology.

"In this study we found that feeding mice house dust from homes that have dogs present protected them against a childhood airway infectious agent, respiratory syncytial virus (RSV). RSV infection is common in infants and can manifest as mild to severe respiratory symptoms. Severe infection in infancy is associated with a higher risk of developing childhood asthma," says Kei Fujimura, a researcher on the study.

In the study Fujimura and her colleagues compared three groups of animals: Mice fed house dust from homes with dogs before being infected with RSV, mice infected with RSV without exposure to dust and a control group of mice not infected with RSV.

"Mice fed dust did not exhibit symptoms associated with RSV-mediated airway infection, such as inflammation and mucus production. They also possessed a distinct gastrointestinal bacterial composition compared to animals not fed dust," says Fujimura.

Pet ownership, in particular dogs, has previously been associated with protection against childhood asthma development, says Fujimura. Recently she and her colleagues demonstrated that the collection of bacterial communities (the microbiome) in house dust from homes that possess a cat or dog is compositionally distinct from house dust from homes with no pets.

"This led us to speculate that microbes within dog-associated house dust may colonize the gastrointestinal tract, modulate immune responses and protect the host against the asthmagenic pathogen RSV," says Fujimura. "This study represents the first step towards determining the identity of the microbial species which confer protection against this respiratory pathogen."

Identification of the specific species and mechanisms underlying this protective effect represents a crucial step towards understanding the critical role of microbes in defining allergic disease outcomes and could lead to development of microbial-based therapies to protect against RSV and ultimately reduce the risk of childhood asthma development, says Fujimura.

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For common toy breed dog windpipe issue, veterinarians use technology and precision

ScienceDaily (Oct. 4, 2011) — Jack, a 12-year-old Yorkshire terrier, was lethargic and gasping for air when he arrived at the University of Missouri Veterinary Hospital. His tongue and gums were a bluish-purple. But, just one day following an innovative procedure, Jack bounced back to his former youthful exuberance.

Jack was suffering from tracheal collapse. Tracheal collapse occurs when the cartilage comprising the c-shaped rings of the trachea collapse, leaving dogs to breathe through a trachea that resembles a narrowed or closed straw. Standard treatment involves medical management with lifestyle changes and drugs aimed at minimizing the consequences of a smaller airway. For many dogs, medical management ultimately ceases to work.

In Jack's case, MU veterinarians inserted an intra-luminal stent, like a tiny spring, within the trachea. Carol Reinero, associate professor of small animal internal medicine, performed the procedure on Jack, which required no incision.

"This condition is very common in toy breeds, but not all dogs with this condition have such severe symptoms," Reinero said. "We start with medical management, but because this is a degenerative disease, further measures are sometimes necessary. The procedure that Jack received is generally considered a last-ditch effort. It takes a great deal of planning and precision. But its success can be seen -- and heard -- almost immediately."

The life-giving treatment Jack received was performed at the MU Veterinary Medical Teaching Hospital, the only facility in Missouri known to offer the particular procedure that allowed Jack to breathe again so quickly. The MU College of Veterinary Medicine's success in the placement of these stents can be attributed to the teaching hospital's high-tech equipment and a full team of skilled veterinary medicine specialists, including board certified internists, anesthesiologists, radiologists and veterinary students.

"When Jack first came to us, he was wheezing and coughing, and we had to carry him around because of his condition," said Heather Wise, a fourth-year veterinary medical student. "At his follow up, we didn't even hear him coming down the hall for his appointment."

Jack's two-week follow-up examination showed remarkable results. The team found that his oral membranes had returned to a healthy pink color and his tracheal and lung sounds were normal. The radiographs show the tracheal areas once absent of air are now propped fully open with the stent.

"We didn't realize how serious his condition was, but it was a great relief to know that it could be treated," said Connie Miller, Jack's owner.

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Is hunting wolves key to their conservation?

ScienceDaily (Aug. 8, 2011) — Hunters have been credited with being strong conservation advocates for numerous game species in multiple countries. Would initiating a wolf hunt invoke the same advocacy for the carnivores?

It's a pressing question as gray wolves were removed from the federal endangered species list in some western states this past May and are poised for delisting in 2012 in Wisconsin, Minnesota, Michigan and other areas of the Midwest. But newly released public opinion surveys conducted in Wisconsin and the northern Rockies suggest that wolves are in a class by themselves and that existing deer, elk, and other game hunts are poor models for a potential wolf hunt.

University of Wisconsin-Madison researchers Adrian Treves and Kerry Martin surveyed 2,320 residents of Wisconsin, Idaho, Montana, and Wyoming -- including both hunters and non-hunters -- between 2001 and 2007. Their findings, appearing in the August issue of the peer-reviewed journal Society and Natural Resources, reveal hunter attitudes toward wolves that are largely inconsistent with stewardship.

Questions assessed a range of factors including acceptance of management policy, tolerance of the carnivores, willingness to kill a wolf illegally, adherence to hunt regulations, and expected financial support of conservation.

"Hunters were some of the least tolerant of wolves among our respondents, and the closer you got to wolf range the less tolerant they were," says Treves, a professor in the UW-Madison Nelson Institute for Environmental Studies.

One issue may be that hunters often view wolves as competition for deer and other game. Opening a wolf hunt may not immediately shift that perception to viewing wolves as another game species to be conserved.

Treves was also surprised by the level of support expressed for a regulated wolf hunt among non-hunters and those living outside wolf range. In Wisconsin, for example, he says, "You find a surprising amount of support for a public regulated harvest of wolves even in places like Madison, Fond du Lac, or Sister Bay."

But these endorsements tend to be conditional, he cautions, and the conditions vary. For example, many people support the idea of a "sustainable" hunt -- though "sustainable" was undefined in this context -- or hunting as a way to reduce attacks on livestock and other conflicts between wolves and humans.

"To me that says that people see hunting as a tool for enabling coexistence," Treves says.

But the evidence simply isn't there to indicate that hunting wolves would affect depredations of domestic animals. No depredation data were reported following a hunt in Idaho and Montana conducted during a window of time in 2009 when the animals were not federally protected. And though wolves have been hunted legally in Alaska for decades, the scarcity of domestic animals and difference in landscape make it nearly impossible to draw conclusions that would apply to the lower 48.

A risk map Treves and others published in June shows that wolf attacks on livestock in Wisconsin are highly localized and attributable to a relatively small number of packs. The majority of packs do not cause problems despite living in close proximity to humans, which raises significant questions about the efficacy of a general hunt to alleviate perceived problems.

"The assumption that hunting and reducing the number of animals will reduce livestock losses would be proven false if hunters are targeting the wrong animals, such as animals in wilderness areas," he says, adding that it will be important to understand hunter motivations. "Wolves in wilderness areas don't kill livestock, it's the wolves on the edge in agricultural areas. Do hunters want to hunt in farmland? I'm not sure."

The uncertainty of how hunting would affect wolf populations could also become a legal issue, says UW-Madison law professor Stephanie Tai, citing a precedent of legal challenges of federal delisting decisions. "People have challenged delistings for a number of reasons, and some of those have been successful," she says. "Often, successful lawsuits bring up factors the Fish and Wildlife Service may not have considered, which could include the effect of allowing hunting."

The challenge, Treves says, is to balance human needs with the need to conserve wolves as an essential component of ecosystems. In a viewpoint piece published in the August issue of the journal BioScience, Treves and Jeremy Bruskotter, an environment and natural resources professor at The Ohio State University, present some possible scenarios for the future of wolf management in the U.S. Those scenarios include reclassifying the wolves as threatened, which would permit lethal control under certain circumstances, or enacting specific federal protections outside the Endangered Species Act, such as those currently in place for bald eagles, wild horses, and migratory birds.

They advocate geographically tailored approaches that will permit local-level control within a federal framework to strike a balance between wolves and humans. Sound long-term management can include a public regulated hunt, they say, but it will unquestionably require compromise.

"A public regulated harvest is a collaboration between hunters and the state, which requires give and take. I think the next few years in Wisconsin will reveal how well that collaboration works," says Treves.

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Adrian Treves, Kerry A. Martin. Hunters as Stewards of Wolves in Wisconsin and the Northern Rocky Mountains, USA. Society & Natural Resources, 2011; 24 (9): 984 DOI: 10.1080/08941920.2011.559654

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Russian and US veterinarians collaborate to solve mysterious wild tiger deaths

ScienceDaily (Sep. 30, 2011) — A team of Russian veterinary colleagues and health experts from the Wildlife Conservation Society's Bronx Zoo are collaborating to understand how distemper -- a virus afflicting domestic dogs and many wildlife species -- may be a growing threat to Siberian (Amur) tigers.

The team presented its results at the first-ever Russian symposium on wildlife diseases recently held in the Russian Far East city of Ussurisk. The symposium underscores the growing recognition of the importance of the health sciences to successful wildlife conservation efforts.

Working at WCS's Wildlife Health Center at the Bronx Zoo, Russian health experts and WCS pathologists used histology along with PCR and DNA sequencing to confirm and characterize the infection in two wild Siberian tigers from the Russian Far East. This diagnosis provides long-awaited genetic confirmation of the fact that distemper is impacting wild tigers, which WCS and Russian colleagues first documented in 2003.

The collaboration will enable conservationists to formulate health measures to counter this latest threat to the world's largest cat.

The participants in the partnership included: Drs. Irina Korotkova and Galina Ivanchuk from the Primorskaya State Agricultural Academy; Elena Lyubchenko, county veterinarian for Ussuriski County, Drs. Anastasia Vysokikh and Mikhail Alshinetskiy from the Moscow Zoo; and Drs. Denise McAloose and Tracie Seimon from WCS.

Last year a tigress "Galia" -- studied by WCS researchers for eight years in Sikhote-Alin Biosphere Reserve in the Russian Far East -- walked into the village of Terney. Galia displayed abnormal neurologic signs, seemingly unfazed by the new surrounding, appeared gaunt, and was searching for dogs as an easy meal. The tiger was shot by local police after several capture attempts failed. In November 2003, a similar event occurred when an otherwise healthy looking wild tigress walked into the village of Pokrovka in Khabarovski Krai. WCS staff working in the area immobilized the animal and worked with local Russian veterinarian Evgeny Slabe in treating the tiger, which later died in captivity. Samples for the diagnosis of distemper were collected only from these two animals.

Several other examples of tigers entering villages or stalling traffic on major roadways -- behavior possibly indicative of distemper -- have been reported in recent years.

"This exchange provides a foundation for elucidating potential disease threats to tigers in the Russian Far East," said Irina Korotkova of the Primorskaya Agricultural Academy. "Understanding the role of distemper in our wild Amur tiger population is vitally important."

Distemper is found worldwide in domestic dogs and has caused infection and death in wild species such as lynx and bobcats in Canada, Baikal seals in Russia, lions in the Serengeti ecosystem in Africa, and raccoons and the endangered black footed ferret in the United States.

"With all the threats facing Siberian tigers from poaching and habitat loss, relatively little research has been done on diseases that may afflict tigers," said Dale Miquelle, WCS Director of Russia Programs. "There are no records of tigers entering villages and behaving so abnormally before 2000, so this appears to be a new development and new threat. Understanding whether disease is a major source of mortality for Siberian tigers is crucial for future conservation efforts."

Anatoly Astafiev, Director of Sikhote-Alin Reserve, said, "We have seen a fall in tiger numbers within our reserve, so it is very important to know that at least one of the causes is a recognizable disease, something we may be able to address and potentially prevent."

Canine distemper is controlled in domestic dogs through vaccination. In Africa, massive vaccination campaigns of dogs in villages surrounding the Serengeti appear to have been effective in reducing the disease's impact on lions.

Dr. Denise McAloose, WCS's Chief Pathologist and leader of the investigation, said, "This is a great example of what international collaboration can achieve. Without our Russian associates there on the spot, knowing what samples to collect and how to preserve these specimens, samples would never have made it to our lab, and the cause of death would remain unknown. It's great that we're all here together to work on this issue as a team."

WCS is working with staff from the Primorskaya Agriculture Academy and other partners to establish a wildlife lab in Ussurisk to facilitate local diagnostic testing, although it will take several years until the lab is adequately funded and fully functional.

McAloose added: "Until then, there's still much to do including identifying the source of the disease."

It is still uncertain how tigers may have contracted the disease and whether it originated in another wild animal species or domestic dogs, both of which can act as reservoirs for the infection.

Latest reports suggest that fewer than 3,500 tigers remain in the wild; 1,000 are breeding females.

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Efficacy of non-Hodgkin's lymphoma vaccine demonstrated in dogs

ScienceDaily (Oct. 18, 2011) — An experimental vaccine developed by researchers at the University of Pennsylvania's schools of Medicine and Veterinary Medicine is the first veterinary cancer vaccine of its kind that shows an increase in survival time for dogs with spontaneous non-Hodgkin's lymphoma. The work shows for the first time the feasibility and therapeutic efficacy of this alternative cell-based vaccine, which could be employed in the treatment of a number of different cancer types.

The research was conducted by Nicola Mason, assistant professor of medicine at Penn Vet; Robert H. Vonderheide, associate professor of hematology and oncology at the Perelman School of Medicine; and Karin U. Sorenmo, associate professor of oncology at Penn Vet. Erika Krick, Beth Overley and Thomas P. Gregor of Penn Vet and Christina M. Coughlin of the School of Medicine also contributed to the research.

Their work was published in the open access journal PLOS ONE.

The team recruited dogs that were brought to Penn's Matthew J. Ryan Veterinary Hospital with newly diagnosed non-Hodgkin's lymphoma to receive the experimental vaccine following standard induction chemotherapy and confirmation of clinical remission. The goal of the study was to determine whether the vaccine would prevent or prolong time to a relapse, a common scenario in both humans and dogs with NHL.

"We vaccinated dogs, which were in clinical remission following chemotherapy, three times," Mason said. "We then tracked them over several years to see if the vaccine would prevent relapse and would prolong overall survival.

"We found that, although the vaccinated dogs still relapsed with clinical disease when they were treated with rescue chemotherapy, they had significantly increased overall survival times when compared to an unvaccinated control group. Some of these dogs are still alive and cancer free more than three years later.

"The results with these dogs indicate that our immunotherapy and rescue chemotherapy appear to act synergistically to prevent a second relapse -- a phenomenon that has been previously recognized in human patients treated with other types of immunotherapy," she said.

Previous cell based vaccines have utilized genetically engineering dendritic cells -- which are part of the immune system -- to stimulate immune responses against cancers. Similar to using weakened viruses in traditional vaccines, scientists load these cells with tumor proteins and inject the cells back into the patient's body. Such cell-based vaccines are already being used to treat prostate cancer in humans, but engineering these cells is expensive and time consuming. Furthermore, patients must also endure long, leukapheresis sessions in which the necessary dendritic cells are harvested from their blood.

The Penn team hypothesized that another kind of immune cell, B-cells, could work just as well under the right conditions. Unlike dendritic cells, many B-cells can be grown from a small blood sample, removing the requirement for leukapheresis.

Mason's team made the vaccine by culturing B-cells from the blood taken from the dogs with NHL. These cells were then loaded with RNA that had been isolated from the patient's own tumor.

The results were impressive.

"Though vaccinated and unvaccinated dogs relapsed with clinical disease at the same time, 40 percent of vaccinated dogs that relapsed experienced long-term survival after a second round of chemotherapy; only 7 percent of unvaccinated dogs that relapsed and were treated with the same rescue chemotherapy protocol survived long term," Mason said. "Furthermore, when the vaccinated long-term survivors did eventually die, they showed no evidence of lymphoma on full necropsy."

While the molecular mechanisms responsible for these observed synergistic effects are currently unknown, Mason believes that the vaccine-primed immune system may be boosted by the effects of rescue chemotherapy leading to long term second remissions.

Though the increases in long-term survival are already unprecedented and the proof-of-concept for B-cell-based cancer vaccines represents a step forward in cell-based vaccine development, future research could have even more exciting results.

"These dogs just received three doses of vaccine, three weeks apart. If we kept boosting the immune system in this way by vaccination, perhaps the dogs would not relapse in the first place" Mason said.

Work is now underway to streamline B-cell vaccine generation and initiate further clinical trials aimed at optimizing this novel cell-based approach.

This work was supported by the National Institutes of Health, Alliance for Cancer Gene Therapy, Onyx and Breezy Foundation, Barry and Savannah Poodle Memorial Fund, Mari Lowe Comparative Oncology Center, Immunobiology Program of the Abramson Cancer Center at the University of Pennsylvania and Oncology Research Fund at the Veterinary Hospital of the University of Pennsylvania.

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Karin U. Sorenmo, Erika Krick, Christina M. Coughlin, Beth Overley, Thomas P. Gregor, Robert H. Vonderheide, Nicola J. Mason. CD40-Activated B Cell Cancer Vaccine Improves Second Clinical Remission and Survival in Privately Owned Dogs with Non-Hodgkin's Lymphoma. PLoS ONE, 2011; 6 (8): e24167 DOI: 10.1371/journal.pone.0024167

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Modern dog breeds genetically disconnected from ancient ancestors

ScienceDaily (May 21, 2012) — Cross-breeding of dogs over thousands of years has made it extremely difficult to trace the ancient genetic roots of today's pets, according to a new study led by Durham University.

An international team of scientists analyzed data of the genetic make-up of modern-day dogs, alongside an assessment of the global archaeological record of dog remains, and found that modern breeds genetically have little in common with their ancient ancestors.

Dogs were the first domesticated animals and the researchers say their findings will ultimately lead to greater understanding of dogs' origins and the development of early human civilization.

Although many modern breeds look like those depicted in ancient texts or in Egyptian pyramids, cross-breeding across thousands of years has meant that it is not accurate to label any modern breeds as "ancient," the researchers said.

Breeds such as the Akita, Afghan Hound and Chinese Shar-Pei, which have been classed as "ancient," are no closer to the first domestic dogs than other breeds due to the effects of lots of cross-breeding, the study found.

Other effects on the genetic diversity of domestic dogs include patterns of human movement and the impact on dog population sizes caused by major events, such as the two World Wars, the researchers added.

The findings were published May 21 in the scientific journal Proceedings of the National Academy of Sciences USA (PNAS). The Durham-led research team was made up of scientists from a number of universities including Uppsala University, Sweden, and the Broad Institute, in the USA.

In total the researchers analysed genetic data from 1,375 dogs representing 35 breeds. They also looked at data showing genetic samples of wolves, with recent genetic studies suggesting that dogs are exclusively descended from the grey wolf.

Lead author Dr Greger Larson, an evolutionary biologist in Durham University's Department of Archaeology, said the study demonstrated that there is still a lot we do not know about the early history of dog domestication including where, when, and how many times it took place.

Dr Larson added: "We really love our dogs and they have accompanied us across every continent.

"Ironically, the ubiquity of dogs combined with their deep history has obscured their origins and made it difficult for us to know how dogs became man's best friend.

"All dogs have undergone significant amounts of cross-breeding to the point that we have not yet been able to trace all the way back to their very first ancestors."

Several breeds, including Basenjis, Salukis and Dingoes, possess a differing genetic signature, which previous studies have claimed to be evidence for their ancient heritage, the research found.

However the study said that the unique genetic signatures in these dogs was not present because of a direct heritage with ancient dogs. Instead these animals appeared genetically different because they were geographically isolated and were not part of the 19th Century Victorian-initiated Kennel Clubs that blended lineages to create most of the breeds we keep as pets today.

The study also suggested that within the 15,000 year history of dog domestication, keeping dogs as pets only began 2,000 years ago and that until very recently, the vast majority of dogs were used to do specific jobs.

Dr Larson said: "Both the appearance and behavior of modern breeds would be deeply strange to our ancestors who lived just a few hundred years ago.

"And so far, anyway, studying modern breeds hasn't yet allowed us to understand how, where and when dogs and humans first started this wonderful relationship."

The researchers added that DNA sequencing technology is faster and cheaper than ever and could soon lead to further insights into the domestication and subsequent evolution of dogs.

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G. Larson, E. K. Karlsson, A. Perri, M. T. Webster, S. Y. W. Ho, J. Peters, P. W. Stahl, P. J. Piper, F. Lingaas, M. Fredholm, K. E. Comstock, J. F. Modiano, C. Schelling, A. I. Agoulnik, P. A. Leegwater, K. Dobney, J.-D. Vigne, C. Vila, L. Andersson, K. Lindblad-Toh. Rethinking dog domestication by integrating genetics, archeology, and biogeography. Proceedings of the National Academy of Sciences, 2012; DOI: 10.1073/pnas.1203005109

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'White-coat effect' elevates greyhounds' blood pressure

ScienceDaily (Sep. 6, 2011) — The "white-coat effect" is not reserved for only the human patients who see their blood pressure rise in response to the stress of a doctor visit.

In a new study, researchers have determined that anxiety associated with being in a veterinary hospital elevates the blood pressure in retired racing greyhounds -- a breed known for having higher-than-average blood pressure in the first place.

The average systolic arterial pressure -- the top number in a blood pressure reading -- in the dogs was about 30 points higher in a veterinary clinic when compared to blood pressure recorded at home.

The environment seemed to make all the difference. Blood pressure readings recorded in a home were similar when taken by either a veterinary student or the dog's owner. In general, normal blood pressure in dogs, as in humans, is 120 over 80.

Some animals' blood pressure readings normalize after they've had time to acclimate to the hospital setting, but in these greyhounds, that trend is less common. According to the researchers, this study suggests that the presence of the dog owner might have a more calming effect than the passage of time in the clinic.

"We see a lot of greyhounds and they are very high-strung dogs," said Guillermo Couto, professor of veterinary clinical sciences at Ohio State University and senior author of the study. "Some greyhounds come in here with blood pressure above what an instrument can read -- that is 300 systolic. We know this could not really be their blood pressure because these dogs would be dead. But we also almost never get blood pressure under 150 or 160 for systolic.

"In the study, their blood pressure was nearly normal at home, independently of whether the researcher or the owner checked the pressure. To my knowledge, nobody has documented that white-coat effect in dogs with hard data before."

Most of the estimated 200,000 pet greyhounds in the United States are former racers that have been adopted at the end of their careers. Couto and colleagues recommend that retired racing greyhounds' blood pressure be recorded in the home if possible to provide a more accurate measure.

The study is published in the current issue of the Journal of Veterinary Internal Medicine.

The scientists performed the study with 22 retired racing greyhounds that are enrolled in a blood donor program at Ohio State's Veterinary Medical Center. The average age of the dogs was 7 ½ years. Twelve were male and 10 were female.

Blood pressure measurements were taken in three different ways: in the veterinary medical center by a veterinary student wearing scrubs; in the dog's home by that same student, again wearing scrubs; and in the home by the dog's owner.

In-home blood pressure readings were taken between seven and 28 days after the hospital measurements to avoid any effects of the dogs' blood donations during their hospital stays. The owners then followed the student's in-home reading 24 hours later.

The student used a specialized machine and instructed each owner on how to use it, providing reading material and offering a demonstration. The machine costs about $1,500, but Couto said manufacturers are currently working on developing a less expensive and more user-friendly device that could be used by dog owners in a home setting.

The researchers recorded systolic pressure, diastolic pressure -- the lower number in a blood pressure reading, mean arterial pressure and heart rate.

The systolic and mean arterial pressures, as well as heart rate readings, taken in the hospital were significantly higher than all of those same measures taken in the home environment. The average hind-limb systolic pressure was 165, compared to at-home measures of 131 and 133 when taken by the researcher and the owner, respectively.

"This study emphasizes the need to consider the environment in which the blood pressure is measured before diagnosing or eliminating hypertension," Couto said.

Unlike the blood pressure readings, heart-rate levels, while still higher than in the home, were lower in the clinic among "veteran" greyhounds that had frequently visited the hospital before the study. According to the researchers, this finding suggested that acclimation to the clinical environment did affect this particular stress response.

The researchers also found that the limb used to measure blood pressure affected the results. Measures were taken in both forelimbs and hind limbs. Measures tended to be higher in the back legs, but the reasons for this were not determined by the study.

Couto and his colleagues are now exploring whether retired racing greyhounds' hypertension resulting from this white-coat effect causes any damage to their kidneys or other organs.

Couto, an oncologist, is leading a number of studies on these animals to gauge the effects of racing on their health, as well as likely genetic contributions to their high risk for bone cancer. Since he adopted his first retired racing greyhound 20 years ago, he has been committed to investigating their physiologic idiosyncrasies.

"They're hypertensive and yet they don't have target organ lesions that people with hypertension get. They have strokes, unlike most dogs, but the strokes they have are different from strokes in hypertensive humans. Their kidneys and eyes don't take a beating from the high blood pressure," he said. "So my thinking is that greyhounds are 'Type-A personality' dogs. They are raised in a racing environment, but they are pack animals, so this stresses them out. And then once they retire, they are couch potatoes. We're trying to put all of this together, and it's all aimed at promoting wellness in these dogs."

This research was supported by the Ohio State University College of Veterinary Medicine Summer Student Research Fellowship Program and Ohio State's Greyhound Health and Wellness Development Funds.

Co-authors include fourth-year student Christina Marino, clinical instructor Richard Cober and Maria Iazbik, managing director of the Animal Blood Bank, all of Ohio State's College of Veterinary Medicine.

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Journal Reference:

C.L. Marino, R.E. Cober, M.C. Iazbik, C.G. Couto. White-Coat Effect on Systemic Blood Pressure in Retired Racing Greyhounds. Journal of Veterinary Internal Medicine, 2011; 25 (4): 861 DOI: 10.1111/j.1939-1676.2011.00735.x

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First dogs came from East Asia, genetic study confirms

ScienceDaily (Nov. 23, 2011) — Researchers at Sweden's KTH Royal Institute of Technology say they have found further proof that the wolf ancestors of today's domesticated dogs can be traced to southern East Asia -- findings that run counter to theories placing the cradle of the canine line in the Middle East.

Dr Peter Savolainen, KTH researcher in evolutionary genetics, says a new study released Nov. 23 confirms that an Asian region south of the Yangtze River was the principal and probably sole region where wolves were domesticated by humans.

Data on genetics, morphology and behaviour show clearly that dogs are descended from wolves, but there's never been scientific consensus on where in the world the domestication process began. "Our analysis of Y-chromosomal DNA now confirms that wolves were first domesticated in Asia south of Yangtze River -- we call it the ASY region -- in southern China or Southeast Asia," Savolainen says.

The Y data supports previous evidence from mitochondrial DNA. "Taken together, the two studies provide very strong evidence that dogs originated in the ASY region," Savolainen says.

Archaeological data and a genetic study recently published in Nature suggest that dogs originate from the Middle East. But Savolainen rejects that view. "Because none of these studies included samples from the ASY region, evidence from ASY has been overlooked," he says.

Peter Savolainen and PhD student Mattias Oskarsson worked with Chinese colleagues to analyse DNA from male dogs around the world. Their study was published in the scientific journal Heredity.

Approximately half of the gene pool was universally shared everywhere in the world, while only the ASY region had the entire range of genetic diversity. "This shows that gene pools in all other regions of the world most probably originate from the ASY region," Savolainen says.

"Our results confirm that Asia south of the Yangtze River was the most important -- and probably the only -- region for wolf domestication, and that a large number of wolves were domesticated," says Savolainen.

In separate research published recently in Ecology and Evolution, Savolainen, PhD student Arman Ardalan and Iranian and Turkish scientists conducted a comprehensive study of mitochondrial DNA , with a particular focus on the Middle East. Because mitochondrial DNA is inherited only from the mother in most species, it is especially useful in studying evolutionary relationships.

"Since other studies have indicated that wolves were domesticated in the Middle East, we wanted to be sure nothing had been missed. We find no signs whatsoever that dogs originated there," says Savolainen.

In their studies, the researchers also found minor genetic contributions from crossbreeding between dogs and wolves in other geographic regions, including the Middle East.

"This subsequent dog/wolf hybridisation contributed only modestly to the dog gene pool," Savolainen explains.

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Journal Reference:

Z-L Ding, M Oskarsson, A Ardalan, H Angleby, L-G Dahlgren, C Tepeli, E Kirkness, P Savolainen, Y-P Zhang. Origins of domestic dog in Southern East Asia is supported by analysis of Y-chromosome DNA. Heredity, 2011; DOI: 10.1038/hdy.2011.114

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