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 le pattern "merle"/ recherches dr Anne Clark.

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Nombre de messages : 12149
Age : 74
Localisation : Beauraing.(Belg.)
Date d'inscription : 02/11/2006

MessageSujet: le pattern "merle"/ recherches dr Anne Clark.   Jeu 1 Sep 2016 - 14:54

Toujours intéressant:

Responsible dog breeders certainly want to sell pups, but not at the price of a dog’s health. They avoid merle-to-merle matings, which can produce double merles—those receiving the dominant variation from both parents. Double merles are mostly white and can have defects in hearing and vision.

Unfortunately some merles are hard to detect.

“A dog can be a ‘cryptic’ merle, which shows only small merle patches or no pattern at all and looks like a non-merle,” Clark says. “If a cryptic merle is mated with an another merle, one in four of the puppies will be a double merle and at risk for deafness and blindness.”

Double merles have been compared with humans who have Waardenburg Syndrome 2. Both groups have a genetic disorder that hampers the growth of pigment cells, which play a role in development of eye shape and color and the nerve endings in the inner ear. The results often are distinctive soft blue eyes and deafness. In humans, a stark white forelock also can be the calling card of the syndrome.

“There’s no cure for Waardenburg syndrome, but the work will help researchers identify the genetics guiding it, which can alert genetic counselors and dog breeders to look for the problem during DNA screening,” Clark says.

Merle figures into another topic of Clark’s research, the harlequin pattern found on Great Danes. The pattern is the bold black-and-white look that is accepted as part of the breed standard, which includes black, brown, and brindle coloring as well. The Great Dane Charitable Trust has funded her work to identify genetic mechanisms that produce the harlequin pattern. She has worked on the harlequin genetic factor since 2005.

“All harlequins are merles, but they are more than merle,” says Clark. “There’s a separate gene for harlequin. It is a dominant modifier of merle that removes the dilute pigment, leaving the background white.”

In other words, the harlequin gene acts as a stronger bleaching agent, eliminating the merle’s light bleach spots on the base coat, resulting in white base-coat spots.
A genetic test

Clark is the only researcher doing this work, which involves finding the gene or group of genes that result in the black-and­-white pattern. It’s important because, like producing merles in a litter, careful breeding is vital. If done without knowing the DNA portrait of the breeding dogs, the result can be lethal; puppies inheriting the harlequin gene from both parents die in the womb. Clark’s research has given breeders a genetic test to identify dogs carrying the harlequin factor.

Best Friends Forever

If dogs had a Facebook page, their relationship status with humans would be: “It’s complicated.”

Dogs descended from the gray wolf. A scant .04 percent difference in DNA coding separates the dog and wolf, the first animal to be domesticated by humans, more than 15,000 years ago. A high tolerance for genetic mutation has enabled dogs to evolve rapidly, becoming our companions and workmates.

At first, natural selection with a bit of human intervention guided the size, shape, coat, color, and other physical traits of the dog, resulting in canine guardians, hunters, shepherds, and cart-pullers. But what was once done for usefulness became a whim of fancy— breeding for a standard of beauty or physical excellence. Selective breeding has made the dog the most diverse land animal on the planet.

The wagging question is, why dogs? There are other domesticated animals that we have selectively bred and not achieved the same portrait gallery of natural variation.

It is the unique genetics of Canis familiaris that makes it happen.

Dogs have a genome of about 20,000 genes; humans have as many as 25,000 in their genetic inventory, estimate researchers. Unlike the case with humans, in which hundreds of genes work in small and many-stepped ways to bring about basics such as height or body size, it takes six or seven gene sites to determine 80 percent of the height and weight differences among dog breeds, according to researchers.

It takes only about 50 genes to account for the many colors, sizes, body types, snout and ear shapes, hair lengths, coat patterns, and leg heights in more than 350 dog breeds. Each breed is like a genetic island in the canine archipelago, isolated but part of a greater whole.

By developing registered purebreds, breeders created a DNA tool for geneticists. Being a member of a registered breed is more exclusive than being a member of the Daughters of the American Revolution. To become a registered purebred progeny, both parents have to be members of the registered breed and so do the grandparents. Each breed is a uniquely bred group, giving geneticists a tightly controlled and genetically identifiable population.

Genetic researchers can sort through breed genomes, analyzing the regions, looking for variations that produce physical characteristics. Statistically, a breed’s distinct genetic profile makes it easier to look for strings of genes that repeat or are different from other breeds or from whole species.

“It’s a complicated pathway,” Clark says, adding that the research may have a human link, too, because the responsible gene is part of a biological process involved in Parkinson’s and Alzheimer’s diseases.

Other dog breeds have found places in Clark’s lab. She is working on a skin and muscle inflammatory disease— dermatomyositis—that affects collies and Shetland sheepdogs. It is also a painful and disfiguring autoimmune disorder in humans, mostly children. Clark, who came to Clemson in 2009, has a longtime relationship with German shepherds going back to her days at Texas A&M, where she studied a pancreatic disorder prominent in the dog breed.
Markers for a deadly disorder

“We are looking for genetic markers for pancreatic acinar atrophy, which causes a lack of digestive enzymes made in the pancreas,” Clark says. “The dog literally starves, even if it is eating well, because it cannot digest and absorb food.”

Dogs with the pancreatic disorder are bags of bones, ravenously hungry and malnourished, startlingly thin, their coat dull, dry, and brittle. There is no cure, but the lack of digestive enzymes can be managed over the dog’s lifetime by adding enzyme powder supplements directly to food or in pills and capsules.

The condition affects more than German shepherds. Chow chows and collies also are at high risk, but researchers say all dog breeds are vulnerable. The condition can occur at any time during a dog’s life and may not be evident until much of the pancreas is damaged or destroyed. Every year about 8,000 dogs worldwide are diagnosed with the disorder.

The research indicates that the condition is inherited in German shepherds. Clark is examining the genetic variations between healthy German shepherds and those with the disorder. If she can identify the genes or group of genes harboring the mutation, researchers could develop a genetic test for it.

“Breeders would have a test to find out which dogs are at risk,” Clark says. “The information could be used to make breeding decisions. Right now, controlled breeding is the only way to reduce the number of dogs with the condition.”

Clark’s pancreatic research has been funded by the American Kennel Club Canine Health Foundation. In support of the more than 140 breeds recognized by the AKC, the foundation has spent more than $22 million on studies in nearly all of the major diseases in dogs, including cancer, epilepsy, thyroid disease, hip dysplasia, allergies, heart disease, progressive retinal atrophy, and cataracts. It is the largest foundation in the world to fund exclusively canine health studies.

Man’s best friend has millions of best friends in return; one happens to be a geneticist using her career to help dogs live healthier and longer lives. “I am not a cat person,” says Leigh Anne Clark.

Leigh Anne Clark is an assistant professor in the Department of Genetics and Biochemistry, College of Agriculture, Forestry, and Life Sciences. Her laboratory is currently funded by the Collie Health Foundation for dermatomyositis research.
American Kennel Club Canine Health Foundation, CAFLS, cancer, canine, College of Agriculture Forestry and Life Sciences, Department of Genetics and Biochemistry, DNA, dog, genetics, merle, Waardenburg Syndrome 2
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