Genetic test and dog’s sex predict disease risk with 75% accuracy

Clemson University researchers have discovered a genetic variation associated with an often-fatal esophageal disorder that is frequently found in German Shepherd dogs.

German Shepherds are predisposed to congenital idiopathic megaesophagus (CIM), an inherited condition in which a puppy develops an enlarged esophagus that fails to move food through its stomach. Puppies with the disease regurgitate their food and fail to thrive, often leading to euthanasia.

While German Shepherds have the highest incidence of the disease, other breeds are also susceptible, including Labrador Retrievers, Great Danes, Dachshunds, and Miniature Schnauzers. Researchers do not yet know if the same genetic variation is involved in the development of the disease in other breeds.

Researcher Leigh Anne Clark, an associate professor in the Department of Genetics and Biochemistry, and her collaborators have developed a genetic test for the disease that German Shepherd breeders can use to reduce the risk of puppies from future litters developing the disease. .

The newspaper PLOS genetics released the results on March 10.

CIM is often discovered when puppies are weaned from mother’s milk to solid food at around four weeks of age.

“They don’t have swallowing activity. When puppies swallow food, it just stays in their esophagus and doesn’t trigger the sequential contractions that normally occur to help push the food into the stomach” , said Sarah Bell, graduate research assistant. in genetics and the first author of the study. “Because a dog’s esophagus is horizontal instead of vertical like ours, gravity doesn’t help transport food into the stomach.”

To get food and water into their stomachs, puppies with megaesophagus must eat and drink while sitting in a dog high chair and stay there for up to 30 minutes afterward. Some will outgrow the condition, but many require lifelong symptomatic management with upright feedings, small liquid meals several times a day, gelatin cubes, and drug therapies.

In the study, Clark and Bell performed a genome-wide analysis to identify genes associated with the disease. The analysis revealed an association on canine chromosome 12 and a variant within the melanin-concentrating hormone receptor 2 (MCHR2), which affects appetite, weight and the way food moves through the gastrointestinal tract. Clark and his team believe that an imbalance in melanin-concentrating hormones plays a role in ICD.

The study also revealed that male puppies are twice as likely to be affected by the disease as females. Researchers suspect that higher estrogen levels allow food to pass through the stomach more efficiently, protecting against disease development.

“What they found in humans is that estrogen has the effect of relaxing the sphincter that connects the esophagus to the stomach. By having more estrogen, smooth muscle is naturally more susceptible to open. It increases the motility of food in the stomach,” Bell said. “In dogs with megaesophageal disease, a drug called sildenafil has shown good results. What it does is relax the sphincter that connects the esophagus and the stomach.”

Sildenafil is the generic name for the active ingredient in Viagra. Clark said sildenafil increases the percentage of dogs that outgrow the disease and no longer need to use a high chair to eat.

The MCHR2 variant, along with the dog’s gender, can predict whether a dog will develop megaesophagus with 75% accuracy. Owners can swab their dog’s gums and submit the sample to genetic testing companies to find out which variant(s) their dog has inherited.

The test is a tool breeders can use to reduce disease incidence while preserving genetic diversity.

“One thing I emphasize with any disease in any breed is not to create a problem where there is none. If you have been raising German Shepherds for 20 years and you don’t ‘ve ever bred a mega-esophagus puppy, so don’t use this test,” she said. “But if you’re a breeder and you’ve had mega-esophagus puppies, you can benefit from the test.”

This work was supported in part by funding from the Collie Health Foundation, the American Kennel Club Canine Health Foundation, the Upright Canine Brigade, the Orthopedic Foundation for Animals, and the National Institute of General Medical Sciences of the National Institutes of Health.