• Researchers discover genetic cause of so

    From ScienceDaily@1:317/3 to All on Thursday, March 10, 2022 21:30:40
    Researchers discover genetic cause of sometimes deadly esophageal
    disorder in dogs
    Genetic test and dog's sex predicts risk of the disease with 75 percent accuracy

    Date:
    March 10, 2022
    Source:
    Clemson University
    Summary:
    German shepherds are predisposed to congenital idiopathic
    megaesophagus (CIM), an inherited disorder where a puppy
    develops an enlarged esophagus that fails to move food into their
    stomachs. Puppies with the condition regurgitate their food and
    fail to thrive, often leading to euthanasia.

    Researchers have now developed a genetic test for the disease
    that German shepherd dog breeders can use to reduce the risk that
    puppies in future litters will develop the disease.



    FULL STORY ========================================================================== Clemson University researchers have discovered a genetic variation
    associated with an often deadly esophageal disorder frequently found in
    German shepherd dogs.


    ========================================================================== German shepherds are predisposed to congenital idiopathic megaesophagus
    (CIM), an inherited disorder where a puppy develops an enlarged esophagus
    that fails to move food into their stomachs. Puppies with the condition regurgitate their food and fail to thrive, often leading to euthanasia.

    While German shepherds have the highest incidence of the disease, other
    breeds are susceptible, too, including Labrador retrievers, Great Danes, dachshunds and miniature schnauzers. Researchers do not yet know if the
    same genetic variation is involved in disease development in other breeds.

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

    The journalPLOS Geneticspublished the findings on March 10.

    CIM is often discovered when the puppies are weaned from the mother's
    milk to solid foods at about four weeks of age.



    ========================================================================== "They don't have swallowing activity. When the puppies swallow food,
    it just sits in their esophagus and doesn't trigger those sequential contractions that normally occur to help push the food into the stomach,"
    said Sarah Bell, a 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 aid the transportation of food into the stomach." To get
    food and water in their stomachs, puppies with megaesophagus must eat
    and drink while sitting upright in a dog highchair and remain there for
    up to 30 minutes afterward. Some will outgrow the condition, but many
    require lifelong symptomatic management with upright feedings, small
    liquid meals multiple times a day, gelatin cubes, and drug therapies.

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

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

    "What they've found in people is that estrogen has the effect of
    relaxing the sphincter that connects the esophagus to the stomach. By
    having more estrogen, the smooth muscle there is naturally more likely
    to open. This increases the motility of food into the stomach," Bell
    said. "In dogs with megaesophagus disease, a drug called sildenafil
    has shown good results. What it does is to relax the sphincter that
    connects the esophagus and 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 have to
    use a high chair when eating.



    ==========================================================================
    The MCHR2 variant, along with the dog's sex, can predict whether a dog
    will develop a megaesophagus with 75 percent accuracy. Owners can swab
    their dog's gums and submit the sample to genetic testing companies to
    learn which variant (s) their dog inherited.

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

    "One thing I stress with any disease in any breed is don't make a problem
    where there isn't one. If you've been breeding German shepherds for 20
    years and you've never bred a megaesophagus puppy, then don't use this
    test," she said.

    "But if you're a breeder and you've had megaesophagus puppies, you may
    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.


    ========================================================================== Story Source: Materials provided by Clemson_University. Note: Content
    may be edited for style and length.


    ========================================================================== Journal Reference:
    1. Sarah M. Bell, Jacquelyn M. Evans, Katy M. Evans, Kate L. Tsai,
    Rooksana
    E. Noorai, Thomas R. Famula, Dolores M. Holle, Leigh Anne Clark.

    Congenital idiopathic megaesophagus in the German shepherd
    dog is a sex- differentiated trait and is associated with an
    intronic variable number tandem repeat in Melanin-Concentrating
    Hormone Receptor 2. PLOS Genetics, 2022; 18 (3): e1010044 DOI:
    10.1371/journal.pgen.1010044 ==========================================================================

    Link to news story: https://www.sciencedaily.com/releases/2022/03/220310143708.htm

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