Genetic Test for Megaesophagus in German Shepherd Dogs

Congenital idiopathic megaesophagus (CIM) is an esophageal motility disorder present at birth. A normal esophagus contracts to allow the passage of food into the stomach but with CIM the esophagus does not contract normally, so food stays in the esophagus and stretches it. Affected puppies regurgitate food and water, cough, can be poor-doers, and are at risk for pneumonia when regurgitated food particles are breathed into the lungs. There is no known treatment for the disorder, but affected puppies are managed with small, frequent meals fed while the dog sits in an upright position, thus allowing gravity to help food move into the stomach. The medication sildenafil has also shown promise in helping treat this disease.

The combination of a genetic mutation and sex can predict a German Shepherd Dog’s risk of being affected by CIM with 75% accuracy.

CIM occurs in many different dog breeds such as Great Danes, Labrador Retrievers, Dachshunds, and more, but German Shepherd Dogs are most commonly affected. The AKC Canine Health Foundation (CHF) has funded a Clemson University research team studying gastrointestinal motility disorders in dogs - including established investigator, Dr. Leigh Anne Clark, and two-time CHF Clinician Scientist Fellowship recipient, Dr. Sarah Bell. Their recent breakthrough provides critical information on what causes this disorder in German Shepherd Dogs and a genetic test is now available to help breeders plan matings to decrease the incidence of this disease.

Complex genetic factors -
Variations in the gene that codes for a signaling molecule linked to appetite, weight, and gut motility are associated with different risk levels for CIM in German Shepherd Dogs. Investigators identified the specific variations that carry the greatest risk for disease, but other factors must influence disease development in this breed since having the mutation alone is not sufficient to cause severe disease.

Males are more commonly affected -
Male German Shepherd Dogs are two times more likely to have CIM than females. This sex bias is also seen in human esophageal disorders. Estrogen can influence molecules that regulate the lower esophageal sphincter, or the gateway from the esophagus to the stomach. Females, which have more estrogen, may therefore be less susceptible to the influence genetic mutations and not experience severe forms of CIM.

A good combo –
The combination of this genetic mutation and sex can predict a German Shepherd Dog’s risk of being affected by CIM with 75% accuracy. A genetic test is now available to help breeders pick mating pairs in order to decrease disease incidence.

CHF-funded investigators are continuing their work, performing genetic analysis in Great Danes. Data is also being examined from dogs with gastric dilatation-volvulus (GDV or bloat), another motility disorder seen in large-breed dogs, to see if there are any shared genetic risk factors between these two conditions. Ultimately, the goal is to understand the genetics that underlie these disorders allowing us to define an individual dog’s risk of disease and to help decrease the number of affected dogs. Learn more about CHF-funded research on gastrointestinal disease at akcchf.org/GIRPA.

Training the Next Generation of Canine Health Researchers
Dr. Sarah M. Bell was awarded an AKC Canine Health Foundation Clinician-Scientist Fellowship in 2019 and 2020, sponsored by the Orthopedic Foundation for Animals (OFA). She earned a Bachelor of Science degree in genetics from Clemson University and has continued there as a graduate research assistant pursuing a doctoral degree in genetics. Under the mentorship of CHF-funded investigator Dr. Leigh Anne Clark, Dr. Bell has been studying the genetic basis of congenital idiopathic megaesophagus (CIM) in German Shepherd Dogs and Great Danes. The goal of her study is to develop a genomic prediction tool to help breeders plan matings that will not produce dogs with CIM without sacrificing genetic diversity.

Reference:
Bell, S. M., Evans, J. M., Evans, K. M., Tsai, K. L., Noorai, R. E., Famula, T. R., Holle, D. M., & Clark, L. A. (2022). 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, 18(3), e1010044. https://doi.org/10.1371/journal.pgen.1010044