AKC Canine Health Foundation - 29

Genomic Studies Reveal Risk Factors for Congenital
Megaesophagus
Leigh Anne Clark, PhD
University of Georgia
BIOGRAPHY
Dr. Leigh Anne Clark earned her doctoral degree in 2004 from
the College of Veterinary Medicine at Texas A&M University
studying exocrine pancreatic insufficiency. After graduation, she
remained in the Department of Pathobiology as a Research Assistant Professor, investigating
the genetics of merle coat patterning and dermatomyositis. In 2009, she joined the faculty of the
Department of Genetics & Biochemistry at Clemson University where she is presently an
Associate Professor. Dr. Clark's group has mapped genetic determinants for many simple and
complex traits, including neuromuscular, autoimmune, and developmental disorders. Her current
research focuses on megaesophagus, pancreatic insufficiency, Addison's disease, and epilepsy.
PRESENTATION ABSTRACT
Congenital idiopathic megaesophagus (CIM) is a genetically complex gastrointestinal motility
disorder found across dog breeds but occurring at uniquely high frequencies in the German
shepherd dog and the Great Dane. Reduced peristaltic activity and dilation of the esophagus
prevent the passage of food into the stomach, causing regurgitation of meals upon introduction
of solid food. Affected puppies that survive to adulthood require lifelong management and are at
risk for aspiration pneumonia. We observed that males are more likely to be affected than
females. Using records from a private German Shepherd Dog breeding program, we show that
this bias is independent of body size differences between sexes. We performed a genome-wide
study in each breed to identify genetic contributors to CIM. In the German Shepherd Dog, we
detected a single region of association on chromosome 12 and subsequently identified a variant
of Melanin Concentrating Hormone Receptor 2 (MCHR2) that is highly associated with CIM.
MCHR2 plays a role in appetite, weight, and gut motility. In the Great Dane, we found a novel
association on chromosome 1 and are currently investigating candidate causal variants. The
risk alleles in both breeds are common and found across breeds, indicating that additional loci
contribute to disease pathogenesis.
CURRENT CHF GRANTS
03134: Use of a Service Dog Breeding Program to Unravel the Genetics of Congenital
Idiopathic Megaesophagus in German Shepherd Dogs
02945-MOU: Understanding the Genetic Basis of Addison's Disease in Portuguese Water Dogs
2023 National Parent Club Canine Health Conference
Presented by the AKC Canine Health Foundation and Nestlé Purina PetCare

AKC Canine Health Foundation

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