Determining the Genetics Underlying Diabetes Mellitus in the Domestic Cat
Principal Investigator: Rory Todhunter
Co-PI: John Loftus
DESCRIPTION (provided by applicant):
Diabetes mellitus (DM) is a common feline disease that is due to the loss or dysfunction of insulin secretion by pancreatic beta cells, or diminished insulin sensitivity, or both. The resulting hyperglycemia and glucosuria cause an osmotic diuresis and polyuria with secondary polydipsia. Impaired cellular glucose transport results in lethargy and weight loss, despite polyphagia. As the disease progresses, derangements in protein and lipid metabolism accelerate, causing ketoacidosis, anorexia, vomiting, diarrhea, dehydration, tachypnea, and weakness. The disease requires careful management, including twice daily insulin injections, and costs of veterinary care and lifestyle changes can significantly impact cat owners. Little is known about the genetics underlying feline DM. However, two recent studies identified loci associated with risk in Australian Burmese, and a polymorphism in the gene MC4R increases risk in obese domestic shorthair cats. We have recently identified a significant association with DM, using a genome-wide association study with a 340k single nucleotide polymorphism (SNP) array. We now have the unique opportunity to genotype cats on a 2 million SNP array, performing the largest genome-wide search for loci associated with DM in the cat. By replicating our association and identifying the variant(s) associated with feline DM, cats with an increased genetic predisposition for DM can be identified. This will allow earlier diagnosis and permit intervention and monitoring before irreversible disease occurs. Further, cat breeders can use the genetic test to make informed breeding decisions in an effort to reduce the frequency of the disease in the population.