Principal Investigator: Adam Boyko

DESCRIPTION (provided by applicant): 

Variations in hematological parameters have been shown to have a strong heritability component in both humans, mice, and cats. In both human and veterinary medicine, the complete blood count (CBC) and clinical chemistry panel (CCP) are a primary means of routine health screening and diagnosing disease. Using a genome-wide association study (GWAS) and 3’-mRNA sequencing, we aim to discover expression quantitative trait loci (eQTL) for blood phenotypes in the domestic cat. We have recently completed a similar GWAS in dogs through which we detected significant genetic associations with 9 CBC and CCP phenotypes using 353 samples, including QTLs for amylase activity relevant for canine diabetes mellitus (DM). Using a unique approach of sampling from both pet and community (stray and/or feral) cats, we aim to detect genetic signatures of insulin resistance and factors predisposing to obesity and diabetes mellitus in environments with varying food security and nutritional challenges. The prevalence of feline DM continues to increase, and although median survival times are increasing, the mortality rate in the first 3 months after diagnosis exceeds 25%.

In addition to CBC and CCP phenotypes, we plan to expand our feline clinical data to include Fructosamine and Thyroxine (T4) to both control for effects of comorbidities such as acute stress hyperglycemia and hyperthyroidism and, more importantly, to increase the likelihood of detecting genetic variants related to metabolism and insulin resistance and their contributions to risk of obesity, diabetes mellitus, and other diseases. This multidisciplinary study involving computational biologists and clinicians will provide the first eQTL database for domestic cats that will be an important resource to improve feline genome annotation and facilitate fine-mapping of functional characterization of diverse feline disorders, including diabetes mellitus.