Genome Wide Association Studies in Cats with Complex Diseases Using a Proprietary High Density Illumina Mapping Array
Principal Investigator: Rory Todhunter
DESCRIPTION (provided by applicant):
Pure and mixed breed cats suffer from many complex genetic diseases. Although genes and mutations that underlie simple Mendelian diseases of cats have been identified, mutations underlying complex diseases are more difficult to uncover due to the small effect of the individual genes and the difficulty in identification of regulatory polymorphisms. Adequately powered genome wide association studies (GWAS) are designed to discover genetic marker-phenotype associations. Their power is influenced by the number of cats and the low genetic marker density of the commercial feline mapping array. The Cornell Feline Health Center has funded the Cornell Veterinary Biobank to support the accumulation of DNA of cats admitted to our hospital (cases) and the accumulation of universal control cats to serve multiple mapping studies. We are in the process of sequencing relevant cat transcriptomes and we have contributed whole genome sequences to a consortium which will enable variant discovery in significantly associated genomic regions in which candidate genes can be pinpointed. Recently, Hills Pet Nutrition agreed to gift 1200 proprietary Illumina feline high density mapping arrays to Cornell. This bead chip recognizes 340,000 single nucleotide polymorphic markers thus eliminating the marker density problem. Over the next 2 years, we propose to conduct genome wide association studies (GWAS) for the following complex genetic diseases of cats: hypertrophic cardiomyopathy, hyperthyroidism, diabetes mellitus, gingivostomatitis, chronic enteropathy, small cell alimentary tract lymphoma, factor XII deficiency, vitamin K-dependent coagulopathy, and juvenile cataract. This grant requests funds to support the salary of Dr. Isabel Hernandez and DVM student stipends to carefully review each electronic medical record of the diseased cats (cases) and identify more appropriate controls. It would also support a fee-for-service of research support specialist, Dr. Jessica Hayward, to perform the statistical analysis in collaboration with Dr. Jeffrey Brockman, the chief scientist at Hills Pet Nutrition. The agreement is in place to share the genotypes and phenotypes with Dr. Brockman and jointly analyze the data. Hills Pet Nutrition has genomic data on hundreds of cats in their colony and the joint analysis with the Hill’s data will markedly improve mapping power. The long-term goal is to identify mutations that contribute to complex debilitating and incurable diseases that afflict cats. The GWAS will pinpoint strong candidate genes that we can propose to sequence in subsequent grants in cases and controls to discover causal mutations. Such mutations would form the basis of new genetic tests for cats for earlier diagnosis, novel treatments, and improved breeding strategies.