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MT08-001: SNP Analysis in Siberian Cats with HCM

Hypertrophic cardiomyopathy (HCM) is the dominant inherited cardiac disorder in domestic cats. Genetic mutations for this disease have been identified in both Maine Coon and Ragdoll cats. HCM has also been identified in the American Shorthair, Devon Rex, Sphynx, Bengal and Siberian breeds, among others. A causative mutation has not been identified in these breeds. Moreover, the known mutation is not completely concordant with disease presentation in Maine Coons. Because the fecundity of affected cats tends to be decreased, multigenerational pedigrees with enough statistical power to find linkage are difficult to obtain. Similarly, candidate gene approaches depending upon educated guesses and negative results do not eliminate a candidate, but merely reflect an inability to detect a causal mutation. The current study conducts case-control research on three breeds of cats: Maine Coon, Ragdoll, Siberian. Proof of principle will be established with limited numbers of known affected and control samples from Maine Coons and Ragdolls. An extensive data set for Siberians, a breed with HCM but no associated causal mutation, will be analyzed against feline single nucleotide polymorphisms (SNPs) identified in or near seven genes known to have mutations that result in human HCM. These include the identified feline HCM mutations in MYBPC3.

Either of two results is possible; 1) SNP haplotypes associated with affected cats will identify a candidate gene for detailed sequence analysis, or, 2) candidate genes will be excluded, eliminating some of the guesswork from future candidate gene approaches. In both instances, time and resources will be conserved.

Grant ID: MT08-001

Status: Active

Year Funded: 2008

Amount awarded: $18,086

Investigator: Robert A. Grahn; University of California, Davis