Analysis of the titin-cap gene (TCAP) as candidate for dilated cardiomyopathy (DCM) in Great Dane.

Dilated cardiomyopathy (DCM) is an inherited disease of the myocardium, which is characterized by left ventricular enlargement and systolic dysfunction, resulting in impaired heart function that causes significant mortality and morbidity, including heart failure. It has been described in humans and several domestic animals, including the dog. Several genes have been identified in human and mouse as causal for DCM. These genes mainly encode proteins of the cytoskeleton of the cardiac myocyte, and titin cap (TCAP) is considerated one of the main candidate gene. The aim of this study was to identify SNPs in two exons of TCAP gene, to evaluate their association with the DCM phenotype in Great Dane dog, using a direct mutation screening approach. Genomic DNA from 4 Great Dane dogs (2 male and 2 female with DCM phenotype and healthy) were used to PCR amplification and sequencing with the ABI PRISM® 3500 (Applied Biosystems). For all animals physical examination, echocardiogram and ambulatory electrocardiogram were performed. The DNA sequences of each fragment were aligned and screened for mutations using MEGA7. In TCAP exon 2, a silent SNP (g. 29957 T>C of AAEX01022011) was detected in both DCM-affected and DCM-unaffected group. Our results showed no evidence that this gene is involved in DCM in the Great Dane dog. Detection of DCM-associated variants would contribute to development of genetic tools for rapid screening of families at risk for inherited disease and to improvement the methods of diagnosis and therapy.