Evaluation of the Titin-Cap Gene (TCAP) as Candidate for Dilated Cardiomyopathy in Irish Wolfhounds

Abstract

Dilated cardiomyopathy (DCM) is a myocardial disorder characterized by left ventricular dilatation and impaired systolic contraction. Irish wolfhounds (IW) and other large breed dogs are most commonly disposed to DCM. We analyzed the titin-cap (TCAP, telethonin) gene as candidate for DCM. Genomic DNA was analyzed in eight DCM affected and five DCM-free IWs. cDNA was sequenced in one DCM-affected IW and two unaffected dogs, one Tibetan terrier and one Dachshund. Compared to the Boxer reference sequence, one sequence difference was identified in the 3′UTR and two in the intron sequence. In the IWs the sequences were monomorphic. In order to rule out a breed-specific haplotype that predisposes to DCM, the polymorphisms were genotyped in 24 Elo dogs, a breed mix established from nine different breeds. The analysis showed that the mutations were not restricted to IW. Moreover, 80% of the Elos were homozygous for the IW haplotype. We conclude that TCAP can most likely be eliminated as cause for DCM in IWs.