Canine candidate genes for dilated cardiomyopathy: annotation of and polymorphic markers for 14 genes

We present the annotation of, and marker development for, 14 of these genes of the dog genome, i.e. α-cardiac actin, caveolin 1, cysteine-rich protein 3, desmin, lamin A/C, LIM-domain binding factor 3, myosin heavy polypeptide 7, phospholamban, sarcoglycan δ, titin cap, α-tropomyosin, troponin I, troponin T and vinculin. A total of 33 Single Nucleotide Polymorphisms were identified for these canine genes and 11 polymorphic microsatellite repeats were developed.The presented polymorphisms provide a tool to investigate the role of the corresponding genes in canine Dilated Cardiomyopathy by linkage analysis or association studies.Dilated cardiomyopathy (DCM) is a myocardial disease characterized by dilatation of the left ventricle, reduced systolic function and increased sphericity of the left ventricle. This disease has been described in different species and multiple genes have been found in the human [1], mouse [2] and hamster [3] causing DCM. These genes mainly encode cyto-skeletal components of the cardiac myocytes and can be divided into sarcomeric and extra-sarcomeric proteins. The identified sarcomeric proteins involved in DCM include α-cardiac actin, encoded by ACTC [4], cysteine-rich protein 3 (CSRP3) [5], LIM-domain binding factor 3 (LDB3, also known as Cypher or ZASP) [6], myosin heavy polypeptide 7 (MYH7) [7], titin cap (TCAP) [8], α-tropomyosin (TPM1), troponin I (TNNI3) [9], troponin T (TNNT2) [7], titin (TTN) [10] and vinculin (VCL) [11]. The extra-sarcomeric proteins implicated in DCM are encoded by the genes including caveolin 1 (CAV1) [2], desmin (DES) [12], lamin A/C (LMNA) [13], phospholamban (PLN) [14] and sarcoglycan δ (SGCD) [3]. The genes encoding all of the above proteins are located on the autosomal chromosomes. X-linked genes implicated in DCM include dystrophin (DYS) [15] and tafazzin (TAZ) [16]. In addition, mitochondrial dysfunction and mitochondrial DNA (mtDNA) mutations have been associated with maternally inherited DCM [17]. Furthermor