Evaluation of 15 Candidate Genes for Dilated Cardiomyopathy in the Newfoundland Dog

• Main Authors: Anje C. Wiersma, Polona Stabej, Peter A. J. Leegwater, Bernard A. Van Oost, William E. Ollier
• Other Authors: The Pennsylvania State University CiteSeerX Archives
• Format: Text
• Language: English
• Published: 2007
• Subjects: Newfoundland
• Online Access: http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.583.1038; http://jhered.oxfordjournals.org/content/99/1/73.full.pdf

Dilated cardiomyopathy (DCM) is a disease of the myocardium, which causes heart failure and premature death. It has been described in humans and several domestic animals. In the Newfoundland dog, DCM is an autosomal dominant disease with late onset and reduced penetrance. We analyzed 15 candidate genes for their involvement in DCM in the Newfoundland dog. Polymorphic microsatellite markers and single Nucleotide Polymorphisms were genotyped in 4 families of Newfoundland dogs segregating dilated cardiomyopathy for the genes encoding a-cardiac actin (ACTC), caveolin (CAVI), cysteine-rich protein 3 (CSRP3), LIM-domain binding factor 3 (LDB3), desmin (DES), lamin A/C (LMNA), myosin heavy polypeptide 7 (MYH7), delta-sarcoglycan (SGCD), troponin I (TNNTI3), troponin T (TNNT2), alpha-tropomyosin (TPMI), titin (TTN) and vinculin (VCL). A Logarithm of the odds (LOD) score of less than2.0 in 2-point linkage analysis indicated exclusion of all but 2 genes, encoding CSRP3 and DES. A (LOD) score between1.5 and2.0 for CSRP3 and DES makes these genes unlikely causes of DCM in this dog breed. For the phospholamban (PLN) and titin cap (TTN) genes, a direct mutation screening approach