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

BackgroundDilated cardiomyopathy is a myocardial disease occurring in humans and domestic animals and is characterized by dilatation of the left ventricle, reduced systolic function and increased sphericity of the left ventricle. Dilated cardiomyopathy has been observed in several, mostly large and giant, dog breeds, such as the Dobermann and the Great Dane. A number of genes have been identified, which are associated with dilated cardiomyopathy in the human, mouse and hamster. These genes mainly encode structural proteins of the cardiac myocyte.ResultsWe present the annotation of, and marker development for, 14 of these genes of the dog genome, i.e. alpha-cardiac actin, caveolin 1, cysteine-rich protein 3, desmin, lamin A/C, LIM-domain binding factor 3, myosin heavy polypeptide 7, phospholamban, sarcoglycan delta, titin cap, alpha-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.ConclusionThe presented polymorphisms provide a tool to investigate the role of the corresponding genes in canine Dilated Cardiomyopathy by linkage analysis or association studies

Cardiopoietic cell therapy for advanced ischemic heart failure: results at 39 weeks of the prospective, randomized, double blind, sham-controlled CHART-1 clinical trial

Cardiopoietic cells, produced through cardiogenic conditioning of patients' mesenchymal stem cells, have shown preliminary efficacy. The Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial aimed to validate cardiopoiesis-based biotherapy in a larger heart failure cohort

Evaluation of 15 candidate genes for dilated cardiomyopathy in the Newfoundland dog

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 approac

Fine mapping of the human biglycan (BGN) gene within the Xq28 region employing a hybrid cell panel

Human biglycan is a small proteoglycan that is expressed at high levels in the growing skeleton and in human skin at the cell surface of differentiating keratinocytes. The human gene for biglycan (BGN) has previously been mapped by in situ hybridization to the Xq27–q28 region. Employing somatic hybrid cell lines with human X chromosome breakpoints within this region, we performed a fine mapping of the gene within Xq28. Our results indicate that the biglycan gene is proximal to the red/green cone pigment genes, G6PD, and coagulation factor {VIII} and is distal to DXS304, DXS305, and GABRA3. The biglycan gene precisely maps to a region of the X chromosome, where, by comparative gene mapping, one would expect to find the gene for X-linked dominant chondrodysplasia punctata/ichthyosis/short stature (Happle) syndrome. Hence, {BGN} is a candidate gene for the Happle syndrome