title: Evaluation of 10 genes encoding cardiac proteins in Doberman Pinschers with dilated cardiomyopathy.
abstract: OBJECTIVE
  To identify a causative mutation for dilated cardiomyopathy (DCM) in Doberman Pinschers by sequencing the coding regions of 10 cardiac genes known to be associated with familial DCM in humans.
  
  
  METHODS
  5 Doberman Pinschers with DCM and congestive heart failure and 5 control mixed-breed dogs that were euthanized or died.
  
  
  METHODS
  RNA was extracted from frozen ventricular myocardial samples from each dog, and first-strand cDNA was synthesized via reverse transcription, followed by PCR amplification with gene-specific primers. Ten cardiac genes were analyzed: cardiac actin, α-actinin, α-tropomyosin, β-myosin heavy chain, metavinculin, muscle LIM protein, myosinbinding protein C, tafazzin, titin-cap (telethonin), and troponin T. Sequences for DCM-affected and control dogs and the published canine genome were compared.
  
  
  RESULTS
  None of the coding sequences yielded a common causative mutation among all Doberman Pinscher samples. However, 3 variants were identified in the α-actinin gene in the DCM-affected Doberman Pinschers. One of these variants, identified in 2 of the 5 Doberman Pinschers, resulted in an amino acid change in the rod-forming triple coiled-coil domain.
  
  
  CONCLUSIONS
  Mutations in the coding regions of several genes associated with DCM in humans did not appear to consistently account for DCM in Doberman Pinschers. However, an α-actinin variant was detected in some Doberman Pinschers that may contribute to the development of DCM given its potential effect on the structure of this protein. Investigation of additional candidate gene coding and noncoding regions and further evaluation of the role of α-actinin in development of DCM in Doberman Pinschers are warranted.
authors: Department of Clinical Studies, University of Guelph, Guelph, ON N1G 2W1, Canada.
authors: M Lynne
authors: ML
authors: O'Sullivan
authors: Michael R
authors: MR
authors: O'Grady
authors: W Glen
authors: WG
authors: Pyle
authors: John F
authors: JF
authors: Dawson
mesh_terms: D000185:Actinin / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000235:genetics / Q000662:veterinary*; D018076:DNA, Complementary / Q000235:genetics; D004283:Dog Diseases / Q000235:genetics*; D004285:Dogs; D005091:Exons; D005260:Female; D006321:Heart / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D009206:Myocardium / Q000378:metabolism; D010375:Pedigree; D016133:Polymerase Chain Reaction
chemical_list: D018076:DNA, Complementary; D009124:Muscle Proteins; D000185:Actinin