Dr. Kate Meurs has identified genetic mutation responsible for causing cardiomyopathy in Dobermans

Stem Cell Therapy for Dilated Cardiomyopathy

Learn more about the process & watch a speach Dr. Estrada gave on 10/04/10

Research

• Abstract
  American Journal of Veterinary Research
  July 2011, Vol. 72, No. 7, Pages 932-939
  doi: 10.2460/ajvr.72.7.932
  
  
  Evaluation of 10 genes encoding cardiac proteins in Doberman Pinschers with dilated cardiomyopathy
  M. Lynne O'Sullivan, DVM, DVSc; Michael R. O'Grady, DVM, MS; W. Glen Pyle, PhD; John F. Dawson, PhD
  Department of Clinical Studies, University of Guelph, Guelph, ON N1G 2W1, Canada. (O'Sullivan, O'Grady); Department of Biomedical Sciences, University of Guelph, Guelph, ON N1G 2W1, Canada. (Pyle); Department of Molecular and Cellular Biology, University of Guelph, Guelph, ON N1G 2W1, Canada. (Dawson)
  
  
  Supported by OVC Pet Trust, Ontario Veterinary College, University of Guelph.
  
  
  The authors thank Shu Chen and Jiping Li for technical assistance.
  Address correspondence to Dr. Dawson (jdawso01@uoguelph.ca).
  
  
  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.
  
  
  Animals-5 Doberman Pinschers with DCM and congestive heart failure and 5 control mixed-breed dogs that were euthanized or died.
  
  
  Procedures-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, a-actinin, a-tropomyosin, B-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 a-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 and Clinical Relevance-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 a-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 a-actinin in development of DCM in Doberman Pinschers are warranted.
  
  http://avmajournals.avma.org/doi/abs/10.2460/ajvr.72.7.932
  
  
  Recap - They belive there are 3 mutations, and on 3 different chromosomes (5, 8 and 14) This new mutation on chromosome 8 has 40% accuracy as 40% of the affected dogs had the mutation. The disease DCM is polygenic, more than one gene can cause DCM. It also gives more support to the studies that DCM is a polygenic heritage.
  
  
• 2011 - A Locus on Chromosome 5 Is Associated with Dilated Cardiomyopathy in Doberman Pinschers
  Received: February 16, 2011; Accepted: April 11, 2011; Published: May 20, 2011
  Mausberg T-B, Wess G, Simak J, Keller L, Drögemüller M, et al. (2011) A Locus on Chromosome 5 Is Associated with Dilated Cardiomyopathy in Doberman Pinschers. PLoS ONE 6(5): e20042. doi:10.1371/journal.pone.0020042
• 2007 - Canine Heart Failure--Current Concepts
  Clarke E. Atkins, DVM, DACVIM (Internal Medicine & Cardiology)
  Department of Clinical Sciences, North Carolina State University, College of Veterinary Medicine
  Therapeutic Advances in the Management of Heart Disease: An Overview
  Canine Heart Failure - WSAV207.pdf
• 2002 - DCM In Doberman Pinschers: Lessons Learned In The First Decade Of Study
  ACVIM 2002
  Michael O'Grady, DVM, MS, DACVIM
  GradyACVIM2002.html
• 2007 - A Prospective Genetic Evaluation of Familial Dilated
  Cardiomyopathy in the Doberman Pinscher
  Kathryn M. Meurs, Philip R. Fox, Michelle Norgard, Alan W. Spier, Allison Lamb, Shianne L. Koplitz, and Ryan D. Baumwart
  i0891-6640-21-5-1016MeursDCM.pdf