Genetics and Genetic Testing of Canine and Feline Heart Disease
Tufts' Canine and Feline Breeding and Genetics Conference, 2011
Mark Rishniw, BVSc, MS, PhD, DACVIM (Internal Medicine and Cardiology)
Cornell University College of Veterinary Medicine, Ithaca, NY, USA

The genetic basis of cardiac disease in humans ranges from simple mutations to complex genetic traits. Until recently, genetics of canine and feline heart disease were poorly understood, with most studies examining inheritance patterns in line-bred individuals. In most cases, the complexity of the traits prevented authors from reaching firm conclusions regarding the mode of inheritance, let alone the specific genes involved.

Subsequent to the identification of genetic abnormalities in a number of cardiac diseases in humans, veterinary cardiologists and others began investigating analogous diseases in dogs and cats using a candidate gene approach. They failed to identify the affected gene(s) in the vast majority of these investigations, demonstrating the inherent problems of this approach.

With the advent of genome-wide association studies (GWAS), several gene candidates have been identified as potentially causal in canine and feline heart disease. This approach allows for rapid identification of regions of inhomogeneity between affected and non-affected individuals, and ignores lineage, or inheritance patterns. However, it does require accurate identification of the phenotype to properly segregate the populations.

Several inherited or familial cardiac diseases have now been shown to have a specific genetic basis in both dogs and cats. Most of these currently revolve around cardiomyopathies, with inheritance of congenital or developmental diseases being relatively uninvestigated at this time. However, with genomic studies growing ever-cheaper, in-roads into the genetic basis of many of the cardiac disease to which specific breeds are predisposed will be made over the coming years.

Canine Diseases With a Known or Highly Suspected Genetic Basis

Dilated cardiomyopathy (DCM) of Doberman Pinschers was the first canine cardiac disease to undergo genetic analysis. Candidate gene approaches, based on genetic mutations identified in humans with DCM failed to identify a gene associated with DCM in Doberman Pinschers. Recently, GWAS identified regions in affected Dobermans, which following more comprehensive analysis, revealed involvement of a mitochondrial gene associated with glucose metabolism (pyruvate dehydrogenase kinase 4, located on chromosome 14), previously unrecognized in DCM in humans. A second group recently identified a locus on chromosome 5 as potentially linked to Doberman DCM.

Similarly, GWAS of arrhythmogenic right ventricular cardiomyopathy (ARVC) in boxer dogs led to the discovery of abnormal striatin as a potential cause of ARVC. Mutations in this gene have not been identified in humans with ARVC. However, genes that interact with striatin have been shown to cause ARVC in humans.

Feline Diseases With a Known or Highly Suspected Genetic Basis

Hypertrophic cardiomyopathy (HCM) of Maine Coons was the first veterinary cardiac disease in which a genetic basis was identified. HCM remains the only feline disease in which a genetic basis has been established. Two different mutations in the same gene (myosin-binding protein C) have been described with HCM in Maine Coons and Ragdolls. Several studies have questioned the validity of these findings, reflecting the complexity of genetic expression in cats with the mutations.

Canine Diseases With Familial or Breed Predispositions

It is most probable that cardiac diseases that occur within specific breeds or lines within a breed have a genetic basis. In most cases, the genetic basis of these diseases is unknown. Limited linkage analysis has identified a likely genetic role for diseases such as subaortic stenosis (SAS) in Newfoundlands, tricuspid valve dysplasia in Labrador Retrievers, patent ductus arteriosus in poodles. However, in most cases, these diseases have been described as having a complex autosomal pattern of inheritance. Mitral valve disease in Cavalier King Charles Spaniels has also been shown to have a strong familial basis, with a complex inheritance pattern. Sudden cardiac death in German Shepherds has been extensively studied, but no genetic basis has been identified.

Diseases in which breed or familial predisposition has been identified (but without any analysis of inheritance) include pulmonic stenosis with aberrant coronary development in boxer dogs and Bulldogs, atrial septal defects in Standard Poodles, vascular ring anomalies in German Shepherds, SAS in Golden Retrievers, German Shepherds, Rottweilers and Boxers, DCM in Portuguese Water Dogs, sick sinus syndrome in Miniature Schnauzers and West-Highland White Terriers, and tetralogy of Fallot in Keeshonds. Multiple other breeds have been variously implicated as predisposed to certain congenital cardiac diseases, often with little solid evidence.

Feline Diseases With Familial or Breed Predispositions

Very few, if any, cardiac diseases, other than HCM, have been demonstrated to have a familial or breed predisposition in cats.


1.  Meurs KM, Mauceli E, Lahmers S, Acland GM, White SN, Lindblad-Toh K. Genome-wide association identifies a deletion in the 3' untranslated region of striatin in a canine model of arrhythmogenic right ventricular cardiomyopathy. Hum Genet 2010;128(3):315–324.

2.  Meurs KM, Ederer MM, Stern JA. Desmosomal gene evaluation in Boxers with arrhythmogenic right ventricular cardiomyopathy. Am J Vet Res 2007;68(12):1338–1341.

3.  Meurs KM, Norgard MM, Kuan M, Haggstrom J, Kittleson M. Analysis of 8 sarcomeric candidate genes for feline hypertrophic cardiomyopathy mutations in cats with hypertrophic cardiomyopathy. J Vet Intern Med 2009;23(4):840–843.

4.  Meurs KM, Sanchez X, David RM, Bowles NE, Towbin JA, Reiser PJ, Kittleson JA, Munro MJ, Dryburgh K, Macdonald KA, Kittleson MD. A cardiac myosin binding protein C mutation in the Maine Coon cat with familial hypertrophic cardiomyopathy. Hum Mol Genet 2005;14(23):3587–3593.

5.  Meurs KM, Norgard MM, Ederer MM, Hendrix KP, Kittleson MD. A substitution mutation in the myosin binding protein C gene in ragdoll hypertrophic cardiomyopathy. Genomics 2007;90(2):261–264.

6.  Wess G, Schinner C, Weber K, Küchenhoff H, Hartmann K. Association of A31P and A74T polymorphisms in the myosin binding protein C3 gene and hypertrophic cardiomyopathy in Maine Coon and other breed cats. J Vet Intern Med 2010;24(3):527–532.

7.  Mary J, Chetboul V, Sampedrano CC, Abitbol M, Gouni V, Trehiou-Sechi E, Tissier R, Queney G, Pouchelon JL, Thomas A. Prevalence of the MYBPC3-A31P mutation in a large European feline population and association with hypertrophic cardiomyopathy in the Maine Coon breed. J Vet Cardiol 2010;12(3):155–161.

8.  Godiksen MT, Granstrøm S, Koch J, Christiansen M. Hypertrophic cardiomyopathy in young Maine Coon cats caused by the p.A31P cMyBP-C mutation - the clinical significance of having the mutation. Acta Vet Scand 2011;53:7.

9.  Meurs KM, Hendrix KP, Norgard MM. Molecular evaluation of five cardiac genes in Doberman Pinschers with dilated cardiomyopathy. Am J Vet Res 2008;69(8):1050–1053.

10. Meurs KM, Fox PR, Norgard M, Spier AW, Lamb A, Koplitz SL, Baumwart RD. A prospective genetic evaluation of familial dilated cardiomyopathy in the Doberman pinscher. J Vet Intern Med 2007;21(5):1016–1020.

11. Spier AW, Meurs KM, Coovert DD, Lehmkuhl LB, O'Grady MR, Freeman LM, Burghes AH, Towbin JA. Use of western immunoblot for evaluation of myocardial dystrophin, alpha-sarcoglycan, and beta-dystroglycan in dogs with idiopathic dilated cardiomyopathy. Am J Vet Res 2001;62(1):67–71.

12. Meurs KM, Magnon AL, Spier AW, Miller MW, Lehmkuhl LB, Towbin JA. Evaluation of the cardiac actin gene in Doberman Pinschers with dilated cardiomyopathy. Am J Vet Res 2001;62(1):33–36.

13. O'Sullivan ML, O'Grady MR, Pyle WG, Dawson JF. Evaluation of 10 genes encoding cardiac proteins in Doberman Pinschers with dilated cardiomyopathy. Am J Vet Res 2011;72(7):932–939.

14. Mausberg TB, Wess G, Simak J, Keller L, Drögemüller M, Drögemüller C, Webster MT, Stephenson H, Dukes-McEwan J, Leeb T. A locus on chromosome 5 is associated with dilated cardiomyopathy in Doberman Pinschers. PLoS One 2011;6(5):e20042. Epub 2011 May 20.

15. Fries R, Heaney AM, Meurs KM. Prevalence of the myosin-binding protein C mutation in Maine Coon cats. J Vet Intern Med 2008;22(4):893–896.

16. MacDonald KA, Kittleson MD, Kass PH, Meurs KM. Tissue Doppler imaging in Maine Coon cats with a mutation of myosin binding protein C with or without hypertrophy. J Vet Intern Med 2007;21(2):232–237.

17. Meurs KM, Lahmers S, Keene BW, Mauceli E, Acland G, Lindblad-Toh K. A splice site mutation in a gene encoding for a mitochondrial protein is associated with the development of dilated cardiomyopathy in the Doberman Pinscher. ACVIM 2010 (abstract)

18. Andelfinger G, Wright KN, Lee HS, Siemens LM, Benson DW. Canine tricuspid valve malformation, a model of human Ebstein anomaly, maps to dog chromosome 9. J Med Genet 2003;40(5):320–324.

19. Famula TR, Siemens LM, Davidson AP, Packard M. Evaluation of the genetic basis of tricuspid valve dysplasia in Labrador Retrievers. Am J Vet Res 2002;63(6):816–820.

20. Pyle RL, Patterson DF, Chacko S. The genetics and pathology of discrete subaortic stenosis in the Newfoundland dog. Am Heart J 1976;92(3):324–334.

21. Werner P, Raducha MG, Prociuk U, Ostrander EA, Spielman RS, Kirkness EF, Patterson DF, Henthorn PS. The keeshond defect in cardiac conotruncal development is oligogenic. Hum Genet 2005;116(5):368–377.

22. Patterson DF, Pexieder T, Schnarr WR, Navratil T, Alaili R. A single major-gene defect underlying cardiac conotruncal malformations interferes with myocardial growth during embryonic development: studies in the CTD line of keeshond dogs. Am J Hum Genet 1993;52(2):388–397.

23. Patterson DF. Lesion-specific genetic factors in canine congenital heart diseases: patent ductus arteriosus in poodles, defects of the conotruncal septum in the Keeshond. Birth Defects Orig Artic Ser 1978;14(7):315–347.

24. Swenson L, Häggström J, Kvart C, Juneja RK. Relationship between parental cardiac status in Cavalier King Charles spaniels and prevalence and severity of chronic valvular disease in offspring. J Am Vet Med Assoc 1996;208(12):2009–2012.


Speaker Information
(click the speaker's name to view other papers and abstracts submitted by this speaker)

Mark Rishniw, BVSc, MS, PhD, DACVIM (Internal Medicine and Cardiology)
Cornell University College of Veterinary Medicine
Ithaca, NY, USA

MAIN : Lectures : Canine & Feline Heart Disease
Powered By VIN