Kathryn Meurs, DVM,PhD; Ohio State
University
The
Genetic Evaluation of Dilated Cardiomyopathy in the Doberman Pinscher:
Dilated
cardiomyopathy (DCM), a primary heart muscle disorder characterized by poor cardiac function, is inherited in the Doberman
Pinscher. Therapy for DCM does not cure or even successfully control the clinical
signs. The inability to control the disease has led to increased interest in
disease prevention through careful selection of unaffected dogs for breeding. However,
since DCM is often not apparent until later in the adult life of the dog, many dogs are selected for breeding before they
are found to be affected. A blood test that could identify affected animals before
they are used for breeding would greatly decrease the prevalence of DCM.
Careful evalulation of a 4 generation, 39 member
family has provided an explanation of the pattern of inheritance of the disease. A
genome wide scan is being performed to identify informative canine markers associated with DCM in the Doberman Pinscher. Genetic markers from the canine genetic map are evaluated by polymerase chain reaction
(PCR) and linkage analysis and evaluated for genetic linkage with MLINK. The
highest linkage score we have identified so far is 1.9. A canine marker with
a score of 3 or greater is considered a significant lead in the identification of the genetic cause of this disease.
The Genetic Evaluation of Canine Subvalvular
Aortic Stenosis:
Subvalvular Aortic Stenosis (SAS) is a congenital heart disease characterized by a fibrous ridge
located below the aortic valve. Affected dogs are at risk of developing heart
valve infections, congestive heart failure or sudden death. Although mildly affected
dogs can live a normal lifespan, severely affected dogs live an average of 19 months.
The defect has been shown to be inherited in the Newfoundland breed, and is
likely to be inherited in the Golden Retriever, Boxer and Rottweiler, among others.
Since this is a familial defect in at least some breeds, affected dogs should not be bred. However, mildly affected dogs can be difficult to diagnose without Doppler echocardiography, an expensive
test with limited availability. Therefore, there is significant interest in developing
a blood test to screen for SAS.
The objectives of the studies are to define the clinical (phenotypic) and genotypic characteristics
of SAS in various breeds of dogs. A genome wide scan is being performed to identify
informative canine markers associated with SAS in individual breeds of dogs. In
the Newfoundland, 3 close families of dogs are being studied to identify a genetic marker
linked to SAS. Genetic markers from the canine genetic map are evaluated by polymerase
chain reaction (PCR) and linkage analysis and evaluated for genetic linkage with MLINK.
This will be the first step in the development of a DNA screening test for this disease.
Steps to Correct Cardiac Concerns
in Your Breed
Stage I
1. Characterize your breed’s heart disease
a. Collect solid, specific information about clinical and familial aspects of disease
in veterinary literature.
b. Use caution when interpreting clinical or genetic data from one breed to another.
2. Participate in clinical studies to determine
specific aspects of a disease
a. Determine whether disease is congenital vs. adult onset acquired
b. Evaluate as many dogs as possible and re-evaluate annually for change, to maintain
current status for acquired defects
c. Apply retrospective research: investigate records already on file
d. Apply prospective research: recruit current information on affected dogs
e. Determine what is normal
1. 50 normal dogs at age of onset are used as a baseline
2. 3 generations are used to check pedigrees to evaluate familial tendencies, using
all normal and affected dogs
Pros and cons to consider:
Retrospective research is inexpensive; prospective
research is accurate but expensive. There is immediate impact in developing screening
programs since they help to positively identify clinical aspect.
Stage II
1. Characterize familial aspects
a. Evaluate pedigrees for mode of inheritance.
b. Perform repeated testing to maintain current status for acquired defects.
c. Evaluate male/female results that could determine if a sex link is involved.
Stage III
1. Characterize molecular aspects of familial heart disease.
a. This process can take up to 30 years to evaluate continuing generations.
b. Compare and search for studies in humans.
Human studies often use the dog as a model, which could allow for possible funding.
Conclusive summary:
Determine what is normal.
Survey specific info: age of onset, clinical manifestations, life span,
determine other conditions present.
Test annually to determine new onset or evaluate changes.
Conduct pedigree analysis to determine mode of inheritance.
Characterize molecular aspects.
Compare and search for studies in humans to propose using dog as model;
look for possible funding.
AWS Partners’
recommended resources:
Canine Dilated Cardiomyopathy – Recognition and Clinical Management
http://www.vin.com/proceedings/Proceedings.plx?CID=WALTHAMOSU2002&PID=2981
Canine Cardiomyopathy and Heart Failure
http://www.pethealthcare.net/html/body_canine_dilated_cardiomyopathy_.html
“The more we learn, the less we know”: A Progress Report
to the ABC Membership
http://www.boxerunderground.com/bu2000/abc2001/drmeurs01.htm
Familial Ventricular Arrhythmia in Boxers
http://www.boxerclubofarizona.org/meursfva.htm
Hypomagnesemia and Mitral Valve Prolapse in Cavalier King Charles Spaniels
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9923143&dopt=Abstract
Mitral Valve Disease in Cavalier King Charles Spaniels
http://home.vicnet.net.au/~cavalier/mitral.htm
Cavalier Health Foundation Grants
http://www.cavalierhealthfoundation.com/grants.htm
Mitral Valve Prolapse: What Causes It?
What Diet Changes Can Help?
http://www.ctds.info.mvp1.html
VetCentric: Dilated Cardiomyopathy
http://www.vetcentric.com/reference/encycEntry.cfm?ENTRY=76&COLLECTION=EncycIllness&MODE=full
Diary of Chronic Valvular Disease
http://www.wtv-zone.com/Marvaline/KD/canineheart.html
Cardiac Heart Disease (Pedigree)
http://www.pedigreebreeder.com.au/features/nutrition/default.asp?s=6
Mitral Valve Disease
http://www.rhiannon-cavaliers.com/mvd.htm
Canine Cardiology
http://www.usask.ca/wcvm/canine
Clinical Cardiology Concepts in the Dog and Cat
http://www.vetgo.com/cardio/concepts/concsect.php?ques
