A prospective genetic evaluation of familial dilated cardiomyopathy in the Doberman pinscher.
BACKGROUND
The Doberman Pinscher is one of the most common breeds of dogs to develop dilated cardiomyopathy (DCM), a primary heart muscle disorder characterized by myocardial dysfunction, cardiac arrhythmias, and congestive heart failure. In the Doberman Pinscher, the disease is typically adult onset, and a familial etiology has been suggested.


OBJECTIVE
DCM in the Doberman Pinscher, is a familial disease linked to a specific genetic marker.


METHODS
The study comprised an extended family of Doberman Pinschers with a history of DCM.


METHODS
Participating dogs were prospectively evaluated over an 8-year period. Phenotype of participating dogs was determined by annual echocardiography and ambulatory electrocardiography, and the pedigree was evaluated to determine a specific mode of inheritance. Three hundred seventy-two microsatellite markers were selected and genotyped to cover the 38 autosomal chromosomes. Phenotyping, genotyping, and pedigree information was entered into a database, and parametric, 2-point analysis was performed. Markers were considered to be linked to the development of DCM if the logarithm of odds LOD score was >/= 3.0.


RESULTS
An autosomal dominant mode of inheritance was defined by the appearance of the disease in multiple generations, equal gender representation (P = .973) and male-to-male transmission. A maximum LOD score of 1.31 was obtained for I marker on chromosome 20, a score not high enough to be associated with DCM.


CONCLUSIONS
DCM in the Doberman Pinscher is a familial disease inherited as an autosomal dominant trait. The causative gene(s) responsible for this condition remain unresolved. Association studies by means of array technology may provide new insights into gene identification.
Meurs
Kathryn M
KM
Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA 99164, USA. Meurs@vetmed.wsu.edu
Fox
Philip R
PR
Norgard
Michelle
M
Spier
Alan W
AW
Lamb
Allison
A
Koplitz
Shianne L
SL
Baumwart
Ryan D
RD
D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000235:genetics / Q000473:pathology / Q000662:veterinary*; D002874:Chromosome Mapping / Q000662:veterinary; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004283:Dog Diseases / Q000235:genetics* / Q000473:pathology; D004285:Dogs; D004452:Echocardiography / Q000662:veterinary; D015716:Electrocardiography, Ambulatory / Q000662:veterinary; D005260:Female; D008040:Genetic Linkage; D005838:Genotype; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D010375:Pedigree; D010641:Phenotype; D011446:Prospective Studies
D004247:DNA