Characterization of the canine desmin (DES) gene and evaluation as a candidate gene for dilated cardiomyopathy in the Dobermann.
Canine-dilated cardiomyopathy (DCM) in dogs is a disease of the myocardium associated with dilatation and impaired contraction of the ventricles and is suspected to have a genetic cause. A missense mutation in the desmin gene (DES) causes DCM in a human family. Human DCM closely resembles the canine disease. In the present study, we evaluated whether DES gene mutations are responsible for DCM in Dobermann dogs. We have isolated bacterial artificial chromosome clones (BACs) containing the canine DES gene and determined the chromosomal location by fluorescence in situ hybridization (FISH). Using data deposited in the NCBI trace archive and GenBank, the canine DES gene DNA sequence was assembled and seven single nucleotide polymorphisms (SNPs) were identified. From the canine DES gene BAC clones, a polymorphic microsatellite marker was isolated. The microsatellite marker and four informative desmin SNPs were typed in a Dobermann family with frequent DCM occurrence, but the disease phenotype did not associate with a desmin haplotype. We concluded that mutations in the DES gene do not play a role in Dobermann DCM. Availability of the microsatellite marker, SNPs and DNA sequence reported in this study enable fast evaluation of the DES gene as a DCM candidate gene in other dog breeds with DCM occurrence.
Stabej
Polona
P
Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 8, 3584 CM Utrecht, The Netherlands. P.Stabej@vet.uu.nl
Imholz
Sandra
S
Versteeg
Serge A
SA
Zijlstra
Carla
C
Stokhof
Arnold A
AA
Domanjko-Petric
Aleksandra
A
Leegwater
Peter A J
PA
van Oost
Bernard A
BA
D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000235:genetics* / Q000662:veterinary; D002874:Chromosome Mapping; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics; D033481:Chromosomes, Mammalian / Q000235:genetics; D003001:Cloning, Molecular; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification; D003893:Desmin / Q000235:genetics*; D004283:Dog Diseases / Q000235:genetics*; D004285:Dogs / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006239:Haplotypes; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA
D003893:Desmin; D004247:DNA