The canine sarcoglycan delta gene: BAC clone contig assembly, chromosome assignment and interrogation as a candidate gene for dilated cardiomyopathy in Dobermann dogs.

Dilated cardiomyopathy (DCM) is a common disease of the myocardium recognized in human, dog and experimental animals. Genetic factors are responsible for a large proportion of cases in humans, and 17 genes with DCM causing mutations have been identified. The genetic origin of DCM in the Dobermann dogs has been suggested, but no disease genes have been identified to date. In this paper, we describe the characterization and evaluation of the canine sarcoglycan delta (SGCD), a gene implicated in DCM in human and hamster. Bacterial artificial chromosomes (BACs) containing the canine SGCD gene were isolated with probes for exon 3 and exons 4-8 and were characterized by Southern blot analysis. BAC end sequences were obtained for four BACs. Three of the BACs overlapped and could be ordered relative to each other and the end sequences of all four BACs could be anchored on the preliminary assembly of the dog genome sequence (www. ensembl.org). One of the BACs of the partial contig was localized by fluorescent in situ hybridization to canine chromosome 4q22, in agreement with the dog genome sequence. Two highly informative polymorphic microsatellite markers in intron 7 of the SGCD gene were identified. In 25 DCM-affected and 13 non DCM-affected dogs seven different haplotypes could be distinguished. However, no association between any of the SGCD variants and the disease locus was apparent.

Dilated cardiomyopathy in Doberman Pinschers: Survival, Causes of Death and a Pedigree Review in a Related Line.

OBJECTIVE: To analyze clinical, electrocardiographic and echocardiographic characteristics, survival, cause of death and possible modes of inheritance of dilated cardiomyopathy (DCM) in Doberman pinschers (DP) and to compare the occurrence and survival with dogs of other breeds. Dogs - Two cohorts of dogs were studied: 1. A consecutive series of 52 dogs of different breeds with DCM were included, 21 were Doberman pinschers and 31 dogs belonged to other breeds: 2. 28 asymptomatic Doberman pinschers, who were screened for DCM. Methods - Medical records of dogs with DCM were reviewed. Physical, electrocardiographic and echocardiographic examinations were performed on asymptomatic Doberman pinschers. Their pedigrees were reviewed. RESULTS: Doberman pinschers survived on average 52 days (range <1-180), while dogs of other breeds survived significantly longer, i.e. 240 days (<1-1230). Survival of Doberman pinschers in congestive heart failure (mean 62, range <1-180) was not different from survival of Doberman pinschers with sudden death (mean 33, range <1-105). High prevalence, short survival time and the clinical course of DCM in Doberman pinschers showed similarities to previous studies. Twenty-one percent of asymptomatic Doberman pinschers had increased left ventricular end-systolic diameter and 14% developed DCM within a year. A line of Doberman pinschers with multiple members affected with DCM was identified by the review of their pedigrees. Exact mode of inheritance could not be established. CONCLUSIONS: The prognosis of Doberman pinschers with DCM is poor. Further molecular genetic studies, which would enable detection and exclusion of disease carriers from the breeding, are necessary.