Molekylärgenetisk analys av dilaterad cardiomyopati hos hund
DCMAttenuated wavy fibersDesminKandidatgenGenetisk predispositionSNPMicrosatelliterAutosomal dominant nedärvning
Canine dilated cardiomyopathy (DCM) is a disease with high morbidity and mortality and with a high prevalence in certain breeds. Predominatly large breeds are affected, such as Great danes, Newfoundlands, Deerhounds and Dobermanns. One exception is Cocker spaniels, where both American and English Cocker spaniels are affected in a quite high frequency.
Cardiomyopathy is characterised as a disease that affects the myocardium and gives an impaired heart function. To diagnose DCM following criteria have to be observed:
1. Dilation of the left ventricle.
2. Reduced systolic heart function.
3. Increased sphericity of the left ventricle.
To be certain of the diagnosis, alternative reasons for the symptoms such as lung- and heart diseases with other etiologies have to be excluded
Two different types of DCM have been found upon histological examination. One type where the myocytes are thinner than normal and have a wavy appearance ? attenuated wavy fibers. There has also been observed a space between the myocytes which indicates edematous fluid.
The alternative histological findings are infiltrates of fatty- and connective tissue.
Since this is a disease of great suffering both for the dog and for its owner it would be of great interest to find the altered genes that gives an increased risk to develop this disease.
Our study was done in a family of Newfoundlands where certain individuals were diagnosed with DCM of the wavy fibers type. Blood samples from dogs representing a few generations were available to us. We started our study with a candidate gene approach, and the gene of our choice was desmin, since it has been documented to be the cause of DCM in certain studies of human families. The histological appearance also indicated that a protein in the cytoskeleton is involved in the disease.
The desmin gene was analysed in a few individuals by Polymerase Chain Reaction (PCR) and nucleotide sequencing of exon 8 in the desmin gene. When analysing our results we found a Single Nucleotide Polymorphism (SNP). The SNP was evaluated for genetic association to DCM. However, the SNP did not cause any change in amino acids and neither of the alleles showed association with DCM.
The identified SNP can be used in future association mapping studies in a larger Newfoundland population to conclusively exclude desmin as a disease gene for DCM.