Looking into a whale's heart: investigating a genetic basis for cardiomyopathy in a non-model species

Understanding the pathogenesis of complex diseases can benefit from multi-species comparative studies. Yet these studies rarely include natural populations of non-model species. Here, we focused on the cause of a heart muscle disease, cardiomyopathy (CM), affecting multiple mammalian species including humans, cats, dogs, and certain species of whales. Mutations in genes coding for sarcomeric proteins have been identified as a leading cause for CM in humans, and some were also revealed to be responsible for CM in cats. We investigated whether similar mutations could be detected in the deep-diving pygmy sperm whale (Kogia breviceps), which is one of two cetacean species known to display CM. We sequenced portions of two candidate genes (MYH7: 3153 bp and MYBPC3: 3019 bp) in 55 whales including affected and unaffected individuals. Mutation screening revealed six nonsynonymous substitutions that were predicted to have an effect on protein function. However, the etiology of CM is likely complex and probably multi-factorial as three of these mutations were observed in unaffected individuals from our control group. This incomplete penetrance could be partly age-related and could also be due to the influence of environmental factors on the development of CM, as seen in humans.