Epilepsy is one of the most common neurologic diseases of dogs and a top concern of dog breeders. In spite of strong evidence that genetics is important in determining the risk of the common idiopathic epilepsy, numerous gene mapping studies have failed to identify a locus that accounts for that risk in either dogs or humans. Seizures occur when excessive activity goes beyond the normal threshold for brain function and many factors contribute to that level of activity. Thus it is thought that mutations in numerous genes can collectively contribute to increased activity until that threshold is exceeded, resulting in epilepsy. Any one of these mutations may be present in non-epileptic dogs as well, but because it only partially alters activity it would not produce seizures. This would, however, cause traditional gene mapping studies to overlook that mutation. Using a novel whole genome sequencing approach we will identify DNA variations in epileptic dogs that could affect the function of genes such as ion channels and neurotransmitter receptors that have been shown to alter the seizure threshold in humans or rodents. We will then directly compare the frequency of those variations in populations of epileptic and non-epileptic dogs rather than using the indirect markers used in traditional mapping studies. We predict that the increased power provided by looking for specific candidate variations rather than linked markers will permit the identification of epilepsy risk factors. These can then be developed into DNA tests to enable breeders to select against those risk factors.
Dr. Gary S. Johnson, DVM PhD
University of Missouri, Columbia