Canine Epilepsy Research Grants

This research is made possible by grants from the AKC Canine Health Foundation and the NIH (National Institutes for Health). Donations to the Canine Health Foundation to fund these grants are encouraged.

Following are the Abstracts from grants supporting the research.

CHF Completed Grant #1718

Molecular Genetic Basis of Epilepsy in Standard Schnauzers and English Springer Spaniels
Gary S. Johnson, DVM PhD
University of Missouri, Columbia

SPONSORS:
English Springer Spaniel Field Trial Association Foundation
Standard Schnauzer Club of America

Abstract: Epilepsy is one of the most common diseases of the nervous system in dogs. The effects of repeated seizures can be devastating physically for the affected dogs and emotionally for the people who care for them. Epilepsy is known to be inherited in several breeds and genetics is thought to play a key role in many others. In preliminary studies of epilepsy in a family of dogs, we found DNA markers which appear to be associated with the disease. Near these markers on human and mouse chromosomes are genes for potassium channels. The potassium channel genes are logical places for an epilepsy-causing mutation, so we are currently looking for the responsible mutation within these genes. If we find the responsible mutation, we can create a DNA marker that will allow breeders to identify puppies destined to develop epilepsy. In addition, the marker will identify epilepsy carriers, enabling breeders to avoid matings that will produce epileptic offspring.

CHF Completed Grant #1729

Canine Epilepsy: Determining the Mode of Inheritance, Mapping the Genes, and Developing a Linkage Test
James R. Mickelson, PhD
University of Minnesota

SPONSORS:
English Springer Spaniel Field Trial Association Foundation
National Beagle Club
Vizsla Club of America

Abstract: We propose to develop a genetic screening test for canine epilepsy, a serious late-onset seizure disorder affecting a large number of breeds. The onset of seizures in dogs with epilepsy is typically from one to five years of age. The late onset means that often a dog has already been bred before it is known to be affected. In some individuals, seizures are well controlled with anticonvulsant medications, but a significant number of dogs have "refractory" seizures needing high doses of medications to achieve control. The severity of seizures may be such that the owner elects to have the dog euthanized. A genetic test for epilepsy would allow breeders to screen potential breeding animals for this common, frustrating, and potentially devastating disorder prior to making breeding decisions. We propose to determine the mode of inheritance for epilepsy in three breeds (English Springer Spaniels, Vizslas, and Beagles) and to use genetic markers to develop a screening linkage test for predicting epilepsy in these breeds. This approach to identifying the region of the canine genome containing the defective gene will ultimately lead to the prediction of candidate genes that can be characterized to define the precise defect responsible.

CHF Completed Grant #1845

Molecular Genetic Causes of Canine Epilepsies
Gary S. Johnson, DVM PhD
University of Missouri, Columbia

SPONSORS:
English Springer Spaniel Field Trial Association
Irish Setter Club of America
Saint Bernard Club of America
Standard Schnauzer Club of America
Welsh Springer Spaniel Club of America

Abstract: Epilepsy is one of the most common diseases of the nervous system in dogs. The effects of repeated seizures can be devastating physically for the affected dogs and emotionally for the people who care for them. Epilepsy is known to be inherited in several breeds and genetics is thought to play a key role in many others. Differences in the age at the onset of symptoms, the type and severity of seizures, and the responsiveness to therapy suggest that many forms of epilepsy can affecte dogs and that mutations in any of a number of different genes may result in canine epilepsy. Although epilepsy is difficult to study in any breed, differences in available family structure make epilepsy more difficult to study in some breeds than in others. We plan to produce DNA marker tests to identify epilepsy carriers in as many breeds as possible; however, we want to focus on the less difficult breeds first. Therefore, we plan to do a preliminary examination of epilepsy in over 50 breeds in the first year of the study. In the second year we will focus on four or more breeds selected because studies of them are most likely to produce useful DNA markers.

CHF Active Grant #2252

Canine Epilepsy: Inheritance, Genes and Linkage Test
James R. Mickelson, PhD; University of Minnesota
Edward E. Patterson, DVM; University of Minnesota


Sponsors:
English Springer Spaniel Field Trial Association Foundation
National Beagle Club
Vizsla Club of America

Abstract: We propose to continue our molecular genetic studies to develop a screening linkage test for predicting epilepsy in Beagles, English Springer Spaniels and Vizslas. Preliminary results of our genetic marker studies in these breeds indicate that we will be able to find linked markers and the chromosomal segment containing the epilepsy gene given sufficiently large and informative pedigrees. The onset of seizures in dogs with epilepsy is typically from one to five years of age. The late onset means that often a dog has already been bred before it is know to be affected. In some individuals, seizures are well controlled with anticonvulsant medications, but a significant number of dogs have "refractory" seizures needing high doses of medications to achieve control. The severity of seizures may be such that the owner elects to have the dog euthanized. A genetic test for epilepsy would allow breeders to screen potential breeding animals for this common, frustrating, and potentially devastating disorder prior to making breeding decisions. Our genome mapping approach to identifying the region of the canine genome containing the defective gene will ultimately lead to the prediction of candidate genes that can be characterized to define the precise defect responsible.

CHF Active Grant #2304

Continued Investigation into the Molecular Genetic Causes of Canine Epilepsies
Gary S. Johnson, DVM, PhD; University of Missouri, Columbia

Sponsors:
American Spaniel Club
American Water Spaniel Partners
Collie Health Foundation
Dalmatian Club of America Foundation
English Springer Spaniel Field Trial Association Foundation
Greater Swiss Mountain Dog Club of America
Irish Setter Club of America
Irish Water Spaniel Club of America
St. Bernard Club of America
Standard Schnauzer Club of America
Welsh Springer Spaniel Club of America

Abstract: In our on-going study of canine epilepsy, we have found that most canine epilepsy families do not follow the simple inheritance patterns described by Gregor Mendel. This suggests that epilepsy results when a dog inherits mutations in two or more different genes. Mutations involving two or more genes are also thought to be responsible for the vast majority of human epilepsy that occurs in families. Mendelian inheritance is encountered in rare types of human epilepsy and in many of these families the epilepsy-causing mutation has been found by genome mapping. We appear to have found Mendelian inheritance in at least one canine family and if this holds true we will attempt to map the mutation. One unexpected finding that is not seen in the human epilepsy families is the predominance of males among the affected dogs in several dog breeds. A similar inheritance pattern in human disease has been attributed to paired mutations on the X chromosome and in the mitochondrial DNA in these breeds. Our ultimate goal is to produce a DNA marker that breeders can use to avoid matings that will result in new generations of epileptic dogs.

NIH Award #1K08NS0224501

Mapping Idiopathic Epilepsy Genes In Canine Models
Edward E (Ned) Patterson, DVM
University of Minnesota, Twin Cities

Abstract:Idiopathic epilepsy (IE) is a common condition in human patients as well as the domestic dog (Canis familiaris). In both species, genetic factors are believed to be a significant factor in conferring susceptibility to seizures. The most common forms of human IE are known to be polygenic, and consequently dissecting out individual genes has been difficult. Dogs have been strongly inbred over the last 100 years, and therefore many of their inherited diseases are caused by a "founder" effect similar to that found in isolated human populations. We hypothesize that idiopathic epilepsy in some dog breeds has a simple mode of inheritance (monogenic or oligogenic), and consequently it will be possible to efficiently map the genetic loci and eventually identify causative mutations. The causative mutation(s) could be used as candidate genes for IE's of human patients, and as a basis for future studies of neuronal hyperexcitability. The overall objective of this proposal is to locate chromosomal loci linked to idiopathic epilepsy in dogs, as a major step towards identifying susceptibility genes and developing a model for human idiopathic epilepsy. This information will help the understanding of epilepsy in dogs and people.

 

University of Missouri-College of Veterinary Medicine In-House Grant

Temporal Distribution of Seizures in a Group of Canine Epileptics
Brian Cellio, DVM, Neurology Resident
Dennis O'Brien, DVM Phd, Associate Professor
Gary Allen, DVM PhD, Associate Professor
C Wagner-Mann, Research Assistant Professor
University of Missouri, Columbia

One of the major difficulties with epilepsy is predicting the occurrence of seizures. The majority of epileptic seizures in humans do not occur randomly. A similar non-random distribution has been suspected clinically in the canine population but data to confirm this suspicion is lacking. Studies of seizure patterns may elucidate underlying mechanisms for seizure precipitation and identify seizure-provoking factors. Knowledge of these factors may provide some predictability for epileptic seizures, which could prove to be a valuable tool in the management of canine epileptics.