00762: The Mapping and Characterization of Canine Epilepsy Loci

Grant Amount: $129,600

Gary S. Johnson, DVM PhD; University of Missouri, Columbia

October 1, 2008 - September 30, 2010

Sponsor(s): American Bloodhound Club, American Pointer Club, American Sealyham Terrier Club, American Shetland Sheepdog Association, AWS Partners, Border Terrier Club of America, Collie Health Foundation, Dalmatian Club of America Foundation, Inc., English Springer Spaniel Field Trial Association Foundation, Estate of Dr. Judith Musladin, Greater Swiss Mountain Dog Club of America, Inc., Greyhound Club of America, Helen Chrysler Greene, Irish Setter Club of America Foundation, Marcia St. Lifer, National Beagle Club, Petit Basset Griffon Vendeen Club of America, Poodle Club of America Foundation, Schipperke Club of America, Siberian Husky Club of America, St. Bernard Club of America, Versatility in Poodles, Inc., Welsh Springer Spaniel Club of America

Breed(s): American Water Spaniel, Border Terrier, Irish Setter, Australian Shepherd, Irish Water Spaniel, English Springer Spaniel, Otterhound, Saint Bernard, Welsh Springer Spaniel, Chesapeake Bay Retriever, Dalmatian, Greater Swiss Mountain Dog, Labrador Retriever, Collie

Research Program Area: Epilepsy Initiative

Project Summary

The projects investigators collected DNA from nearly 10,000 epileptic dogs and their close relatives and they have assembled epilepsy?family pedigrees in 28 different dog breeds. The investigators have re?contacted the owners of over 2,000 dogs in this collection to obtain additional clinical information or to confirm that the "normal" dogs have remained seizure free. They have used samples from 13 different breeds in 15 different experimental attempts to identify the chromosomal locations of epilepsy?causing genetic mutations. They used an experimental procedure known as a genome?wide association study (GWAS) which is done with a device known as a SNPchip. SNPchips compare the DNAs from epileptic dogs to the DNAs from non?epileptic family members at tens or hundreds sites in all of the chromosomes. Eight of the GWASs were done in collaborations with other laboratories and seven were done at the University of Missouri. Thirteen of the GWASs were applied to epilepsies in which seizures were the only symptoms. None of these studies provided strong evidence about the chromosomal locations of epilepsy?causing mutation; however, some of them provided weak evidence, suggesting possible chromosomal sites for epilepsy mutations. The investigators examined genes at five of these sites, but failed to find any epilepsy?causing mutations. By contrast, both GWAS for diseases with symptoms in addition to seizures successfully identified the chromosomal locations of the responsible locations. The GWASs for the pure epilepsies probably failed because causes of epilepsy in some of the family members were different from the causes in other family members and/or because the epilepsies resulted from a complex combination of genes and acquired factors.

Publication(s)

Katz, M. L., Farias, F. H., Sanders, D. N., Zeng, R., Khan, S., Johnson, G. S., & O’Brien, D. P. (2011). A Missense Mutation in Canine CLN6 in an Australian Shepherd with Neuronal Ceroid Lipofuscinosis. Journal of Biomedicine and Biotechnology, 2011, 1–6. https://doi.org/10.1155/2011/198042

Packer, R. A., Patterson, E. E., Taylor, J. F., Coates, J. R., Schnabel, R. D., & O’Brien, D. P. (2010). Characterization and Mode of Inheritance of a Paroxysmal Dyskinesia in Chinook Dogs: Paroxysmal Dyskinesia. Journal of Veterinary Internal Medicine, 24(6), 1305–1313. https://doi.org/10.1111/j.1939-1676.2010.0629.x

Sanders, D. N., Farias, F. H., Johnson, G. S., Chiang, V., Cook, J. R., O’Brien, D. P., … Katz, M. L. (2010). A mutation in canine PPT1 causes early onset neuronal ceroid lipofuscinosis in a Dachshund. Molecular Genetics and Metabolism, 100(4), 349–356. https://doi.org/10.1016/j.ymgme.2010.04.009