Canine Epilepsy Research

Ned Patterson, DVM
University of Minnesota, College of Veterinary Medicine

 

Gary Johnson, DVM, PhD
University of Missouri, College of Veterinary Medicine

 

The Canine Epilepsy Project is a collaborative study into the causes of epilepsy in dogs. It is supported by grants from the AKC Canine Health Foundation (CHF), National Institutes of Health (NIH), individual breed clubs and private donations. Grants supporting this research are CHF Completed Grant #1718, CHF Completed Grant #1729, CHF Completed Grant #1845, CHF Active Grant #2252, CHF Active Grant #2304, and NIH Award #1K08NS0224501.

Our goal is to find the genes responsible for epilepsy in dogs so that wise breeding can decrease the incidence of the disease in dogs. We also hope that knowing what genes regulate epilepsy in dogs may help us better tailor our therapy to the specific cause.

The objectives of our investigations into hereditary canine epilepsy are:

1. Recruit samples from a large number of affected individuals and their immediate family members (siblings, parents, and grandparents), from many breeds of dogs.
2. Evaluate the genotype of selected families to search for linkage between DNA markers and clinical epilepsy, then use this information to identify the causative mutation or mutations.
3. Devise a DNA marker test that detects and distinguishes normal and mutant (epilepsy-causing) alleles, and make this test available to dog breeders so that they can produce epilepsy-free dogs.

 

Progress to Date

As of September 1, 2006, samples from 8066 dogs representing 90 different breeds have been submitted for epilepsy research. Included in this total are 1207 affected dogs. As samples arrive, families are assembled and data compiled. We have reached the initial goal of 50 breeds included in the project, but not all breeds have informative families sampled at this time. At present, all breeds with more than 20 affected dogs are being evaluated and prepared for possible mapping, and the mapping process has begun in some breeds. Samples from potentially useful families of any breed are still needed, and we encourage owners to participate.

 

Breed	Total Number	Affected Total	Affected Males	Affected Females
Akbash Dog	14	1	1	0
Alaskan (Racing) Husky	11	3	1	2
Australian Shepherd	1080	128	63	65
Beagle	184	36	18	18
Bloodhound	66	4	1	3
Border Collie	83	22	13	9
Border Terrier	124	39	15	24
Brittany	39	9	5	4
Canaan Dog	26	9	5	4
Chinook + Chinook cross	280	35	17	18
Collie	111	22	14	8
Dachshund	74	10	3	7
Dalmatian	95	33	13	20
English Shepherd	22	2	0	2
Finnish Spitz	78	16	7	9
Fox Terrier (Wire)	11	4	3	1
German Pinscher	36	4	2	2
German Shepherd Dog	23	11	6	5
Giant Schnauzer	20	2	1	1
Great Dane	29	1	0	1
Great Pyrenees	23	5	1	4
Greater Swiss Mountain Dog	887	63	41	22
Ibizan Hound	66	15	7	8
Italian Greyhound	50	18	8	10
Jack Russell Terrier	27	10	5	5
Mastiff	21	2	2	0
Newfoundland	14	2	1	1
Otterhound	131	18	13	5
Petit Basset Griffon Vendeen	46	8	4	4
Pointer	241	17	12	5
Pointer, German Shorthaired	33	8	3	5
Pomeranian	32	13	7	6
Poodle (Standard)	291	26	9	17
Pyrenean Shepherd	22	4	2	2
Retriever, Chesapeake Bay	86	21	14	7
Retriever, Curly Coated	75	12	5	7
Retriever, Golden	64	18	10	8
Retriever, Labrador	201	50	29	21
Rottweiler	14	4	3	1
Saint Bernard	106	21	13	8
Samoyed	18	1	1	0
Schipperke	39	14	6	8
Setter, English	126	21	10	11
Setter, Irish	229	58	45	13
Shetland Sheepdog	31	12	6	6
Siberian Husky	80	23	15	8
Spaniel, American Water	253	27	16	11
Spaniel, Cocker (American)	128	28	16	12
Spaniel, English Springer	869	85	45	40
Spaniel, Field	109	6	2	4
Spaniel, Irish Water	310	37	22	15
Spaniel, Welsh Springer	413	25	17	8
Standard Schnauzer	183	17	15	2
Tibetan Mastiff	24	3	2	1
Vizsla	264	53	26	27
Weimeraner	21	5	3	2
Welsh Terrier	34	9	7	2
*Other breeds	100	57	31	26
TOTALS (09-01-06)	8066	1207	663	544
*includes less that 10 dogs per breed of the following:   Akita, Alaskan Malamute, American Bulldog, Australian Terrier, Basenji, Belgian Malinois, Belgian Tervuren,   Bernese Mountain Dog, Bichon Frise, Bluetick Coonhound, Borzoi, Boston Terrier, Briard, Bullmastiff,   Cavalier King Charles Spaniel, Chinese Shar-Pei, Dandie Dinmont Terrier, Flat-Coated Retriever, French Bulldog,   Irish Wolfhound, Keeshond, Leonberger, Mi-Ki, Nova Scotia Duck Tolling Retriever,Pembroke Welsh Corgi,   Pit Bull Terrier, Poodle (Miniature), Portugese Water Dog, Saluki, Scottish Terrier, Small Munsterlander   Spinone Italiano, Tibetan Terrier, Welsh Corgi-Pembroke

The level of participation by any breed should not be interpreted as an indication of the frequency of this problem within the breed, but can serve to demonstrate the commitment by fanciers of that breed to help researchers solve this problem.

PUBLISHED RESEARCH

Dr Patterson is the lead author on an article that appeared in the Journal of Veterinary Internal Medicine, May-June 2003 issue. Following is the abstract from this article:

Clinical characteristics and inheritance of idiopathic epilepsy in Vizslas.

Patterson EE, Mickelson JR, Da Y, Roberts MC, McVey AS, O'Brien DP, Johnson GS, Armstrong PJ.

Department of Small Animal Clinical Sciences, University of Minnesota, College of Veterinary Medicine, St Paul, MN 55108, USA.

Medical record, seizure survey, and telephone interview information was obtained for 29 Vizslas with idiopathic epilepsy (IE), 74 unaffected siblings, and 41 parents to determine the common clinical characteristics and most likely mode of inheritance. IE was diagnosed on the basis of the age of seizure onset, laboratory results, and neurologic examination findings. Computerized tomography (CT) or magnetic resonance imaging (MRI) scan with cerebrospinal fluid (CSF) analysis was required for the inclusion of dogs with an age of seizure onset of < 6 months or > 5 years. Simple segregation analysis was performed with an ascertainment correction and chi-square analysis. IE appeared to be familial in these pedigrees, with 79% of affected Vizslas exhibiting partial onset seizures. Partial seizure signs included a combination of limb tremors, staring, pupillary dilatation, or salivation without loss of consciousness in > 50% of the dogs with partial signs. The estimated segregation frequency of P = .22 (95% CI, P = .08 to .36) was consistent with autosomal recessive inheritance; however, polygenic inheritance could not be excluded as a possibility. Simulated linkage with FASTSLINK estimated that the average logarithm of odds (LOD) score would be 3.23 with a 10-centimorgan (cM) whole-genome scan for these families, indicating that these families would be useful for a whole-genome scan to potentially find the chromosomal segment(s) containing the epilepsy gene or genes. We conclude that IE in Vizslas appears to be primarily a partial onset seizure disorder that may be inherited as an autosomal recessive trait.

J Vet Intern Med. 2003 May-Jun;17(3):319-25.
 

 

How can I help?

If you have an epileptic dog, you can supply samples and information for the project.

Participation by the owners of affected dogs and their relatives is essential to the success of this project. Researchers need DNA samples from dogs who have experienced seizures, and immediate relatives, both normal and affected. Specifically, we need samples from all available siblings, parents, and grandparents. If the affected dog has been bred, all offspring and mates should be sampled as well. Useful research families are explained in more detail here. Participation in this research project is confidential - the names of individual owners or dogs will not be revealed. Data and sample collection instructions and sample submission forms are available to download here, or the packet will be mailed or faxed upon request.
 

Dog clubs can contribute to the success of this project by making their members aware that this research is underway, and encouraging those who have affected dogs or relatives to participate.
 

Your financial support makes this project possible.
 

You can continue to help through donations to any of the following funds:

 

	The Canine Health Foundation of the American Kennel Club. The CHF often matches the funds donated by clubs or individuals, thus doubling the impact your donation may have. You may specify that your donation is used for epilepsy research, and they will honor your request.
	Individual breed club foundations dedicated to epilepsy research.

American Kennel Club	Canine Health Foundation

The Canine Epilepsy Research Consortium is a group of scientists who have agreed to:

share DNA samples, phenotype data, and genotype data

share credit for scientific contribution by co-authoring manuscripts

agree that discoveries will be put into public domain.

The group currently includes:

	University of Missouri   Gary Johnson, DVM, PhD Dennis O'Brien, DVM, PhD Joan Coates, DVM, MS Shahnawaz Khan, PhD Liz Hansen
	University of Minnesota   James Mickelson, PhD Ned Patterson, DVM
	Animal Health Trust Matthew Binns, PhD Cathryn Mellersh, PhD

CERC Information Exchange