Canine Epilepsy Research

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

Ned Patterson, DVM
University of Minnesota, 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.

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 January 28, 2011, samples from 9909 dogs representing 108 different breeds have been submitted for epilepsy research. Included in this total are 1578 affected dogs. As samples arrive, families are assembled and data compiled. Some of the breeds with extended family groups sampled, and a minimum of 20 "sib pairs" (an affected dog paired with it's normal sibling) in the collection, have been or soon will be included in mapping experiments. For family groups that have been mapped, if there are potential areas of interest on specific chromosomes, those areas are being further examined. Although a few genes have been discovered in a few breeds for specific rare diseases that include seizures as one of many symptoms of the disease, at present there are no genes identified for "classic" epilepsy in any breed. The tools available for genetic studies are better than they have ever been, and research is ongoing wherever it appears that progress is possible. Samples from potentially useful families of any breed are still needed, and we encourage owners to participate by sending samples from epilepsy-affected dogs and their normal close relatives (see SAMPLE SUBMISSION page for instructions and forms).

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Breed	Total Number	Affected Total	Affected Males	Affected Females
Akbash Dog	14	1	1	0
Alaskan (Racing) Husky	11	3	1	2
Alaskan Malamute	170	9	3	6
American Water Spaniel	266	27	16	11
Anatolian Shepherd Dog	14	1	1	0
Australian Shepherd	1221	158	80	78
Beagle	198	38	19	19
Bernese Mountain Dog	19	4	2	2
Bloodhound	73	5	1	4
Border Collie	144	35	22	13
Border Terrier	184	70	32	38
Borzoi	21	2	1	1
Boxer	13	5	2	3
Brittany	41	10	5	5
Bulldog (English Bulldog)	10	3	2	1
Bullmastiff	21	1	1	0
Canaan Dog	26	9	5	4
Cardigan Welsh Corgi	19	1	0	1
Chesapeake Bay Retriever	87	24	16	8
Chinook + Chinook cross	304	39	19	20
Cocker Spaniel (American)	133	38	20	18
Collie	121	29	16	13
Curly Coated Retriever	75	12	5	7
Dachshund	84	15	6	9
Dalmatian	102	36	15	21
English Shepherd	39	8	3	5
English Springer Spaniel	921	99	49	50
Field Spaniel	115	8	2	6
Finnish Spitz	80	16	7	9
Fox Terrier (Wire)	15	4	3	1
German Pinscher	36	4	2	2
German Shepherd Dog	31	16	10	6
German Shorthaired Pointer	63	16	7	9
Giant Schnauzer	63	3	2	1
Golden Retriever	67	20	12	8
Great Dane	30	4	2	2
Great Pyrenees	23	5	1	4
Greater Swiss Mountain Dog	1247	86	58	28
Ibizan Hound	94	18	9	9
Irish Setter	250	66	50	16
Irish Water Spaniel	310	41	22	19
Italian Greyhound	52	20	8	12
Jack Russell Terrier	28	11	5	6
Komondor	48	1	0	1
Labrador Retriever	308	81	44	37
Mastiff	26	4	3	1
Newfoundland	14	2	1	1
Norwich Terrier	94	7	4	3
Otterhound	261	40	29	11
Petit Basset Griffon Vendeen	78	19	11	8
Pointer	337	28	16	12
Pomeranian	34	11	7	4
Poodle - Miniature	25	11	5	6
Poodle - Standard	232	63	33	30
Pyrenean Shepherd	26	7	2	5
Rottweiler	14	4	3	1
Saint Bernard	343	32	17	15
Samoyed	52	1	1	0
Schipperke	52	18	7	13
Shetland Sheepdog	42	16	8	8
Siberian Husky	98	26	15	11
Silky Terrier	26	10	5	5
Spinone Italiano	30	8	4	4
Standard Schnauzer	183	17	15	2
Tibetan Mastiff	25	4	2	2
Vizsla	282	29	14	15
Weimeraner	22	5	3	2
Welsh Springer Spaniel	243	25	17	8
Welsh Terrier	47	12	8	4
mixes/cross-bred dogs	12	6	1	5
*Other breeds	155	70	42	28
TOTALS (01-28-11)	9909	1577	861	719
*includes less that 10 dogs per breed of the following:   Akita, American Bulldog, Australian Terrier, Basenji, Belgian Laekenois, Belgian Malinois, Belgian Tervuren, Bichon   Frise, Black Russian Terrier, Bluetick Coonhound, Boston Terrier, Briard, Cavalier King Charles Spaniel, Chinese   Crested, Chinese Shar-Pei, Dandie Dinmont Terrier, English Cocker Spaniel, English Setter, English Toy Spaniel,   Flat-Coated Retriever, French Bulldog, Irish Wolfhound, Keeshond, Leonberger, Mi-Ki, Nova Scotia Duck Tolling   Retriever, Old English Sheepdog, Papillon, Pembroke Welsh Corgi, Pit Bull Terrier, Poodle-Toy, Portuguese Water   Dog, Saluki, Scottish Deerhound, Scottish Terrier, Small Munsterlander, Staffordshire Bull Terrier, Tibetan Terrier,   Whippet

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.

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

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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 Liz Hansen
	University of Minnesota James Mickelson, PhD Ned Patterson, DVM
Animal Health Trust Matthew Binns, PhD Cathryn Mellersh, PhD

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