Epilepsy Genetic Study Update
By Mary L. Mandich
January 12, 2006

 

Six years have passed since we started our quest to find the genetic cause of idiopathic epilepsy in Welsh Springer Spaniels. Slowly, but surely, progress is being made. DNA samples have been collected from over 400 Welsh Springers including 23 affected dogs (16M/7F) in the set. We have been contributing to our WSSCA donor advised fund at the AKC Canine Health Foundation (AKC-CHF) so that research on our behalf can continue. Specific genetic markers have not yet been found but work is continuing at the College of Veterinary Medicine, University of Minnesota under the guidance of Dr. James Mickelson and Dr. Ned Patterson. There also appears to be new hope for better control of seizures in Welsh Springers using potassium bromide therapy in addition to more traditional antiepileptic medications such as Phenobarbital or diazepam. (Ref 1).

In November 2005, I received a progress report on the work at University of Minnesota. Since this work has not yet been published, the AKC-CHF will not allow me to reproduce or hand out copies of this report. However, I do want to keep WSSCA members informed as to where this research stands without violating the confidentiality of the information provided. I hope the following update accomplishes this.

Genome mapping has begun in Vizslas to find regions of the canine genome containing the genes responsible for epilepsy in this breed. Based on pedigree analysis of more than 50 affected dogs, the University of Minnesota group had previously reported that two independent recessive genes participate in causing idiopathic epilepsy in this breed (Ref 2). Isolation of these genes is well underway. 

English Springer Spaniels are the second focus breed under study at the University of Minnesota with a large data base of over 800 DNA samples including 79 affected dogs (45M/34F). This is very good news for Welsh Springer Spaniels given their intertwined genetic relationship before the mid-1900’s. Patterson et al had previously published a clinical description of idiopathic epilepsy in English Springers, reporting that 47% of affected dogs have generalized seizures and 53% have partial seizures (Ref 2). The typical age for onset of seizures was 3 years. They analyzed pedigree information and reported that the mode of inheritance appeared to involve either a single major recessive gene locus with modifying genes or a polygenic mode of inheritance. They also ruled out several modes of inheritance including X-chromosome linked inheritance, a single recessive autosomal gene, and a dominant autosomal gene with modifying genes. The suspected modes of inheritance for English Springer Spaniels make it much more difficult to use the genome mapping approach being used for Vizslas. Nonetheless, the University of Minnesota group is starting this work. 

Patterson and Mickelson report that the DNA data base collection for Welsh Springer Spaniels may be nearly sufficient to initiate genome mapping for our breed. They will also immediately test any genetic linkages found for English Springer Spaniels in the Welsh Springer Spaniel families. 

Their statement that there is “nearly sufficient” DNA information on Welsh Springers sends us a strong message that our work to collect DNA from affected animals and their close relatives must continue. I know that there have been reports of seizuring Welsh Springers in the past two years. I urge owners of these dogs and of their parents and siblings to step forward and submit blood samples for study. Information on how to do this, including forms, is contained on our WSSCA website under “Health Issues, Epilepsy Registry Form.” The data you provide is priceless. The dog you save may be your next puppy.

 

Some resources and references regarding causes, treatment and research of canine idiopathic epilepsy:

1) The Canine Epilepsy Network sponsored by The College of Veterinary Medicine at the University of Missouri-Columbia:  www.canine-epilepsy.net

2) E. E. Patterson, J. R. Mickelson at al, Journal of Veterinary Internal Medicine, May-June 2003 issue, pages 319-325.

 

Brief Glossary of Terms

Idiopathic epilepsy: Primary epilepsy where the cause of seizures cannot be determined.  Researchers believe that idiopathic epilepsy is almost always inherited.

Recessive versus dominant mode of inheritance: In recessive modes of inheritance, two copies of the gene(s), one from each parent, are required to produce a particular trait or disease. In dominant modes of inheritance, only one copy, from either parent, is required.

Polygenic mode of inheritance: Two or more genes control a particular trait or disease.

Autosomal versus X or Y chromosomes: Dog genomic DNA consists of 38 pairs of non-sex-linked autosomal chromosomes plus the 39th chromosome pair which contains the sex-linked X/Y chromosomes. 

Modifying genes: Genes that modify the expression of the principle gene(s) responsible for a particular trait or inheritance.