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Research Update for CHF Grant:
Genetics of Idiopathic Epilepsy in Labrador Retrievers
Dr. Hannes T Lohi, PhD, The FolkhÄlsan Institute of Genetics
October 2020
Epilepsy is the most common neurological disease in dogs and affects most breeds. Prevalence estimates vary from 1% up to 20% depending on the breed, suggesting a genetic contribution. Despite several gene discoveries that have been made in both symptomatic and idiopathic epilepsies, the genetic background in most dog breeds remains unknown, hampering progress in diagnostics, treatment and prevention. Challenges remain in incomplete clinical diagnostics to distinguish specific syndromes and to identify true cases and controls for genetic analyses. This study will develop a multilingual user-friendly mobile application for a validated epilepsy questionnaire to harmonize global data collection of epilepsies in different breeds. The app will enable automatic categorization of the epileptic dogs based on the reported symptoms, easy data sharing and regular follow-up of the affected dogs. It will also provide an opportunity for online consultation with registered neurologists for additional seizure information and treatment options, and aid recruitment of cases and controls for genetic studies. To specifically address the genetics of epilepsy in Labrador Retrievers (LR), the investigators will analyze the genomes of >300 dogs with a very high-density genotyping array (712K SNPs) to map the epilepsy loci, and will combine this information with whole genome sequencing data. The team has set up a global research collaboration to maximize the number of epileptic and non-epileptic LR samples to further confirm promising findings from the association studies. If successful, the study will provide new tools for epilepsy diagnostics and management in LRs and potentially other breeds.
March 2017
Research reports are in for the grants we co-sponsor and exciting progress has been made in Canine Epilepsy research. What the researchers learn in one breed can help other breeds. Below is a report from Dr. Hannes Lohi who has had a major breakthrough.
We have made a major breakthrough in our epilepsy study in the Rhodesian Ridgeback breed. We have utilized an advanced wireless video-EEG approach in clinical studies to identify a juvenile myoclonic epilepsy (JME) with characteristic phenotype, age of onset and photosensitivity. We have now also confirmed the discovery of a novel recessive JME gene and mutation in the RR breed. The entire study about clinical and genetic characterization has been submitted for peer review publication in high impact journal (PNAS, in revision). The confirmation of the genetic defect enables us to develop a genetic test for breeding purposes, and ongoing clinical and functional studies aim to improve our understanding how myoclonic seizures develop and how they could be better treated in future in the affected dogs.
Research Update for Toby's Foundation co-sponsored CHF Grant:
Identification of a Novel Juvenile Myoclonic Epilepsy Gene and Its Underlying Disease Mechanism
Dr. Hannes T Lohi, PhD, The FolkhÄlsan Institute of Genetics
Grant Status: Closed
December 2017
Epilepsy is the most common neurological disease in dogs and affects almost all breeds. Genetics is likely to play a major role in seizure risk, and gene discovery remains as an important goal to better understand the disease and its treatments. The investigators have recently utilized an advanced wireless video-EEG approach in clinical studies to identify juvenile myoclonic epilepsy (JME) in Rhodesian Ridgebacks with characteristic epilepsy phenotype, age of onset and photosensitivity.
This project has been very successful. It resulted in the first breakthrough with an original article publication in a highly ranked Journal, (Proc Natl Acad Sci U.S.A. 2017 Mar 7;114(10):2669-2674. doi: 10.1073/pnas.1614478114), describing the clinical features and the genetic cause. The study has enabled the development of a genetic test, which is now available worldwide from different genetic testing laboratories. Ongoing additional clinical and functional studies aim to improve our understanding how myoclonic seizures develop and how they could be better treated in future in the affected dogs. A second article has been accepted for publication in a journal with a wide veterinary audience (JVIM). This article will have a high impact on future studies of epilepsy in dogs as it describes clinical features and EEG diagnosis of absence seizures in this genetic epilepsy. This article also highlights the use of awake EEG for seizure diagnosis and documentation of treatment response in dogs.
December 2016
Epilepsy is the most common neurological disease in dogs and affects almost all breeds. Genetics is likely to play a major role in seizure risk, and gene discovery remains as an important goal to better understand the disease and its treatment. However, genetic breakthroughs have been rare partially due to incomplete clinical diagnostics to identify true cases and controls, or to distinguish specific syndromes for genetic analyses. We have recently utilized an advanced wireless video-EEG approach in clinical studies to identify juvenile myoclonic epilepsy (JME) in Rhodesian Ridgebacks with characteristic epilepsy phenotype, age of onset and photosensitivity. The pedigree established using the JME cases suggests a strong genetic contribution and is supported by our preliminary genetic data that proposes a novel disease locus and a deleterious mutation in a neuronal candidate gene. These promising early findings necessitate further electroclinical and genetic studies for confirmation. In this study, the investigators' objectives are to: i) further characterize EEG, imaging and disease features of JME, ii) confirm the presence and segregation of an epilepsy gene, iii) investigate the breed-specificity, prevalence and penetrance of the mutation, iv) conclude the inheritance model, and v) define the pathogenicity of the mutation. The confirmation of the genetic defect would allow us not only to develop a genetic test for breeding purposes but also to understand how myoclonic seizures develop. This could ultimately lead to improved treatments for canine epilepsy.
July 2011
Toby's Foundation (TF) is proudly sponsoring a grant entitled Identification of Epilepsy-Causing Mutations in Australian Shepherds for Dr. Hannes Lohi and his research group at the University of Helsinki, Finland for one year for $10,000, Toby's Foundation, TF Grant Number 5-2011.
In collaboration with Dr. Ned Patterson and his team from the University of Minnesota who recently mapped the first epilepsy (IE) locus in the Australian Shepherd (AS), Dr. Hannes Lohi will utilize the latest next - generation sequencing approaches to identify the gene(s) causing or contributing to epilepsy in the AS. The latest next-generation sequencing recently became available and is already being used in Finland. Dr Lohi will sequence genes in the area of the Chromosome that Dr. Ned Patterson and his team recently got the significant hit on. Dr. Lohi says that "identification of the epilepsy-causing mutations would enable us to develop genetic tests for AS for breeding purposes. It would also improve our understanding of the pathogenesis of the disease, and provide a novel candidate gene for other IE breeds and as well human IEs."
We are very excited about our grant which will help Aussie epilepsy research continue to move forward using the latest technology while Dr. Patterson applies for his next CHF grant. We stand ready with your help to co-sponsor that grant.
Our 7th Anniversary is fast approaching and our anniversary theme is "Let's Keep the Ball Rolling" for Aussie epilepsy research and that is precisely what we are doing by sponsoring a TF grant for Dr. Lohi. Please see our current ad.
Progress is being made and outstanding research is being done. We appreciate the commitment and dedication of Drs. Patterson and Lohi and their research groups to canine epilepsy research and to the Australian Shepherd. Please continue to help us support the research to find the causative genes and develop a screening test by making a donation today. Your help is needed. Your donation is tax deductible to the fullest extent allowed by law.
If you haven't already, please donate a blood sample today to Dr. Ned Patterson's Aussie epilepsy research at the University of Minnesota on your affected dog and your dog 10 + years old that have never had a seizure.
June 2008
As we celebrate the 4th anniversary of Toby's Foundation, the timing and tools to find a gene marker for canine epilepsy have never been better! We are in a very good position with two outstanding researchers, Dr. Ned Patterson at the University of Minnesota and Dr. Hannes Lohi at the University of Helsinki, doing research on canine epilepsy in the Australian Shepherd to find the gene(s) responsible and develop a screening test.
Dr. Patterson and Dr. Lohi recently had the opportunity to meet for the first time in France in May. Dr. Patterson is coordinating with both Dr. Johnson and Dr. Lohi. In a progress report from Dr. Patterson, he said SNP Chip analysis has been completed on 30 affected and 30 unaffected Australian Shepherds by Dr. Hannes Lohi in Finland in collaboration with Dr. Gary Johnson at UMO-Columbia. Dr. Patterson at UMN is collaborating on statistical analysis of this data with them and is prepared to perform SNP chip genotypes and analysis on 20-30 additional affected and 20-30 additional unaffected Aussies in the next 6-9 months if significant association is not found and additional power is need for this breed. SNP markers are run by the Mayo Clinic in Rochester, MN who collaborate with Dr. Patterson.