What stage are we at with this research?

Scientists at the AHT have conducted a genome-wide association study (genome scan) in the Italian Spinone in an attempt to identify regions of the DNA that might be involved in idiopathic epilepsy, as currently the mode of inheritance or genetic complexity of idiopathic epilepsy in this breed is unknown.  This report summarises the results of our investigations and suggests future directions.
What did the whole genome scan involve?
We compared thousands of DNA markers in Italian Spinoni with epilepsy (cases) with those in Italian Spinoni free of seizures (controls) to look for regions in the genome that are consistently shared among cases, but that are different in the controls.  This is called a Genome Wide Association Study (GWAS)
 
Our cases were 31 Italian Spinoni confirmed as having idiopathic epilepsy by Dr Luisa De Risio, Head of Neurology, through survey or examination at the AHT.  The controls used were 29 Italian Spinoni over the age of seven which had never had a seizure.  One of the cases was removed from the study due to poor quality DNA, leaving 30 cases and 29 controls to be used in the analysis.
 
The GWAS results indicated a region in the genome which might be of interest, but further confirmation was required as the association with idiopathic epilepsy did not reach the required statistical threshold.
 
DNA samples from additional Italian Spinoni with and without epilepsy had been received while the genome scan was being carried out and we were also able to utilise some samples that had been submitted previously to our DNA testing department which met our criteria.  In total an additional nine cases and 18 controls were available for us to use to attempt to confirm the genome scan results.  For these samples we used DNA sequencing to look at markers from the region of interest identified in the genome scan.
 
Unfortunately the additional samples tested did not confirm the genome scan results.  This means that we have not yet identified any regions of the DNA that are associated with epilepsy in the Italian Spinone at a sufficient level of significance for us to investigate further at this stage.  Therefore we are still unable to confirm the mode of inheritance of this condition in this breed.  It could be that there are multiple recessive mutations, dominant mutation(s), or that the disease is genetically complex with several regions of the genome involved, perhaps with the involvement of environmental factors.
 
What happens next?
To progress the study we need DNA from additional dogs with a confirmed diagnosis of idiopathic epilepsy as well as older unaffected dogs.
 
What can we do to further this research?
As before, we continue to encourage submission of samples from Italian Spinoni with idiopathic epilepsy and it helps us considerably if owners can complete our epilepsy questionnaire when submitting.  We also require samples from older Italian Spinoni, aged seven years or over, who have never had a seizure of any kind to act as controls in our study.  We would be grateful for any health updates for dogs for which we currently hold DNA samples.  For further information on how to submit a sample, or to send us updated health information, please email Chris Jenkins at This email address is being protected from spambots. You need JavaScript enabled to view it..
 
Acknowledgements
We would like to thank all Italian Spinone owners and breeders who have submitted samples and information from their dogs.
 
Click here to read the full research article