Canine Genetics Progress Report
Breed: Norwich Terrier
Condition: Epileptoid Cramping Syndrome
Recent / Current Funding:
The project is currently being funded, in part, by the LUPA project ( www.eurolupa.org ), of which the AHT is a participant, and by donations from individuals. The Lupa project aims to investigate several conditions (including epilepsy) that affect both humans and dogs. As part of the LUPA project the AHT has been able to access funds, and also samples owned by collaborative partners at the University of Helsinki, Finland, to begin research to identify the mutation(s) responsible for epilepsy/cramping in the Norwich Terrier.
We have now collected samples from 260 Norwich Terriers, of which 53 are reported by their owners or their vets to suffer from ‘epilepsy' or ‘cramps'. We continue to collect samples from affected dogs and their close relatives. The affected dogs we have collected so far are all relatively closely related to one another, and all descend from a single founding dog within 5 or 6 generations, which is indicative of an inherited condition.
We are still keen to collect samples from new cases and close relatives of cases, especially siblings.
To request a free DNA swab kit please email Bryan McLaughlin
( firstname.lastname@example.org ).
We are also still keen to collect video clips and more information about affected dogs. If you have any video clips or would like to provide us with an update about your dog please contact Oliver Forman
( email@example.com )
We reported previously that we had undertaken a Whole Genome Scan (WGS) with samples from 38 affected (referred to as cases) and 38 unaffected Norwich Terriers (referred to as controls) . A WGS involves comparing 49,663 DNA markers from the DNA of affected and unaffected dogs to find regions of the genome that are shared between affected dogs and different in unaffected dogs. When we analyzed the data from the WGS we were very excited to identify at least three regions of the canine genome that seemed to be associated with epilepsy/cramping. Because of concern over the possibility of false positive results that we stated in our last report, after discussion with our Finnish collaborators we have decided to focus on the two regions of the DNA with the strongest association with the condition. These two regions have been moved forward to the next stage of the DNA analysis.
This next stage, which will be performed in Finland, involves determining the exact DNA sequence, letter by letter, of the two associated regions in 5 affected and 5 unaffected dogs. The entire canine genome consists of 2,500,000,000 (two and a half thousand million) letters of DNA. Each of our associated regions is about a million letters of DNA long (a tiny fraction of all the whole genome but still a lot of DNA!). Experiments are underway in Finland to literally cut the first of the million letter stretches of DNA away form the rest of the genome, so it can be sequenced. This procedure is complicated and lengthy and is expected to take until the end of October to complete. Once the region has been ‘captured' it will be sequenced, a procedure that will generate over a gigabase of sequence information (i.e. 1,000,000,000 or a thousand million letters of DNA sequence, divided between 10 dogs being analyzed). Our job will then be to closely analyse this DNA sequence information and find any important differences between the DNA of the cases and the controls (i.e. positions in the DNA where the cases have an altered sequence, but the controls appear normal). The analysis for this experiment is likely to take several more months to complete. Any DNA differences that are detected between the 5 affected and 5 unaffected dogs will be followed up in the remaining affected and unaffected dogs we have DNA samples from, to conclusively decide which are truly associated with the disease and can be used as the basis of a DNA test.