REPORT FROM THE ANIMAL HEALTH TRUST
NORWICH TERRIER RESEARCH PROGRAMME
August 2011 with update from 6 th . February 2012
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. The data revealed at least three regions that are potentially associated with epilepsy/cramping. This is very suggestive that epilepsy/cramping is a complex disease , potentially involving many genes.
The two most highly associated regions were selected for a very high throughput sequencing experiment that was coordinated by our Finnish collaborators and outsourced to an external service provider. This experiment would involve sequencing the DNA, ‘letter' by ‘letter,' from the two most provocative regions of the genome. The two regions were sequenced in 4 cases and 3 controls, with the aim of revealing DNA mutations that could potentially be risk factors for epilepsy/cramping. Although the experiment worked and produced a huge amount of data, the quality of the dataset is unfortunately lower than expected. As a result the analysis is still ongoing and may not reveal mutations with the same degree of certainty as we would like.
Because the analyses have revealed that this condition appears to be genetically complex, the AHT would like to carry out a second Whole Genome Scan (WGS) using new cases and controls to confirm the already identified potential regions of association. This approach is routinely used in the human research field for complex conditions such as heart disease for example. To enable us to perform this second research phase, we aim to collect at least 36 new cases and 36 new controls. When investigating complex diseases, which require larger case/control sets, careful selection of appropriate cases and controls is vital for maximizing the chances of having a successful study.
For this reason the AHT would like to collect DNA samples from new cases, with video recordings of epilepsy/cramping wherever possible. They would also like to collect DNA samples from close relatives of cases, especially siblings.
T o request a free DNA swab kit please email Bryan McLaughlin ( firstname.lastname@example.org ).
AHT Update - 06.02.2012
The latest update from the AHT gives a revision of sample numbers. Since the Whole Genome Scan was originally undertaken at the end of 2008, the AHT have received new DNA samples from 44 Norwich Terriers ( 17 of those are affected by some type of seizure/cramps, although many are suspected undiagnosed cases or owner reported information and very few are provided with a record of clinical workup for the disease.
The sample collection is considered to be going quite well, and it is felt by the AHT that they may be getting close to approach another WGS (whole genome scan) using 36 new samples of affected Norwich & 36 new samples of controls i.e. unaffected Norwich, but that should be considered by those researchers involved, with advice from the AHT's clinical experts. THIS MEANS WE NEED AT LEAST 20 NEW NORWICH SAMPLES FROM AFFECTED DOGS (Preferably with clinical information about their condition) AND ABOUT 10 FROM UNAFFECTED NORWICH. This will complete the number required for another WGS by the AHT.
The recent sample collection has come from the USA, UK, Germany, Austria & Switzerland and the Norwich Terrier Club thanks those Norwich owners overseas for their support, but new samples from both affected and unaffected Norwich continue to be sought to bring up the sample numbers to reach the new totals quoted in the previous paragraph .
The Norwich Terrier Club would be delighted if those sample numbers could be added to in order to bring the totals to those required for a second WGS.
Thank you for your continued support of the genetics research program at the Animal Health Trust and to the Norwich Terrier Club commitment to that research.
Eileen Needham, Secretary, Norwich Terrier Club Health Sub-Committee & Kennel Club Norwich Terrier Breed Health Co-ordinator.