February 23, 2010

Update on CA research in Kelpies at University of New South Wales. (Feb 2010)

Previously we have reported that we have identified the region of DNA containing the Cerebellar Abiotrophy gene that results in ataxia in affected kelpies. This was made possible partly through funding from Terry Snow and from Working Kelpie Council to use newly available technology. We have localised the ataxia mutation to a region of 5 million bases (0.2% of the dog genome) which still makes the search for the mutation like looking for a needle in a haystack. There are 44 genes in this region, and at first glance, none stand out as likely to be involved in ataxia. 

Recent work has been to pull this haystack apart and examine the contents closely in search of differences between ataxia affected dogs and unaffected dogs. Utilising recent technological advances this entire region has been isolated from two affected dogs and one unaffected control dog. Using next generation sequencing technology at the Ramaciotti Centre at UNSW we have obtained the genetic sequence for almost the entire 5 million base region for each of the two ataxia affected dogs and the unaffected control dog. Comparing the affected dogs to the control dog identifies 2107 differences, any of which could be the actual cause of Ataxia. By employing a process of elimination, 691 of these differences are within gene regions, 27 are within regions that code for protein (cellular machinery) production and 9 of these change the protein. Six other differences have also been identified which may be the cause of ataxia. Each of these 15 differences are currently being investigated by checking all our 200 other kelpie DNA samples to see if the difference is inherited exclusively with the disease. While we have chosen to focus our attention on these 15 differences it is possible that the real cause is not one of these 15 and we may have to check all of the differences to find the cause. The genetic cause of the disease looks to be very difficult to identify but we will persevere until a DNA test is developed.

Jeremy Shearman

Alan Wilton