925: Identification of Mutations Causing Hereditary Cerebellar Cortical Degeneration in American Staffordshire Terriers and Old English Sheepdogs
Grant Status: Closed
Grant Amount: $64,800
Natasha J Olby, VetMB PhD; North Carolina State University
April 1, 2008 - March 31, 2012
Sponsor(s): Akita Club of America, Inc., Flat-Coated Retriever Foundation, Golden Retriever Foundation, Great Pyrenees Club of America, Rottweiler Health Foundation, Samoyed Club of America Education & Research Foundation, St. Bernard Club of America
Breed(s): American Staffordshire Terrier, Old English Sheepdog
Research Program Area: Neurology
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Project Summary
In previous reports we described how our work using linkage analysis and association studies had confirmed that cerebellar degeneration in Old English Sheepdogs was linked to one particular region of one chromosome. However, we had been unable to find the mutation in that region because of the large size of the region and the high number of genes located there. Since our last report we have sequenced the entire region in six dogs and have filtered our sequence data to include only mutations that affect coding regions (regions that directly code for the protein the gene produces), that produce a change in amino acid and protein function, and that segregate with the affected phenotype. This allowed us to identify only 6 mutations that fulfilled the above criteria. We sequenced these mutations on a wider population of dogs and found that only 1 of the mutations segregated with phenotype. We have now sequenced over 600 normal dogs and over 140 dogs of other breeds and can confirm that this mutation is highly associated with the disease. We are currently performing additional work to confirm our findings and hope to have a final publication ready by the end of the summer. We anticipate that we can develop a genetic test for this mutation that will allow breeders to select dogs to breed from, and veterinarians to diagnose the disease. We are grateful for the patience and support of the Old English Sheepdog Society of America and are hopeful that our final experiments will confirm our findings.Publication(s)
Abitbol, M., Thibaud, J.-L., Olby, N. J., Hitte, C., Puech, J.-P., Maurer, M., … Tiret, L. (2010). A canine Arylsulfatase G (ARSG) mutation leading to a sulfatase deficiency is associated with neuronal ceroid lipofuscinosis. Proceedings of the National Academy of Sciences, 107(33), 14775–14780. https://doi.org/10.1073/pnas.0914206107
Agler, C., Nielsen, D. M., Urkasemsin, G., Singleton, A., Tonomura, N., Sigurdsson, S., … Olby, N. J. (2014). Canine Hereditary Ataxia in Old English Sheepdogs and Gordon Setters Is Associated with a Defect in the Autophagy Gene Encoding RAB24. PLoS Genetics, 10(2), e1003991. https://doi.org/10.1371/journal.pgen.1003991
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