Nova Scotia duck tolling retrievers (NSDTRs, Tollers) are strongly predisposed to many immune-mediated diseases, including a systemic lupus erythematosus (SLE)-related disease complex. We identified five genomic regions associated with the disease using GWAS, and validated them with fine-mapping and gene expression analysis in independent cohorts of patient and control dogs. We also found a strong correlation between particular disease phenotypes and specific genes affected by risk variants. We further study the effect of altered gene functions and proteins on disease pathogenesis using wet-lab experiments.
Humans with autoimmune diseases are at increased risk for developing certain cancers, and also tollers show a higher frequency of tumors, mainly lymphomas, mast cell tumors and malignant melanomas. Therefore, they may represent an excellent model suitable to study the link between cancer and autoimmunity. To examine this relationship between immune and oncogenic pathways, we have now initiated a new project using NSDTRs as model dogs. We will perform a comprehensive integrative analysis of the affected pathways using various omics-approaches.
The project is performed in collaboration with veterinary clinicians at the Swedish University of Agricultural Sciences.
A Nova Scotia duck tolling retriever.
Wilbe, M., Kozyrev, S.V., Farias, F.H.G., Bremer, H.D., Hedlund, A., Pielberg, G.R., Seppala, E.H., Gustafson, U., Lohi, H., Carlborg, O., Andersson, G., Hansson-Hamlin, H., Lindblad-Toh, K., 2015. Multiple Changes of Gene Expression and Function Reveal Genomic and Phenotypic Complexity in SLE-like Disease. PLoS Genet 11, e1005248
Wilbe, M., Jokinen, P., Truve, K., Seppala, E.H., Karlsson, E.K., Biagi, T., Hughes, A., Bannasch, D., Andersson, G., Hansson-Hamlin, H., Lohi, H., Lindblad-Toh, K., 2010. Genome-wide association mapping identifies multiple loci for a canine SLE-related disease complex. Nat Genet 42, 250–254. doi:10.1038/ng.525