PRESENTATION ABSTRACTS
similar performance as described in humans with high correlations defined between the true expression levels and the predicted ones (Pearson correlations median =0.66). We then investigated the impact of sequence variations in the promoter sequences of 1300 dog-human orthologous cancer genes. We identifed >15500 genetic variations occuring in the promoter regions using the whole genome sequences of 1929 canids generated by the dog10K con- sortium. Using the dog-specific model, we assigned 6% of the variants a low to moderate impact and 1% a high impact on the expression levels of the cancer genes. We thus predict an evaluation and classification of variants of regulatory regions of genes that contribute to cancers in dogs. Here, we developed a deep-learning based tool (BLIMP) to predict the impact of non-coding mutations on gene expression dedicated to the dog genome. Our tool and models are freely available through GitHub: https://github.com/ckergal/BLIMP
#6 A monogenic cause of calcium oxalate urolithiasis is shared by multiple dog breeds
Eva Furrow, Katie Minor, Jonah Cullen, Steven Friedenberg and Jody Lulich furro004@umn.edu
Department of Veterinary Clinical Sciences, University of Minnesota College of Veterinary Medicine, USA Calcium oxalate (CaOx) urinary stones are a common and painful problem in dogs. While CaOx stones primarily affect middle-aged to geriatric dogs, certain breeds are predisposed to an ear- ly-onset form of the disease, including the English Bulldog. Our aim was to identify a major genetic risk factor for early-onset CaOx stones. We performed whole genome sequencing of three English Bulldogs with early-onset CaOx stones (diagnosed at ≤2 years old) and filtered variants against an internal database of 241 dogs of 42 breeds. A single variant passed filtering: a missense variant in uromodulin. Uromodulin is the most abundant protein secreted in urine. It inhibits CaOx crystalli- zation and regulates renal calcium excretion. Genotyping of 37 English Bulldogs with CaOx stones and 96 with unknown CaOx status revealed a strong association between a homozygous genotype and stones (OR = 156, p = 4x10-15). All except one homozygote (a one-year-old female) had CaOx stones, with a median age of 2.5 years at diagnosis. Genotype analysis of over 1,300 dogs revealed that the variant is present at low frequency in at least seven other breeds. In addition to risk for early-onset CaOx stones, homozygotes have increased urinary calcium and decreased uromodulin excretion. The location of the variant within the protein suggests an impact on post-translational modifications. Further analyses are underway to determine the variant effects. In conclusion, a uromodulin variant underlies risk for early-onset CaOx stones across multiple dog breeds. We are referring to this condition as Hereditary Calcium Oxalate Urolithiasis Type 1 (Hereditary CaOx1).
31
Made with FlippingBook - Online magazine maker