POSTER ABSTRACTS
AMS-affected and unaffected Miniature pinschers (MP, n=11), Fox terriers (FT, n=9), and German spitzes (GS, n=4) were whole-genome sequenced in order to search for causal genetic variants using the reference genome assembly UU_Cfam_GSD_1.0. Although all cases presented the same clinical features, they likely represent separate forms of autosomal recessive AMS. Preliminary analyses showed no evidence for large chromosomal aberrations but identified 199,405 homozy- gous small variants in two related FT and 450,156 in an MP case. Using the minor allele frequency of 1% in public datasets (~3000 canids), 35 in FT and 60 in MP candidate protein-changing variants in functionally important genes were selected for further investigation. An update on this effort as well as the ongoing GS analyses will be presented. The spontaneous dog model will help identify further HSAN-associated genes, mechanisms involved in pain sensitivity, and support breeding plans for selection against the fatal disease. #3 A comparative canine model for human bladder cancer with environmental applications Ashley Donnellan¹ , Carly Ruslander,¹ Claire Wiley¹, Catherine F. Wise², Rachael Thomas¹,3 , Carly Ruslander¹, Valerie Ortiz¹, Shelly Vaden4, Mark Dunn5, Heather Stapleton 2,6, Matthew Breen 1,3,6,7 cawiley2@ncsu.edu 1Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA; 2Nicholas School of the Environment, Duke University, Durham, NC, USA; 3Comparative Medicine Institute, North Carolina State University, Raleigh, NC, USA; 4Department of Clinical Sciences, North Carolina State University, Raleigh, NC, USA; 5American Kennel Club, Raleigh, NC, USA; 6Duke Cancer Institute, Durham, NC, USA; 7Center for Human Health and the Environment, North Carolina State University, Raleigh, NC, USA Identifying an association between environmental exposures and human cancers is challenging. Our household dogs share our daily domestic environment and also exhibit a markedly shorter latency period between exposure and development of disease. As such, our dogs offer a highly relevant sentinel species for assessment of the health impacts of shared exposures. There is growing Interest in the relationship between exposure to environmental toxicants and bladder cancer (BC). In this study, we identified a population of dogs to provide a unique opportunity to identify environmental risk factors for BC for both species. Using state of the art molecular screening, we identified a cohort of dogs comprising 25 cases with preclinical BC, paired with 53 age, sex, and breed matched controls. Across the cohort we evaluated exposures to chlorine and disinfection byproducts. We hypothesized that exposure to these chemicals is associated with the development of canine BC through two mechanisms: differential exposure and varied metabolism. Levels of chlorine, total trihalomethanes, and haloacetic acids in household drinking water were obtained from municipal reports and no statistical differences were noted between cases and controls (p=0.7535, 0.1836, 0.2512, respectively). Varied metabolism was investigated via assess- ment of the genotypes of functional variants in three genes with known association with human BC: MTHFR (C677T and A1298C), CYP1A1 (A4889G), and LSP1 (promoter region, dbSNP rs907611). Data thus far does not show an association between the targeted variant genotype and canine BC. An extended case-control cohort is currently being evaluated.
55
Made with FlippingBook - Online magazine maker