ICCFGG 2022
#60 Investigation of host factors influencing susceptibility and disease severity in spontaneous canine respiratory coronavirus infection Thomas K. Hiron*1,2, Marsha D. Wallace*1,2 , Sara Falcone2, Kate Hughes3, Androniki Psifidi1, Rachael Tarlinton4, Lorna J. Kennedy5, Chris A. O’Callaghan2, Judy Mitchell1, Lucy J. Davison1,2,6 * these authors contributed equally thiron@rvc.ac.uk 1Royal Veterinary College, London, UK; 2University of Oxford, Oxford, UK; 3University of Cambridge, Cambridge, UK; 4University of Nottingham, Nottingham, UK; 5The University of Manchester, Manchester, UK; 6MASCOT Consortium Canine respiratory coronavirus (CRCoV) is a highly infectious beta-coronavirus associated with canine infectious respiratory disease (CIRD) complex. Mild self-limiting ‘kennel cough’ is common, but in some cases severe bronchopneumonia necessitates euthanasia. This study aimed to identify transcriptomic signatures and genetic factors associated with CRCoV infection and disease severity. Using RNA-seq, our MASCOT (Mapping Animal Susceptibility to Coronaviruses: Outcomes and Transcriptomics) consortium analysed gene expression in lung tissue samples from 24 dogs archived during an outbreak of CRCoV in a UK rehoming shelter. Based on RT-PCR for CRCoV (C+ or C-) and evidence of pathology on lung histology (P+ or P-), samples were selected from 4 groups: C+P+, C+P-, C-P+, C-P-. Whole genome sequencing (WGS) of the same 24 samples was undertak- en to identify candidate variants associated with host susceptibility and disease severity. Unsupervised hierarchical clustering of normalised gene expression profiles identified 3 clusters with distinct gene expression patterns. Cluster 1 (highly expressed in C+P+ lungs) was enriched for genes involved in leukocyte migration, humoral immune response, and macrophage activation. Cluster 2 (highly expressed in C+P- lungs) was enriched for genes involved in protein translation, viral gene expression and oxidative phosphorylation. Cluster 3 (highly expressed in C-P- lungs) included genes involved in epithelial cell adhesion. Current work is focused on prioritisation of candidate disease-associated genetic variants identified by WGS for follow-up genotyping in a further 96 dogs. The molecular signatures of symptomatic and asymptomatic CRCoV infection identified in this study will offer novel insights into host responses to coronaviruses. #61 Genome-wide Association Study of Weight in Dogs from the Dog Aging Project Vista Sohrab1,2, Kathleen Morrill1,2, Elinor Karlsson1,2,3 vsohrab@broadinstitute.org 1University of Massachusetts Chan Medical School, Worcester, MA, USA ; 2Broad Institute of MIT and Harvard, Cambridge, MA, USA 3The Dog Aging Project Consortium In dogs, body size varies dramatically by breed and is negatively correlated with lifespan. Here, we perform the largest genomic study of canine body size (n=4158) by combining two genomic resources from ancestrally diverse companion dogs: the Dog Aging Project, a longitudinal study that aims to understand healthy aging, and the Darwin‚Äôs Ark project, a cross-sectional study focusing on dog behavior. We assembled the first genetic cohort of 3163 dogs enrolled in the Dog Aging Project (DAP). DNA collected from cheek swabs were subject to low-pass whole-genome
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