POSTER ABSTRACTS
In an all-comers cohort of cancer-diagnosed subjects, the overall test sensitivity was 55%. In a subgroup of cancer-diagnosed subjects with three of the most aggressive canine cancers (lymphoma, hemangiosarcoma, osteosarcoma), the detection rate was 85%; and, in eight of the most common canine cancers, the detection rate was 62%. The specificity of the test was 98.5%, corresponding to a 1.5% false positive rate. At least 2 presumably-cancer free dogs in the study received a Cancer Signal Detected result and were diagnosed with cancer after undergoing confir- matory cancer evaluations. A novel, multi-cancer early detection (MCED) liquid biopsy test has demonstrated the ability to identify cancer-associated genomic markers (in some cases months prior to the onset of clinical signs) in canine patients. #31 A large animal model of RDH5-associated retinopathy recapitulates important features of the human phenotype Laura M. Ford1 , Laurence M.Occelli2, Paige A. Winkler2, Kelian Sun2, Nathanial Pasmanter2, Janice Querubin2, Leslie A. Lyons3, 99 Lives Consortium, Simon M. Petersen-Jones1,2 fordla10@msu.edu 1Genetics and Genome Sciences Graduate Program, Michigan State University, East Lansing, MI, USA, 2Department of Small Animal Clinical Sciences, Michigan State University, East Lansing, MI, USA, 3Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO, USA We identified a cat with a phenotype comparable to macular degeneration (MD) in humans. The area centralis (AC; region similar to the human macula) progressively degenerated and the visual streak showed abnormal hyporeflectivity. The proband was bred to phenotypically normal females to establish a colony. Segregation of the phenotype was supportive of an autosomal recessive mode of inheritance. Under the 99lives cat genome sequencing initiative, two clinically affected and one obligate carrier cats were submitted for whole genome sequencing. Three candidate variants exclusive to the two homozygous affected and heterozygous cats were identified using a variant calling analysis. On genotyping further affected cats in the colony a missense variant in the Retinol Dehydrogenase 5 (RDH5) gene (c.542G>T;p.Gly181Val) was the only one to segregate with the disease phenotype. RDH5 catalyzes the final oxidation in the visual cycle, producing 11-cis-retinal which is needed for regeneration of the photoreceptor photopigments for continued vision. Western blotting and immunohistochemistry of retinal samples from cats homozygous for the p.Gly181Val mutation had no detectable RDH5. Humans with RDH5 mutations develop fundus albipunctatus (FA) characterized by night blindness and white-yellow flecks on the fundus with a subset experiencing MD. Similarly to RDH5-mutant humans, RDH5-/- cats show variable, age of onset, and severity of AC degeneration. As the cats are identically housed, environmental influences on phenotype variation are less likely, implicating a possible modifier locus. This large animal model and potential modifier locus will provide further understanding of macular degeneration and allow the develop- ment and testing of treatments for human RDH5-associated retinopathies.
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