POSTER ABSTRACTS
vitreal degeneration, macroglobus, anterior to posterior flattened lenses, and reduced photorecep- tor function. The WGS of the affected dog was aligned to CanFam3.1 and variants filtered based on predicted functional consequence and correlation with disease phenotype in 867 WGS of various canine breeds not known to be affected with MOD. Variants private to the case and flagged as del- eterious were further investigated. Seventeen candidate variants were genotyped in an additional cohort of OES MOD cases and controls (dogs that had been certified clear of inherited eye disease). Only one variant segregated correctly in this cohort, a SNP located in the COL11A1 gene, causing a missense phenylalanine to serine amino acid change. Mutations in this gene have been reported to cause Stickler Syndrome and Marshall Syndrome in humans, both of which share clinical features with MOD in the OES. Genotyping additional OES with healthy eyes or a diagnosis of either MOD or HC revealed a dominant mode of inheritance, and has enabled us to improve our understanding of the genetics of MOD and HC in this breed. #28 Modifiers complicate the current DNA testing for canine RPGRIP1- cone-rod dystrophy: My dog never became blind! Keiko Miyadera, DVM PhD kmiya@upenn.edu School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA Canine RPGRIP1-cone-rod dystrophy (cord1/crd4-PRA) was first identified as a simple Mendelian, autosomal recessive disease characterized by early-onset blindness in a research colony of Miniature Longhaired Dachshunds. DNA testing of the RPGRIP1 variant has been commercially available for over 15 years. With the prevailing use of panel testing, the RPGRIP1 variant turned out to be rather common across multiple canine breeds. Still, many RPGRIP1 homozygous affected dogs hardly show vision issues per the owners, raising questions about the usefulness of the DNA testing. In our earlier survey of the broader Dachshund population, the extensive phenotypic variability among RPGRIP1 homozygous affected dogs led to GWAS mapping and identification of a genetic modifier in MAP9 linked to earlier onset. Further, we have GWAS mapped an additional modifier, associated with cone photoreceptor function. Clinically, to establish the natural disease history of cord1/crd4-PRA in the context of different modifier contributions, we have studied RPGRIP1 homozygous affected dogs in Dachshunds-mixes as well as in English Springer Spaniels. Retinal phenotype was analyzed both functionally (electroretinography, vision-guided navigation) and structurally (ophthalmoscopy, spectral-domain optical coherence tomography). At present, we recognize cord1/crd4-PRA as an oligogenic disease for which the RPGRIP1 variant is required for the disease while the modifiers exacerbate the phenotype, individually or cumulatively. While DNA testing of RPGRIP1 remains the recommended approach to best evaluate the risk for cord1/ crd4-PRA, the results must be interpreted in light of the effect of modifiers.
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