ICCFGG 2022
#32 Phenotypic assessment and genetic dissection of cataract in American Cocker Spaniel
Leonardo Murgiano , Jessica K Niggel, Anil Sigdel, and Gustavo D Aguirre leomur@vet.upenn.edu Section of Ophthalmology, Department of Clinical Sciences & Advanced Medicine University of Pennsylvania, Philadelphia, PA, USA
Cataract is a common eye disorder in canine patient that leads to vision impairment and ulti- mately blindness in dogs. An excellent model for human cataract, canine cataract shows a similar clinical presentation and progression. In American Cocker Spaniel (ACS) the disease prevalence exceeds 10%. We performed phenotypic assessment and investigated genetic variants associated with inherited cataract using data collected over a 7-year period. We propose a reclassification of juvenile/inherited cataracts in the ACS population based on age of onset, phenotype, and progres- sion. We observed a highly diverse cataract presentation in the ACS population including anterior, posterior, antero-posterior, cortical and full cataract that is remarkably different as reported in other breeds; and based on laterality including bilateral and unilateral cataract. Our study also reported early onset (2-5 years of age) and late onset (5-8 years of age). Pedigree analysis was used to explore the possible patterns of inheritance, suggesting that the assumed autosomal recessive pattern is incorrect, and that the trait hasn‚Äôt a straightforward mendelian inheritance. Since cataract phenotype was recorded as a binary trait (i.e., case/control), we implemented a probit linear mixed model. To account for ancestral population structure in the study dogs, single marker linear mixed model (LMM) analysis was performed using GenABEL. Age of onset and sex influences risk of cataract, and were included as a covariates. PCA reveals two major subpopulations for the ACS population to which cases and control population belongs. The frequency and segregation of candidate haplotype reveals a complex and incomplete inheritance of cataract in the ACS population. #33 Development of a high-density DNA array for the domestic cat Leslie A. Lyons1 , Reuben M. Buckley2, Theodore S. Kalbfleisch3, J. Claiborne Stephens4, Curt Van Tassell5, Mahesh Neupane5, Jeffrey A. Brockman6 lyonsla@missouri.edu 1University of Missouri; Columbia, MO, USA; 2NIH - NHGRI, Bethesda, MA, USA; 3Invictus Informatics, LLC, Louisville, KY, USA; 4Genomics GPS, LLC, Guilford, CT,USA; 5USDA-ARS, Beltsville, MD, USA; 6Hill’s Pet Nutrition, Inc., Topeka, KS, USA The Online Mendelian Inheritance in Animals (OMIA) documents cats as potential models for 260 human traits, including 99 Mendelian traits with 165 likely causal variants. Historically, many causal disease or trait variants were identified in breeds due to ascertainment biases and inbred animals being more feasible for genetic studies. However, the 99 Lives project has demonstrated rare Mendelian traits can be identified using whole genome and exome sequencing efforts, including random bred cat singleton cases. Like WGS/WES studies in other species, only ~40% of cases are considered resolved with a genetic diagnosis. Thus, other genetic resources are still needed to help prioritize and target WGS variants considered variants of unknown significance. An additional
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