PRESENTATION ABSTRACTS
Chronic superficial keratitis (CSK) is a progressive inflammatory condition of the cornea that can cause discomfort and blindness. CSK is considered to have a genetic basis due to elevated breed dispositions in certain breeds. The occurrence of CSK can be exacerbated by exposure to ultraviolet light. The current study considered a genome-wide association analysis including 109 greyhounds: 70 with CSK and the remainder with normal phenotype at an age over four years. Three co-located variants on CFA18 near the 5’ region of the Epidermal Growth Factor Receptor (EGFR) gene were associated with genome-wide significance after multiple-test correction [BICF2P579527, CFA18: 6,068,508, praw=1.765e-07, pgenome= 0.017; BICF2P1310662, CFA18: 6,077,388, praw=4.09e-07, pgenome= 0.040; BICF2P160719, CFA18: 6,087,347, praw= 4.09e-07, pgenome= 0.040) (canFam4)]. The associated haplotype on CFA18 is protective for the CSK condition. EGFR coding variants in the associated haplotype were identified that possibly reduce the efficacy of the protein. EGFR is known to play a role in corneal healing, where it initiates differentiation and proliferation of epithelial cells that in turn signal the involvement of stromal keratocytes to commence apoptosis. We propose that the reduced risk results from a reduction in the wound healing response that is corrupted in dogs with CSK. Further validation of the putative functional variants is required prior to their use in genetic testing for breeding programs. #3 Cell type specific differences in the prefrontal cortex of young and aging tame and aggressive foxes Jennifer L. Johnson 1 , Erin E. Hecht 2 , Darya V. Shepeleva 3 , Rimma G. Gulevich 3 , Anastasiya V. Vladimirova 3 , Svetlana G. Shishkevich 3 , Anastasiya V. Kharlamova 3 , Yuri E. Herbek 3 , Lyudmila N. Trut 3 , Anna V. Kukekova 1 jjohnso@illinois.edu 1 Department of Animal Sciences, College of Agriculture, Consumer, and Environmental Sciences, University of IL Urbana-Champaign, Urbana, IL, USA, 2 Department of Human Evolutionary Biology, Harvard University, Cambridge, MA, USA, 3 Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia Genetic analysis of tame and aggressive fox populations (Vulpes vulpes), developed by 60 years of selection for behavior, previously identified SorCS1, an Alzheimer’s associated gene, as one of the main loci implicated in behavioral differences between the populations. To identify brain tran- scriptomic differences associated with behavior and aging we performed single nucleus RNAseq (snRNAseq) analysis of the prefrontal cortex (PFC) of six young (9 months) and six old (7-9 years) female foxes with an equal number of tame and aggressive individuals. After processing, we obtained an average of 5,808 nuclei per sample with an average of 3,867 genes per nucleus. The snRNAseq analysis identified cell type composition of fox PFC and assigned populations of excitatory neurons to cortex layers using single cell resources available for human and mouse. Differential expression (DE) analysis highlighted excitatory neurons in cortex layers 2/3/4 in both comparisons, between populations and between age groups. A larger number of DE genes and stronger enrichment for KEGG pathways were identified between ages than between populations. Glutamatergic and GABA signaling were among the top pathways enriched in both comparisons, in former it was driven by genes upregulated in tame samples while in latter by genes upregulated in young samples. The well-established fox populations with genetically determined differences in behavior and a life span exceeding ten years provide a promising animal model for studying tradeoffs between evolution of social behavior and brain aging.
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