PRESENTATION ABSTRACTS
cell RNA sequencing (scRNAseq) to examine tissues sampled from OSA patients and investigate the heterogeneity seen in a highly metastasizing canine OSA cell line (HMPOS) when exposed to chemotherapeutics. This approach allows for the identification of novel cell populations and gene expression patterns to inform on drug resistance and immune evasion. We investigated the OSA microenvironment by performing scRNAseq on the tumor, the tumor infiltrating margin (TIM), the bone marrow distal to the tumor, and healthy bone marrow of 3 canine OSA patients. We investi- gated exosome-mediated chemoresistance by culturing naïve HMPOS cells with exosomes derived from HMPOS cells resistant to either 2.5uM or 10uM carboplatin and compared these populations with scRNAseq. Exploration of the tumor microenvironment revealed unique populations of tu- mor-involved immune cells. Comparison of HMPOS cell populations indicates genes potentially involved in chemoresistance. The novel mechanisms revealed by these data are critical to under- stand the novel bone marrow niche and to consider when developing immunotherapy and tumor drug resistance treatments for OSA.
#35 Investigation of heritability of behavioral traits in service dogs
Persoon EK1 , Norton E1, Karlsson E2, Durward-Akhurst SA1, Mickelson J3, Tseng A4 McCue ME1 perso208@umn.edu 1Department of Veterinary Population Medicine, University of Minnesota, Minneapolis, MN, USA; 2Vertebrate Genomics, Broad Institute of MIT and Harvard, Cambridge, MA, USA; 3Department of Veterinary Medicine and Biological Sciences, University of Minnesota, Minneapolis, MN, USA; 4Department of Psychiatry and Behavioral Disorders, University of Minnesota, Minneapolis, MN, USA The service dog industry uses selective breeding to improve the quality and consistency of dogs in training programs. Effective selective breeding requires knowledge of the genetic architecture un- derlying the behavioral traits contributing to assistance dog success. Heritability estimates inform the likelihood that selective breeding will change phenotypic distributions. Assistance dogs are phe- notyped using the Behavior Checklist (BCL), a standardized evaluation of 50 traits. Our objective was to calculate heritability of BCL traits in dogs from 4 organizations. This cohort included 478 Labrador Retrievers: 290 dogs with BCL’s at 7-9 weeks old, and 365 dogs with BCLs when the dogs entered professional training (IFT, 13-23 months old). Heritability was estimated using a restricted maximum likelihood as implemented in LDAK and GCTA with standard and linkage disequilibri- um-weighted relatedness matrices. P<0.001 was considered statistically significant. Of 48 puppy test traits, 11 were highly heritable (range: 0.408 to 0.908), 8 were moderately heritable (0.200 to 0.389), and 6 were lowly heritable (0 to 0.146). Of 48 IFT traits, 2 were highly heritable (0.410 to 0.801), 8 were moderately heritable (0.200 to 0.388), and 13 were lowly heritable (0 to .197). Often traits that had high heritability estimates for the puppy test were low to moderately heritable on the IFT test. In contrast, “Fear of Novel Objects” is highly heritable on both the puppy test (GRM: 0.682, SE: 0.114; wGRM: 0.908, SE: 0.148) and the final training test (GRM: 0.485, SE: 0.120; wGRM: 0.608, SE: 0.126), suggesting that it can be selected against. These results lay the groundwork for genome-enabled selection and developing genetic predictive assays for assistance dog success.
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