Ashley Turner, Biology
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1:30-1:40pm | Houston Cole Library, 11th Floor
Type 2 diabetes is a complex metabolic disorder with interactions between genetic and environmental factors, making it more complicated to understand the clinical implications of identified genetic variants and disease pathology. Many of the diabetes-associated variants are currently classified as VUS and occur within the genes involved in insulin signaling and regulation, so we turned our focus on the human INSR gene. INSR encodes the insulin receptor protein that plays a major role in insulin signaling. Furthermore, C. elegans provides a simple model system to examine the functional consequences of these diabetes-associated VUS. We examined INSR diabetes-associated VUS through the orthologous C. elegans gene daf-2. Preliminary genetic and evolutionary conservation analyses suggest functional impact for some of these VUS with the potential to impact protein structure and function. Further bioinformatic analysis of pathogenicity predictions supported the conservation we observed across species. I chose the most interesting VUS c.1628C>T (p.Thr543Met) to move forward with based on its genetic loci, level of evolutionary conservation, and predicted pathogenicity. These provided support for further in vivo studies. Next, we designed and tested primers to amplify the VUS region within daf-2. We are currently working to optimize this polymerase chain reaction-based genotyping assay to assess CRISPR-Cas9-engineered C. elegans models containing the VUS. Our goal is to assess the functional impact of the VUS on the daf-2 gene in vivo through phenotyping the mutant C. elegans VUS model. Studies such as this help us to begin to understand the functional impact of identified genetic variants in diabetes patients, paving the way for personalized medicine.
student research, biology
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Elston, Trinity, "Diving into the Unknown: A Genetic Investigation of Type-2 Diabetes-associated INSR Variants of Uncertain Significance" (2022). JSU Student Symposium 2022. 47.