Exploring the Pathogenicity of a Type 2 Diabetes Mellitus Associated INSR Missense Variant of Uncertain Significance through Daf-2 in the C. elegans Model
Date
2-13-2024
Faculty Mentor
Ashley Turner, Biology
Loading...
Files
Submission Type
Conference Proceeding
Location
10:15-10:25am | Houston Cole Library, 11th Floor
Description
Type 2 diabetes mellitus is hallmarked by insulin resistance, with the INSR gene identified as a key player in this condition. This gene is known to harbor genetic variants with a wide range of clinical significance from pathogenic to variants of uncertain significance (VUS). This project investigates a VUS identified through ClinVar. The missense VUS was located at INSR c.1628C>T (p.Thr543Met). PolyPhen-2 predicted this variant to be probably damaging, assigning a HumVar score of 0.954. The ortholog VUS loci was identified in the C. elegans at daf-2 c.2084C>T (p.Thr698Met). Evolutionary conservation of the VUS loci was confirmed through multiple sequence alignment in Benchling. The mutation induces a class change from the polar, hydrophilic amino acid threonine to the nonpolar, hydrophobic amino acid methionine. Utilizing SWISS-MODEL, homology-based protein models were generated for both wildtype and VUS mutant proteins. Subsequent bioinformatic analysis in PyMOL revealed an RMSD value of 0.001. The affected amino acid resides in the extracellular alpha subunit, which may contribute to its potential pathogenicity. To understand the in vivo implications of this structural alteration, we will observe phenotypic differences between a wildtype N2 C. elegans strain and a CRISPR-Cas9 engineered variant strain carrying the daf-2 mutation. Expected phenotypic variations encompass dauer formation, enhanced stress resistance, and increased lifespan. This research aims to elucidate the functional changes of the INSR variant and provide valuable insight into its role in the context of insulin resistance and type 2 diabetes mellitus.
Keywords
student research, biology
Rights
This content is the property of Jacksonville State University and is intended for non-commercial use. Video and images may be copied for personal use, research, teaching or any "fair use" as defined by copyright law. Users are asked to acknowledge Jacksonville State University. For more information, please contact digitalcommons@jsu.edu.
Disciplines
Biology
Recommended Citation
White, Brittany and Elston, Trinity, "Exploring the Pathogenicity of a Type 2 Diabetes Mellitus Associated INSR Missense Variant of Uncertain Significance through Daf-2 in the C. elegans Model" (2024). JSU Student Symposium 2024. 58.
https://digitalcommons.jsu.edu/ce_jsustudentsymp_2024/58