Hailey McMillen
Pronouns: she/her
Research Mentor(s): Adelaide Tovar
Research Mentor School/College/Department: Computational Medicine & Bioinformatics / Medicine
Program: UROP
Session: Session 7 (4:40pm – 5:30pm)
Authors: Hailey McMillen, Adelaide Tovar, Jacob Kitzman, Stephen Parker
Abstract
Diabetes mellitus, including type 1 (T1D) and type 2 diabetes (T2D), encompasses a group of metabolic diseases characterized by persistent hyperglycemia. Both T1D and T2D are caused by genetic variation in combination with various environmental factors. While many studies have identified genetic signals associated with these diseases, most alter gene regulation using unknown mechanisms. Interestingly, though these diseases are caused by distinct agents, recent research indicates that there are some shared genetic loci and potentially not as much of a distinction as initially thought. The goal of this project is to evaluate the regulatory activity of diabetes-associated genetic variants using massively parallel reporter assays (MPRAs) in human tissue culture. MPRAs are used to screen thousands of sequences simultaneously and identify patterns of activity and allelic bias. Using T1D signal variants from published genome-wide association studies (GWAS), we generated a proxy list, annotated and filtered them for high linkage, and looked for common variants between T1D and T2D. We used the final proxy list to synthesize DNA oligonucleotides, which we then barcoded and cloned into a reporter plasmid. We are currently performing sequencing to pair barcodes to oligos, which we will use as a dictionary for downstream studies. Eventually we will use these MPRAs in relevant cell models including pancreatic beta cells, macrophages, and T cells, to determine whether shared T1D and T2D genetic variants have similar effects on gene expression.
