Virginia Via Research Day Book 2026

Medical Student Research Biomedical

23 UNRAVELING THE GENETIC BASIS OF ULCERATIVE COLITIS THROUGH SIBLING COMPARISONS

David Grace, OMS-II; Sarah Grace, BS; Robin Varghese, PhD; Ramu Anandakrishnan, PhD Corresponding author: dgrace@vcom.edu

VCOM-Virginia, Blacksburg, Virginia

AFDN, a gene involved in epithelial barrier integrity, and a copy loss of SIRPB1, a gene contributing to the innate immune system through inflammatory signaling. Both findings represent biologically plausible contributors to UC pathogenesis through disruption of epithelial junction stability and immune regulatory pathways. Conclusions: These variants are currently being evaluated using external population-level genomic and clinical datasets; comparative analysis using genomic and electronic health record (EHR) data from the eMERGE Network and dbGaP. These resources will enable assessment of CNV presence among other clinically diagnosed UC patients. Further investigation and comparison will help determine whether these CNVs are unique familial findings or if they represent broader, previously unrecognized genomic loci associated with UC. This study highlights

two candidate loci that may contribute to inherited susceptibility of UC and role of these genes in UC pathogenesis. IRB Statement: This study was approved by the VCOM IRB in the Spring of 2025, protocol number 2025-015.

Context: Ulcerative Colitis (UC) is a chronic inflammatory bowel disease with a substantial genetic component, yet many genomic variants remain incompletely characterized. Objective: The purpose of this study is to utilize a sibling study and later a population level analysis to identify and then conform novel genetic variations shared by two siblings of a family who have UC but not by a third who does not have UC that play a role in the pathogenesis of Ulcerative Colitis. Methods: We conducted whole-genome sequencing in a family of three siblings two affected by UC and one unaffected. Whole-genome sequencing copy number variant (CNV) analysis identified two candidate variants shared by the affected individuals and absent in the unaffected sibling. Results: The two variants are a copy gain involving

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112 Edward Via College of Osteopathic Medicine (VCOM)