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Undergraduate Poster Session

Undergraduate Poster #26

Subevent of Undergraduate Poster Session

Times: 2026 Mar 28 from 10:45AM to 12:00PM (Central Time (US & Canada))

Using Bioinformatics to Characterize Missense Variants of SERPINA1 Associated with Bronchiectasis

Joseph Pope <jpope7@una.edu>, University of North Alabama

Coauthors: Lucas Hasting, Dr. Cynthia Stenger

Abstract:

Bioinformatics is the intersection of statistics, biology, and computer science. The abundance and open-source nature of data from clinical submissions of genome sequencing can allow one to study genetic mutations without the need for expensive lab equipment and wet-lab time. Bioinformatics research is an important tool for lowering cost and reducing time to wait for genomic results. This study investigates missense swaps of the SERPINA1 gene. SERPINA1 is the gene that carries the instructions to produce the Alpha-1 antitrypsin (AAT) protein. AAT is a protease inhibitor created in the liver that protects the airways from pollutants. Mutations in SERPINA1 can cause not enough AAT to be produced, halt creation of AAT altogether, or deform the folding of the protein causing it to not reach its intended destination; the lungs. Such a deficiency in AAT can cause non-cystic fibrosis bronchiectasis. This study aims to predict the pathogenicity of the missense swaps S38F and S69F. These swaps were chosen due to their proximity to an alpha-helix, their possible harmful effects on other bonds throughout the protein, and their relationship to the pathogenicity of other serine to phenylalanine swaps. Pathogenicity scores were compared to the known pathogenic swap S77F and the average of all known benign scores using the in-silico prediction analysis from SIFT, PolyPhen, REVEL, MetaLR, and CADD scores. ConSurf modeling over 150 homologues revealed conservation scores and predicted if the amino acid positions of interest were exposed, buried, structural, or functional. Molecular dynamic simulations were used to predict the movement of the protein, comparing the wild type and the selected variants of uncertain significance to determine differences in movement. These simulations indicate a statistically significant increase in movement for the selected uncertain variants. These findings contribute to the understanding of genetic factors influencing non-cystic fibrosis bronchiectasis and define the importance of further investigation of these variants for improved diagnostics in clinical diagnosis.

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