Evaluation of Genetic Variants Associated with Undiagnosed Rare Disease Using Drosophila

Abstract

Undiagnosed Rare Disease (URD) is a rare disease without a name, as it is difficult to diagnose. Most cases of URD are found in adolescents, and approximately 80% of them are genetic disorders. With the advancement of molecular biology technology, many genetic variations related to URD are being discovered, and an in vivo platform is needed to evaluate newly discovered candidate genes and their variants. Drosophila melanogaster is an ideal model for evaluating the biological function of candidate genes due to its short lifespan and easy genetic characteristics. In this thesis study, I used the Gal4-UAS system to express 82 URD candidate genes and their variants in fruit flies and observed their motor abilities and investigated developmental effects on eye and wing morphology. Subsequently, I analyzed the transcriptome of fruit flies expressing genes with changes in phenotype. Through this approach, I evaluated 49 genetic variants isolated from URD patients in comparison with their respective reference gene using in vivo bioassay and transcriptome analysis. In future, this study will help development of an experimental platform that connects biological phenotypes and gene expression profiles related to URD variants.