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AN INVESTIGATION INTO SPLICING VARIATION AND EXPRESSION PATTERNS OF INSULIN-LIKE PEPTIDE 4 (ILP4) WITHIN THE DROSOPHILA GENUS **

Abstract

This ongoing research focuses on understanding the genetic mechanisms underlying acceptor site variant mutations in the insulin-signaling pathway in Drosophila, particularly within the Ilp4 gene. The study aims to elucidate the distribution of these mutations across various Drosophila species and explore sex-specific expression patterns of Ilp4. Additionally, it investigates the relative utilization of acceptor sites within the variant mutation and assesses the potential functionality of resulting isoforms. The insulin-signaling pathway plays a crucial role in regulating metabolic homeostasis in both humans and insects. Dysregulation of this pathway can lead to diseases such as diabetes mellitus and insulin resistance. In Drosophila, Ilp4 shares structural and functional similarities with mammalian insulin, making it an excellent model to study genetic variations in this pathway. This research proposes several key goals. First, it aims to uncover the genetic mechanisms behind the acceptor site variant mutation through phylogeny-aware sequence alignment. Second, it seeks to map the distribution of this mutation across different Drosophila species using genomic data. Third, the study explores sex-specific expression patterns of Ilp4 across species, employing RNA sequencing data, phylogenetic analysis, and the UCSC Genome Browser to view RNA-seq data and gene structure. Fourth, it analyzes the relative utilization of acceptor sites within the mutation using RNA-sequencing and splice junction data, validated by RT-PCR experiments. Finally, the research assesses the potential functionality of both isoform variants through prediction models and genomic data. This ongoing investigation into the Ilp4 gene's acceptor site variant mutation in Drosophila contributes to our understanding of the evolution of the insulin-signaling pathway and its impact on metabolic activities and nervous system function in insects. Additionally, it sheds light on the splicing mechanisms that can lead to variations in gene products, potentially providing insights into similar processes in other organisms.

Acknowledgements

Columbus State University SRACE, Genomics Education Partnership

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