Drosophila melanogaster’de Kaygı Benzeri Davranışa Neden Olan Genetik Elementlerin Genom Boyu İlişkilendirme Çalışması İle Saptanması

Abstract

The primary goal of this thesis is to identify genetic variants associated with anxiety-like behavior in Drosophila melanogaster through a genome-wide association study (GWAS) and to investigate the human homology of these genes. This thesis is a comprehensive scientific study aimed at elucidating the intricate genetic background of anxiety disorder. One hundred and one “Drosophila Genetic Reference Panel” (DGRP) lines were utilized in the experiments conducted as part of this thesis. An open field test was used to assess anxiety-like behavior in Drosophila melanogaster, and ten-minute recordings were obtained. In the contect of the thesis, three phenotypic measures were focused; average distance from the center, total distance travelled and total mobility ratio. The primary phenotypic focus of this thesis is on, center avoidance and wall-following behaviors, which are commonly associated with anxiety in the literature. When examining the variance analyses conducted separately for each of the three parameters, it was observed that the interactions involving the term strain were significant (p<0,001). Average values of each of the three parameters (distance from the center, total distance traveled, and overall activity) calculated separately for both sexes were used in the GWAS analysis. In consequence of Genome-Wide Association studies, a total of 166 Drosophila genes associated with the anxiety-like behavior phenotype were identifed and accordingly the biological processes, phenotypes, and diseases in which these genes are involved in

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Drosophila have been investigated. Furthermore, ontology analyses revealed orthology between these genes and 421 human genes. Various database analyses of these 166 genes indicated that 48 of them were key genes involved in systems associated with anxiety-like behaviors.

Upon examination of studies focusing on anxiety-like behaviors with Drosophila, the candidate genes put forth in these studies were not identified within the scope of this thesis.

The thesis approaches the genetic background analysis from the perspective that biological processes are influenced by the interplay of multiple genes, rather than being determined by a single gene. The main reason why the candidate genes were not found in the GWAS results obtained within the scope of this thesis is thought to be the use of individuals of both sexes from 101 DGRP lines, each with a distinct genetic background.

While this thesis represents the most comprehensive study of anxiety-like behaviors in Drosophila, the identified genes have been linked to anxiety-like behaviors for the first time.