Drosophila Melanogaster’de Monosodyum Glutamat Etkisi Altında Larval Beslenme Davranışı ve Bu Davranışı Etkileyen Genlerin Genom Boylu İlişkilendirme Analizi ile Belirlenmesi

Abstract

In this thesis, it is aimed to detect the genetic variants affecting feeding behavior and consumption of Monosodium Glutamate (MSG), a food additive. Feeding behavior which is regulated by both homeostatic and hedonic pathways, is a complex character with a multi-gene control mechanism. Determination of genes that are effective in feeding behavior would be helpful for development of preventions against and treatments of related diseases. Although gene sets involved in both feeding behavior and MSG consumption have been widely investigated, the genetic background of the related phenotypes hasn’t been fully elucidated. The study was carried out by using lines chosen from the Drosophila Genetic Reference Panel (DGRP), which was developed for use in Genome Wide Association Study (GWAS) of the model organism Drosophila melanogaster, which is advantageous for genetics research. For the experiments, lines that maintain their lives in optimal conditions (25oC, 65% Relative Humidity) were laid in a controlled manner, and third instar larvae were collected at the 72nd hour from the beginning of egg laying were used. The collected larvae were placed on control medium (10% w/v sucrose, 2.5% w/v agar-agar) and MSG containing medium (control medium + 3% MSG w/v). Afterwards, their movements were recorded with a camera integrated to a dissection microscope. The recordings were watched by being slowed down, and the count of snatches in a minute exhibited by each larvae were determined and recorded. The data obtained were calculated for each line; for the control group, for the MSG group and for the mean difference percentage score calculated by division of difference of MSG score and control score to control score. These three data sets were used as input for GWA analysis. As a result of the GWAS, total of 62 single nucleotide polymorphisms (SNPs) were found to be significantly associated with the phenotypes of interest, 32 Drosophila genes were identified in which the SNPs hit. Screening on the biological functions of the identified genes showed that these genes are getting involved in many different biological processes, dominantly in the nervous system, development, and metabolic processes. Human orthologs of the identified genes and human diseases they are associated with were examined, genes were previously found to be associated with not only nutrition related disorders such as obesity and diabetes; but also nervous system, developmental and metabolic disorders. With this thesis study, 32 genes that have not been previously associated with feeding behavior and MSG consumption were identified as candidate genes for association: With the validation studies to be conducted in the following period, the genes whose association with the phenotypes of interest will be confirmed and be published to the literature.