Drosophila Melanogaster’ De Pgrp-Lf Geninin Otoinflamasyon Bakımından Etkileştiği Diğer Genlerin Genom Çaplı İlişkilendirme Modeliyle Saptanması

Abstract

Autoinflammatory diseases are a group of clinical conditions characterized by recurrent inflammatory attacks. From a pathogenetic point of view, specific immunity is not involved and can only be identified by disorders in the innate immune regulatory mechanisms. They occur due to chronic uncontrolled activation of the immune system. There is a biological relationship between aging and the immune system that has not yet been fully elucidated. However, as noted above, the symptoms observed with disorders in the immune system are quite similar to those observed with the aging process. Aging contributes to the deterioration of immune function and makes the organism susceptible to infections. In particular, the Drosophila immune system is greatly influenced by degenerative processes associated with aging. Although disorders occurring in the regulation of the immune system are thought to accelerate the aging process, the mechanisms associated with increased mortality are not known since the mechanisms are not fully unterstood. To understand this mechanism, it is necessary to determine which genes the gene interacts with. The aim of this thesis is to elucidate the genetic infrastructure of the immune system and its relationship with aging by using the PGRP-LF gene mutant in the Drosophila melanogaster for pathways related to the genome-wide association (GWAS). For this purpose, Drosophila Genetic Reference Panel (DGRP) lines were used in the experiments. The control line with the PGRP-LF mutant line and the same genetic background was crossed with DGRP lins. The obtained F1 offspring was aged until all individuals died. Multivariate analysis of variance (ANOVA) was performed with the data obtained from the aging experiments. As a result of the analysis, it was determined that the silenced mutant form of the PGRP-LF gene showed a statistically significant change throughout the DGRP lines. GWA analyzes were performed within the framework of the Genotype X Line and Genotype X Line X Sex interactions that were significant after ANOVA. In the GWAS results, both sexes (female, male) were focused on genetic variants with p values of 10-5 and less (p <10-5). As a result of the analysis, a genetic variant was obtained which interacted with 52 SNPs. Gene ontology analysis of these genes, their functions in biological processes, molecular functions, diseases related to human orthologs and properties were examined. As a result of the literature search, the genes were found to be related to the immune system and aging. In addition to genes associated with the immune system and aging, many new candidate genes have been obtained. As a result, it is thought that important findings about the genetic infrastructure of the immune system and aging relationship, which is the aim of the thesis, are obtained.