Identification of genetic variants determining the effect of maternal age on offspring longevity in drosophila melanogaster by genome-wide association analysis

This thesis aims to identify candidate variants that determine the effects of maternal aging on offspring longevity using Genome-Wide Association Studies (GWAS). The effect of parental age on offspring longevity has been one of the most widely studied topics in different organisms. In particular, the effect of maternal age has been studied more specifically because of decreased egg production in most organisms and decreased egg quality mostly in humans. The Lansing Effect, which is the definition of the general view that maternal age shortens the longevity of the offspring, has been found to vary between intraspecific lines. And in some lines, on the contrary, it has been found to increase longevity. This thesis is a comprehensive study in which the genetic elements determining intraspecific line variation were determined by GWAS. Using 90 Drosophila Genetic Reference Panel (DGRP) lines, life span data were obtained by aging the offspring from crosses of 5-days-old (young) - 35-days-old (old) mothers of each line and 5-days-old young fathers of the same lines. Variation in the life spans of the offspring of 90 inbred lines were observed, in some lines shortened depending on the age of the mother or be lengthened i.e. contrary to the Lansing effect. The analytical model established as Maternal Age x Sex x Line interaction and yielded statistically significant results (p < 0.001). GWAS was performed with the mean longevity data of individuals from 5-day- old mothers, individuals from 35-day-old mothers and individuals from 5-35-day-old mothers. As a result of 3 different GWAS, 146 candidate variants of various genes were identified and 118 human orthologs of those genes were obtained from gene ontology analysis. The identified candidate genes were found to be involved in biological processes such as reproduction, aging, epigenetics and development, which are thought to be associated with maternal aging. Candidate genes that are thought to cause diseases associated with the effect of maternal age in humans were also identified. As a result of this thesis, the knowledge of the effect of maternal aging on the longevity of the offspring obtained by genome wide anaylses is boradened significantly which is expected to be an important contribution to the literature.