Determination of genomic variants affecting the phenotypic expression of the gene lim homeobox 1 in Drosophila melanogaster

In this thesis, it is aimed to determine the genes that affect the expression of lim1 homeobox gene which is known to have an important role in leg development. The lim1 gene from homeobox genes, which is known to have an effect on the leg development, has been studied only in terms of the formation of tarsal segments. lim1 gene was studied for the first time in terms of the effect on femur length during the leg development process. One hundred and twenty two DGRP strains, the mutant strain having the homozygous mutant allele of the lim1 gene and the control strain from which this strain was created were used during the experiments. The femoral lengths of the control strain and the mutant strain were examined, and the difference between the femur lengths was found to be dependent on both genotype and sex. Only female individuals from the F1 progeny obtained as a result of the crosses were analyzed. When the femur lengths of the F1 individuals obtained from the crosses were analyzed by the analysis of variance, it was seen that the resulting differences were related to Strain, Genotype and Genotype x Strain interaction terms and the correlation was statistically significant (p <0.001). In the genome wide association study, DGRP x Control mean femoral length averages, DGRP x Mutant femur length mean differences were obtained and the results were used as GWAS input. GWAS was performed in all three legs in this way. A total of 54 variants were identified in the three GWAS results. Twenty-two of these variants were identified as Drosophila genes and were associated with 53 human genes showing orthology with these genes. These genes have been found to be important genes for cell mobility, cell differentiation and metabolic pathways. For the first time in this thesis, 20 Drosophila genes, which are thought to have an effect on leg development, were introduced into the literature as a candidate gene. The gce gene found among the identified candidate genes has been associated with juvenile hormone activation only in previous studies. As a result of the three GWAS performed in the scope of this study, the related with the leg development was revealed. When CG44153, Cp1, Doc1 and Egfr genes were examined in relation to their developmental stages, human orthologs of these genes were found to be related to different types of cancer. As a result, it is thought that this thesis will make significant contributions to the literature of developmental biology.