Matiytsiv N. Molecular-Genetic Analysis of Drosophila melanogaster Neurodegenerative Mutations Localized in X Chromosome

Molecular-genetic analysis of ethylmethanesulphonate-induced D.melanogaster neurodegenerative mutations was done and both functional and morphological changes in mutant brain tissue were studied in this dissertation work. Early death and lowered average and maximum lifespan parameters were observed in mutant lines. Brain tissue degeneration progressed with age. Complementation analysis helped divide mutants into four complementation groups. With deletion mapping, some mutations were mapped and candidate genes were specified for further study in certain lines. Lines mapped in X chromosome 7D1 region were subject of detailed genetic analysis, both classical and molecular. This region corresponded to the swiss cheese neurodegenerative mutation. (SWS-A) gene large transcript cDNA of swsolfE, 2-14, 61-7, 72-7, 76-15 lines and Oregon R wild type line was cloned and sequenced. It was found out that 76-15 mutant carries a new sws gene allele form represented by point mutation that causes amino acid substitution in the C-end domain of SWS-A protein. Functional changes in 76-15 mutant are connected with brain axons cytoskeleton pathology. Axon pathology is specific phenotype under SWS-A protein esterase activity loss. In swsolfE, 2-14, 72-7 flies age-dependent degeneration of dophamine neurons of PPL1 group was observed.