We propose to map and deposit a collection of well defined chemically induced mutations in essential genes on the Drosophila melanogaster X chromosome for distribution by the Bloomington Drosophila Stock Center (BDSC) to the fly community. This resource will be very valuable as the mutations were induced on an isogenized y w FRT19A chromosome using low concentrations of ethyl methanesulfonate to minimize genetic load. The chromosomes were screened for the presence of lethal mutations and subsequently assayed in an ey-FLP and Ubx-FLP FRT screen. We screened for mutations that affect numerous biological processes, including eye, head, wing, thorax and bristle development, photoreceptor growth cone guidance, synapse formation, synaptic transmission, and neurodegeneration. We also identified mutations that cause a head overgrowth phenotype as well as tumorous unpatterned growth. We propose to map the molecular lesion in 380 different complementation groups, to rescue the phenotype with small X chromosome duplications, to deposit the stocks in the BDSC, and to provide all the data relevant to each mutant to FlyBase. This collection will cover 40-45% of all the essential genes on the X chromosome. This is a very valuable collection of mutations that will be much used by the members of the Drosophila community (see 22 letters of support). This collection of mutations will promote our basic understanding of many different biological processes, as well as help us better understand the pathogenesis of cancer, developmental, and neurological diseases.
Basic research using Drosophila melanogaster has led to discovery of numerous genes that affect many biological processes, including homeotic genes, genes controlling numerous signaling pathways, trp and potassium channels, and circadian rhythm genes. It has now become apparent that much of this research is very beneficial to our understanding of numerous diseases, including common and rare genetic disorders, neurological diseases, and cancer. This proposal aims at broadening the tool set in the fruit fly to perform better and more sophisticated experiments more efficiently. It will undoubtedly help us better understand numerous disease mechanisms.
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