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Genomic Deletion and Duplication Coverage in Drosophila

$259,823R24FY2008RRNIH

Trustees Of Indiana University, Bloomington IN

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Abstract

[unreadable] DESCRIPTION (provided by applicant): The fly Drosophila melanogaster is studied by thousands of biomedical researchers, because of the sophistication of its experimental genetics. Indeed, many kinds of experiments can be conducted only in the handful of nonmammalian model organisms amenable to extensive genetic manipulation like flies. Basic cellular processes are usually quite similar in flies and humans, so they can be explored in Drosophila using approaches unique to fly experimental genetics and the discoveries can be applied directly to understanding human biology and disease. Investments in research resources for Drosophila genetic experimentation are worthwhile, because many experiments important to human biomedicine are possible only in flies or are conducted most easily in flies. Drosophila experimental genetics relies quite heavily on chromosomal deletions and duplications for gene discovery and analysis. Whether an investigator is trying to identify the DNA sequence mutated to produce an abnormal trait, or trying to determine the functional consequences of disrupting a DNA sequence of interest, deletions are almost always used in the course the analysis. Likewise, duplications used along with deletions are nearly indispensable for analyzing genes on the X chromosome. It is important for fly geneticists to have deletions and duplications with chromosomal breakpoints positioned exactly where they are needed for experiments. At the Bloomington Drosophila Stock Center, the NIH- and NSF-sponsored, comprehensive repository for fly genetic strains, we have worked to improve deletions and duplication resources for fly geneticists. To continue our efforts, we propose the following aims: 1) complete the generation of a set of Y-linked duplications of X chromosome segments for full X chromosome coverage, 2) characterize the endpoints of these duplications by microarray analysis, and 3) generate deletions to subdivide the genome into maximal intervals of 12 genes. Genetic studies using the fly Drosophila melanogaster lead directly to understanding basic biological processes in humans. Many important experiments related to human health and disease are possible or practical only in nonmammalian model organisms with readily-manipulated genetic components, such as Drosophila. Fly geneticists need improved tools to do their work more effectively and we propose to improve the selections of chromosomal deletion and duplication strains so crucial to the success of their projects. [unreadable] [unreadable] [unreadable]

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