Genomic Deletion and Duplication Coverage in Drosophila

描述（由申请人提供）：成千上万的生物医学研究人员研究了黑腹果蝇，因为它的实验遗传学很复杂。事实上，许多种类的实验只能在少数非哺乳动物模式生物（如苍蝇）中进行，这些生物可以接受广泛的基因操作。果蝇和人类的基本细胞过程通常非常相似，因此可以使用果蝇实验遗传学的独特方法在果蝇中进行探索，这些发现可以直接应用于理解人类生物学和疾病。投资果蝇基因实验的研究资源是值得的，因为许多对人类生物医学重要的实验只能在果蝇身上进行，或者最容易在果蝇身上进行。果蝇实验遗传学在很大程度上依赖于染色体缺失和重复来发现和分析基因。无论研究人员是试图识别产生异常特征的DNA序列突变，还是试图确定破坏感兴趣的DNA序列的功能后果，在分析过程中几乎总是使用缺失。同样，在分析X染色体上的基因时，与缺失一起使用的复制几乎是必不可少的。对于果蝇遗传学家来说，将染色体断点精确地定位在实验需要的位置是很重要的。在布卢明顿果蝇储备中心，由美国国立卫生研究院和美国国家科学基金会资助的果蝇遗传菌株综合储存库，我们一直致力于为果蝇遗传学家改善缺失和复制资源。为了继续我们的工作，我们提出了以下目标：1)完成一组X染色体y连锁重复片段的生成，以实现完整的X染色体覆盖；2)通过微阵列分析表征这些重复的终点；3)生成缺失，将基因组细分为12个基因的最大间隔。利用黑腹果蝇进行遗传研究，可以直接理解人类的基本生物过程。许多与人类健康和疾病有关的重要实验只有在具有易于操纵的遗传成分的非哺乳动物模式生物（如果蝇）中才有可能或可行。果蝇遗传学家需要改进的工具来更有效地完成他们的工作，我们建议改进染色体缺失和重复菌株的选择，这对他们的项目的成功至关重要。

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.