Genomic Deletion and Duplication Coverage in Drosophila

描述(申请人提供)：果蝇黑腹果蝇由于其实验遗传学的复杂性，被数以千计的生物医学研究人员研究。事实上，许多类型的实验只能在少数几种非哺乳动物模式生物上进行，这些生物可以接受广泛的基因操作，比如苍蝇。果蝇和人类的基本细胞过程通常非常相似，因此可以使用飞行实验遗传学独有的方法在果蝇身上进行探索，这些发现可以直接应用于了解人类生物学和疾病。对果蝇基因实验研究资源的投资是值得的，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。果蝇的实验遗传学在很大程度上依赖于染色体的缺失和复制来发现和分析基因。无论研究人员是试图确定突变的DNA序列以产生异常特征，还是试图确定扰乱感兴趣的DNA序列的功能后果，在分析过程中几乎总是使用缺失。同样，与缺失一起使用的复制对于分析X染色体上的基因几乎是必不可少的。对于果蝇遗传学家来说，重要的是在实验需要的地方精确定位染色体断裂点的缺失和复制。在布鲁明顿果蝇种群中心，NIH和NSF赞助的苍蝇遗传菌株综合存储库，我们一直在努力改善苍蝇遗传学家的缺失和复制资源。为了继续我们的努力，我们提出了以下目标：1)完成一组Y连锁的X染色体片段的复制，以实现完整的X染色体覆盖；2)通过微阵列分析来表征这些重复的端点；以及3)产生缺失以将基因组细分为最大的12个基因间隔。利用果蝇进行的遗传学研究直接导致了对人类基本生物学过程的了解。许多与人类健康和疾病相关的重要实验只有在非哺乳动物模式生物中才有可能或实用，这些生物的遗传成分很容易操纵，比如果蝇。苍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复制品系的选择，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.