SGER: A Method to Identify and Characterize Potentially Redundant Genes within the Drosophila Genome

对黑腹果蝇的遗传学分析已经为控制动物发育和生活的许多方面的机制提供了实质性的见解。然而，尽管我们从这些研究中学到了很多东西，但仍有许多我们不知道的地方。这一点在检查注释基因组的初始阶段时变得令人震惊，在那里发现超过三分之二的果蝇基因没有从之前的研究中被识别出来。此外，尽管已经完成了大量的基因筛查，但我们的理解仍然存在许多差距，即使是在经过充分研究的过程中也是如此。这可能有几个原因；一个重要的原因是，由于遗传冗余，一些基因很难通过传统的遗传筛查进行分析。鉴于具有冗余或重叠功能的基因可能具有重要的作用，而且在果蝇中可能存在大量基因功能重叠的情况，因此我们有必要开发方法来检测和测试潜在的冗余基因的功能，但过去还没有使用系统的方法来识别冗余基因。马哈菲将进行一项筛查，以确定在果蝇胚胎发育过程中可能存在的冗余基因对。该方案首先通过相似性确定潜在的候选基因，然后克隆并使用原位杂交来确定表达是否存在重叠。最后，将使用RNA干扰来确定基因对是否具有重叠的作用。为了测试这种方法的有效性，马哈菲博士将首先选择编码锌指蛋白的候选基因对。值得注意的是，这个项目的设计并不局限于果蝇；它应该对其他生物(当然是线虫，以及使用吗啉反义程序的其他模式生物)中的冗余基因的研究有用。

0121111MahaffeyGenetic analyses of Drosophila melanogaster have yielded substantial insight into the mechanisms governing many aspects animal development and life. However, though we have learned much from these studies, there is still much that we do not know. This became alarmingly apparent upon examining the initial phase of the annotated genome where it was found that over two thirds of Drosophila genes had not been identified from prior studies. Further, though numerous genetic screens have been completed, there are still many gaps in our understanding, even in well-studied processes. There may be several reasons for this; one significant reason is that some genes are refractory to analysis by conventional genetic screens because of genetic redundancy. Given that genes with redundant or overlapping functions are likely to have important roles, and that there may be numerous cases of overlapping gene functions in Drosophila, it is essential that we develop methods to detect and to test the function of potentially redundant genes, yet a systematic method to identify redundant genes has not been employed in the past.Dr. Mahaffey will conduct a screen to identify potentially redundant gene pairs functioning during Drosophila embryonic development. The scheme involves first identifying potential candidates by similarity, then cloning and using in situ hybridization to determine if there is overlap in expression. Finally, RNA interference will be used to determine whether or not the gene pairs have overlapping roles. To test the validity of this method, Dr. Mahaffey will initially select candidate gene pairs that encode zinc finger proteins. It is important to note that the design of this project is not limited to Drosophila; it should be useful in studies of redundant genes in other organisms (certainly; C. elegans, and in other model organisms using morpholino antisense procedures).