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

[121111 . 11]对黑腹果蝇的遗传分析使我们对动物发育和生命的许多方面的调控机制有了实质性的了解。然而，尽管我们从这些研究中学到了很多，但仍有很多我们不知道的。在检查注释基因组的初始阶段时，发现超过三分之二的果蝇基因没有从先前的研究中被识别出来，这一点变得非常明显。此外，尽管已经完成了许多基因筛选，但即使在充分研究的过程中，我们的理解仍有许多空白。这可能有几个原因；一个重要的原因是，由于遗传冗余，一些基因难以通过传统的遗传筛选进行分析。考虑到具有冗余或重叠功能的基因可能具有重要的作用，并且在果蝇中可能存在许多重叠基因功能的情况，我们有必要开发检测和测试潜在冗余基因功能的方法，但过去尚未采用系统的方法来识别冗余基因。Mahaffey将进行筛选，以确定果蝇胚胎发育过程中潜在的冗余基因对。该方案包括首先通过相似性识别潜在的候选者，然后克隆和使用原位杂交来确定是否有表达重叠。最后，RNA干扰将用于确定基因对是否有重叠的作用。为了测试这种方法的有效性，Mahaffey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；它在研究其他生物（当然，秀丽隐杆线虫和其他模式生物中使用morpholino反义程序）的冗余基因方面应该是有用的。

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).