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捕获一个基因并弄清楚其功能:迈向果蝇功能基因组学

Trap a gene and find out its function: toward functional genomics in Drosophila.

作者信息

Lukacsovich T, Yamamoto D

机构信息

Advanced Institute for Science and Engineering and School of Human Sciences, Waseda University, Tokorozawa, Saitama, Japan.

出版信息

J Neurogenet. 2001;15(3-4):147-68. doi: 10.3109/01677060109167373.

DOI:10.3109/01677060109167373
PMID:12092900
Abstract

Many declared aims of the genome projects have been achieved. The total genomic sequences of several relatively noncomplex/complex organisms (such as E. coli, yeast, Caenorhabditis, Drosophila) are being determined, and the nucleotide sequencing of the entire human genome will be complete in the near future. However, this achievement is not the end of the road but rather the first step toward the functional understanding of the genome of humans and other organisms. The determined linear nucleotide sequences remain only lists of A, C, G and T, unless they are given functional significance. The coding sequences of genes can be identified in a relatively reliable manner by computational methods, but the exact function of their protein products can rarely be determined without obtaining much additional information, e.g., by biochemical or cell biological methods. Thus, following sequencing, the next step must be to assign functions to the identified genes. The final goal of genome research today may look futuristic, but the knowledge of the function of every single gene and the interactions between them will finally allow us to understand the development and functioning of an organism as a whole. Gene-trapping methodology is a powerful strategy for cloning and identifying functional genes, as it marks a gene with a tag and simultaneously generates a corresponding genetic variation for that particular locus. Therefore, gene trapping is an extremely useful tool for functional genomics, establishing a correlation between the physical and genetic maps of the genome. The relative simplicity of its genome and the availability of huge bodies of genetic and molecular information make Drosophila melanogaster one of the most important model organisms. Its genome will serve as a "reference" for the in-depth analysis of the organization of more complex eukaryotic genomes. Multifaceted approaches to Drosophila functional genomics and the dual-tagging gene trap system newly developed for functional analysis of Drosophila genes are discussed in this review.

摘要

基因组计划的许多既定目标已经实现。几种相对简单/复杂的生物体(如大肠杆菌、酵母、秀丽隐杆线虫、果蝇)的全基因组序列正在被测定,整个人类基因组的核苷酸测序也将在不久后完成。然而,这一成果并非终点,而是迈向对人类和其他生物体基因组功能理解的第一步。所测定的线性核苷酸序列仅仅是A、C、G和T的罗列,除非赋予它们功能意义。基因的编码序列可以通过计算方法以相对可靠的方式识别,但如果不获取更多额外信息,例如通过生化或细胞生物学方法,其蛋白质产物的确切功能很少能够确定。因此,测序之后的下一步必须是为已识别的基因赋予功能。如今基因组研究的最终目标可能看起来颇具未来感,但了解每一个基因的功能以及它们之间的相互作用最终将使我们能够从整体上理解生物体的发育和功能。基因捕获方法是克隆和识别功能基因的有力策略,因为它用一个标签标记一个基因,并同时为该特定位点产生相应的遗传变异。因此,基因捕获是功能基因组学极为有用的工具,能在基因组的物理图谱和遗传图谱之间建立关联。黑腹果蝇基因组相对简单,且有大量的遗传和分子信息可用,这使其成为最重要的模式生物之一。其基因组将作为深入分析更复杂真核生物基因组组织的“参考”。本文将讨论黑腹果蝇功能基因组学的多方面方法以及新开发的用于果蝇基因功能分析的双标签基因捕获系统。

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