从数量表型数据出发构建遗传互作网络--毒理学网
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从数量表型数据出发构建遗传互作网络

来源:   浏览量:803   更新日期:2009年12月31日
生物的表型是由复杂的基因的相互作用以及环境因素决定的,所以说可以通过生物的各种表型分析基因的相互关系以及基因与环境的相互关系。但是,以往的研究多是通过对单个基因或几个基因的突变体的表型进行研究来推测基因功能及基因之间的联系,这种方法虽然建立了很多经典的基因表达调控途径以及代谢网络等,但是基因组成千上万个基因的功能以及互作分析使用这种传统方法一个一个的研究显得吃力而效率低下。对整个基因组中基因的功能及互作的全面认识显然是路漫漫而修远兮。

      最近,一个基因组范围内的表型分析逐渐发展起来,这种方法通过对基因组中大量基因的表型进行统一的观察来构建基因互作图谱。

      这篇论文基于对酵母的研究,首先对选择了127个基因进行单基因缺失以及双基因缺失(本研究对基因缺失使用一种基于PCR的高效方法),然后对这些突变体在96孔板上进行大量的表型分析,接着将这些表型数据用软件分析,最后得到这些基因的遗传互作网络图。


   基因之间的关系可以概括为下面这几种类型
Noninteractive interaction
(非交互关系)
 A has no effect in the WT and B backgrounds (for example, ΦWT = ΦA < ΦB = ΦAB), or B has no effect in the A and WT backgrounds, or both hold true (5 inequalities). 

Epistatic interaction(上位关系)
 A and B have different effects (in terms of direction or magnitude) on the wild-type background and the double mutant has the same phenotype as either A or B (for example, ΦA < ΦWT < ΦB = ΦAB) (12 inequalities). 

Conditional interaction(条件相互作用)
 A has an effect only in the B background, or the B mutant has an effect only in the A background (12 inequalities). 

Suppressive interaction(抑制相互作用)
 A has an effect on WT, but that effect is abolished by adding the suppressor B, which itself shows no single-mutant effect (for example, ΦWT = ΦB = ΦAB <ΦA); or, the corresponding holds under exchange of A and B (4 inequalities). 

Additive interaction(加成相互作用)
 Single-mutant effects combine to give a double-mutant effect as per ΦWT <ΦA= ΦB<ΦAB, ΦB < ΦWT = ΦAB < ΦA, ΦWT < ΦA < ΦB < ΦAB, ΦB < ΦWT < ΦAB < ΦA, and all additional inequalities obtained by interchanging A and B, or reversing the effect of both A and B (12 inequalities). 

Synthetic interaction(合成相互作用)
 A and B have no effect on the WT background, but the AB combination has an effect (2 inequalities). 

Asynthetic interaction(非合成相互作用)
 A, B, and the AB combination all have the same effect on the WT background (2 inequalities). 

Single-nonmonotonic interaction(单非单调相互作用)
 B shows opposing effects in the WT and A backgrounds (for example, ΦB > ΦWT and ΦAB< ΦA); or, A shows opposing effects in the WT and B backgrounds, but not both (8 inequalities). 

Double-nonmonotonic interaction(双非单调相互作用)
 Both A and B show opposing effects in the WT background and the background with the other mutant gene (18 inequalities).

参考文献:
Becky L Drees, Vesteinn Thorsson, GregoryWCarter, AlexanderW Rives, Marisa Z Raymond, Iliana Avila-Campillo, Paul Shannon and Timothy Galitski Derivation of genetic interaction networks from quantitative phenotype data.Genome Biology 2005, 6:R38 (doi:10.1186/gb-2005-6-4-r38). Subject areas: Genetics, Bioinformatics, Model organisms.
http://genomebiology.com/2005/6/4/R38


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