From phenologs to silent suppressors: Identifying potential therapeutic targets for human disease.
From phenologs to silent suppressors: Identifying potential therapeutic targets for human disease.
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DOI：
10.1002/mrd.22880
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发表时间：
2017-11
影响因子：
2.5
通讯作者：
Golden A
中科院分区：
文献类型：
--
作者：
Golden A
直系表型或表型，是由一组保守基因突变产生的看似无关的表型。表型学已经被研究模式生物的人广泛观察和接受，并允许人们研究模式生物中的一组基因，以更多地了解这些基因在其他生物（包括人类）中的功能。在细胞和分子水平上，这些保守基因可能以非常相似的模式发挥作用，但在不同的组织或细胞类型中发挥作用，并可能导致不同的表型效应。例如，动物中的RAS-RAF-MEK-MAPK途径是动物用于许多生物过程的高度保守的信号传导途径，例如秀丽隐杆线虫中的外阴诱导和哺乳动物细胞中的细胞增殖;但是，该相同的基因组已被增选以在多种细胞环境中发挥作用。在这篇综述中，我将给出几个在模式生物中抑制基因筛选的例子（重点是C。elegans）可以识别在许多其他生物中在保守途径中起作用的新基因。我还将展示如何识别这些基因可以导致重要的见解哺乳动物生物学。从这样的屏幕上，偶尔沉默的抑制基因，不引起表型本身被发现，这样的抑制基因，从而使良好的候选人作为治疗目标。
Orthologous phenotypes, or phenologs, are seemingly unrelated phenotypes generated by mutations in a conserved set of genes. Phenologs have been widely observed and accepted by those who study model organisms, and allow one to study a set of genes in a model organism to learn more about the function of those genes in other organisms, including humans. At the cellular and molecular level, these conserved genes likely function in a very similar mode, but are doing so in different tissues or cell types and can result in different phenotypic effects. For example, the RAS-RAF-MEK-MAPK pathway in animals is a highly conserved signaling pathway that animals adopted for numerous biological processes, such as vulval induction in Caenorhabditis elegans and cell proliferation in mammalian cells; but, this same gene set has been co-opted to function in a variety of cellular contexts. In this review, I will give a few examples of how suppressor screens in model organisms (with a emphasis on C. elegans) can identify new genes that function in a conserved pathway in many other organisms. I will also demonstrate how the identification of such genes can lead to important insights into mammalian biology. From such screens, an occasional silent suppressor that does not cause a phenotype on its own is found; such suppressors thus make for good candidates as therapeutic targets.
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影响因子：
64.8
作者：
Barr, MM;Sternberg, PW
通讯作者：
Sternberg, PW
影响因子：
64.8
作者：
FORTINI, ME;SIMON, MA;RUBIN, GM
通讯作者：
RUBIN, GM
影响因子：
2
作者：
De Maria, Beatrice;Mazzanti, Laura;Hennekam, Raoul C.
通讯作者：
Hennekam, Raoul C.
影响因子：
5.3
作者：
Eichers, Erica R.;Abd-El-Barr, Muhammad M.;Lupski, James R.
通讯作者：
Lupski, James R.
DOI：
10.1016/j.trsl.2012.08.005
发表时间：
2013-01
期刊：
Translational research : the journal of laboratory and clinical medicine
影响因子：
--
作者：
Giudicessi JR;Ackerman MJ
通讯作者：
Ackerman MJ