Innate immunity and the new forward genetics.
Innate immunity and the new forward genetics.
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DOI：
10.1016/j.beha.2016.10.018
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发表时间：
2016-12
期刊：
影响因子：
--
通讯作者：
Beutler B
中科院分区：
文献类型：
--
作者：
Beutler B
由于先天免疫是一个对微生物做出反应的硬连线系统，因此它特别容易受到经典遗传分析的影响。突变导致了先天免疫传感和信号通路的许多分子元件的发现。反过来，需要一种更快的方法来找到突变诱导表型的分子原因，这引发了正向遗传学的巨大转变。在20世纪80年代和90年代，许多可遗传的表型被归因于通过定位克隆的突变。在小鼠中，这需要三个步骤。首先，使用遗传作图步骤来显示给定的表型源自基因组的限定区域。其次，进行物理作图步骤，克隆所有区域并确定其基因含量。最后，进行突变的协同搜索。这些项目通常持续数年，但可能会在我们对生物过程的理解上产生突破。2002年发表的注释小鼠基因组序列使得物理作图变得不必要。最近，我们设计了一种新的自动遗传图谱技术，它消除了遗传图谱和候选基因之间的突变搜索。显型的原因现在可以立即确定。我们已经创造了超过100，000个编码/剪接突变。通过筛选先天免疫和适应性免疫的缺陷，我们发现了许多先天免疫功能所需的“新”蛋白质。
As it is a hard-wired system for responses to microbes, innate immunity is particularly susceptible to classical genetic analysis. Mutations led the way to the discovery of many of the molecular elements of innate immune sensing and signaling pathways. In turn, the need for a faster way to find the molecular causes of mutation-induced phenotypes triggered a huge transformation in forward genetics. During the 1980s and 1990s, many heritable phenotypes were ascribed to mutations through positional cloning. In mice, this required three steps. First, a genetic mapping step was used to show that a given phenotype emanated from a circumscribed region of the genome. Second, a physical mapping step was undertaken, in which all of the region was cloned and its gene content determined. Finally, a concerted search for the mutation was performed. Such projects usually lasted for several years, but could produce breakthroughs in our understanding of biological processes. Publication of the annotated mouse genome sequence in 2002 made physical mapping unnecessary. More recently we devised a new technology for automated genetic mapping, which eliminated both genetic mapping and the search for mutations among candidate genes. The cause of phenotype can now be determined instantaneously. We have created more than 100,000 coding/splicing mutations. And by screening for defects of innate and adaptive immunity we have discovered many “new” proteins needed for innate immune function.
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影响因子：
64.8
作者：
Hoebe, K;Georgel, P;Beutler, B
通讯作者：
Beutler, B
T细胞和B细胞静止的损失是在GIMAP5缺陷型小鼠中微生物菌群依赖的浪费疾病和肠炎的发作之前。
DOI：
10.4049/jimmunol.0903164
发表时间：
2010-04-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Barnes MJ;Aksoylar H;Krebs P;Bourdeau T;Arnold CN;Xia Y;Khovananth K;Engel I;Sovath S;Lampe K;Laws E;Saunders A;Butcher GW;Kronenberg M;Steinbrecher K;Hildeman D;Grimes HL;Beutler B;Hoebe K
通讯作者：
Hoebe K
影响因子：
3.2
作者：
HEPPNER, G;WEISS, DW
通讯作者：
WEISS, DW
影响因子：
30.8
作者：
Croker, Ben;Crozat, Karine;Beutler, Bruce
通讯作者：
Beutler, Bruce
影响因子：
3.3
作者：
Arnold, Carrie N.;Xia, Yu;Beutler, Bruce
通讯作者：
Beutler, Bruce