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Homing endonuclease mediated gene targeting in Anopheles gambiae cells and embryos.归巢内切酶介导的冈比亚按蚊细胞和胚胎中的基因靶向
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Engineered I-CreI derivatives cleaving sequences from the human XPC gene can induce highly efficient gene correction in mammalian cells.工程化的I-CreI衍生物可切割人类XPC基因序列,能在哺乳动物细胞中诱导高效的基因校正。
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在载体和害虫管理中使用归巢内切酶基因的群体遗传学。

The population genetics of using homing endonuclease genes in vector and pest management.

作者信息

Deredec Anne, Burt Austin, Godfray H C J

机构信息

NERC Centre for Population Biology, Department of Biology, Imperial College London, Ascot, Berks, United Kingdom.

出版信息

Genetics. 2008 Aug;179(4):2013-26. doi: 10.1534/genetics.108.089037. Epub 2008 Jul 27.

DOI:10.1534/genetics.108.089037
PMID:18660532
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2516076/
Abstract

Homing endonuclease genes (HEGs) encode proteins that in the heterozygous state cause double-strand breaks in the homologous chromosome at the precise position opposite the HEG. If the double-strand break is repaired using the homologous chromosome, the HEG becomes homozygous, and this represents a powerful genetic drive mechanism that might be used as a tool in managing vector or pest populations. HEGs may be used to decrease population fitness to drive down population densities (possibly causing local extinction) or, in disease vectors, to knock out a gene required for pathogen transmission. The relative advantages of HEGs that target viability or fecundity, that are active in one sex or both, and whose target is expressed before or after homing are explored. The conditions under which escape mutants arise are also analyzed. A different strategy is to place HEGs on the Y chromosome that cause one or more breaks on the X chromosome and so disrupt sex ratio. This strategy can cause severe sex-ratio biases with efficiencies that depend on the details of sperm competition and zygote mortality. This strategy is probably less susceptible to escape mutants, especially when multiple X shredders are used.

摘要

归巢内切酶基因(HEGs)编码的蛋白质在杂合状态下会在同源染色体上与HEG相对的精确位置导致双链断裂。如果利用同源染色体修复双链断裂,HEG就会变成纯合状态,这代表了一种强大的基因驱动机制,可作为控制媒介或害虫种群的工具。HEGs可用于降低种群适合度以压低种群密度(可能导致局部灭绝),或者在病媒中,敲除病原体传播所需的基因。本文探讨了靶向生存力或繁殖力、在一种性别或两种性别中都有活性、且其靶点在归巢前或归巢后表达的HEGs的相对优势。还分析了产生逃逸突变体的条件。另一种策略是将HEGs置于Y染色体上,使其在X染色体上造成一个或多个断裂,从而扰乱性别比例。这种策略可导致严重的性别比例偏差,其效率取决于精子竞争和受精卵死亡率的细节。这种策略可能较不易受到逃逸突变体的影响,尤其是在使用多个X染色体切割器时。