非洲疟媒冈比亚按蚊基因驱动株中cas9介导的母系效应及衍生抗性等位基因

IF 3.3 3区 生物学
Genetics Pub Date : 2022-05-31 DOI:10.1093/genetics/iyac055
Rebeca Carballar-Lejarazú, Taylor Tushar, Thai Binh Pham, Anthony A James
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引用次数: 0

摘要

摘要CRISPR/Cas9技术是开发基因驱动系统的重要工具,用于改变蚊子媒介种群,以控制导致疟疾等疾病的病原体的传播。然而,当前基于Cas9的驱动系统的挑战之一是它们产生驱动抗性等位基因的能力,该等位基因由主要由染色体切割后的非同源末端连接引起的插入和缺失(indel)引起。这种等位基因频率的快速增加可能损害基因驱动动力学。我们使用基因驱动系AgNosCd-1和野生型蚊子之间的一系列选择性杂交,探索了雌性基因驱动谱系的种系和体细胞中indel的产生。我们发现,潜在的驱动抗性突变等位基因主要在胚胎发育过程中产生,很可能是由纯合和半合基因驱动母亲在卵母细胞中沉积Cas9核酸内切酶和引导RNA以及由此产生的胚胎引起的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Cas9-mediated maternal effect and derived resistance alleles in a gene-drive strain of the African malaria vector mosquito, Anopheles gambiae.

CRISPR/Cas9 technologies are important tools for the development of gene-drive systems to modify mosquito vector populations to control the transmission of pathogens that cause diseases such as malaria. However, one of the challenges for current Cas9-based drive systems is their ability to produce drive-resistant alleles resulting from insertions and deletions (indels) caused principally by nonhomologous end-joining following chromosome cleavage. Rapid increases in the frequency of such alleles may impair gene-drive dynamics. We explored the generation of indels in the germline and somatic cells in female gene-drive lineages using a series of selective crosses between a gene-drive line, AgNosCd-1, and wild-type mosquitoes. We find that potential drive-resistant mutant alleles are generated largely during embryonic development, most likely caused by deposition of the Cas9 endonuclease and guide RNAs in oocytes and resulting embryos by homozygous and hemizygous gene-drive mothers.

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来源期刊
Genetics
Genetics 生物-遗传学
CiteScore
6.20
自引率
6.10%
发文量
177
期刊介绍: GENETICS is published by the Genetics Society of America, a scholarly society that seeks to deepen our understanding of the living world by advancing our understanding of genetics. Since 1916, GENETICS has published high-quality, original research presenting novel findings bearing on genetics and genomics. The journal publishes empirical studies of organisms ranging from microbes to humans, as well as theoretical work. While it has an illustrious history, GENETICS has changed along with the communities it serves: it is not your mentor''s journal. The editors make decisions quickly – in around 30 days – without sacrificing the excellence and scholarship for which the journal has long been known. GENETICS is a peer reviewed, peer-edited journal, with an international reach and increasing visibility and impact. All editorial decisions are made through collaboration of at least two editors who are practicing scientists. GENETICS is constantly innovating: expanded types of content include Reviews, Commentary (current issues of interest to geneticists), Perspectives (historical), Primers (to introduce primary literature into the classroom), Toolbox Reviews, plus YeastBook, FlyBook, and WormBook (coming spring 2016). For particularly time-sensitive results, we publish Communications. As part of our mission to serve our communities, we''ve published thematic collections, including Genomic Selection, Multiparental Populations, Mouse Collaborative Cross, and the Genetics of Sex.
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