non-mendelian dominant maternal effects caused by crispr/cas9 transgenic components in drosophila melanogaster

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ID: 135395
2016
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Abstract
The CRISPR/Cas9 system has revolutionized genomic editing. The Cas9 endonuclease targets DNA via an experimentally determined guide RNA (gRNA). This results in a double-strand break at the target site . We generated transgenic Drosophila melanogaster in which the CRISPR/Cas9 system was used to target a GAL4 transgene in vivo. To our surprise, progeny whose genomes did not contain CRISPR/Cas9 components were still capable of mutating GAL4 sequences. We demonstrate this effect was caused by maternal deposition of Cas9 and gRNAs into the embryo, leading to extensive GAL4 mutations in both somatic and germline tissues. This serves as a cautionary observation on the effects of maternal contributions when conducting experiments using genomically encoded CRISPR/Cas9 components. These results also highlight a mode of artificial inheritance in which maternal contributions of DNA editing components lead to transmissible mutant defects even in animals whose genomes lack the editing components. We suggest calling this a dominant maternal effect to reflect it is caused by the gain of maternally contributed products. Models of CRISPR-mediated gene drive will need to incorporate dominant maternal effects in order to accurately predict the efficiency and dynamics of gene drive in a population.
Reference Key
lin2016g3:non-mendelian Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors ;Chun-Chieh Lin;Christopher J. Potter
Journal separation and purification technology
Year 2016
DOI
10.1534/g3.116.034884
URL
http://g3journal.org/lookup/doi/10.1534/g3.116.034884
Keywords
gene drive maternal effect

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