title: Non-Mendelian Dominant Maternal Effects Caused by CRISPR/Cas9 Transgenic Components inDrosophila melanogaster.
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 transgenicDrosophila melanogasterin which the CRISPR/Cas9 system was used to target aGAL4transgenein vivoTo our surprise, progeny whose genomes did not contain CRISPR/Cas9 components were still capable of mutatingGAL4sequences. We demonstrate this effect was caused by maternal deposition of Cas9 and gRNAs into the embryo, leading to extensiveGAL4mutations 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.
authors.affiliation: The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
authors.forename: Chun-Chieh
authors.initials: CC
authors.lastname: Lin
authors.affiliation: The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205 cpotter@jhmi.edu.
authors.forename: Christopher J
authors.identifier: http://orcid.org/0000-0002-5223-8112
authors.initials: CJ
authors.lastname: Potter
keywords: HACK; MCR; gene drive; maternal effect; mutagenic chain reaction