Non-Mendelian Dominant Maternal Effects Caused by CRISPR/Cas9 Transgenic Components in Drosophila melanogaster
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 targe...
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Oxford University Press
2016-11-01
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Online Access: | http://g3journal.org/lookup/doi/10.1534/g3.116.034884 |
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doaj-2142d8479e7946a8aa57a124bfb08b712021-07-02T18:13:48ZengOxford University PressG3: Genes, Genomes, Genetics2160-18362016-11-016113685369110.1534/g3.116.03488425Non-Mendelian Dominant Maternal Effects Caused by CRISPR/Cas9 Transgenic Components in Drosophila melanogasterChun-Chieh LinChristopher J. PotterThe 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.http://g3journal.org/lookup/doi/10.1534/g3.116.034884gene drivematernal effectHACKmutagenic chain reactionMCR |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Chun-Chieh Lin Christopher J. Potter |
spellingShingle |
Chun-Chieh Lin Christopher J. Potter Non-Mendelian Dominant Maternal Effects Caused by CRISPR/Cas9 Transgenic Components in Drosophila melanogaster G3: Genes, Genomes, Genetics gene drive maternal effect HACK mutagenic chain reaction MCR |
author_facet |
Chun-Chieh Lin Christopher J. Potter |
author_sort |
Chun-Chieh Lin |
title |
Non-Mendelian Dominant Maternal Effects Caused by CRISPR/Cas9 Transgenic Components in Drosophila melanogaster |
title_short |
Non-Mendelian Dominant Maternal Effects Caused by CRISPR/Cas9 Transgenic Components in Drosophila melanogaster |
title_full |
Non-Mendelian Dominant Maternal Effects Caused by CRISPR/Cas9 Transgenic Components in Drosophila melanogaster |
title_fullStr |
Non-Mendelian Dominant Maternal Effects Caused by CRISPR/Cas9 Transgenic Components in Drosophila melanogaster |
title_full_unstemmed |
Non-Mendelian Dominant Maternal Effects Caused by CRISPR/Cas9 Transgenic Components in Drosophila melanogaster |
title_sort |
non-mendelian dominant maternal effects caused by crispr/cas9 transgenic components in drosophila melanogaster |
publisher |
Oxford University Press |
series |
G3: Genes, Genomes, Genetics |
issn |
2160-1836 |
publishDate |
2016-11-01 |
description |
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. |
topic |
gene drive maternal effect HACK mutagenic chain reaction MCR |
url |
http://g3journal.org/lookup/doi/10.1534/g3.116.034884 |
work_keys_str_mv |
AT chunchiehlin nonmendeliandominantmaternaleffectscausedbycrisprcas9transgeniccomponentsindrosophilamelanogaster AT christopherjpotter nonmendeliandominantmaternaleffectscausedbycrisprcas9transgeniccomponentsindrosophilamelanogaster |
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1721324691764805632 |