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CRISPR-Cas9 induces...
CRISPR-Cas9 induces large structural variants at on-target and off-target sites in vivo that segregate across generations
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- Höijer, Ida (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Medicinsk genetik och genomik
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- Emmanouilidou, Anastasia (author)
- Uppsala universitet,Medicinsk genetik och genomik,Science for Life Laboratory, SciLifeLab,Uppsala Univ, Beijer Lab, Uppsala, Sweden.
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- Östlund, Rebecka (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab
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- van Schendel, Robin (author)
- Leiden Univ, Med Ctr, Dept Human Genet, Leiden, Netherlands.
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- Bozorgpana, Selma (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab
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- Tijsterman, Marcel (author)
- Leiden Univ, Med Ctr, Dept Human Genet, Leiden, Netherlands.
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- Feuk, Lars (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Medicinsk genetik och genomik
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- Gyllensten, Ulf B. (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Medicinsk genetik och genomik
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- den Hoed, Marcel, 1980- (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Medicinsk genetik och genomik,Uppsala Univ, Beijer Lab, Uppsala, Sweden.
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- Ameur, Adam (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab
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(creator_code:org_t)
- 2022-02-02
- 2022
- English.
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In: Nature Communications. - : Springer Nature. - 2041-1723. ; 13
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Abstract
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- CRISPR-Cas9 genome editing has potential to cure diseases without current treatments, but therapies must be safe. Here we show that CRISPR-Cas9 editing can introduce unintended mutations in vivo, which are passed on to the next generation. By editing fertilized zebrafish eggs using four guide RNAs selected for off-target activity in vitro, followed by long-read sequencing of DNA from >1100 larvae, juvenile and adult fish across two generations, we find that structural variants (SVs), i.e., insertions and deletions >= 50 bp, represent 6% of editing outcomes in founder larvae. These SVs occur both at on-target and off-target sites. Our results also illustrate that adult founder zebrafish are mosaic in their germ cells, and that 26% of their offspring carries an off-target mutation and 9% an SV. Hence, pre-testing for off-target activity and SVs using patient material is advisable in clinical applications, to reduce the risk of unanticipated effects with potentially large implications.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Höijer, Ida
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Emmanouilidou, A ...
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Östlund, Rebecka
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van Schendel, Ro ...
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Bozorgpana, Selm ...
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Tijsterman, Marc ...
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show more...
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Feuk, Lars
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Gyllensten, Ulf ...
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den Hoed, Marcel ...
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Ameur, Adam
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
- Articles in the publication
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Nature Communica ...
- By the university
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Uppsala University