Supplementary data for "CRISPR-Cas9 induces large structural variants at on-target and off-target sites in vivo" Supplementary data for "CRISPR-Cas9 induces large structural variants at on-target and off-target sites in vivo" 2024-335-1 https://doi.org/10.57804/h5c9-h093 Swedish National Data Service Svensk nationell datatjänst Landing page Supplementary data for "CRISPR-Cas9 induces large structural variants at on-target and off-target sites in vivo" Supplementary data for "CRISPR-Cas9 induces large structural variants at on-target and off-target sites in vivo" 2024-335-1 https://doi.org/10.57804/h5c9-h093 10.1038/s41467-022-28244-5 urn:nbn:se:uu:diva-450143 Höijer, Ida Höijer, Ida Emmanouilidou, Anastasia Emmanouilidou, Anastasia Östlund, Rebecka Östlund, Rebecka van Schendel, Robin van Schendel, Robin Feuk, Lars Feuk, Lars Gyllensten, Ulf B. Gyllensten, Ulf B. Ameur, Adam Ameur, Adam Swedish National Data Service Svensk nationell datatjänst Landing page medicine (science) medicin genetics genetik genetic research genforskning DNA analysis dna-analys genome arvsmassa DNA DNA 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. The data files contain supplementary information for the manuscript "CRISPR-Cas9 induces large structural variants at on-target and off-target sites in vivo". The dataset was originally published in DiVA and moved to SND in 2024. Datafilerna innehåller kompletterande information för manuskriptet "CRISPR-Cas9 induces large structural variants at on-target and off-target sites in vivo". Se engelsk version av denna katalogpost för längre beskrivning. Datasetet har ursprungligen publicerats i DiVA och flyttades över till SND 2024. Numeric Text Still image Access to data through SND. Data are freely accessible. Åtkomst till data via SND. Data är fritt tillgängliga. openAccess Höijer, I., Emmanouilidou, A., Östlund, R. et al. CRISPR-Cas9 induces large structural variants at on-target and off-target sites in vivo that segregate across generations. Nat Commun 13, 627 (2022). https://doi.org/10.1038/s41467-022-28244-5 Höijer, I., Emmanouilidou, A., Östlund, R. et al. CRISPR-Cas9 induces large structural variants at on-target and off-target sites in vivo that segregate across generations. Nat Commun 13, 627 (2022). https://doi.org/10.1038/s41467-022-28244-5 10.1038/s41467-022-28244-5 urn:nbn:se:uu:diva-450143 2022