2026-10-14 https://api.researchdata.se/oai-pmh

oai:researchdata.se:2024-335/1 2024-08-21 subject:ssif:30107 subject:ssif:301 subject:ssif:3 principal:slug:uppsala-university

info:eu-repo/semantics/other http://purl.org/dc/dcmitype/Dataset https://doi.org/10.57804/h5c9-h093 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" https://orcid.org/0000-0002-3915-3384 Anastasia Emmanouilidou Rebecka Östlund Robin van Schendel https://orcid.org/0000-0003-2355-2919 https://orcid.org/0000-0002-6316-3355 https://orcid.org/0000-0001-6085-6749 Medical Genetics and Genomics Medicinsk genetik och genomik 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. info:eu-repo/semantics/openAccess Uppsala University Uppsala universitet 2021-08-11T00:00:00Z eng