Journal article
Mitchell L. Leibowitz, Stamatis Papathanasiou, Phillip A. Doerfler, Logan J. Blaine, Lili Sun, Yu Yao, Cheng-Zhong Zhang, M. Weiss, D. Pellman
Nature Genetics, 2020
Nature Genetics, 2020
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APA
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Leibowitz, M. L., Papathanasiou, S., Doerfler, P. A., Blaine, L. J., Sun, L., Yao, Y., … Pellman, D. (2020). Chromothripsis as an on-target consequence of CRISPR-Cas9 genome editing. Nature Genetics.
Chicago/Turabian
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Leibowitz, Mitchell L., Stamatis Papathanasiou, Phillip A. Doerfler, Logan J. Blaine, Lili Sun, Yu Yao, Cheng-Zhong Zhang, M. Weiss, and D. Pellman. “Chromothripsis as an on-Target Consequence of CRISPR-Cas9 Genome Editing.” Nature Genetics (2020).
MLA
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Leibowitz, Mitchell L., et al. “Chromothripsis as an on-Target Consequence of CRISPR-Cas9 Genome Editing.” Nature Genetics, 2020.
BibTeX Click to copy
@article{mitchell2020a,
title = {Chromothripsis as an on-target consequence of CRISPR-Cas9 genome editing},
year = {2020},
journal = {Nature Genetics},
author = {Leibowitz, Mitchell L. and Papathanasiou, Stamatis and Doerfler, Phillip A. and Blaine, Logan J. and Sun, Lili and Yao, Yu and Zhang, Cheng-Zhong and Weiss, M. and Pellman, D.}
}
Abstract
Genome editing has therapeutic potential for treating genetic diseases and cancer. However, the currently most practicable approaches rely on the generation of DNA double-strand breaks (DSBs), which can give rise to a poorly characterized spectrum of chromosome structural abnormalities. Here, using model cells and single-cell whole-genome sequencing, as well as by editing at a clinically relevant locus in clinically relevant cells, we show that CRISPR–Cas9 editing generates structural defects of the nucleus, micronuclei and chromosome bridges, which initiate a mutational process called chromothripsis. Chromothripsis is extensive chromosome rearrangement restricted to one or a few chromosomes that can cause human congenital disease and cancer. These results demonstrate that chromothripsis is a previously unappreciated on-target consequence of CRISPR–Cas9-generated DSBs. As genome editing is implemented in the clinic, the potential for extensive chromosomal rearrangements should be considered and monitored. Chromothripsis, a chromosomal shattering event, can be elicited by micronuclei and chromosome bridges formed by CRISPR–Cas9-generated double-stranded breaks. Extensive chromosomal rearrangements may thus be an on-target effect of genome editing.