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A large CRISPR-induced bystander mutation causes immune dysregulation
- Simeonov, Dimitre R;
- Brandt, Alexander J;
- Chan, Alice Y;
- Cortez, Jessica T;
- Li, Zhongmei;
- Woo, Jonathan M;
- Lee, Youjin;
- Carvalho, Claudia MB;
- Indart, Alyssa C;
- Roth, Theodore L;
- Zou, James;
- May, Andrew P;
- Lupski, James R;
- Anderson, Mark S;
- Buaas, F William;
- Rokhsar, Daniel S;
- Marson, Alexander
- et al.
Published Web Location
https://doi.org/10.1038/s42003-019-0321-xAbstract
A persistent concern with CRISPR-Cas9 gene editing has been the potential to generate mutations at off-target genomic sites. While CRISPR-engineering mice to delete a ~360 bp intronic enhancer, here we discovered a founder line that had marked immune dysregulation caused by a 24 kb tandem duplication of the sequence adjacent to the on-target deletion. Our results suggest unintended repair of on-target genomic cuts can cause pathogenic "bystander" mutations that escape detection by routine targeted genotyping assays.
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