Skip to main content

A large CRISPR-induced bystander mutation causes immune dysregulation.

Citation
Simeonov, D. R., et al. “A Large Crispr-Induced Bystander Mutation Causes Immune Dysregulation.”. Communications Biology, p. 70.
Author Dimitre R Simeonov, Alexander J Brandt, Alice Y Chan, Jessica T Cortez, Zhongmei Li, Jonathan M Woo, Youjin Lee, Claudia M B Carvalho, Alyssa C Indart, Theodore L Roth, James Zou, Andrew P May, James R Lupski, Mark S Anderson, William Buaas, Daniel S Rokhsar, Alexander Marson
Abstract

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.

Year of Publication
2019
Journal
Communications biology
Volume
2
Number of Pages
70
Date Published
12/2019
ISSN Number
2399-3642
DOI
10.1038/s42003-019-0321-x
Alternate Journal
Commun Biol
PMID
30793048
PMCID
PMC6379443
Download citation