Skip to main content
Open Access Publications from the University of California

A large CRISPR-induced bystander mutation causes immune dysregulation.

  • Author(s): 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.

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.

Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.

Main Content
Current View