A large CRISPR-induced bystander mutation causes immune dysregulation

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 duplicatio...

Descripción completa

Detalles Bibliográficos
Autores principales: Simeonov, Dimitre R., Brandt, Alexander J., Chan, Alice Y., Cortez, Jessica T., Li, Zhongmei, Woo, Jonathan M., Lee, Youjin, Carvalho, Claudia M. B., 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6379443/
https://www.ncbi.nlm.nih.gov/pubmed/30793048
http://dx.doi.org/10.1038/s42003-019-0321-x
Descripción
Sumario: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.

Ejemplares similares