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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 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.
Afiliação
  • Simeonov DR; Biomedical Sciences Graduate Program, University of California, San Francisco, CA, 94143, USA.
  • Brandt AJ; Department of Microbiology and Immunology, University of California, San Francisco, CA, 94143, USA.
  • Chan AY; Diabetes Center, University of California, San Francisco, CA, 94143, USA.
  • Cortez JT; Innovative Genomics Institute, University of California, Berkeley, CA, 94720, USA.
  • Li Z; Innovative Genomics Institute, University of California, Berkeley, CA, 94720, USA.
  • Woo JM; Department of Chemistry, University of California, Berkeley, CA, 94720, USA.
  • Lee Y; Diabetes Center, University of California, San Francisco, CA, 94143, USA.
  • Carvalho CMB; Department of Pediatrics, University of California, San Francisco, CA, 94143, USA.
  • Indart AC; Biomedical Sciences Graduate Program, University of California, San Francisco, CA, 94143, USA.
  • Roth TL; Department of Microbiology and Immunology, University of California, San Francisco, CA, 94143, USA.
  • Zou J; Diabetes Center, University of California, San Francisco, CA, 94143, USA.
  • May AP; Innovative Genomics Institute, University of California, Berkeley, CA, 94720, USA.
  • Lupski JR; Department of Microbiology and Immunology, University of California, San Francisco, CA, 94143, USA.
  • Anderson MS; Diabetes Center, University of California, San Francisco, CA, 94143, USA.
  • Buaas FW; Innovative Genomics Institute, University of California, Berkeley, CA, 94720, USA.
  • Rokhsar DS; Department of Microbiology and Immunology, University of California, San Francisco, CA, 94143, USA.
  • Marson A; Diabetes Center, University of California, San Francisco, CA, 94143, USA.
Commun Biol ; 2: 70, 2019.
Article em En | MEDLINE | ID: mdl-30793048
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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Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Linfócitos T / Linfócitos T Reguladores / Subunidade alfa de Receptor de Interleucina-2 / Sistemas CRISPR-Cas / Edição de Genes / Mutação Tipo de estudo: Etiology_studies Limite: Animals Idioma: En Revista: Commun Biol Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
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XML
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Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Linfócitos T / Linfócitos T Reguladores / Subunidade alfa de Receptor de Interleucina-2 / Sistemas CRISPR-Cas / Edição de Genes / Mutação Tipo de estudo: Etiology_studies Limite: Animals Idioma: En Revista: Commun Biol Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos