Format

Send to

Choose Destination
PLoS One. 2017 Jun 1;12(6):e0178700. doi: 10.1371/journal.pone.0178700. eCollection 2017.

Frameshift indels introduced by genome editing can lead to in-frame exon skipping.

Author information

1
Montreal Heart Institute, Montreal, Quebec, Canada.
2
Department of Biochemistry & Biophysics, UCSF, San Francisco, California, United States of America.
3
Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
4
Faculty of Medicine, Université de Montréal, Montreal, Quebec, Canada.
5
Department of Biomedical Data Science, Stanford University, Stanford, California, United States of America.

Abstract

The introduction of frameshift indels by genome editing has emerged as a powerful technique to study the functions of uncharacterized genes in cell lines and model organisms. Such mutations should lead to mRNA degradation owing to nonsense-mediated mRNA decay or the production of severely truncated proteins. Here, we show that frameshift indels engineered by genome editing can also lead to skipping of "multiple of three nucleotides" exons. Such splicing events result in in-frame mRNA that may encode fully or partially functional proteins. We also characterize a segregating nonsense variant (rs2273865) located in a "multiple of three nucleotides" exon of LGALS8 that increases exon skipping in human erythroblast samples. Our results highlight the potentially frequent contribution of exonic splicing regulatory elements and are important for the interpretation of negative results in genome editing experiments. Moreover, they may contribute to a better annotation of loss-of-function mutations in the human genome.

PMID:
28570605
PMCID:
PMC5453576
DOI:
10.1371/journal.pone.0178700
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center