Abstract
Unintended on-target chromosomal instability following CRISPR/Cas9 single gene targeting
Highlights
We report that Clustered regularly interspaced short palindromic repeats (CRISPR)/Cas[9] targeting of genes in close proximity to telomeres can result in chromosome arm truncations
The proportion of samples affected by loss of heterozygosity (LOH) of all heterozygous single-nucleotide polymorphisms (SNPs) downstream of ZNF516 varied between 2% for CRISPR RNAs (crRNAs) ‘C’ and 7% for crRNA ‘A’, indicating that perhaps the efficiency of a particular crRNA to induce mutation could correlate with its efficiency of chromosome arm truncation
In this study we demonstrate that CRISPR/Cas[9] targeting can induce inadvertent arm truncation
Summary
We report that CRISPR/Cas[9] targeting of genes in close proximity to telomeres can result in chromosome arm truncations. We suggest assessing heterozygous single-nucleotide polymorphisms (SNPs) downstream of targeted genes to select clones without arm truncations.
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