Long-read individual-molecule sequencing reveals CRISPR-induced genetic heterogeneity in human ESCs

Long-read individual-molecule sequencing reveals CRISPR-induced genetic heterogeneity in human ESCs

Abstract Quantifying the genetic heterogeneity of a cell population is essential to understanding of biological systems. We develop a universal method to label individual DNA molecules for single-base-resolution haplotype-resolved quantitative characterization of diverse types of rare variants, with...

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Bibliographic Details
Main Authors: Chongwei Bi, Lin Wang, Baolei Yuan, Xuan Zhou, Yu Li, Sheng Wang, Yuhong Pang, Xin Gao, Yanyi Huang, Mo Li
Format: Article
Language:English
Published: BMC 2020-08-01
Series:Genome Biology
Subjects:
Human embryonic stem cell
CRISPR-Cas9
Genome editing
Nanopore sequencing
Long-read sequencing
Next-generation sequencing
Online Access:http://link.springer.com/article/10.1186/s13059-020-02143-8
Description
Summary:Abstract Quantifying the genetic heterogeneity of a cell population is essential to understanding of biological systems. We develop a universal method to label individual DNA molecules for single-base-resolution haplotype-resolved quantitative characterization of diverse types of rare variants, with frequency as low as 4 × 10−5, using both short- or long-read sequencing platforms. It provides the first quantitative evidence of persistent nonrandom large structural variants and an increase in single-nucleotide variants at the on-target locus following repair of double-strand breaks induced by CRISPR-Cas9 in human embryonic stem cells.
ISSN:1474-760X

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