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

Chongwei Bi; Lin Wang; Baolei Yuan; Xuan Zhou; Yu Li; Sheng Wang; Yuhong Pang; Xin Gao; Yanyi Huang; Mo Li

doi:10.1186/s13059-020-02143-8

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

Authors

Bi, Chongwei¹
Wang, Lin^{1, 2}
Yuan, Baolei¹
Zhou, Xuan¹
Li, Yu³
Wang, Sheng³
Pang, Yuhong⁴
Gao, Xin³
Huang, Yanyi^{4, 5}
Li, Mo¹

¹ King Abdullah University of Science and Technology (KAUST), Thuwal, 23955-6900, Kingdom of Saudi Arabia , Thuwal (Saudi Arabia)
² Jilin University, Changchun, China , Changchun (China)
³ King Abdullah University of Science and Technology (KAUST), Thuwal, 23955-6900, Saudi Arabia , Thuwal (Saudi Arabia)
⁴ Peking University, Beijing, China , Beijing (China)
⁵ Shenzhen Bay Laboratory, Shenzhen, China , Shenzhen (China)

Type

Published Article

Publication Date

Aug 24, 2020

Volume

21

Issue

1

Identifiers

DOI: 10.1186/s13059-020-02143-8

Source

Springer Nature

Keywords

License

Green

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.

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