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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 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.

SUBMITTER: Bi C

PROVIDER: S-EPMC7444080 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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

Bi Chongwei C Wang Lin L Yuan Baolei B Zhou Xuan X Li Yu Y Wang Sheng S Pang Yuhong Y Gao Xin X Huang Yanyi Y Li Mo M

Genome biology 20200824 1

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<sup>-5</sup>, using both short- or long-read sequencing platforms. It provides the first quantitative evidence of persistent nonrandom large structural variants and an increase in s ...[more]

PMID: 32831134

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