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

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 frequenc...

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Autores principales: Bi, Chongwei, Wang, Lin, Yuan, Baolei, Zhou, Xuan, Li, Yu, Wang, Sheng, Pang, Yuhong, Gao, Xin, Huang, Yanyi, Li, Mo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Method
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7444080/
https://www.ncbi.nlm.nih.gov/pubmed/32831134
http://dx.doi.org/10.1186/s13059-020-02143-8
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author Bi, Chongwei
Wang, Lin
Yuan, Baolei
Zhou, Xuan
Li, Yu
Wang, Sheng
Pang, Yuhong
Gao, Xin
Huang, Yanyi
Li, Mo
author_facet Bi, Chongwei
Wang, Lin
Yuan, Baolei
Zhou, Xuan
Li, Yu
Wang, Sheng
Pang, Yuhong
Gao, Xin
Huang, Yanyi
Li, Mo
author_sort Bi, Chongwei
collection PubMed
description 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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spelling pubmed-74440802020-08-26 Long-read individual-molecule sequencing reveals CRISPR-induced genetic heterogeneity in human ESCs Bi, Chongwei Wang, Lin Yuan, Baolei Zhou, Xuan Li, Yu Wang, Sheng Pang, Yuhong Gao, Xin Huang, Yanyi Li, Mo Genome Biol Method 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. BioMed Central 2020-08-24 /pmc/articles/PMC7444080/ /pubmed/32831134 http://dx.doi.org/10.1186/s13059-020-02143-8 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Method
Bi, Chongwei
Wang, Lin
Yuan, Baolei
Zhou, Xuan
Li, Yu
Wang, Sheng
Pang, Yuhong
Gao, Xin
Huang, Yanyi
Li, Mo
Long-read individual-molecule sequencing reveals CRISPR-induced genetic heterogeneity in human ESCs
title Long-read individual-molecule sequencing reveals CRISPR-induced genetic heterogeneity in human ESCs
title_full Long-read individual-molecule sequencing reveals CRISPR-induced genetic heterogeneity in human ESCs
title_fullStr Long-read individual-molecule sequencing reveals CRISPR-induced genetic heterogeneity in human ESCs
title_full_unstemmed Long-read individual-molecule sequencing reveals CRISPR-induced genetic heterogeneity in human ESCs
title_short Long-read individual-molecule sequencing reveals CRISPR-induced genetic heterogeneity in human ESCs
title_sort long-read individual-molecule sequencing reveals crispr-induced genetic heterogeneity in human escs
topic Method
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7444080/
https://www.ncbi.nlm.nih.gov/pubmed/32831134
http://dx.doi.org/10.1186/s13059-020-02143-8
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