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.

中文翻译：

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长读长个体分子测序揭示了 CRISPR 诱导的人类 ESC 遗传异质性

量化细胞群的遗传异质性对于理解生物系统至关重要。我们开发了一种通用方法来标记单个 DNA 分子，以使用短读长或长读长测序平台对不同类型的稀有变异进行单碱基分辨率单倍型分辨率定量表征，频率低至 4 × 10 -5 。它提供了第一个定量证据，证明在人胚胎干细胞中由 CRISPR-Cas9 诱导的双链断裂修复后，在目标基因座上存在持久性非随机大结构变异和单核苷酸变异增加。