Whole genome sequencing of mouse embryos with Cas9-induced chromosomal instability

Karyotype alterations have emerged as on-target complications from CRISPR-Cas9 germline genome editing. Using imaging and single-cell genome sequencing of 8-cell blastomeres, we tracked both spontaneous and Cas9-induced karyotype aberrations through the first three divisions of embryonic development. We elucidate mechanisms generating common karyotype aberrations, including the loss of entire targeted chromosome that has been commonly observed after genome editing in embryos.

染色体组型改变（Karyotype alterations）已成为CRISPR-Cas9生殖系基因组编辑所引发的靶向相关并发症。本研究通过对8细胞期卵裂球（8-cell blastomeres）进行成像分析与单细胞基因组测序，追踪了胚胎发育前三次卵裂过程中自发产生及Cas9诱导的染色体组型畸变。本研究阐明了常见染色体组型畸变的产生机制，其中包括胚胎基因组编辑后常被观测到的整条靶向染色体丢失现象。