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.