PT - JOURNAL ARTICLE AU - Dan Liang AU - Nuria Marti Gutierrez AU - Tailai Chen AU - Yeonmi Lee AU - Sang-Wook Park AU - Hong Ma AU - Amy Koski AU - Riffat Ahmed AU - Hayley Darby AU - Ying Li AU - Crystal Van Dyken AU - Aleksei Mikhalchenko AU - Thanasup Gonmanee AU - Tomonari Hayama AU - Han Zhao AU - Keliang Wu AU - Jingye Zhang AU - Zhenzhen Hou AU - Jumi Park AU - Chong-Jai Kim AU - Jianhui Gong AU - Yilin Yuan AU - Ying Gu AU - Yue Shen AU - Susan B. Olson AU - Hui Yang AU - David Battaglia AU - Thomas O’Leary AU - Sacha A. Krieg AU - David M. Lee AU - Diana H. Wu AU - P. Barton Duell AU - Sanjiv Kaul AU - Jin-Soo Kim AU - Stephen B. Heitner AU - Eunju Kang AU - Zi-Jiang Chen AU - Paula Amato AU - Shoukhrat Mitalipov TI - FREQUENT GENE CONVERSION IN HUMAN EMBRYOS INDUCED BY DOUBLE STRAND BREAKS AID - 10.1101/2020.06.19.162214 DP - 2020 Jan 01 TA - bioRxiv PG - 2020.06.19.162214 4099 - http://biorxiv.org/content/early/2020/06/20/2020.06.19.162214.short 4100 - http://biorxiv.org/content/early/2020/06/20/2020.06.19.162214.full AB - Applications of genome editing ultimately depend on DNA repair triggered by targeted double-strand breaks (DSBs). However, repair mechanisms in human cells remain poorly understood and vary across different cell types. Here we report that DSBs selectively induced on a mutant allele in heterozygous human embryos are repaired by gene conversion using an intact wildtype homolog as a template in up to 40% of targeted embryos. We also show that targeting of homozygous loci facilitates an interplay of non-homologous end joining (NHEJ) and gene conversion and results in embryos which carry identical indel mutations on both loci. Additionally, conversion tracks may expand bidirectionally well beyond the target region leading to an extensive loss of heterozygosity (LOH). Our study demonstrates that gene conversion and NHEJ are two major DNA DSB repair mechanisms in preimplantation human embryos. While gene conversion could be applicable for gene correction, extensive LOH presents a serious safety concern.Competing Interest StatementThe authors have declared no competing interest.