RT Journal Article
SR Electronic
T1 Inter-homologue repair in fertilized human eggs?
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 181255
DO 10.1101/181255
A1 Dieter Egli
A1 Michael V. Zuccaro
A1 Michal Kosicki
A1 George M. Church
A1 Allan Bradley
A1 Maria Jasin
YR 2017
UL http://biorxiv.org/content/early/2017/08/28/181255.abstract
AB Many human diseases have an underlying genetic component. The development and application of methods to prevent the inheritance of damaging mutations through the human germline could have significant health benefits, and currently include preimplantation genetic diagnosis and carrier screening. Ma et al. take this a step further by attempting to remove a disease mutation from the human germline through gene editing1. They assert the following advances: (i) the correction of a pathogenic gene mutation responsible for hypertrophic cardiomyopathy in human embryos using CRISPR-Cas9 and (ii) the avoidance of mosaicism in edited embryos. In the case of correction, the authors conclude that repair using the homologous chromosome was as or more frequent than mutagenic nonhomologous end-joining (NHEJ). Their conclusion is significant, if validated, because such a “self-repair” mechanism would allow gene correction without the introduction of a repair template. While the authors’ analyses relied on the failure to detect mutant alleles, here we suggest approaches to provide direct evidence for inter-homologue recombination and discuss other events consistent with the data. We also review the biological constraints on inter-homologue recombination in the early embryo.