Inter-homologue repair in fertilized human eggs?

Published on Aug 1, 2018in Nature43.07
· DOI :10.1038/s41586-018-0379-5
Dieter Egli34
Estimated H-index: 34
(Columbia University),
Michael V. Zuccaro2
Estimated H-index: 2
(Columbia University)
+ 3 AuthorsMaria Jasin76
Estimated H-index: 76
(MSK: Memorial Sloan Kettering Cancer Center)
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 editing (1). 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. (1) Ma, H. et al. Correction of a pathogenic gene mutation in human embryos. Nature, doi:10.1038/nature23305 (2017).
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Cited By21
#1Yiping Fan (Boston Children's Hospital)H-Index: 1
#2Jerry Kok Yen Chan (NUS: National University of Singapore)H-Index: 1
#1Jonathan J Wilde (MIT: Massachusetts Institute of Technology)H-Index: 1
#2Tomomi Aida (MIT: Massachusetts Institute of Technology)H-Index: 11
Last.Guoping Feng (MIT: Massachusetts Institute of Technology)H-Index: 1
view all 6 authors...
#1Jessica Cussins (University of California, Berkeley)
#2Leah Lowthorp (University of California, Berkeley)H-Index: 2
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