CRISPR/Cas9-induced gene conversion between paralogs.

TitleCRISPR/Cas9-induced gene conversion between paralogs.
Publication TypeJournal Article
Year of Publication2022
AuthorsYanovsky-Dagan, S, Frumkin, A, Lupski, JR, Harel, T
JournalHGG Adv
Date Published2022 Apr 14

Paralogs and pseudogenes are abundant within the human genome, and can mediate non-allelic homologous recombination (NAHR) or gene conversion events. The locus contains three paralogs situated in tandem, and is therefore prone to NAHR-mediated deletions and duplications associated with severe neurological phenotypes. To study this locus further, we aimed to generate biallelic loss-of-function variants in by CRISPR/Cas9 genome editing. Unexpectedly, two of the generated clones underwent gene conversion, as evidenced by replacement of the targeted sequence of by a donor sequence from its paralog We highlight the complexity of CRISPR/Cas9 design, end-product formation, and recombination repair mechanisms for CRISPR/Cas9 delivery as a nucleic acid molecular therapy when targeting genes that have paralogs or pseudogenes, and advocate meticulous evaluation of resultant clones in model organisms. In addition, we suggest that endogenous gene conversion may be used to repair missense variants in genes with paralogs or pseudogenes.

Alternate JournalHGG Adv
PubMed ID35199044
PubMed Central IDPMC8844715