CRISPR/Cas9-induced gene conversion between ATAD3 paralogs.

ABSTRACT: Paralogs and pseudogenes are abundant within the human genome, and can mediate non-allelic homologous recombination (NAHR) or gene conversion events. The ATAD3 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 ATAD3A by CRISPR/Cas9 genome editing. Unexpectedly, two of the generated clones underwent gene conversion, as evidenced by replacement of the targeted sequence of ATAD3A by a donor sequence from its paralog ATAD3B. We highlight the complexity of CRISPR/Cas9 design, end-product formation, and recombination repair mechanisms for CRISPR/Cas9 delivery as a nuc

SUBMITTER: Yanovsky-Dagan S 

PROVIDER: S-EPMC8844715 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature