Thus, a key question for human iPSC-based modeling of sporadic diseases is how to generate paired isogenic cell lines that only differ at relevant risk variants14. Recently, the CRISPR/Cas9 gene editing approach has been used to generate isogenic iPSC lines that differ at a PD-associated risk variant55. The ability to generate genetically controlled isogenic iPSC lines in which specific disease-associated genetic risk variants are the sole variable creates a well-controlled system, which in combination with an allele-specific assay has enabled robust dissection of a genetic risk variant for Parkinson’s disease55. This experimental paradigm could be applied to studying genetic risk factors associated with other diseases.
