Importantly, such experiments also allow the identification of the causative lesion that defines the cellular phenotype and results in the disease (Nishizaki and Boyle 2016). This is not possible from comparisons of iPSC lines derived from patients with the disease and healthy controls, due to the inheritance patterns of linked SNPs. Often several SNPs are in linkage disequilibrium (LD) with each other, and as such are always inherited together (Weiss and Clark 2002) (Fig. 3). Deciphering which of these are causative is therefore a challenge, and although it is possible to infer some information from their position relative to known important genomic features (e.g. protein coding sequence, DNAse hypersensitive sites, etc.), experimentally identifying the important genetic aberration is still not trivial. Genome editing allows the attractive possibility of either repairing the putative causative lesions in patient-derived cells, or introducing them in cells derived from healthy individuals (Fig. 2), to unambiguously identify the mutations involved in the disease phenotype.
