There are two main strategies for using genome editing techniques in iPSC models of disease. The first involves repairing a pre-existing, presumed causative allele from an iPSC line derived from a patient with the disease (Fig. 2, isogenic pair 1). This establishes whether this particular genetic change contributes to the disease phenotype, but does not provide any information about whether it is sufficient to cause disease. It also has the substantial benefit that the patient-derived cell line would be expected to express whatever cellular or molecular phenotype that is causing the disease, and therefore reversion of this phenotype in the edited line can be used as a readout. The second strategy involves taking an iPSC line from a healthy patient, and introducing a putatively important lesion (Fig. 2, isogenic pair 2). This is perhaps a more stringent assay, since it establishes whether this single genetic change is sufficient to cause the disease phenotype, since it removes it from the genetic background of the diseased individual. However, if no effect is seen on the molecular or cellular phenotype of interest, it
