HiPSCs have proved to be useful in modeling of monogenic disorders, but the real power of these models lies in their ability to model complex genetic disorders, where multiple genes and multiple genetic backgrounds are typically at work in disease pathogenesis and for which it is not informative to engineer a single penetrant mutation into an ESC line or rodent. The approach for modeling complex genetic disorders with hiPSCs has been to compare phenotypes and gene expression in a sufficient number of patient-derived and control lines in order to get mechanistic insights into the neurobiological bases of the disorder (Table 1). In these studies, the choice of patients and controls, the overall design of the study and the clinical phenotyping are key.
