process (Ma et al., 2014). Genetic and epigenetic errors can distinguish hiPSC lines from the same individual. Since such mutations are assumed to arise at equal frequency in hiPSCs reprogrammed from cases and controls, they are not typically considered serious impediments to disease-modeling studies if multiple hiPSC lines are used in comparisons. Although hiPSC-based models are generally assumed to capture the genetic variants contributing to a disease state, notable exceptions have been reported. First, not only can trisomy correction be facilitated by selecting against a transgene (TKNEO) targeted to one copy of chromosome 21 (chr 21) (Li et al., 2012), but spontaneous derivation of isogenic controls can also occur in Down syndrome trisomy 21 hiPSCs (Weick et al., 2013). Second, in hiPSCs derived from a patient with Miller-Dieker syndrome (MDS; MIM #247200), patient fibroblasts lost an abnormal ring chr 17 during hiPSC derivation and duplicated the wild-type homolog, apparently via a compensatory uniparental disomy mechanism (Bershteyn et al., 2014).
