Growing evidence suggests that hiPSCs are fundamentally similar regardless of reprogramming methods (Choi et al., 2015, Schlaeger et al., 2015) or donor cell types (Kyttala et al., 2016) and that reprogramming increases the number of genes with a detectable donor effect in disease models (Thomas et al., 2015). Mitochondrial heteroplasmy (Perales-Clemente et al., 2016), genetic (Gore et al., 2011, Hussein et al., 2011, Liu et al., 2014), and epigenetic (Mekhoubad et al., 2012, Nazor et al., 2012) differences all contribute to intra-individual variability between hiPSCs. While genetic errors likely reflect both pre-existing mutations in the source somatic cells (Abyzov et al., 2012, Young et al., 2012) and the stresses associated with cellular replication (Laurent et al., 2011, Lu et al., 2014), epigenetic aberrations occur in hiPSCs regardless of the somatic cell type of origin and likely arise during the reprogramming 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
