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 is not possible to infer whether this allele contributes to the disease. Equally, the effect of genetic background can be investigated in this manner by introducing putative causative lesions into a panel of “WT” iPSCs established from healthy donors from diverse genetic ancestries.