Stem cell research offers new tools to help treat and cure diseases that affect diverse cells types in the body such as neurological diseases, heart disease and diabetes by producing human cells for transplantation or to enable drug discovery . Recent advances have allowed researchers to generate patient-matched cell types from the skin or other tissues of patients. These patient-matched cells are important because they are unlikely to cause immune rejection upon transplantation and they may help to model diseases caused by gene variations found only in rare individuals. Despite their promise, patient-matched cells differ from traditional stem cells in ways that may cause them to be less stable or increase their potential to cause tumors. This is because patient-matched cells are generated from tissues taken from adult patients using methods that dramatically alter the chromosomes of these cells. These factors could endow these reprogrammed cells with mutations that would not be present in cells derived from embryonic sources. To ensure the safety and clinical utility of reprogrammed cells, it is critical to establish methods to identify potentially oncogenic or detrimental mutations. This proposal is designed to identify the source and scope of mutations in reprogrammed pluripotent cell lines using cutting edge whole genome sequencing methods. Results of these studies will establish the relative safety of current methods to produce patient-matched reprogrammed cells and help to improve methods to speed the translation of these advances into therapies.