The use of induced pluripotent stem cells (iPSCs) in research and translational medicine depends on our ability to identify iPSC cell lines that do not contain potentially dangerous mutations that can lead to cancer, degeneration or uncontrolled variability in cell survival or function. Such mutations may arise from numerous sources including somatic mutations that originated in patient donor cells during development or aging, and as a consequence of particular reprogramming methods. In order to identify the cause of mutations in iPSCs we have developed and successfully optimized a lineage tracing approach to identify clonally related sister iPSCs that we produce from fibroblasts and blood cells, which are the two most promising sources for patient specific iPSCs. This advance now allows us to perform whole genome sequencing on these iPSCs and determine the major source and type of mutation that arise under different commonly used conditions for iPSC generation. Results of genome sequencing of these iPSCs will inform future efforts to identify the best means to produce iPSCs for research and therapeutic applications.