Double-strand DNA breaks are introduced into genomic DNA by an endonuclease system such as a zinc finger (ZFN), TALEN, or CRISPR-Cas system. The break is repaired by an endogenous DNA repair mechanism using non-homologous end-joining (NHEJ) or homology-directed repair (HDR). NHEJ may create insertions or deletions, whereas HDR uses a donor DNA template to insert a sequence into the target genomic region to create the desired insertion, deletion, or alteration of genomic sequence.