Abstract: The present invention provides materials and methods for correcting an undesirable nucleic acid sequence (such as a deleterious recessive mutation) in the genome of animals (such as cattle) using site-specific nucleases to facilitate gene correction. In certain embodiments, the present invention can be used to correct mutations associated with a heritable disease selected from alpha-mannosidosis, beta-mannosidosis, arthrogryposis multiplex (AM), contractural arachnodactyly (CA), developmental duplication (DD), neuropathic hydrocephalus (NH), idiopathic epilepsy, osteopetrosis, protoporphyria, pulmonary hypoplasia and anasarca (PHA), titbial hemimelia (TH), Spider Lamb Syndrome (SLS), and Brisket Disease.