Cellular libraries useful for in vitro phenotyping and gene mapping. In a representative approach, a method for preparing a homozygous cellular library includes the steps of providing a heterozygous cellular library comprising a plurality of isolated parent cells; inducing site-specific mitotic recombination in the plurality of isolated parent cells; culturing the plurality of isolated parent cells, whereby a population of daughter cells is produced; and selecting daughter cells comprising a homozygous genetic modification, whereby a homozygous cellular library is prepared.