The comparison of Ends-In and Ends-Out homologous recombination. Ends-In and Ends-Out are two paradigms for gene targeting. The major difference is whether the DSB is located within the region of homology (Ends-In) or at the ends (Ends-Out). The figure compares the basic outcomes of these two methods. With ends-in (left), a break is made within the region of homology. Recombination with the target results in a tandem duplication of all the homologous sequence carried on the donor, separated by any sequences that are between the FRT sites (in this case, the white+ and I-CreI site). In contrast, Ends-Out provides a simple replacement event between the genome and the homologous sequence. The result is to interrupt the targeted gene with a modified, heterologous sequence, such as the w+ marker (right).