Correction of the marked β^6I globin gene by HR. Southern analysis of DNA derived from G418-resistant ES cell clones. DNA was digested with EcoRV and BglII and hybridized with the internal probe. Shown above each lane is the genotype of the individual ES cell clone. The fragments marked with a star (*) were generated by the randomly integrated vector DNA sequences. The ES cell clones represented in lanes 1-5 and 7-8 contained randomly integrated correcting DNA within the genome (WT/β^6I + RI). The ES clone represented in lane 6 did not produce a mutant 2.7-kb band (marked with an open circle [○]), revealing that this clone had undergone HR-mediated correction of the β^6I mutation (WT/C). WT indicates wild-type allele; C, corrected allele; and RI, random integrant.