Our ultimate goal was to obtain clonal blood, which provided us with a physiological method to amplify stem-cell genomes. As outlined (Fig. 4a), four months after transplantation, we isolated the CD45.2+ HSC progeny and performed whole-genome sequencing at 20× coverage; tail DNA from the donor mouse served as the germline reference. This allowed us to detect heterozygous somatic changes, which are absent in the matched germline reference and represent mutations in the HSC. Genomes of Aldh2−/−Fancd2−/− HSCs were mutated with increased prevalence of indels, rearrangements and translocations (Fig. 5a, Extended Data Fig. 4).
