Reply to: APP gene copy number changes reflect exogenous contamination

Analyses of independently published data sets4 produced by whole-exome pull-down of DNA from laser-captured human hippocampus or blood revealed ten different APP insertion sites within eight different chromosomes (Fig. 1, Supplementary Table 1). The DISH and RISH results support the existence ofAPP gencDNAs and IEJs (see Supplementary Discussion and Lee et al.2 Fig. 2, Extended Data Figs. 1, 2) by using custom-designed and validated commercial probe technology (Advanced Cell Diagnostics, ACD), which was independently shown to detect exon-exonjunctions10 and single-nucleotide mutations11. [...]gencDNAs and IEJs can be detected in the absence of targeted PCR. The change is also apparent when comparing cell types; signals are vastly more prevalent in neurons than in non-neuronal cells from the same brains of individuals with SAD when the samples are processed at the same time by DISH (Lee et al.2 Fig. 5). Independent peptide nucleic acid fluorescence in situ hybridization (PNA-FISH) and dual-point-paint experiments from our previous work further support APP gencDNAs3 (Table 1).