Reply: Evidence that APP gene copy number changes reflect recombinant vector contamination

摘要: In the accompanying comment1, Kim et al. concluded that somatic gene recombination (SGR) and amyloid precursor protein (APP) genomic complementary DNAs (gencDNAs) in brain are contamination artifacts do not naturally exist. We disagree. Here we address three types of analyses used by to reach their conclusions: informatic contaminant identification, plasmid PCR, single-cell sequencing. Additionally, requested "reads supporting novel APP insertion breakpoints", now provide 10 different examples support gencDNA within eight chromosomes beyond wildtype on chromosome 21 from Alzheimer9s disease (AD) samples. If SGR exists as experimentally supported here previously2,3, scenarios become moot. Our data generated an independent laboratory (Park al.)4, complement entirely consistent with what Lee al.2 presented via nine distinct lines evidence, addition a prior publication3. Plasmid was identified single pull-down dataset after publication al.2; however subsequent did alter any our conclusions including those publications3,5 contamination-free replication this approach ourselves others original conclusions. Novel retro-insertion sites, alterations number form cell type same pathogenic SNVs occurring only AD, all existence gencDNAs produced SGR.