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

By Ming-Hsiang Lee, Christine S. Liu, Yunjiao Zhu, Gwendolyn E. Kaeser, Richard Rivera, William J Romanow, Yasuyuki Kihara, Jerold Chun

Posted 13 Aug 2019
bioRxiv DOI: 10.1101/730291

Kim et al. conclude that somatic gene recombination (SGR) and amyloid precursor protein (APP) genomic complementary DNAs (gencDNAs) in brain are plasmid PCR artifacts and do not naturally exist. We disagree. Lee et al. presented a total of nine distinct approaches, in addition to three from a prior publication, which support the existence of APP gencDNAs, and seven of these are independent of APP PCR (Table 1). Contamination in our pull-down dataset was identified after publication of Lee et al.; however subsequent analyses showed that the contamination does not change any of our conclusions including those in our other publications (see below). Notably, alterations of APP gencDNA number and form by Alzheimer's disease (AD) and cell-type cannot be explained by plasmid contamination and PCR artifact. Here we provide data and discussion, which address the three analyses used by Kim et al. to reach their conclusions: plasmid contaminant identification, plasmid PCR, and single-cell sequencing.

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