Evidence that APP gene copy number changes reflect recombinant vector contamination

Citation:

Kim J, Zhao B, Huang AY, Miller MB, Lodato MA, Walsh CA**, Lee EA**. Evidence that APP gene copy number changes reflect recombinant vector contamination [Internet]. Nature Submitted;

Abstract:

Lee et al. (hereafter “the Lee study”) have recently reported that RNA-mediated somatic recombination or somatic retrotransposition of the APP gene occurs in neurons from both control individuals and those with sporadic Alzheimer's disease (AD). As evidence of somatic APP retrotransposition, the authors present various forms of APP genomic cDNA (gencDNA) in PCR-based (Sanger sequencing, SMRT sequencing) and non-PCR-based (targeted hybrid-capture sequencing, DNA in situ hybridization (DISH)) experiments. They also report greater prevalence of APP gencDNA in AD neurons compared to control neurons (69% vs 25% of neurons with at least one APP retrogene insertion on average, Fig. 5 and Extended Data Fig. 5 in the Lee study) as well as its greater diversity. We reanalyzed the APP-targeted sequencing data from the Lee study, revealing evidence that APP gencDNA originates mainly from the contamination by exogenous APP recombinant vectors, rather from true somatic retrotransposition of endogenous APP. We also present our own single-cell whole genome sequencing (scWGS) data that show no evidence for somatic APP retrotransposition in AD neurons or in neurons from normal individuals of various ages.

Publisher's Version

Last updated on 07/29/2019