Evidence that APP gene copy number changes reflect recombinant vector contamination

Kim, Junho; Zhao, Boxun; Huang, August Yue; Miller, Michael B.; Lodato, Michael A.; Walsh, Christopher A.; Lee, Eunjung Alice

doi:10.1101/706788

Search citation statements

Order By: Relevance

Paper Sections

Select...

Trends In Genetics1

Citation Types

Supporting

Mentioning

Contrasting

Year Published

2019

2020

Publication Types

Select...

Article1

Preprint1

Relationship

Self Cite0

Independent2

Authors

Journals

Cited by 2 publications

(1 citation statement)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, much remains unclear about the role of TEs in AD and there are conflicting reports on the topic (see e.g., [100]). It is not known if TE activation and somatic transposition have a role in the disease process, or if they are by-products of other more important pathological processes.…”

Section: Trends In Geneticsmentioning

confidence: 99%

Transposable Elements: A Common Feature of Neurodevelopmental and Neurodegenerative Disorders

et al. 2020

View full text Add to dashboard Cite

Section: Trends In Geneticsmentioning

confidence: 99%

Transposable Elements: A Common Feature of Neurodevelopmental and Neurodegenerative Disorders

et al. 2020

View full text Add to dashboard Cite

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

Lee

Liu

Zhu

et al. 2019

Preprint

View full text Add to dashboard Cite

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

show abstract

Evidence that APP gene copy number changes reflect recombinant vector contamination

Cited by 2 publications

References 20 publications

Transposable Elements: A Common Feature of Neurodevelopmental and Neurodegenerative Disorders

Transposable Elements: A Common Feature of Neurodevelopmental and Neurodegenerative Disorders

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

Contact Info

Product

Resources

About