Evidence map›Paper›PMID 30955886›Full record

ArticleCell2019

Genome-wide de novo L1 Retrotransposition Connects Endonuclease Activity with Replication.

Diane A Flasch, Ángela Macia, Laura Sánchez, Mats Ljungman, Sara R Heras, José L García-Pérez, Thomas E Wilson, John V Moran

Open access · greenAbstract read
In one paragraph

Article in Cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.

0numbers the graph read from it
0cells of the map it votes in
88citing papers in PubMed
19.8field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

88 citing papers in PubMed, 125 citations in OpenAlex.

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  11. Long-read sequencing reveals genomic and epigenomic variation in the dark genome of human Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
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28 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 3 countries.

Diane A FlaschDepartment of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan, 48109, USA. Electronic address: daflasch@umich.edu.
Ángela MaciaDepartment of Genomic Medicine, GENYO: Centre for Genomics and Oncology (Pfizer-University of Granada and Andalusian Regional Government), PTS Granada, 18016, Spain.
Laura SánchezDepartment of Genomic Medicine, GENYO: Centre for Genomics and Oncology (Pfizer-University of Granada and Andalusian Regional Government), PTS Granada, 18016, Spain.
Mats LjungmanDepartment of Radiation Oncology, University of Michigan Comprehensive Cancer Center, Translational Oncology Program and Center for RNA Biomedicine, University of Michigan, Ann Arbor, Michigan, 48109, USA; Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, Michigan, 48109, USA.
Sara R HerasDepartment of Genomic Medicine, GENYO: Centre for Genomics and Oncology (Pfizer-University of Granada and Andalusian Regional Government), PTS Granada, 18016, Spain.
José L García-PérezDepartment of Genomic Medicine, GENYO: Centre for Genomics and Oncology (Pfizer-University of Granada and Andalusian Regional Government), PTS Granada, 18016, Spain; Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine (IGMM), University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, UK.
Thomas E WilsonDepartment of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan, 48109, USA; Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, 48109, USA. Electronic address: wilsonte@umich.edu.
John V MoranDepartment of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan, 48109, USA; Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, 48109, USA. Electronic address: moranj@umich.edu.
University of Michigan–Ann Arbor · USPfizer-University of Granada-Junta de Andalucía Centre for Genomics and Oncological Research · ESMedical Research Council · GB

Funding

University of Michigan Training Program in Genomic ScienceT32HG000040 · NHGRI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Sebastian Zoellner · 1995 to 2026
$16.4M
Gen. &Mol. Analysis of Human LINE-1 RetrotranspositionR01GM060518 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MORAN, JOHN V. · 1999 to 2024
$4.8M
2/3 Schizophrenia Genetics and Brain Somatic MosaicismU01MH106892 · NIMH · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MORAN, JOHN V. · 2015 to 2019
$4.7M
Systematic Genetic Analysis of Yeast NHEJR01GM120767 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI WILSON, THOMAS EDWARD · 2016 to 2025
$2.8M
Extreme genomic instability at large transcribed genes: mechanisms and consequences for the cancer genomeR01CA200731 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI GLOVER, THOMAS W, WILSON, THOMAS EDWARD · 2016 to 2020
$2.4M
Mapping of Novel Candidate Functional Elements with Bru-Seq TechnologyUM1HG009382 · NHGRI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LJUNGMAN, MATS · 2017 to 2021
$2.3M
Howard Hughes Medical Institute IECS-55007420NCI NIH HHS R01 CA200731NHGRI NIH HHS T32 HG000040NHGRI NIH HHS UM1 HG009382NIGMS NIH HHS R01 GM060518NIGMS NIH HHS R01 GM120767NIMH NIH HHS U01 MH106892
6 · The paper itself

Abstract

L1 retrotransposon-derived sequences comprise approximately 17% of the human genome. Darwinian selective pressures alter L1 genomic distributions during evolution, confounding the ability to determine initial L1 integration preferences. Here, we generated high-confidence datasets of greater than 88,000 engineered L1 insertions in human cell lines that act as proxies for cells that accommodate retrotransposition in vivo. Comparing these insertions to a null model, in which L1 endonuclease activity is the sole determinant dictating L1 integration preferences, demonstrated that L1 insertions are not significantly enriched in genes, transcribed regions, or open chromatin. By comparison, we provide compelling evidence that the L1 endonuclease disproportionately cleaves predominant lagging strand DNA replication templates, while lagging strand 3'-hydroxyl groups may prime endonuclease-independent L1 retrotransposition in a Fanconi anemia cell line. Thus, acquisition of an endonuclease domain, in conjunction with the ability to integrate into replicating DNA, allowed L1 to become an autonomous, interspersed retrotransposon.

Indexed as

Cell LineEndonucleasesGenome, HumanGenome-Wide Association StudyGenomicsHeLa CellsHumansLong Interspersed Nucleotide ElementsMutagenesis, InsertionalRetroelementsEndonucleasesRetroelementschromatinDNA replicationevolutionFanconi anemiahuman genomeintegrationLINE-1retrotransposontranscriptiontransposable element

Identifiers

PMID30955886
PMCPMC6558663
OpenAlexW2929611872

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.