Evidence map›Paper›PMID 31649251›Full record

ArticleNature communications2019

Genome-wide microhomologies enable precise template-free editing of biologically relevant deletion mutations.

Janin Grajcarek, Jean Monlong, Yoko Nishinaka-Arai, Michiko Nakamura, Miki Nagai, Shiori Matsuo, David Lougheed, Hidetoshi Sakurai, Megumu K Saito, Guillaume Bourque and 1 more

Abstract read
In one paragraph

Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
–field-weighted citation impact
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

30 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Genetic Contributions to Lower Urinary Tract Dysfunction.American journal of medical genetics. Part A · 2025
    Article
  10. Article
  11. Review
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. The origin of unwanted editing byproducts in gene editing.Acta biochimica et biophysica Sinica · 2022
    Article
  20. Article
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

11 authors.

Janin GrajcarekCenter for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, 606-8507, Japan.ORCID http://orcid.org/0000-0002-9894-8208
Jean MonlongDepartment of Human Genetics, McGill University, Montréal, QC, H3A 0G4, Canada.ORCID http://orcid.org/0000-0002-9737-5516
Yoko Nishinaka-AraiCenter for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, 606-8507, Japan.ORCID http://orcid.org/0000-0002-7013-4640
Michiko NakamuraCenter for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, 606-8507, Japan.
Miki NagaiCenter for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, 606-8507, Japan.
Shiori MatsuoCenter for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, 606-8507, Japan.
David LougheedCanadian Center for Computational Genomics, Montréal, QC, H3A 0G1, Canada.ORCID http://orcid.org/0000-0003-0962-543X
Hidetoshi SakuraiCenter for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, 606-8507, Japan.
Megumu K SaitoCenter for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, 606-8507, Japan.ORCID http://orcid.org/0000-0001-8813-3614
Guillaume BourqueDepartment of Human Genetics, McGill University, Montréal, QC, H3A 0G4, Canada.ORCID http://orcid.org/0000-0002-3933-9656
Knut WoltjenCenter for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, 606-8507, Japan. woltjen@cira.kyoto-u.ac.jp.ORCID http://orcid.org/0000-0003-2293-1183

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The functional effect of a gene edit by designer nucleases depends on the DNA repair outcome at the targeted locus. While non-homologous end joining (NHEJ) repair results in various mutations, microhomology-mediated end joining (MMEJ) creates precise deletions based on the alignment of flanking microhomologies (µHs). Recently, the sequence context surrounding nuclease-induced double strand breaks (DSBs) has been shown to predict repair outcomes, for which µH plays an important role. Here, we survey naturally occurring human deletion variants and identify that 11 million or 57% are flanked by µHs, covering 88% of protein-coding genes. These biologically relevant mutations are candidates for precise creation in a template-free manner by MMEJ repair. Using CRISPR-Cas9 in human induced pluripotent stem cells (hiPSCs), we efficiently create pathogenic deletion mutations for demonstrable disease models with both gain- and loss-of-function phenotypes. We anticipate this dataset and gene editing strategy to enable functional genetic studies and drug screening.

Indexed as

Base SequenceCRISPR-Cas SystemsDNA End-Joining RepairGain of Function MutationGene EditingHumansInduced Pluripotent Stem CellsLoss of Function MutationSequence Deletion

Identifiers

PMID31649251
PMCPMC6813315

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.