Evidence map›Paper›PMID 26755636›Full record

ArticleGenome research2016

Exome sequencing and CRISPR/Cas genome editing identify mutations of ZAK as a cause of limb defects in humans and mice.

Malte Spielmann, Naseebullah Kakar, Naeimeh Tayebi, Catherine Leettola, Gudrun Nürnberg, Nadine Sowada, Darío G Lupiáñez, Izabela Harabula, Ricarda Flöttmann, Denise Horn and 13 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Genome research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing 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

34 citing papers in PubMed, 60 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Testing for fitness epistasis in a transplant experiment identifies a candidate adaptive locus inPhilosophical transactions of the Royal Society of London. Series B, Biological sciences · 2022
    Article
  17. Genomic adaptations for arboreal locomotion in Asian flying treefrogs.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  18. Article
  19. Review
  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

23 authors at 10 institutions in 4 countries.

Malte SpielmannMax Planck Institute for Molecular Genetics, 14195 Berlin, Germany; Institute for Medical Genetics and Human Genetics, Charité Universitätsmedizin Berlin, 13353 Berlin, Germany; Berlin-Brandenburg School for Regenerative Therapies (BSRT), 13353 Berlin, Germany;
Naseebullah KakarInstitute of Human Genetics, University of Ulm, 89081 Ulm, Germany; International Graduate School in Molecular Medicine Ulm, University of Ulm, 89081 Ulm, Germany; Department of Biotechnology and Informatics, BUITEMS, Quetta, 57789 Pakistan;
Naeimeh TayebiMax Planck Institute for Molecular Genetics, 14195 Berlin, Germany;
Catherine LeettolaDepartment of Chemistry and Biochemistry, UCLA-DOE Institute of Genomics and Proteomics, University of California, Los Angeles, Los Angeles, California 90095, USA;
Gudrun NürnbergCologne Center for Genomics, University of Cologne, 50931 Cologne, Germany;
Nadine SowadaInstitute of Human Genetics, University of Ulm, 89081 Ulm, Germany; International Graduate School in Molecular Medicine Ulm, University of Ulm, 89081 Ulm, Germany;
Darío G LupiáñezMax Planck Institute for Molecular Genetics, 14195 Berlin, Germany; Institute for Medical Genetics and Human Genetics, Charité Universitätsmedizin Berlin, 13353 Berlin, Germany; Berlin-Brandenburg Center for Regenerative Therapies (BCRT), 13353 Berlin, Germany;
Izabela HarabulaMax Planck Institute for Molecular Genetics, 14195 Berlin, Germany;
Ricarda FlöttmannInstitute for Medical Genetics and Human Genetics, Charité Universitätsmedizin Berlin, 13353 Berlin, Germany;
Denise HornInstitute for Medical Genetics and Human Genetics, Charité Universitätsmedizin Berlin, 13353 Berlin, Germany;
Wing Lee ChanInstitute for Medical Genetics and Human Genetics, Charité Universitätsmedizin Berlin, 13353 Berlin, Germany;
Lars WittlerMax Planck Institute for Molecular Genetics, 14195 Berlin, Germany;
Rüstem YilmazInstitute of Human Genetics, University of Ulm, 89081 Ulm, Germany; International Graduate School in Molecular Medicine Ulm, University of Ulm, 89081 Ulm, Germany;
Janine AltmüllerCologne Center for Genomics, University of Cologne, 50931 Cologne, Germany;
Holger ThieleCologne Center for Genomics, University of Cologne, 50931 Cologne, Germany;
Hans van BokhovenDepartment of Human Genetics, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands;
Charles E SchwartzJ.C. Self Research Institute, Greenwood Genetic Center, Greenwood, South Carolina 29646, USA;
Peter NürnbergCologne Center for Genomics, University of Cologne, 50931 Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany; Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany;
James U BowieDepartment of Chemistry and Biochemistry, UCLA-DOE Institute of Genomics and Proteomics, University of California, Los Angeles, Los Angeles, California 90095, USA;
Jamil AhmadDepartment of Biotechnology and Informatics, BUITEMS, Quetta, 57789 Pakistan;
Christian KubischInstitute of Human Genetics, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
Stefan MundlosMax Planck Institute for Molecular Genetics, 14195 Berlin, Germany; Institute for Medical Genetics and Human Genetics, Charité Universitätsmedizin Berlin, 13353 Berlin, Germany; Berlin-Brandenburg School for Regenerative Therapies (BSRT), 13353 Berlin, Germany;
Guntram BorckInstitute of Human Genetics, University of Ulm, 89081 Ulm, Germany;
University of Cologne · DEBerlin-Brandenburger Centrum für Regenerative Therapien · DEBerlin Institute of Health at Charité - Universitätsmedizin Berlin · DEMax Planck Institute for Molecular Genetics · DEUniversität Ulm · DEBalochistan University of Information Technology, Engineering and Management Sciences · PKUniversity of California, Los Angeles · USGreenwood Genetic Center · USRadboud University Nijmegen · NLUniversität Hamburg · DE

Funding

UCLA NIGMS T32 Program AssessmentT32GM007185 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI TORRES, JORGE · 1985 to 2020
$21.7M
A SAM domain network in Polycystic Kidney DiseaseR01DK100482 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BOWIE, JAMES U · 2014 to 2017
$1.1M
NIDDK NIH HHS R01 DK100482NIGMS NIH HHS T32 GM007185
6 · The paper itself

Abstract

The CRISPR/Cas technology enables targeted genome editing and the rapid generation of transgenic animal models for the study of human genetic disorders. Here we describe an autosomal recessive human disease in two unrelated families characterized by a split-foot defect, nail abnormalities of the hands, and hearing loss, due to mutations disrupting the SAM domain of the protein kinase ZAK. ZAK is a member of the MAPKKK family with no known role in limb development. We show that Zak is expressed in the developing limbs and that a CRISPR/Cas-mediated knockout of the two Zak isoforms is embryonically lethal in mice. In contrast, a deletion of the SAM domain induces a complex hindlimb defect associated with down-regulation of Trp63, a known split-hand/split-foot malformation disease gene. Our results identify ZAK as a key player in mammalian limb patterning and demonstrate the rapid utility of CRISPR/Cas genome editing to assign causality to human mutations in the mouse in <10 wk.

Indexed as

Amino Acid SequenceAnimalsBacterial ProteinsCell LineClustered Regularly Interspaced Short Palindromic RepeatsCoculture TechniquesCRISPR-Associated Protein 9EndonucleasesExomeFemaleHumansLimb Deformities, CongenitalLod ScoreMaleMAP Kinase Kinase KinasesMiceBacterial ProteinsCas9 endonuclease Streptococcus pyogenesCRISPR-Associated Protein 9EndonucleasesMAP3K20 protein, humanMap3k20 protein, mouseMAP Kinase Kinase KinasesProtein Kinases

Identifiers

PMID26755636
PMCPMC4728371
OpenAlexW2257942547

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.