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Record W2529947402 · doi:10.1101/gad.286351.116

Mutations in genes encoding condensin complex proteins cause microcephaly through decatenation failure at mitosis

2016· article· en· W2529947402 on OpenAlex
Carol-Anne Martin, Jennie Murray, Paula Carroll, Andrea Leitch, Karen J. Mackenzie, Mihail Halachev, Ahmed E. Fetit, Charlotte Keith, Louise S. Bicknell, Adeline Fluteau, Philippe Gautier, Emma A. Hall, Shelagh Joss, Gabriela Soares, João Silva, Michael B. Bober, Angela L. Duker, Carol A. Wise, Alan J. Quigley, Shubha R. Phadke, Andrew J. Wood, Paola Vagnarelli, Andrew P. Jackson

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

fundA Canadian funder is recorded on the work.
no affNo Canadian affiliation: this work is invisible to an affiliation-only frame.
No Canadian affiliation. An affiliation-only frame, the usual design, would never have seen this work. It is one of the works that make the case for inverting the frame.

Bibliographic record

VenueGenes & Development · 2016
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicMicrotubule and mitosis dynamics
Canadian institutionsnot available
FundersEuropean Research CouncilMedical Research CouncilInstitute of GeneticsIndian Council of Medical ResearchDirectorate for Biological SciencesWellcomeMedical Research ScotlandNational Institute for Health and Care ResearchBiotechnology and Biological Sciences Research CouncilDepartment of Health and Social CareLister Institute of Preventive MedicineWellcome Trust
KeywordsBiologyMitosisCondensinMicrocephalyGeneticsGeneMutationCell biologyChromosome segregationChromosome

Abstract

fetched live from OpenAlex

Compaction of chromosomes is essential for accurate segregation of the genome during mitosis. In vertebrates, two condensin complexes ensure timely chromosome condensation, sister chromatid disentanglement, and maintenance of mitotic chromosome structure. Here, we report that biallelic mutations in NCAPD2, NCAPH, or NCAPD3, encoding subunits of these complexes, cause microcephaly. In addition, hypomorphic Ncaph2 mice have significantly reduced brain size, with frequent anaphase chromatin bridge formation observed in apical neural progenitors during neurogenesis. Such DNA bridges also arise in condensin-deficient patient cells, where they are the consequence of failed sister chromatid disentanglement during chromosome compaction. This results in chromosome segregation errors, leading to micronucleus formation and increased aneuploidy in daughter cells. These findings establish "condensinopathies" as microcephalic disorders, with decatenation failure as an additional disease mechanism for microcephaly, implicating mitotic chromosome condensation as a key process ensuring mammalian cerebral cortex size.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.136
Threshold uncertainty score0.739

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.023
GPT teacher head0.257
Teacher spread0.234 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it