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Record W2916153399 · doi:10.1002/ajmg.c.31672

How do genes that escape from X‐chromosome inactivation contribute to Turner syndrome?

2019· review· en· W2916153399 on OpenAlexafffund
Samantha B. Peeters, Andrea J. Korecki, Sarah E.L. Baldry, Christine Yang, Kira Tosefsky, Bradley P. Balaton, Elizabeth M. Simpson, Carolyn J. Brown

Bibliographic record

VenueAmerican Journal of Medical Genetics Part C Seminars in Medical Genetics · 2019
Typereview
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
Canadian institutionsBC Children's Hospital3v Geomatics (Canada)University of British Columbia
FundersNational Center for Advancing Translational SciencesCanadian Institutes of Health ResearchPatient-Centered Outcomes Research Institute
KeywordsGene silencingGeneBiologyX-inactivationDosage compensationGeneticsX chromosomeXISTSkewed X-inactivationmicroRNAPhenotype

Abstract

fetched live from OpenAlex

X-chromosome inactivation generally results in dosage equivalence for expression of X-linked genes between 46,XY males and 46,XX females. The 20-30% of genes that escape silencing are thus candidates for having a role in the phenotype of Turner syndrome. Understanding which genes escape from silencing, and how they avoid this chromosome-wide inactivation is therefore an important step toward understanding Turner Syndrome. We have examined the mechanism of escape using a previously reported knock-in of a BAC containing the human escape gene RPS4X in mouse. We now demonstrate that escape from inactivation for RPS4X is already established by embryonic Day 9.5, and that both silencing and escape are faithfully maintained across the lifespan. No overt abnormalities were observed for transgenic mice up to 1 year of age despite robust transcription of the human RPS4X gene with no detectable downregulation of the mouse homolog. However, there was no significant increase in protein levels, suggesting translational compensation in the mouse. Finally, while many of the protein-coding genes have been assessed for their inactivation status, less is known about the X-linked RNA genes, and we propose that for many microRNA genes their inactivation status can be predicted as they are intronic to genes for which the inactivation status is known.

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.

How this classification was reachedexpand

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)0.002
metaresearch head score (Gemma)0.002
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow), Research integrity
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Other design · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.992
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0020.002
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0030.001
Bibliometrics0.0010.001
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0030.001
Research integrity0.0020.002
Insufficient payload (model declined to judge)0.0010.000

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 head0.027
GPT teacher head0.329
Teacher spread0.302 · 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

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designOther design
Domainnot available
GenreReview

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations33
Published2019
Admission routes2
Has abstractyes

Explore more

Same venueAmerican Journal of Medical Genetics Part C Seminars in Medical GeneticsSame topicGenetic and Clinical Aspects of Sex Determination and Chromosomal AbnormalitiesFrench-language works237,207