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Molecular Genetics of Choroideremia

2012· other· en· W1606598443 on OpenAlexaff
Paul R. Freund, Ian M. MacDonald

Bibliographic record

VenueEncyclopedia of Life Sciences · 2012
Typeother
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicRetinal Development and Disorders
Canadian institutionsUniversity of Alberta
Fundersnot available
KeywordsChoroideremiaRetinal pigment epitheliumBiologyExonRetinal DisorderRetinal degenerationMacular degenerationChoroidGeneticsGeneRetinaMedicineOphthalmologyNeuroscience

Abstract

fetched live from OpenAlex

Abstract Choroideremia (CHM) is an X‐linked disorder that causes progressive loss of vision. Affected males initially present with nyctalopia (night blindness) and experience progressive loss of peripheral vision until they are legally blind by middle age. Degeneration continues until there is a complete loss of vision. CHM is caused by mutations in theCHMgene, which encodes Rab escort protein (REP) 1. Molecular genetic techniques have identified more than 100 mutations affecting in theCHMgene and all but one results in the absence of REP1 protein. The degenerative process of CHM initially affects rod photoreceptors and the retinal pigment epithelium (RPE), then progresses to involve the choroid and cone photoreceptors. The exact pathophysiological mechanism of this degradation has not yet been elucidated. There is no established treatment for CHM available at this time but gene therapy trials are currently underway. Key Concepts: Choroideremia is a progressive degenerative disorder affecting the photoreceptor, retinal pigment epithelium and choroid layers of the retina. Mutations in theCHMgene result in the absence of REP1 protein, causing low levels of prenylation of RAB proteins. Confirmatory testing for CHM can be done by direct sequencing of theCHMexons or through immunoblot analysis for CHM protein expression. Zebrafish and mouseCHMknock‐out models have significant limitations due to the lack of viability. A conditional knock‐out mouse model has been developed and used in pre‐clinical testing of CHM therapies. Successful techniques in gene therapy for Leber congenital amaurosis‐2, another single gene disorder of blindness, are currently being applied to choroideremia.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Other · Consensus signal: none
Teacher disagreement score0.003
Threshold uncertainty score0.011

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0000.001
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0030.001

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 head0.009
GPT teacher head0.251
Teacher spread0.242 · 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 source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designNot applicable
Domainnot available
GenreOther

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

Citations0
Published2012
Admission routes1
Has abstractyes

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