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Record W2340927445

The Chr X-linked Gct6 locus: A granulosa cell tumor suppressor in mice

2015· dissertation· en· W2340927445 on OpenAlexfundno aff
Zoha Rabie

Bibliographic record

VenueMemorial University Research Repository (Memorial University) · 2015
Typedissertation
Languageen
FieldMedicine
TopicOvarian cancer diagnosis and treatment
Canadian institutionsnot available
FundersCanadian Institutes of Health ResearchMemorial University of Newfoundland
KeywordsBiologyCongenicGeneticsLocus (genetics)GeneAlleleSanger sequencingCandidate geneDNA sequencing
DOInot available

Abstract

fetched live from OpenAlex

Juvenile-type granulosa cell tumors (GCT) originate in the somatic tissues that surround the germ cells of the ovarian follicle in children and young women. Unlike Adult-type GCT that share a common, acquired mutation in the FOXL2 gene, the genetic determinants for juvenile-type GCT susceptibility are not so well defined. A spontaneous, early-onset GCT phenotype in SWR inbred female mice has revealed multiple Gct loci: Gct1 on Chromosome (Chr) 4 initiates the tumorigenic program; Gct4 on Chr X modifies trait penetrance and Gct6 on Chr X is a suppressor of GCT initiation. The Gct6 locus has been mapped to a 1.02 million base pair region with over 20 annotated genes. Two complementary approaches were taken to help prioritize Gct6 gene candidates. First, a congenic strain approach was taken to determine the tumor suppressor phenotype of the Gct6C57 allele in SWR.C57-X females. Second, a whole-locus capture and Next Generation Sequencing (NGS) protocol was applied to identify all nucleotide variations between SWR (tumor-susceptible SW) and Castaneus (CAST; tumor-resistant CA) alleles vs. the C57BL/6J (C57) genome. The congenic strain data supported the hypothesis that a common Gct6 tumor suppressor allele in C57 and CAST genomes was distinct from the permissive Gct6SW allele, which reduced the prioritized list of NGS variants (SNPs, INDELs) to 746. Priority was given to non-synonymous variants identified in the coding region of 5 candidate genes: BC065397, Esx1, Slc25a53, Tmsb15b1 and Tmsb15l. Sanger sequencing confirmed the 5 non-synonymous variants between C57 and SWR strains and identified a novel 28 bp deletion in the coding region of the Slc25a53 gene. Allele association analysis between 5 Gct6 permissive and 2 Gct6 suppressive strains demonstrated that the 5 non-synonymous variants were not conserved between permissive strains. However, all 5 permissive strains tested (SWR, SJL/J, PL/J, BUB/BnJ, ST/bJ) had deletion mutations with inferred deleterious frameshift effect in the Slc25a53 gene when compared to the GC tumor suppressive strains (CAST and C57), making Slc25a53 a promising candidate for shared identity with Gct6.

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: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.005
Threshold uncertainty score0.017

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0020.001
Science and technology studies0.0010.001
Scholarly communication0.0010.000
Open science0.0010.001
Research integrity0.0010.002
Insufficient payload (model declined to judge)0.0050.002

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 head0.026
GPT teacher head0.284
Teacher spread0.258 · 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 designBench or experimental
Domainnot available
GenreEmpirical

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
Published2015
Admission routes1
Has abstractyes

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