Abstract A9: A whole-locus sequencing approach to identify polymorphisms associated with juvenile-onset granulosa cell tumor susceptibility in SWR mice
Bibliographic record
Abstract
Abstract Genes that are fundamental for normal development and regulation of the mammalian ovary have been identified through genetic investigations of unusual cases of altered fecundity, infertility or ovarian pathology in model species. In the SWR/Bm (SWR) inbred mouse, we have mapped three distinct loci on Chromosome (Chr) 4 (Gct1) and Chr X (Gct4, Gct6) that have a deleterious effect on ovarian development leading to the formation of juvenile-onset granulosa cell (GC) tumors. GC tumors in SWR female mice have strong parallels with juvenile-type GC tumors that appear in infants and young girls based on endocrinological, histological and malignant criteria. As such, the genetic and epigenetic determinants for tumorigenic processes operative in SWR mice will provide novel information for translational investigations of human juvenile-type GC tumors. The Gct1 allele derived from the SWR strain (Gct1SW) is unique in its support of androgen-sensitive GC tumor-susceptibility, with the expectation that a unique mutation underlies this trait. The X-linked Gct4 locus is a modifier locus for early-onset GC tumorigenesis, acting in conjunction with the Gct1 allele to enhance or diminish tumor susceptibility with a strong paternal, parent-of-origin effect. The X-linked Gct6 locus harbors a tumor suppressor for GC tumorigenesis, with a unique allele contributed by the Castaneus mouse strain. Forward genetic crosses and congenic strain mapping have resolved the candidate gene intervals for Gct1, Gct4 and Gct6 to 1.31, 1.34 and 1.02 Mb, respectively. It was our goal to evaluate all potential protein-coding or regulatory sequence polymorphisms between the GC tumor-sensitive SWR inbred strain and SWR-derived congenic strains that are resistant to androgen-inducible GC tumorigenesis. The individual locus regions were subsequently captured in a custom library approach prior to high-throughput, next generation sequencing. Informatics analyses of all polymorphisms are underway in the search for unique variants that will be investigated for their causal role in GC tumor susceptibility in this mouse model. For the Gct1SW locus, protein-coding variants have been excluded by our analysis, suggesting that regulatory variant(s) support the juvenile-onset GC tumor susceptible phenotype. Citation Format: Ann M. Dorward, Kerri N. Smith, Zoha Rabie, Edward S. Yaskowiak, Laura G. Reinholdt. A whole-locus sequencing approach to identify polymorphisms associated with juvenile-onset granulosa cell tumor susceptibility in SWR mice. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: From Concept to Clinic; Sep 18-21, 2013; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2013;19(19 Suppl):Abstract nr A9.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".