The M53I mutation in <i>CDKN2A</i> is a founder mutation that predominates in melanoma patients with Scottish ancestry
Bibliographic record
Abstract
Germline mutations in the tumor suppressor gene CDKN2A have been shown to predispose to cutaneous malignant melanoma. The M53I mutation is the most common CDKN2A mutation identified in Scottish melanoma patients and is also found in a small number of families in other countries. The aim of this study was to determine whether the occurrence of this mutation is due to a common ancestor originating from Scotland, and if so, to estimate how long ago the mutation arose. We examined 18 families carrying the M53I mutation: six from Scotland, five from Canada, four from Australia, and three from America. Haplotypes derived from segregation of seven informative microsatellite markers flanking CDKN2A were constructed in each family. Our findings show that 14 of 18 families carry a common ancestral haplotype on which the mutation arose approximately 88 generations ago (1-LOD-unit support interval 44-198 generations). This haplotype is very rare in controls, which supports the idea that it is a common founder mutation haplotype. The four M53I families that do not share the consensus haplotype may in fact have arisen from the same founder, but this is potentially obscured by presumed replication slippage for some of the microsatellite markers tested.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 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) | 0.002 | 0.000 |
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.
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".