The effect of <i>TERC</i> haploinsufficiency on the inheritance of telomere length
Bibliographic record
Abstract
Telomeres protect chromosome ends from end-to-end fusion and degradation. Loss of telomere function causes cell-cycle arrest or cell death. Autosomal dominant dyskeratosis congenita (AD DC), a rare inherited bone marrow failure syndrome, is caused by mutations in TERC, the RNA component of telomerase. Here, we studied the telomere dynamics over three generations in a 32-member extended family with AD DC due to a TERC gene deletion. Our analysis shows that peripheral blood cells from family members haploinsufficient for TERC have very short telomeres. Telomeres are equally short in all individuals carrying the TERC gene deletion irrespective of their age. Chromosome-specific telomere analysis distinguishing the parental origin of telomeres showed that in gene deletion carriers, paternal and maternal telomeres are similarly short and similar in length to those of the affected parent. In children of affected parents who have normal TERC genes, parental telomeres are again similar in length, but two generations appear to be necessary to fully restore normal telomere length. These results are consistent with a model in which telomerase preferentially acts on the shortest telomeres. When TERC is limiting, this preference leads to the accelerated shortening of longer telomeres. The limited amount of active telomerase in TERC RNA haploinsufficiency may not be able to maintain the minimal length of the increasing number of short telomeres. Thus, the number of cells with excessively short telomeres and the degree of residual telomerase activity may determine the onset of disease in patients with AD DC.
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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 | 0.000 |
| Bibliometrics | 0.000 | 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) | 0.002 | 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".