Sex differences in reproductive fitness contribute to preferential maternal transmission of 22q11.2 deletions
Bibliographic record
Abstract
BACKGROUND: 22q11.2 deletion syndrome (22q11.2DS) is the most common microdeletion syndrome in humans. In a minority of patients, the underlying 22q11.2 deletion is found to have been inherited, usually from an affected mother. Serious neuropsychiatric conditions that are commonly associated features of 22q11.2DS could disproportionately affect reproductive success in males. METHODS: This study compared standard measures of reproductive fitness (mean number of liveborn offspring and proportion childless) in 141 Canadian adults with 22q11.2DS (cases) and their 200 unaffected siblings (controls). Multivariate regression models were used to identify phenotypic predictors of fitness in 22q11.2DS. RESULTS: The adults with 22q11.2DS had significantly fewer children than their siblings (p<0.0001, relative fitness=0.28); 85.8% were childless. As expected, younger age (p<0.0001), mental retardation (p=0.0211), and schizophrenia (p=0.0046) were significant negative predictors of reproductive fitness in 22q11.2DS; however, serious congenital heart disease was not. Female sex emerged as a significant positive predictor of fitness independent of the major neuropsychiatric phenotypes (p=0.0082). Post-hoc analyses corroborated these sex differences. Notably, fitness in women with 22q11.2DS with neither mental retardation nor schizophrenia was not significantly different from that of unaffected female siblings. CONCLUSIONS: There is a strong negative selective pressure against 22q11.2 deletions. This appears to be primarily mediated by the severity of the neuropsychiatric phenotype and an independent sexual selection effect. The latter also contributes to the observed excess of transmitting mothers. These results may have implications both for the evolutionary biology of this structural rearrangement and for genetic counselling and reproductive services for adolescents and adults with 22q11.2DS.
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| 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 | 0.000 |
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".