Novel <i>Cardiac Troponin-I</i> Missense Variant (c.593C>T) Is Associated With Familial Hypertrophic Cardiomyopathy in Golden Retrievers
Bibliographic record
Abstract
BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a naturally occurring cardiac disorder afflicting humans, cats, rhesus macaques, pigs, and rarely dogs. The disease is characterized by maladaptive left ventricular wall thickening. Over 1500 sarcomere-coding mutations explain HCM in humans, whereas only 3 have been reported in cat breeds. To date, no mutations have been described in dogs. HCM in a nuclear family of Golden Retrievers was identified following the sudden cardiac death of 3 related puppies <2 years of age from 2 dam-offspring repeat matings. METHODS: Whole-genome sequencing on the 3 affected puppies, along with nuclear family members (ie, sire, dam, 4 unaffected littermates, 4 unaffected half-siblings), and 1 distantly related, geriatric, cardiovascularly normal Golden Retriever was performed (n=14). Candidate variant genotyping was performed in an unphenotyped cohort of dogs (n=2771) and an expanded population of phenotyped, unrelated Golden Retrievers (n=45). Left ventricular tissue immunofluorescence staining was subsequently performed to investigate incorporation and expression of mutant protein within the cardiac sarcomere of HCM-affected cases. RESULTS: variant is not related to abnormal protein incorporation within the sarcomere. CONCLUSIONS: This variant represents the first-ever reported HCM-associated variant in any canine species, and its identification holds promise for establishing translational models, genetic screening, and early disease prevention within the breed.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".