Abstract 2721: Linkage of Left Ventricular Outflow Tract Obstruction to Xq28 in 3 French-Canadian Pedigrees
Bibliographic record
Abstract
BACKGROUND: Statistical genetic analysis of cohorts with left ventricular outflow tract obstruction (LVOTO) shows high heritability of such lesions. We have identified three X-linked French-Canadian pedigrees with a total of 54 family members with multiple cases of LVOTO and septal defects. AIMS: The aim of this study was to evaluate the three pedigrees with LVOTO and septal defects for genetic linkage to the X chromosome. METHODS: Detailed family history, physical exam, ECG, echocardiography and chart review was performed. Informed consent was obtained from all participants. Genomic DNA was isolated from peripheral blood samples. Twenty-four STR markers from the X chromosome were genotyped. We used a dominant genetic model with the following penetrances: 0.99 for homozygous women, 0.75 for heterozygous women, 0.99 for hemizygous men. Phenocopy rate was set to 0.01 and disease allele frequency to 0.001. Reference allele frequencies from the Quebec population were used. Analyses were performed with MLINK and MERLIN. RESULTS: Sixteen family members were affected (13 males, 3 females). Predominant lesions were atrial (n = 5) and ventricular (n = 6) septal defects, coarctation (n = 4) and aortic lesions (stenosis (n = 4), bicuspid/abnormal aortic valve (n = 6)), as well as mitral valve lesions (n = 4). Males had a high incidence of supraventricular arrhythmias postoperatively (4 with atrial flutter/fibrillation, one with ICD implantation). LOD scores above 2 were obtained in parametric two-point linkage analysis for 3 markers in the Xq28 region. Multipoint non-parametric linkage analysis confirmed these results with a NPL score of 9.1 (P < .00001) over a STR marker in intron 13 of the F8C gene. Haplotype analysis allowed the definition of a candidate interval flanked by marker DXS8069 spanning to the telomeric end of Xq. CONCLUSIONS: By analysing 3 multi-generation French-Canadian pedigrees, we mapped a syndrome of LVOTO and septal defects to the Xq28 region. Further work will refine our candidate region with dense SNP coverage to search for a shared haplotype identical by descent between the three French Canadian families, to complete the sequencing of candidate genes including FLNA, and to search for a possible founder effect in our population.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.002 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.004 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.007 | 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".