Progress Determining the Mechanism of Segmental Duplication and Deletion in Axenfeld Rieger Phenotypes
Bibliographic record
Abstract
PurposeTo identify the cause(s) of chromosome 6p25 segmental duplication and deletion, which result in a spectrum of Axenfeld Rieger phenotypes. MethodsArray Comparative Genome Hybridization (CGH) was undertaken to refine the location of breakpoints in segmental deletion (n=1) and duplication (n=5) pedigrees. Subsequently, long range PCR was performed to amplify breakpoint-spanning junctional fragments with sequencing and in silico analysis used to determine the genomic architecture of the junctional fragment and the region flanking the breakpoints. ResultsCGH accurately defined the extent of 6p25 segmental anomalies [deletion 1216 kb; duplications 474, 477.5 and 492kb]. A 1.2kb junctional fragment amplified in the deletion pedigree (n=5 affected) segregated with the clinical phenotype. The breakpoints lie within simple repeats with 368bp of novel sequence, comprising two 100% homologous motifs in head to tail orientation, inserted between them separated by a 13bp insert. Analyses of the segmental duplications are commencing. ConclusionsArray CGH represents a powerful technique to define the extent of chromosomal anomalies and facilitate analysis of the mechanism(s) that cause glaucoma-associated segmental duplications and deletions. The segmental deletion exhibits features of both homologous recombination and non-homologous end joining with an unusually large insert of DNA at the breakpoint. The variation in segmental duplication size indicates existence of a common causative mechanism and elucidation of this will clarify the etiology of a proportion of Axenfeld Rieger syndrome cases
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 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) | 0.002 | 0.001 |
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".