GTPBP2 in-frame deletion in canine model with non-syndromic progressive retinal atrophy
Bibliographic record
Abstract
Progressive retinal atrophy (PRA), caused by aberrant functioning of rod/cone photoreceptors, leads to blindness affecting mammals, including dogs. We identified a litter of three Labrador retrievers affected by non-syndromic PRA; the parents and three other siblings were unaffected. Homozygosity mapping and whole-genome sequencing detected a homozygous 3-bp deletion in the coding region of GTPBP2, located in CFA12 (NC_049233.1:12,264,348_12,264,350del, c.1606_1608del, p.Ala536del). The variant was absent from the online European Variation Archive (EVA) database, the Dog Biomedical Variants Database Consortium, and the Dog10k database. We tested 91 non-affected dogs from the same kennel and found 75 wild-type (WT) and 16 carriers, all clinically normal, and 569 Labradors from the general population (USA), all WT. GTPBP2 is associated with Jaberi-Elahi syndrome (JES) in Homo sapiens, and splice variants in Mus musculus are associated with neurodegeneration; in both cases photoreceptor degeneration may be included in its manifestation. Heterologous cellular systems were transfected with cDNA encoding WT or A536del mutant GTPBP2 protein and immunoblot analysis of total cell lysate with anti-GTPBP2 antibodies showed that the expression level of the GTPBP2 mutant protein A536del is slightly but not significantly reduced compared to WT. Immunofluorescent methods and confocal analysis of cells transfected with WT or A536del GTPBP2 protein revealed that the WT form is diffuse throughout the cytosol, while the mutant form resulted in the formation of cytoplasmic aggregates in ~70-80% of cells. The deleted amino acid falls within a conserved interval outside the GTP domain of GTPBP2, suggesting a potentially novel role of the sequence on cellular localization of the protein.
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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) | 0.001 | 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 | 0.001 | 0.001 |
| 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".