Cloning and characterization of the insulin receptor-related receptor (IRR) reveals that it is closely associated with trkA in the genome and maps to human chromosome 1q22, A type 2 diabetes susceptibility locus
Bibliographic record
Abstract
The insulin receptor-related receptor (IRR) is structurally and functionally related to the insulin receptor and IGF-IR, but its physiological ligand and role are unknown. Cloning of the mouse IRR gene in this study has revealed that the IRR gene is positioned extremely close to the trkA gene in the genome; this genomic orientation is conserved in humans. The IRR and trkA genes are arranged head-to head, with their transcription start only ∼1.6 kb apart. This close proximity raises the interesting possibility that this intergenic region functions as a bidirectional (divergent) promoter, responsible for the temporal and spatial coordinate expression of these genes seen in specific neurons. This observation also supports the possible existence of other members of these receptor tyrosine kinase families, and provides considerations for the development and analysis of knockout mice. Cross-species promoter analysis in this study identifies several well conserved motifs, (including a putative insulin response element (IRE)), supporting their potential involvement in the regulation of gene expression The identification of a polymorphic marker within the first intron of IRR allowed the precise mapping of this gene to human chromosome 1q22, with respect to several known polymorphic markers. This revealed that IRR lies in a region that has been shown to be linked to the development of type 2 diabetes in several populations, indicating that IRR is a candidate gene for the development of this disease. A human genomic clone carrying IRR was identified in the high throughput genome sequencing database, providing the full genomic sequence of IRR, to allow for investigations of polymorphisms within this gene. Other candidate genes, including hypothetical genes, within this chromosomal region have been identified, and a novel mathematical model to help evaluate coding regions of DNA and colon reading frames has been developed. This model has been used as a tool to further investigate hypothetical genes in the IRR chromosomal region, showing that this tool can be applied to further predict the validity and accuracy of these potential coding regions, which are additional candidate genes for the development of type 2 diabetes.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 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 | 0.001 |
| 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".