Identification of a new malaria susceptibility locus (Char4) in recombinant congenic strains of mice
Bibliographic record
Abstract
The genetic component of susceptibility to malaria is complex, both in humans and in the mouse model of infection. Two murine loci on chromosomes 8 (Pchr/Char2) and 9 (Char1) have previously been mapped in F(2) crosses, and play an important role in regulating blood parasitemia and survival to infection with Plasmodium chabaudi. These loci explain only part of the interstrain phenotypic variance, and their penetrance and expressivity vary in different inbred strains. Novel loci regulating response to P. chabaudi infection were investigated by using an alternative strategy based on a newly derived set of AcB/BcA recombinant congenic strains bred from malaria-susceptible A/J (A) and resistant C57BL/6J (B6). One of the AcB strains, AcB55, is shown to be highly resistant to infection despite 83% susceptible A genomic composition, including susceptibility alleles at Char1 and Pchr/Char2. Early onset of parasite clearance in AcB55 is associated with lower peak parasitemia and absence of mortality. Linkage analysis in an informative (AcB55 x A)F(2) population, using peak parasitemia as a quantitative trait, located a new B6-derived resistance locus on chromosome 3 (lod score = 6.57) that we designate Char4. A second, suggestive linkage on chromosome 10 (lod score = 2.53) shows additive effect with Char4 on peak parasitemia. Char4 maps to a small congenic B6 fragment in AcB55 that should facilitate the search for candidate genes. Our findings provide an entry point for parallel association studies in humans between the syntenic 4q21-4q25 region and susceptibility to disease in endemic areas of malaria.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.003 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 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".