QTL Analysis of a Trade‐off in Bone Length within the Mouse Zygomatic Arch
Bibliographic record
Abstract
We use a powerful mouse resource to identify candidate genes associated with a negative correlation in the length of bones that contribute to the zygomatic arch. Because system‐wide growth factors contribute to all skeletal dimensions, most skull linear distances are positively correlated with each other. However, the lengths of two adjacent zygomatic arch bones are negatively correlated in our Diversity Outbred (DO) mice. This is evidence for an opposite pleiotropic effect or developmental constraint during zygomatic arch formation, which appears to limit variation in total zygomatic arch length. Determining the basis for this negative correlation will help us understand developmental mechanisms that limit phenotypic variation and underlie variation in how individual bones contribute to overall skull form. We completed high‐resolution genetic mapping with 563 DO mice to identify genomic regions and candidate genes associated with this negative correlation. DO mice are ideal for this, because each mouse carries a high degree of heterozygosity and a unique combination of alleles. We separately mapped 1) jugal bone length, 2) jugal process of maxilla length, and 3) total zygomatic arch length. Analysis was completed on raw linear distances without scaling or removing the allometric component of variation, because these procedures remove variation associated with overall size and artificially create negative associations between linear distance measurements. A genomic interval between 85 and 86 Mb on chromosome 17 was significantly associated with variation in jugal bone length and jugal process length, but not total zygomatic arch length. In addition, founder haplotypes under this peak displayed opposite phenotypic effects on individual bone lengths, suggesting it includes a genetic factor driving relative length of these zygomatic bones, but not total arch length. This interval includes Six2 , Six3 , and Six3os1 , which are expressed in the pharyngeal arches or forebrain during facial development, as well as Camkmt , which is pivotal for calmodulin methylation. Ongoing real‐time PCR will show whether expression of these genes within the maxillary arch at E10.5 in three founder strains is correlated with measured founder haplotype effects. Understanding the genetic and developmental basis for this negative correlation is important because it results in a developmental constraint on total zygomatic arch length, which will act to limit evolvability of this structure. Support or Funding Information Funding graciously provided by the NIH (U01DE020054, 2R01DE019638, R01DE021708, R01GM070683), NSERC (238992‐12), and to CJP by the Alberta Innovates Health Solutions.
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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 | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".