ArticleNature communications2025
A quadratic paradigm describes the relationship between phenotype severity and variation.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
1 citing paper in PubMed.
- Early ultraviolet exposure disrupts late dorsal fin skeletal development in zebrafish.Developmental dynamics : an official publication of the American Association of Anatomists · 2026Article
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Authors and funding
9 authors.
Funding
Abstract
In 1942 Waddington observed that phenotype variation among mutant animals is greater than in wild types. Here we update this observation to depict unexpected relationships between phenotype severity and variation. Using a zebrafish mef2ca allelic series representing a range in craniofacial phenotype severity, we tested the straightforward hypothesis that as phenotype severity increases, variation increases. We found that severity and variation were positively correlated, but only to a point. Variation collapsed in the most severe conditions. Mathematically, we found that the best fit for the relationship between severity and variation is a quadratic function. Across both zebrafish craniofacial phenotypes and human genetic disease, wild-type conditions produced low variation, moderate severity was associated with high variation, and conditions of extreme severity resulted in low variation. We propose that the quadratic relationship between severity and variation is a universal principle of biology that until now has not been formally tested.
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Registered trials
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