Genetic analysis of bone morphometry and ivory vertebrae in threespine stickleback
- 1Department of Developmental Biology, Stanford University School of Medicine , Stanford, CA 94305 ,
- 2Howard Hughes Medical Institute, Stanford University School of Medicine , Stanford, CA 94305 ,
Abstract
Previous genetic studies of skeletal variation in threespine stickleback fish (Gasterosteus aculeatus) have focused primarily on striking morphological differences. Here, we examine the largely unexplored genetic architecture of internal bone microstructural variation between marine and freshwater stickleback. Micro-computed tomography X-ray analysis revealed differences in the porosity, bone thickness, and bone volume fraction within armor plates and vertebrae from a marine and freshwater stickleback. Quantitative trait locus mapping in F2 progeny from a marine × freshwater stickleback cross identified a significant locus on chromosome 4 influencing multiple aspects of armor plate internal microstructure. This locus overlaps the well-characterized Eda region previously known to control armor plate number and size. Co-mapping of bone microstructure could be due to pleiotropic effects of Eda on multiple aspects of plate development or to changes in closely linked genes including Itm2a, which also plays a role in bone formation. Most bone microstructure traits in vertebrae showed weak or no genetic signal, consistent with a polygenic architecture. However, we identified a highly significant locus on chromosome 17 that is strongly associated with abnormally thickened “ivory vertebrae” that occurred in 8.4% of F2 offspring. This phenotype resembles Paget’s disease in humans, and the major locus region contains Tnfrsf1b, the stickleback ortholog of a human Paget’s disease susceptibility gene TNFRSF11A. Together, our findings identify genetic loci underlying natural variation in bone microstructure in wild fish and reveal a candidate gene associated with a disease-like skeletal phenotype, highlighting stickleback as a model for studying both evolutionary and pathological bone biology.
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BibTeX
@article{behrens2026genetic,
title = {{Genetic analysis of bone morphometry and ivory vertebrae in threespine stickleback}},
author = {Veronica C Behrens and David Lee and Julia I Wucherpfennig and David M Kingsley},
journal = {G3: Genes, Genomes, Genetics},
year = {2026},
month = oct,
doi = {10.1093/g3journal/jkag164},
url = {https://academic.oup.com/g3journal/advance-article/doi/10.1093/g3journal/jkag164/8885764},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Genetic analysis of bone morphometry and ivory vertebrae in threespine stickleback
AU - Veronica C Behrens
AU - David Lee
AU - Julia I Wucherpfennig
AU - David M Kingsley
PY - 2026
DA - 2026/10/08
JO - G3: Genes, Genomes, Genetics
DO - 10.1093/g3journal/jkag164
UR - https://academic.oup.com/g3journal/advance-article/doi/10.1093/g3journal/jkag164/8885764
AB - Previous genetic studies of skeletal variation in threespine stickleback fish (Gasterosteus aculeatus) have focused primarily on striking morphological differences. Here, we examine the largely unexplored genetic architecture of internal bone microstructural variation between marine and freshwater stickleback. Micro-computed tomography X-ray analysis revealed differences in the porosity, bone thickness, and bone volume fraction within armor plates and vertebrae from a marine and freshwater stickleback. Quantitative trait locus mapping in F2 progeny from a marine × freshwater stickleback cross identified a significant locus on chromosome 4 influencing multiple aspects of armor plate internal microstructure. This locus overlaps the well-characterized Eda region previously known to control armor plate number and size. Co-mapping of bone microstructure could be due to pleiotropic effects of Eda on multiple aspects of plate development or to changes in closely linked genes including Itm2a, which also plays a role in bone formation. Most bone microstructure traits in vertebrae showed weak or no genetic signal, consistent with a polygenic architecture. However, we identified a highly significant locus on chromosome 17 that is strongly associated with abnormally thickened “ivory vertebrae” that occurred in 8.4% of F2 offspring. This phenotype resembles Paget’s disease in humans, and the major locus region contains Tnfrsf1b, the stickleback ortholog of a human Paget’s disease susceptibility gene TNFRSF11A. Together, our findings identify genetic loci underlying natural variation in bone microstructure in wild fish and reveal a candidate gene associated with a disease-like skeletal phenotype, highlighting stickleback as a model for studying both evolutionary and pathological bone biology.
SN - 2160-1836
ER -