{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:35:57Z","timestamp":1785411357834,"version":"3.56.0"},"posted":{"date-parts":[[2026,4,14]]},"group-title":"Genetics","reference-count":64,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"id":[{"id":"https:\/\/ror.org\/006w34k90","id-type":"ROR","asserted-by":"publisher"}]},{"award":["2T32GM007790"],"award-info":[{"award-number":["2T32GM007790"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"id":[{"id":"https:\/\/ror.org\/00f54p054","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,6,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Previous genetic studies of skeletal variation in threespine stickleback fish (\n                  <jats:italic>Gasterosteus aculeatus<\/jats:italic>\n                  ) 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. \u00b5CT 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 \u00d7 freshwater stickleback cross identified a significant locus on chromosome 4 influencing multiple aspects of armor plate internal microstructure. This locus overlaps the well-characterized\n                  <jats:italic>Eda<\/jats:italic>\n                  region previously known to control armor plate number and size. Co-mapping of bone microstructure could be due to pleiotropic effects of\n                  <jats:italic>Eda<\/jats:italic>\n                  on multiple aspects of plate development or to changes in closely linked genes including\n                  <jats:italic>Itm2a<\/jats:italic>\n                  , 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 \u201civory vertebrae\u201d that occurred in 8.4% of F2 offspring. This phenotype resembles Paget\u2019s disease in humans, and the major locus region contains\n                  <jats:italic>Tnfrsf1b<\/jats:italic>\n                  , the stickleback ortholog of a human Paget\u2019s disease susceptibility gene\n                  <jats:italic>TNFRSF11A<\/jats:italic>\n                  . 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.\n                <\/jats:p>","DOI":"10.64898\/2026.04.13.718284","type":"posted-content","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T05:05:21Z","timestamp":1776229521000},"source":"Crossref","is-referenced-by-count":0,"title":["Genetic analysis of bone morphometry and ivory vertebrae in threespine stickleback"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2006-9350","authenticated-orcid":false,"given":"Veronica C.","family":"Behrens","sequence":"first","affiliation":[{"name":"Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3471-6624","authenticated-orcid":false,"given":"Julia I.","family":"Wucherpfennig","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6401-6461","authenticated-orcid":false,"given":"David M.","family":"Kingsley","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA"},{"name":"Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026060917151830000_2026.04.13.718284v2.1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.4288"},{"key":"2026060917151830000_2026.04.13.718284v2.2","doi-asserted-by":"publisher","DOI":"10.1038\/75556"},{"key":"2026060917151830000_2026.04.13.718284v2.3","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2023.1131182"},{"key":"2026060917151830000_2026.04.13.718284v2.4","doi-asserted-by":"publisher","DOI":"10.1093\/oso\/9780198577287.001.0001"},{"key":"2026060917151830000_2026.04.13.718284v2.5","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.141"},{"key":"2026060917151830000_2026.04.13.718284v2.6","doi-asserted-by":"publisher","DOI":"10.1038\/nature01658"},{"key":"2026060917151830000_2026.04.13.718284v2.7","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btg112"},{"key":"2026060917151830000_2026.04.13.718284v2.8","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btn615"},{"key":"2026060917151830000_2026.04.13.718284v2.9","unstructured":"Carroll SB . 2005. 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