Integrative multi-omics analysis of growth plate regulation underlying body size in miniature pigs

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Abstract Body size represents a complex phenotype driven by genetic variation and epigenetic regulation, with the molecular processes underlying this trait remaining a central challenge to disentangle. To elucidate these fundamental mechanisms, we applied a multi-omics approach that combines ROH-based selection mapping with growth plate epigenomics in pigs, a valuable model species for skeletal development. Taking advantage of divergent selection that separates pigs into miniature and larger-sized types, we targeted genomic regions under this intense selection for height, which harbour functional variants with pronounced effects. We assembled a multi-omics dataset, identifying 23 homozygous mutant variants in Aachen Minipigs and 13 distinct variants in Mini-LEWE predicted to affect cis-regulatory elements and potentially interact with differentially expressed genes that drive body size in breed-dependent ways. Our results pointed to an lncRNA (ENSSSCG00000048200) near SDR16C5 and PLAG1, HPX and NET-related pathways, as central players in impaired growth in the growth plates. Furthermore, network propagation across protein-protein interaction networks highlighted 16 proteins with consistent interaction network changes between miniature and larger-sized pig breeds. In summary, our study offers a multi-layered characterisation of regulatory mechanisms in the growth plates, using miniature pigs as a model to understand the genetic and epigenetic control of long-bone growth. *Nadia Khaveh and Jan Berghöfer contributed equally.
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Integrative multi-omics analysis of growth plate regulation underlying body size in miniature pigs | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Integrative multi-omics analysis of growth plate regulation underlying body size in miniature pigs Nadia Khaveh*, Jan Berghöfer*, Brehm Ralph, René Buschow, Karsten Cirksena, and 13 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7865536/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Body size represents a complex phenotype driven by genetic variation and epigenetic regulation, with the molecular processes underlying this trait remaining a central challenge to disentangle. To elucidate these fundamental mechanisms, we applied a multi-omics approach that combines ROH-based selection mapping with growth plate epigenomics in pigs, a valuable model species for skeletal development. Taking advantage of divergent selection that separates pigs into miniature and larger-sized types, we targeted genomic regions under this intense selection for height, which harbour functional variants with pronounced effects. We assembled a multi-omics dataset, identifying 23 homozygous mutant variants in Aachen Minipigs and 13 distinct variants in Mini-LEWE predicted to affect cis-regulatory elements and potentially interact with differentially expressed genes that drive body size in breed-dependent ways. Our results pointed to an lncRNA (ENSSSCG00000048200) near SDR16C5 and PLAG1, HPX and NET-related pathways, as central players in impaired growth in the growth plates. Furthermore, network propagation across protein-protein interaction networks highlighted 16 proteins with consistent interaction network changes between miniature and larger-sized pig breeds. In summary, our study offers a multi-layered characterisation of regulatory mechanisms in the growth plates, using miniature pigs as a model to understand the genetic and epigenetic control of long-bone growth. *Nadia Khaveh and Jan Berghöfer contributed equally. Biological sciences/Genetics/Genomics/Epigenomics Biological sciences/Genetics/Functional genomics/Gene expression profiling Biological sciences/Genetics/Gene regulation Biological sciences/Computational biology and bioinformatics/Data integration Biological sciences/Genetics/Genomics/Comparative genomics Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SupplementaryData6.xlsx Supplementary Data 6 SupplementaryData4.xlsx Supplementary Data 4 SupplementaryData3.xlsx Supplementary Data 3 SupplementaryData7.xlsx Supplementary Data 7 SupplementaryData1.xlsx Supplementary Data 1 SupplementaryData2.xlsx Supplementary Data 2 SupplementaryData5.xlsx Supplementary Data 5 SupplementaryData9.xlsx Supplementary Data 9 SupplementaryData8.xlsx Supplementary Data 8 SupplementaryInformation.docx Supplementary Information Cite Share Download PDF Status: Under Review Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Portfolio","twitterHandle":"","acdcEnabled":false,"dfaEnabled":false,"editorialSystem":"ejp","reportingPortfolio":"","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-7865536/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7865536/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBody size represents a complex phenotype driven by genetic variation and epigenetic regulation, with the molecular processes underlying this trait remaining a central challenge to disentangle. To elucidate these fundamental mechanisms, we applied a multi-omics approach that combines ROH-based selection mapping with growth plate epigenomics in pigs, a valuable model species for skeletal development. Taking advantage of divergent selection that separates pigs into miniature and larger-sized types, we targeted genomic regions under this intense selection for height, which harbour functional variants with pronounced effects. We assembled a multi-omics dataset, identifying 23 homozygous mutant variants in Aachen Minipigs and 13 distinct variants in Mini-LEWE predicted to affect cis-regulatory elements and potentially interact with differentially expressed genes that drive body size in breed-dependent ways. Our results pointed to an lncRNA (ENSSSCG00000048200) near SDR16C5 and PLAG1, HPX and NET-related pathways, as central players in impaired growth in the growth plates. Furthermore, network propagation across protein-protein interaction networks highlighted 16 proteins with consistent interaction network changes between miniature and larger-sized pig breeds. In summary, our study offers a multi-layered characterisation of regulatory mechanisms in the growth plates, using miniature pigs as a model to understand the genetic and epigenetic control of long-bone growth.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e*Nadia Khaveh and Jan Berghöfer contributed equally.\u003c/strong\u003e\u003c/p\u003e","manuscriptTitle":"Integrative multi-omics analysis of growth plate regulation underlying body size in miniature pigs","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-01 05:47:37","doi":"10.21203/rs.3.rs-7865536/v1","editorialEvents":[],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"communications-biology","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"commsbio","sideBox":"Learn more about [Communications Biology](http://www.nature.com/commsbio/)","snPcode":"","submissionUrl":"","title":"Communications Biology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Communications Series","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"da0de003-4d23-426e-a9c2-4ae4eb307a2d","owner":[],"postedDate":"December 1st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":56763274,"name":"Biological sciences/Genetics/Genomics/Epigenomics"},{"id":56763275,"name":"Biological sciences/Genetics/Functional genomics/Gene expression profiling"},{"id":56763276,"name":"Biological sciences/Genetics/Gene regulation"},{"id":56763277,"name":"Biological sciences/Computational biology and bioinformatics/Data integration"},{"id":56763278,"name":"Biological sciences/Genetics/Genomics/Comparative genomics"}],"tags":[],"updatedAt":"2025-12-01T05:47:38+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-01 05:47:37","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7865536","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7865536","identity":"rs-7865536","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}

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