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