Hu sheep (Ovis aries) is a rare white sheep breed, with four different types of lambskin patterns that have different values. However, the genetic mechanisms underlying different types of pattern formation remains unclear. This research aimed to characterize the molecular mechanism of differentially expressed gene PAPPA2 affecting the pattern type of Hu sheep’s lambskin at the cellular level. Thus, RT-qPCR, EdU and Cell Cycle detection were used to explore the effect of PAPPA2 and IGFBP5 (a protein that can be hydrolyzed by PAPPA2) on the proliferation of dermal papilla cells (DPCs) after overexpression or interference with PAPPA2 and IGFBP5. The expression level of PAPPA2 in straight DPCs was 4.79 ± 1.84 times higher than curved. Overexpression of PAPPA2 promoted the proliferation of DPCs and also increased the expression of IGFBP5. Conversely, overexpression of IGFBP5 reduced the proliferation of DPCs. However, the proliferation of DPCs was restored by co-overexpression of PAPPA2 and IGFBP5 compared with overexpression of IGFBP5 alone. Thus, PAPPA2 can affect the proliferation of DPCs through regulating IGFBP5 and then participate in lambskin pattern determination. Overall, we preliminarily clarified the critical role played by PAPPA2 during the formation of different pattern in Hu sheep lambskin.

Body weight is a polygenic trait with intricate inheritance patterns. Functional genomics enriched with multi-layer annotations offers essential resources for exploring the genetic architecture of complex traits. In this study, we conducted an extensive characterization of regulatory variants associated with body weight-related traits in cattle using multi-omics analysis. First, we identified seven candidate genes by integrating selective sweep analysis and multiple genome-wide association study (GWAS) strategies using imputed whole-genome sequencing data from a population of 1577 individuals. Subsequently, we uncovered 3340 eGenes (genes whose expression levels are associated with genetic variants) across 227 muscle samples. Transcriptome-wide association studies (TWASs) further revealed a total of 532 distinct candidate genes associated with body weight-related traits. Colocalization analyses unveiled 44 genes shared between expression quantitative trait loci (eQTLs) and GWAS signals. Moreover, a comprehensive analysis by integrating GWAS, selective sweep, eQTL, TWAS, epigenomic profiling, and molecular validation highlighted a positively selected genomic region on Bos taurus autosome 6 (BTA6). This locus harbors pleiotropic genes (LAP3, MED28, and NCAPG) and a prioritized functional variant involved in the complex regulation of body weight. Additionally, convergent evolution analysis and phenome-wide association studies underscored the conservation of this locus across species. Our study provides a comprehensive understanding of the genetic regulation of body weight through multi-omics analysis in cattle. Our findings contribute to unraveling the genetic mechanisms governing weight-related traits and shed valuable light on the genetic improvement of farm animals.