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Background <p>Horns are an important breed-specific trait in sheep; however, under intensive housing conditions, they pose potential safety risks during management. Understanding the developmental mechanisms of horn formation has significant application value for breeding polled sheep varieties.</p> Results <p>This study investigates the regulatory mechanism of horn development mediated by the Fibroblast Growth Factor 2 (<i>FGF2</i>) gene, which plays a key role in skin formation, using integrated multi-omics approaches. First, we analyzed the tissue-specific expression of the <i>FGF2</i> gene using RNA sequencing (RNA-seq) data. Then, based on whole-genome sequencing (WGS) data from 99 sheep, we identified potential functional variants in the <i>FGF2</i> gene. Additionally, we integrated epigenomic data to identify regulatory elements associated with <i>FGF2</i>, and finally investigated allele-specific expression (ASE) of this gene. The results showed that <i>FGF2</i> was specifically expressed in horn and skin tissues, with significantly higher expression levels in large-horned sheep compared to small-horned sheep (<i>P</i> &lt; 0.05). Cross-species protein sequence alignment revealed a species-specific amino acid variant between sheep and Bighorn sheep, suggesting a potential role in horn morphology regulation. Population genetic analysis of the WGS data identified 20 potential functional variants related to horn development, as determined by fixation index (Fst) screening. Combined with horn length phenotypic data and Kompetitive Allele-Specific PCR (KASP) genotyping, we identified a SNP at chr17:35071069 that is significantly associated with horn length. Integration with epigenomic data revealed that this SNP is located within an enhancer regulatory region. Finally, three allele-specific expression sites were identified from the RNA-seq data.</p> Conclusion <p>In summary, this study suggests that the <i>FGF2</i> gene may influence horn development in sheep by modulating enhancer activity. The identified SNP and ASE sites provide valuable molecular markers for breeding polled sheep varieties.</p>

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Functional analysis of the FGF2 gene in horn development in sheep and identification of key regulatory variants

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月29日

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  • Fei Liu,
  • Hao Li,
  • Zhu Meng,
  • Shiwen Zhang,
  • Huaiqiang Yang,
  • Yangshuo Hu,
  • Renzeng Ciwang,
  • Jianning He,
  • Zhangyuan Pan

摘要

Background

Horns are an important breed-specific trait in sheep; however, under intensive housing conditions, they pose potential safety risks during management. Understanding the developmental mechanisms of horn formation has significant application value for breeding polled sheep varieties.

Results

This study investigates the regulatory mechanism of horn development mediated by the Fibroblast Growth Factor 2 (FGF2) gene, which plays a key role in skin formation, using integrated multi-omics approaches. First, we analyzed the tissue-specific expression of the FGF2 gene using RNA sequencing (RNA-seq) data. Then, based on whole-genome sequencing (WGS) data from 99 sheep, we identified potential functional variants in the FGF2 gene. Additionally, we integrated epigenomic data to identify regulatory elements associated with FGF2, and finally investigated allele-specific expression (ASE) of this gene. The results showed that FGF2 was specifically expressed in horn and skin tissues, with significantly higher expression levels in large-horned sheep compared to small-horned sheep (P < 0.05). Cross-species protein sequence alignment revealed a species-specific amino acid variant between sheep and Bighorn sheep, suggesting a potential role in horn morphology regulation. Population genetic analysis of the WGS data identified 20 potential functional variants related to horn development, as determined by fixation index (Fst) screening. Combined with horn length phenotypic data and Kompetitive Allele-Specific PCR (KASP) genotyping, we identified a SNP at chr17:35071069 that is significantly associated with horn length. Integration with epigenomic data revealed that this SNP is located within an enhancer regulatory region. Finally, three allele-specific expression sites were identified from the RNA-seq data.

Conclusion

In summary, this study suggests that the FGF2 gene may influence horn development in sheep by modulating enhancer activity. The identified SNP and ASE sites provide valuable molecular markers for breeding polled sheep varieties.