Li Chenyu, Ge Mei, Long Keren, Han Ziyin, Li Jing, Li Mingzhou, Zhang Zhiyan
National Key Laboratory for Swine Genetic Improvement and Germplasm innovation Technology, Jiangxi Agricultural University, Nanchang 330045, China.
State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China.
Animals (Basel). 2025 May 21;15(10):1494. doi: 10.3390/ani15101494.
Understanding how hybrids integrate lineage-specific regulatory variants at the haplotype level is crucial for elucidating the genetic basis of heterosis in livestock. In this study, we established three crossbred pig families derived from distant genetic lineages and systematically identified variants from different lineages, including single nucleotide polymorphisms (SNPs) and structural variations (SVs). At the phase level, we quantitatively analyzed gene expression, four histone modifications (H3K4me3, H3K27ac, H3K4me1, and H3K27me3), and the binding strength of transcription factor (CTCF) in backfat (BF) and longissimus dorsi (LD) muscle. By colocalization analysis of phased genetic variants with phased gene expression levels and with phased epigenetic modifications, we identified 18,670 expression quantitative trait loci (eQTL) (FDR < 0.05) and 8,652 epigenetic modification quantitative trait loci (epiQTL) (FDR < 0.05). The integration of eQTL and epiQTL allowed us to explore the potential regulatory mechanisms by which lineage-specific genetic variants simultaneously influence gene expression and epigenetic modifications. For example, we identified a Large White lineage-specific duplication (DUP) encompassing the gene that was significantly associated with its promoter activity (FDR = 7.83 × 10) and expression levels (FDR = 9.03 × 10). Additionally, we found that a Duroc lineage-specific SNP located upstream of was significantly associated with a Duroc-specific H3K27ac peak (FDR = 0.035) and also showed a significant association with expression levels (FDR = 5.12 × 10). These findings underscore the importance of phased regulatory variants in shaping lineage-specific transcriptional programs and highlight how the haplotype-resolved integration of eQTL and epigenetic signals can reveal the mechanistic underpinnings of hybrid regulatory architecture. Our results offer insights for molecular marker development in precision pig breeding.
了解杂种如何在单倍型水平上整合特定谱系的调控变异对于阐明家畜杂种优势的遗传基础至关重要。在本研究中，我们建立了三个源自远缘遗传谱系的杂交猪家族，并系统地鉴定了来自不同谱系的变异，包括单核苷酸多态性（SNP）和结构变异（SV）。在相位水平上，我们定量分析了背膘（BF）和背最长肌（LD）中基因表达、四种组蛋白修饰（H3K4me3、H3K27ac、H3K4me1和H3K27me3）以及转录因子（CTCF）的结合强度。通过将相位遗传变异与相位基因表达水平以及相位表观遗传修饰进行共定位分析，我们鉴定出18,670个表达数量性状位点（eQTL）（FDR < 0.05）和8,652个表观遗传修饰数量性状位点（epiQTL）（FDR < 0.05）。eQTL和epiQTL的整合使我们能够探索特定谱系的遗传变异同时影响基因表达和表观遗传修饰的潜在调控机制。例如，我们鉴定出一个大白猪谱系特异性重复（DUP），其包含与启动子活性（FDR = 7.83 × 10）和表达水平（FDR = 9.03 × 10）显著相关的基因。此外，我们发现位于 上游的一个杜洛克猪谱系特异性SNP与杜洛克猪特异性H3K27ac峰显著相关（FDR = 0.035），并且也与 表达水平显著相关（FDR = 5.12 × 10）。这些发现强调了相位调控变异在塑造特定谱系转录程序中的重要性，并突出了eQTL和表观遗传信号的单倍型解析整合如何能够揭示杂种调控结构的机制基础。我们的结果为精准猪育种中的分子标记开发提供了见解。
