Jové-Juncà Teodor, Crespo-Piazuelo Daniel, Hernández-Banqué Carles, González-Rodríguez Olga, Fang Lingzhao, Quintanilla Raquel, Ballester Maria
Animal Breeding and Genetics Program, Institute of Agrifood Research and Technology (IRTA), Torre Marimon, Caldes de Montbui, Spain.
R&D Department, Cuarte S.L., Monzalbarba, Spain.
Front Immunol. 2025 Jun 5;16:1582982. doi: 10.3389/fimmu.2025.1582982. eCollection 2025.
Genome wide association studies (GWAS) have been widely used to investigate the association of genetic markers with complex traits in both humans and livestock species. A particular trait of interest, when studying animal robustness and general immunocompetence, is the transcriptomic profile of blood. To identify genetic variants affecting gene expression in pig blood, we performed expression GWAS (eGWAS) in 255 animals from a commercial Duroc population between 8,499,177 imputed single nucleotide polymorphisms (SNPs) and the expression levels of 14,642 genes obtained from RNA sequencing. Out of the nearly 125 million associations tested, 23 million were found to be significant, grouped in 9,930 expression quantitative trait loci (eQTLs) associated to the expression levels of 6,051 genes. Over 36% of detected eQTLs mapped in close proximity to the genomic location of their associated gene and were classified as eQTLs. Moreover, 430,694 variants were found to be associated with the expression of 10 or more different genes and were annotated as transcriptional hotspots. Among genes regulated by these hotspots, we identified genes that encode transcription factors and co-factors regulating immune responses, such as , or co-expressed genes related to immunity (, , , and ) and associated with health traits, such as phagocytic activity or haptoglobin concentration. In addition, several of the regulating variants for immunity candidate genes overlapped with previously described immunity QTLs. Colocalization studies revealed putative common causal variants between the proportion of memory and helper T cells and the candidate genes , , , and . In conclusion, the associations identified in this study enable the characterization of transcriptional regulators of the pig blood transcriptome. Moreover, the colocalization between immunity QTLs and eQTLs has revealed potential causative mutations regulating immunocompetence in pigs. All these data and results contribute to shedding light on the regulatory mechanisms of blood gene expression and porcine immune regulation.
全基因组关联研究(GWAS)已被广泛用于研究人类和家畜物种中遗传标记与复杂性状之间的关联。在研究动物健壮性和一般免疫能力时,一个特别感兴趣的性状是血液的转录组图谱。为了鉴定影响猪血液中基因表达的遗传变异,我们对来自一个商业杜洛克种群的255头动物进行了表达全基因组关联研究(eGWAS),研究对象包括8499177个估算的单核苷酸多态性(SNP)以及通过RNA测序获得的14642个基因的表达水平。在近1.25亿次检测的关联中,发现2300万次具有显著性,归为9930个表达数量性状位点(eQTL),与6051个基因的表达水平相关。超过36%的检测到的eQTL定位在与其相关基因的基因组位置附近,并被归类为顺式eQTL。此外,发现430694个变异与10个或更多不同基因的表达相关,并被注释为转录热点。在这些热点调控的基因中,我们鉴定出编码调节免疫反应的转录因子和辅助因子的基因,如 ,或与免疫相关的共表达基因( 、 、 、 和 ),并与健康性状相关,如吞噬活性或触珠蛋白浓度。此外,一些免疫候选基因的调控变异与先前描述的免疫QTL重叠。共定位研究揭示了记忆T细胞和辅助性T细胞比例与候选基因 、 、 、 和 之间可能存在共同的因果变异。总之,本研究中鉴定出的关联能够对猪血液转录组的转录调节因子进行表征。此外,免疫QTL和eQTL之间的共定位揭示了调节猪免疫能力的潜在致病突变。所有这些数据和结果有助于阐明血液基因表达的调控机制和猪的免疫调节。
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