Quantitative Genomics, Bioinformatics and Computational Biology Group, Department of Applied Mathematics and Computer Science, Technical University of Denmark, Kongens Lyngby, Denmark.
PLoS One. 2020 Sep 17;15(9):e0239143. doi: 10.1371/journal.pone.0239143. eCollection 2020.
Feed efficiency (FE) is a key trait in pig production, as improvement in FE has positive economic and environmental impact. FE is a complex phenotype and testing animals for FE is costly. Therefore, there has been a desire to find functionally relevant single nucleotide polymorphisms (SNPs) as biomarkers, to improve our biological understanding of FE as well as accuracy of genomic prediction for FE. We have performed a cis- and trans- eQTL (expression quantitative trait loci) analysis, in a population of Danbred Durocs (N = 11) and Danbred Landrace (N = 27) using both a linear and ANOVA model based on muscle tissue RNA-seq. We analyzed a total of 1425x19179 or 2.7x107 Gene-SNP combinations in eQTL detection models for FE. The 1425 genes were from RNA-Seq based differential gene expression analyses using 25880 genes related to FE and additionally combined with mitochondrial genes. The 19179 SNPs were from applying stringent quality control and linkage disequilibrium filtering on genotype data using a GGP Porcine HD 70k SNP array. We applied 1000 fold bootstrapping and enrichment analysis to further validate and analyze our detected eQTLs. We identified 13 eQTLs with FDR < 0.1, affecting several genes found in previous studies of commercial pig breeds. Examples include MYO19, CPT1B, ACSL1, IER5L, CPT1A, SUCLA2, CSRNP1, PARK7 and MFF. The bootstrapping results showed statistically significant enrichment (p-value<2.2x10-16) of eQTLs with p-value < 0.01 in both cis and trans-eQTLs. Enrichment analysis of top trans-eQTLs revealed high enrichment for gene categories and gene ontologies associated with genomic context and expression regulation. This included transcription factors (p-value = 1.0x10-13), DNA-binding (GO:0003677, p-value = 8.9x10-14), DNA-binding transcription factor activity (GO:0003700,) nucleus gene (GO:0005634, p-value<2.2x10-16), negative regulation of expression (GO:0010629, p-value<2.2x10-16). These results would be useful for future genome assisted breeding of pigs to improve FE, and in the improved understanding of the functional mechanism of trans eQTLs.
饲料效率（FE）是猪生产中的一个关键特性，因为提高 FE 具有积极的经济和环境影响。FE 是一种复杂的表型，对动物进行 FE 测试成本很高。因此，人们一直希望找到功能相关的单核苷酸多态性（SNP）作为生物标志物，以提高我们对 FE 的生物学理解以及对 FE 的基因组预测的准确性。我们使用基于肌肉组织 RNA-seq 的线性和 ANOVA 模型，对丹麦长白杜洛克（N = 11）和丹麦长白兰德瑞斯（N = 27）群体进行了顺式和反式 eQTL（表达数量性状基因座）分析。我们总共分析了 1425x19179 或 2.7x107 个基因-SNP 组合，用于 FE 的 eQTL 检测模型。这 1425 个基因是基于与 FE 相关的 25880 个基因的 RNA-Seq 差异基因表达分析，并与线粒体基因结合。19179 个 SNP 是通过在 GGP Porcine HD 70k SNP 阵列上应用严格的质量控制和连锁不平衡过滤从基因型数据中获得的。我们应用了 1000 倍的自举和富集分析来进一步验证和分析我们检测到的 eQTLs。我们鉴定了 13 个 FDR<0.1 的 eQTL，这些 eQTL 影响了之前对商业猪种的研究中发现的几个基因。例如，MYO19、CPT1B、ACSL1、IER5L、CPT1A、SUCLA2、CSRNP1、PARK7 和 MFF。自举结果显示，cis 和 trans-eQTL 中 p 值<0.01 的 eQTL 具有统计学意义的富集（p 值<2.2x10-16）。顶级 trans-eQTL 的富集分析显示，与基因组背景和表达调控相关的基因类别和基因本体论高度富集。这包括转录因子（p 值=1.0x10-13）、DNA 结合（GO:0003677，p 值=8.9x10-14）、DNA 结合转录因子活性（GO:0003700）、核基因（GO:0005634，p 值<2.2x10-16）、表达负调控（GO:0010629，p 值<2.2x10-16）。这些结果将有助于未来通过基因组辅助猪的选育来提高 FE，并深入了解 trans-eQTL 的功能机制。
