Banerjee Priyanka, Carmelo Victor Adriano Okstoft, Kadarmideen Haja N
Quantitative Genomics, Bioinformatics and Computational Biology Group, Department of Applied Mathematics and Computer Science, Technical University of Denmark, Kongens Lyngby, Denmark.
Front Genet. 2020 Feb 28;11:121. doi: 10.3389/fgene.2020.00121. eCollection 2020.
Interactions among genomic loci have often been overlooked in genome-wide association studies, revealing the combinatorial effects of variants on phenotype or disease manifestation. Unexplained genetic variance, interactions among causal genes of small effects, and biological pathways could be identified using a network biology approach. The main objective of this study was to determine the genome-wide epistatic variants affecting feed efficiency traits [feed conversion ratio (FCR) and residual feed intake (RFI)] based on weighted interaction SNP hub (WISH-R) method. Herein, we detected highly interconnected epistatic SNP modules, pathways, and potential biomarkers for the FCR and RFI in Duroc and Landrace purebreds considering the whole population, and separately for low and high feed efficient groups. Highly interacting SNP modules in Duroc (1,247 SNPs) and Landrace (1,215 SNPs) across the population and for low feed efficient (Duroc-80 SNPs, Landrace-146 SNPs) and high feed efficient group (Duroc-198 SNPs, Landrace-232 SNPs) for FCR and RFI were identified. Gene and pathway analyses identified , , , , , and from chromosomes 1, 2, 5, and 13 underlying ErbB, Ras, Rap1, thyroid hormone, axon guidance pathways in Duroc. , and genes from chromosomes 1, 3, and 6 pointed towards thyroid hormone, cGMP-PKG and cAMP pathways in Landrace. From Duroc low feed efficient group, the gene was found involved with thiamine metabolism, whereas , were involved with the hippo signaling pathway in high feed efficient group. and genes were involved with lysine degradation in low feed efficient group in Landrace, while high feed efficient group pointed to genes underpinning valine, leucine, isoleucine degradation, and fatty acid elongation. Some SNPs and genes identified are known for their association with feed efficiency, others are novel and potentially provide new avenues for further research. Further validation of epistatic SNPs and genes identified here in a larger cohort would help to establish a framework for modelling epistatic variance in future methods of genomic prediction, increasing the accuracy of estimated genetic merit for FE and helping the pig breeding industry.
基因组位点之间的相互作用在全基因组关联研究中常常被忽视,而这种研究能够揭示变异对表型或疾病表现的组合效应。可以使用网络生物学方法来识别无法解释的遗传变异、小效应因果基因之间的相互作用以及生物途径。本研究的主要目的是基于加权相互作用单核苷酸多态性中心(WISH-R)方法,确定影响饲料效率性状[饲料转化率(FCR)和剩余采食量(RFI)]的全基因组上位性变异。在此,我们检测了杜洛克猪和长白猪中FCR和RFI的高度互联的上位性单核苷酸多态性模块、途径和潜在生物标志物,这是综合考虑整个群体以及分别针对低饲料效率组和高饲料效率组进行的检测。确定了杜洛克猪(1247个单核苷酸多态性)和长白猪(1215个单核苷酸多态性)群体中以及针对FCR和RFI的低饲料效率组(杜洛克猪-80个单核苷酸多态性,长白猪-146个单核苷酸多态性)和高饲料效率组(杜洛克猪-198个单核苷酸多态性,长白猪-232个单核苷酸多态性)的高度相互作用的单核苷酸多态性模块。基因和途径分析确定了杜洛克猪中位于1号、2号、5号和13号染色体上的、、、、、基因,这些基因涉及ErbB、Ras、Rap1、甲状腺激素、轴突导向途径。长白猪中位于1号、3号和6号染色体上的、和基因指向甲状腺激素、cGMP-PKG和cAMP途径。在杜洛克猪低饲料效率组中,发现基因与硫胺素代谢有关,而在高饲料效率组中,、与河马信号通路有关。在长白猪低饲料效率组中,和基因与赖氨酸降解有关,而高饲料效率组则指向与缬氨酸、亮氨酸、异亮氨酸降解以及脂肪酸延长相关的基因。所确定的一些单核苷酸多态性和基因因其与饲料效率的关联而为人所知,其他的则是新发现的,可能为进一步研究提供新途径。在更大的队列中对这里确定的上位性单核苷酸多态性和基因进行进一步验证,将有助于建立一个框架,以便在未来的基因组预测方法中对上位性变异进行建模,提高FE估计遗传价值的准确性,并有助于养猪业。