Faculty of Agriculture, Kyoto University, Kyoto, Japan.
Graduate School of Agriculture, Kyoto University, Kyoto, Japan.
J Anim Sci. 2018 Jun 29;96(7):2553-2566. doi: 10.1093/jas/sky170.
Genome-wide association studies (GWAS) of quantitative traits have detected numerous genetic associations, but they encounter difficulties in pinpointing prominent candidate genes and inferring gene networks. The present study used a systems genetics approach integrating GWAS results with external RNA-expression data to detect candidate gene networks in feed utilization and growth traits of Japanese Black cattle, which are matters of concern. A SNP coassociation network was derived from significant correlations between SNPs with effects estimated by GWAS across 7 phenotypic traits. The resulting network genes contained significant numbers of annotations related to the traits. Using bovine transcriptome data from a public database, an RNA coexpression network was inferred based on the similarity of expression patterns across different tissues. An intersection network was then generated by superimposing the SNP and RNA networks and extracting shared interactions. This intersection network contained 4 tissue-specific modules: nervous system, reproductive system, muscular system, and glands. To characterize the structure (topographical properties) of the 3 networks, their scale-free properties were evaluated, which revealed that the intersection network was the most scale-free. In the subnetwork containing the most connected transcription factors (URI1, ROCK2, and ETV6), most genes were widely expressed across tissues, and genes previously shown to be involved in the traits were found. Results indicated that the current approach might be used to construct a gene network that better reflects biological information, providing encouragement for the genetic dissection of economically important quantitative traits.
全基因组关联研究(GWAS)已发现许多与数量性状相关的遗传关联,但在确定主要候选基因和推断基因网络方面仍存在困难。本研究采用系统遗传学方法,将 GWAS 结果与外部 RNA 表达数据相结合,以检测日本黑牛饲料利用和生长性状的候选基因网络,这些性状是关注的重点。从通过 GWAS 估计的 7 个表型性状的 SNP 效应之间的显著相关性中得出 SNP 共关联网络。所得网络基因包含大量与性状相关的注释。利用公共数据库中的牛转录组数据,根据不同组织中表达模式的相似性推断出 RNA 共表达网络。然后通过叠加 SNP 和 RNA 网络并提取共享相互作用来生成交集网络。该交集网络包含 4 个组织特异性模块:神经系统、生殖系统、肌肉系统和腺体。为了描述 3 个网络的结构(拓扑性质),评估了它们的无标度性质,结果表明交集网络是最无标度的。在包含最连接转录因子(URI1、ROCK2 和 ETV6)的子网络中,大多数基因在组织中广泛表达,并且发现了先前与性状相关的基因。结果表明,当前的方法可能用于构建更好地反映生物学信息的基因网络,为经济上重要的数量性状的遗传解析提供了鼓励。