A single nucleotide polymorphism-derived regulatory gene network underlying puberty in 2 tropical breeds of beef cattle
A single nucleotide polymorphism-derived regulatory gene network underlying puberty in 2 tropical breeds of beef cattle
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DOI：
10.2527/jas.2010-3681
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发表时间：
2011-06-01
影响因子：
3.3
通讯作者：
Hawken, R. J.
中科院分区：
文献类型：
--
作者：
Fortes, M. R. S.;Reverter, A.;Hawken, R. J.
恶劣的热带环境给适应不良的物种带来了严峻的挑战。对于肉牛来说，以温度和抗病性为形式的热带适应，加上对季节性和有限饲料的适应，是以生产效率为代价的。这些成本中最突出的是青春期延迟，这是通过传统育种机制操纵的具有挑战性的表型。最近，包括基因网络在内的系统生物学方法已应用于复杂表型的遗传解析。我们的目标是开发和研究牛青春期的基因网络。我们的起始材料包含 22 个性状（包括青春期年龄）和 2 个牛品种群体的 50,000 个 SNP 的关联结果：婆罗门 (Brahman) (n = 843) 和热带复合 (Tropical Composite) (n = 866)。我们将青春期年龄定义为第一黄体年龄（AGECL）。通过捕获与 AGECL 或与 AGECL 相关的一组性状最小相关（P < 0.05）的突变基因，我们分别为每个品种导出了一个基因网络，并为组合数据集导出了第三个网络。在三个网络的交叉点，我们确定了两个品种共有的候选基因和途径。根据这些分析，我们确定了涉及轴突导向、细胞粘附、ErbB 信号传导和谷氨酸活性的基因富集，这些基因已知会影响 GnRH 的脉冲式释放，而 GnRH 是青春期开始所必需的。此外，我们采用网络连接性和中心性参数以及调节影响因子指标来确定负责青春期分子调节的关键转录因子（TF）。作为一项新颖的发现，我们报告了 5 个 TF（HIVEP3、TOX、EYA1、NCOA2 和 ZFHX4）位于与两个品种交叉并与其他 TF 相互作用的网络中，形成了一个与青春期最新文献相一致的调节网络。最后，我们用来自成年牛下丘脑组织基因表达的证据来支持我们的网络预测。
Harsh tropical environments impose serious challenges on poorly adapted species. In beef cattle, tropical adaptation in the form of temperature and disease resistance, coupled with acclimatization to seasonal and limited forage, comes at a cost to production efficiency. Prominent among these costs is delayed onset of puberty, a challenging phenotype to manipulate through traditional breeding mechanisms. Recently, system biology approaches, including gene networks, have been applied to the genetic dissection of complex phenotypes. We aimed at developing and studying gene networks underlying cattle puberty. Our starting material comprises the association results of similar to 50,000 SNP on 22 traits, including age at puberty, and 2 cattle breed populations: Brahman (n = 843) and Tropical Composite (n = 866). We defined age at puberty as the age at first corpus luteum (AGECL). By capturing the genes harboring mutations minimally associated (P < 0.05) to AGECL or to a set of traits related with AGECL, we derived a gene network for each breed separately and a third network for the combined data set. At the intersection of the 3 networks, we identified candidate genes and pathways that were common to both breeds. Resulting from these analyses, we identified an enrichment of genes involved in axon guidance, cell adhesion, ErbB signaling, and glutamate activity, pathways that are known to affect pulsatile release of GnRH, which is necessary for the onset of puberty. Furthermore, we employed network connectivity and centrality parameters along with a regulatory impact factor metric to identify the key transcription factors (TF) responsible for the molecular regulation of puberty. As a novel finding, we report 5 TF (HIVEP3, TOX, EYA1, NCOA2, and ZFHX4) located in the network intersecting both breeds and interacting with other TF, forming a regulatory network that harmonizes with the recent literature of puberty. Finally, we support our network predictions with evidence derived from gene expression in hypothalamic tissue of adult cows.