USING SYSTEMS BIOLOGY TO UNDERSTAND POLYGENIC CONTROL OF PRIMATE PUBERTY

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 该项目的具体目的是使用新开发的恒河猴特异Affymetrix基因芯片(MK基因芯片)来为灵长类青春期的开始与先前已知的肿瘤抑制作用的基因网络的表达的协调变化相关的概念提供原则证据。 几年前，我们使用了一个包含有限数量的探针(8400个；75%对应于已知基因)的人类cDNA阵列(OHSU基因微阵列共享资源)来询问青春期雌性猴子的下丘脑。虽然这项研究导致了一组可能参与控制这一发育过程的基因的鉴定，但很可能只鉴定了一小部分相关基因，这是因为阵列中的探针数量较少，以及所使用的物种间杂交方案，这特别限制了我们的敏感性。由于新的Affymetrix MK基因芯片包含恒河猴整个转录组，并包括几个与青春期表达增加的基因产生共鸣的探针，拟议的研究应该有助于开发第一个系统生物学方法，迄今试图剖析参与灵长类性别发育神经内分泌控制的基因网络的复杂结构。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The specific aim of this project is to use the newly developed rhesus macaque-specific Affymetrix gene chips (MK GeneChip) to provide proof of principle for the concept that the onset of primate puberty is associated with a coordinated change in expression of a network of genes previously known for their role in tumor suppression. A few years ago we employed a human cDNA array (OHSU Gene MicroArray Shared Resource) containing a limited number of probes (8,400; 75% corresponding to known genes) to interrogate the female monkey hypothalamus at the time of puberty. Although this study resulted in the idenification of a group of genes potentially involved in the control of this developmental process, it is likely that only a fraction of the relevant genes were identified due to the small number of probes in the array, and the interspecies-hybridization protocol used, which especially limited our sensitivity. Since the new Affymetrix MK GeneChip contains the entire rhesus monkey transcriptome, and includes several probes corresonding to genes whose expression is known to increase at puberty, the proposed study should be instrumental in developing the first Systems Biology approach thus far attempted to dissect the complex architecture of the gene networks involved in the neuroendocrine control of primate sexual development.