USING SYSTEMS BIOLOGY TO UNDERSTAND POLYGENIC CONTROL OF PRIMATE PUBERTY

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 该项目的具体目的是使用新开发的恒河猴特异性Affyphin基因芯片（MK GeneChip）为灵长类动物青春期的开始与先前已知的肿瘤抑制基因网络表达的协调变化相关的概念提供原理证明。 几年前，我们使用了一个人类cDNA阵列（OFISU基因微阵列共享资源），其中包含有限数量的探针（8，400个; 75%对应于已知基因），以询问青春期的雌性猴子下丘脑。尽管这项研究鉴定了一组可能参与控制这一发育过程的基因，但由于阵列中探针数量较少，以及所使用的种间杂交协议，可能仅鉴定了一小部分相关基因，这特别限制了我们的灵敏度。由于新的Affyssin MK基因芯片包含了整个恒河猴转录组，并包括几个探针对应的基因，其表达是已知的增加，在青春期，拟议的研究应有助于发展第一个系统生物学的方法，迄今试图解剖复杂的结构的基因网络参与灵长类动物性发育的神经内分泌控制。

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 (OFISU 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 identification 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 corresponding 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.