EARLY DETECTION AND PROGRESSION OF OBESITY AND DIABETES

这个子项目是许多研究子项目中的一个 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。 该项目的具体目标是：1。测量500只小鼠F2杂交分离肥胖和糖尿病性状的肝脏和脂肪组织样品中的代谢物水平。2.使用来自特定目标#1的数据鉴定代谢物数量性状基因座（mQTL）。我们对代谢物QTL的初步研究表明，存在复杂的相互作用，这是不容易使用传统方法处理。新的mQTL定位方法将被开发和应用，以高效和有效地定位mQTL。3.将特定目标#2中获得的代谢物数据和mQTL结果与临床数据相结合，构建调控网络，揭示基因组区域、代谢物和临床性状之间的关键关系。现在存在使用基因表达和表达QTL（eQTL）数据结合相关临床性状来鉴定调控网络的方法。这些方法将被应用和扩展，以解释代谢物，并允许代谢物，表达和临床表型之间的相互作用。改进后的方法将为从基因位点开始构建包括mRNA和代谢物的网络提供有力的基础。

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 Aims of this project are: 1. Measure levels of metabolites in liver and adipose tissue samples in a 500 mouse F2 intercross segregating for obesity and diabetes traits. 2. Identify metabolite quantitative trait loci (mQTL) using the data from Specific Aim #1. Our preliminary studies of metabolite QTLs indicate the presence of complex interactions that are not easily handled using traditional methods. New mQTL mapping methods will be developed and applied to efficiently and effectively localize mQTLs. 3. Combine the metabolite data and mQTL results obtained in Specific Aim #2 with clinical data to construct regulatory networks that reveal key relationships among genome regions, metabolites, and clinical traits. Methods now exist for identifying regulatory networks using gene expression and expression QTL (eQTL) data combined with related clinical traits. These approaches will be applied and extended to account for metabolites and to allow for interactions among metabolites, expression and clinical phenotypes. The improved methods will provide a powerful basis for network construction that begins with gene loci and forms a network involving mRNAs and metabolites.