RGAP: The heritable transcriptome and alcoholism

描述(由申请人提供)：这是一个“修订申请”，目的是获得资金，以便将雌性和雄性的信息纳入啮齿动物转录组的系统遗传分析的资源中。我们资源的核心是一个网站http://phenogen.ucdenver.edu，它提供了来自重组近亲交配和近亲交配的小鼠和大鼠面板的基因表达数据，以及使用基因表达遗传学来识别与成瘾和其他精神健康问题等复杂特征相关的基因和转录网络的分析工具。此次修订的母公司R24使用RNA-Seq方法对来自HXB/BXH重组近交系和遗传多样性近交系大鼠品系的雄性大鼠的大脑和肝脏转录进行表征和量化。在过去的一年里，我们已经确定了HXB/BXH RI小组的亲本菌株(SHR/Ola和BN-LX菌株)的基因组序列，并使用来自这些大鼠大脑的RNA-Seq数据进行了转录组重建，使用了序列特定的基因组比对。我们还从两个HXB/BXH RI株获得了链RNA-Seq数据，并正在开发使用ERCC尖峰标准进行转录定量的方法。在继续开发雄性大鼠小组的转录组数据的同时，我们建议增加雌性SHR/Ola和BN-LX大鼠发情周期每个阶段的脑和肝脏转录组数据。我们还将收集雄性和雌性大鼠伏隔核外壳和核心区域的转录组数据，因为这些区域对我们和其他研究人员感兴趣的酒精相关复杂特征(强化、奖励反应、学习)特别重要。在我们自己的工作中，我们将在发情周期的每个阶段测量雌性大鼠自由选择饮酒的表型和与酒精代谢相关的一些变量，以与亲本R24赠款中的雄性大鼠的研究进行比较，并将整合转录组和表型数据以确定这些特征中易受遗传、性别和发情周期影响的差异的候选转录本。所有经过注释和整理的数据将在Phenogen网站上提供给其他研究人员用于他们的遗传、基因组和表型分析。

DESCRIPTION (provided by applicant): This is a "revision application" to obtain funds for including information on females as well as males in a resource for systems genetic analysis of the rodent transcriptome. The core of our resource is a website, http://phenogen.ucdenver.edu that makes available gene expression data from recombinant inbred and inbred panels of mice and rats, as well as analytical tools to use the genetics of gene expression for identification of genes and transcriptional networks associated with complex traits such as addiction and other mental health problems. The parent R24 grant for this revision uses RNA-Seq methodology to characterize and quantify the brain and liver transcriptomes from male rats from the HXB/BXH recombinant inbred panel and a genetically diverse panel of inbred rat strains. In the past year, we have determined the genome sequence of the parental strains for the HXB/BXH RI panel (SHR/Ola and BN-Lx strains) and have used RNA-Seq data from the brains of these rats to perform a transcriptome reconstruction, using sequence-specific genomic alignment. We have also obtained stranded RNA-Seq data from two of the HXB/BXH RI strains and are developing methods for transcript quantification using ERCC spike-in standards. While continuing to develop the transcriptome data for the male rat panels, we propose to add brain and liver transcriptome data from female SHR/Ola and BN-Lx rats at each stage of the estrus cycle. We will also gather transcriptome data from the nucleus accumbens shell and core regions of both strains of male and female rats, as these regions are particularly important for the alcohol-related complex traits (reinforcement, reward response, learning) that are of interest to us and other investigators. We will, in our own work, measure the phenotypes of free-choice alcohol consumption and a number of variables related to alcohol metabolism in the female rats at each stage of the estrus cycle, for comparison to the studies of male rats in the parent R24 grant, and will integrate the transcriptome and phenotypic data to identify candidate transcripts predisposing to genetic, sex and estrus cycle dependent differences in these traits. All annotated and curated data will be made available to other investigators for their genetic, genomic and phenotypic analysis on the Phenogen website.