RGAP: The heritable transcriptome and alcoholism

描述（由申请人提供）：这是一份“修订申请”，旨在获得资金，用于在啮齿动物转录组系统遗传分析资源中包括雌性和雄性信息。我们资源的核心是一个网站http://phenogen.ucdenver.edu，该网站提供了来自重组自交系和自交系小鼠和大鼠的基因表达数据，以及使用基因表达遗传学来识别与成瘾和其他心理健康问题等复杂特征相关的基因和转录网络的分析工具。本修订的亲本R24基金使用RNA-Seq方法来表征和量化来自HXB/BXH重组自交系和遗传多样性自交系大鼠的雄性大鼠的脑和肝脏转录组。在过去的一年里，我们已经确定了HXB/BXH RI组亲本菌株（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数据进行转录组重建，使用序列特异性基因组比对。我们还从两个HXB/BXH RI菌株获得了链RNA-Seq数据，并正在开发使用ERCC尖峰标准的转录物定量方法。在继续开发雄性大鼠组的转录组数据的同时，我们建议添加雌性SHR/Ola和BN-Lx大鼠在发情周期的每个阶段的脑和肝脏转录组数据。我们还将收集来自雄性和雌性大鼠两种品系的伏隔核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与酒精相关的复杂特征（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的自由选择饮酒的表型和与酒精代谢相关的许多变量，以便与父本R24资助的雄性大鼠的研究进行比较，并将转录组和表型数据整合起来，以确定这些性状的遗传、性别和发情周期依赖性差异的候选转录本。所有注释和整理的数据将提供给其他研究者，以便他们在Phenogen网站上进行遗传、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.