Center for Genetic Studies of Drug Abuse in Outbred Rats

项目摘要(核心C) 这个核心的目的是获得来自老鼠的~5,000个DNA样本的基因类型 根据项目1、2和3的表型。此外，我们将执行RNA测序(RNAseq)以支持 研究项目1和2。最后，我们使用这些数据进行全基因组关联研究(GWAS)。 以及一些相关的分析。在之前的资助期间，帕尔默博士是这个核心和一个 开发基因分析技术的研究项目。在这份续签申请中，这两个人 功能已经整合到这个核心中。 使这个中心成为可能的关键技术进步之一是我们发展了基因分型- 用于大鼠的副测序(GBS)。只有三个SNP基因分型微阵列被开发出来用于 在老鼠身上使用。这三种产品都很昂贵(每个样品300美元)，目前没有一种正在生产中。缺乏 负担得起的基因分型平台是使用GWAS和相关数量遗传学的一个主要障碍 在老鼠身上的方法。在过去的资助期，我们的P50中心扭转了局面，进一步完善和 广泛部署GBS用于大鼠。我们一直在不断改进我们的GBS技术，现在能够 以每个样本不到50美元的价格获得约370万个SNP。因此，我们的产量增加了超过 30倍，同时将成本削减一半。 除了获得基因类型和执行RNAseq之外，该核心还将执行基因分析，这 包括GWAS、表型全关联分析(PheWAS)、转录组全关联分析 (Twas)、遗传力估计、遗传相关性和我们称为多基因转录分割的新方法 风险评分(PTRS)预测。所有这些分析都是在我们的实验室常规进行的，并且已经 以前使用大鼠、小鼠和人的出版物的主题。

Project Summary (Core C) The purpose of this core is to obtain genotypes for ~5,000 DNA samples derived from rats that are phenotyped by Projects 1, 2, and 3. In addition, we will perform RNA Sequencing (RNASeq) in support of Research Projects 1 and 2. Finally, we use these data to perform genome wide association studies (GWAS) and a number of related analyses. In the prior funding period, Dr. Palmer was the PI of both this core and a research project that developed techniques for genetic analysis. In this renewal application, those two functions have been consolidated into this core. One of the critical technical advances that made this center possible was our development of genotyping- by-sequencing (GBS) for use in rats. Only three SNP genotyping microarrays have ever been developed for use in rats. All three are expensive (>$300 per sample) and none are currently in production. The lack of affordable genotyping platforms was a major impediment to the use of GWAS and related quantitative genetic approaches in rats. In the past funding period, our P50 center has turned the tide by further improving and widely deploying GBS for use in rats. We have continued to refine our GBS techniques, and are now able to obtain ~3.7 million SNPs for less than $50 per sample. Thus, we have increased our output by more than 30-fold while cutting the costs in half. In addition to obtaining genotypes and performing RNASeq, this core will perform genetic analyses, which include GWAS, phenome-wide association analyses (PheWAS), transcriptome wide association analyses (TWAS), heritability estimates, genetic correlations, and a new approach that we call polygenic transcriptomic risk score (PTRS) prediction. All of these analyses are routinely performed in our laboratory and have been the subjects of prior publications that used rats, mice, and humans.