Center for Genetic Studies of Drug Abuse in Outbred Rats

近交系大鼠药物滥用基因研究中心

基本信息

批准号：
10160845
负责人：
ABRAHAM A PALMER
金额：
$ 50.61万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-06-15 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10160845
关键词：
Behavior Behavioral Biological Biology Brain Cocaine Communities DNA DNA Sequencing Facility Data Development Drug abuse Early Intervention Ecosystem Female Fishes Funding Gene Expression Genetic Genetic Techniques Genetic study Genotype Grant Heritability Human Individual Intravenous Laboratories Lead Libraries Light Maps Measures Mus Nicotine Output Phenotype Physiological Procedures Production Publications Quantitative Genetics Quantitative Trait Loci RNA Rattus Reaction Time Regulation Research Research Project Grants Research Support Resources Risk SNP genotyping Sampling Self Administration Services Societies Techniques Technology Work comparison group cost discounting expectation genetic analysis genetic approach genome sequencing genome wide association study improved male novel novel strategies personalized medicine phenome public repository reference genome response skills trait transcriptome transcriptome sequencing transcriptomics whole genome

项目摘要

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.

项目摘要（核心C）该核心的目的是获得约5,000个DNA样品的基因型，这些DNA样品来自大鼠由项目1、2和3进行表型。此外，我们将执行RNA测序（RNASEQ）支持研究项目1和2。最后，我们使用这些数据来执行基因组广泛的关联研究（GWAS）以及许多相关分析。在以前的资助期间，帕尔默博士是该核心和一个核心的PI 开发用于遗传分析的技术的研究项目。在此续约应用中，这两个功能已合并到该核心中。使该中心成为可能的关键技术进步之一是我们发展基因分型 - 通过测序（GB）用于大鼠。为了开发三个SNP基因分型微阵列在老鼠中使用。这三个都是昂贵的（每个样本> $ 300），目前没有生产。缺乏负担得起的基因分型平台是使用GWA和相关定量遗传的主要障碍在老鼠中接近。在过去的资金期间，我们的P50中心通过进一步改善和广泛部署GB用于大鼠。我们继续完善我们的GBS技术，现在能够每样本少于50美元，获得约370万个SNP。因此，我们的产出超过了将成本减少一半时30倍。除了获得基因型和执行RNASEQ外，该核心还将进行遗传分析，这包括GWAS，现象全面关联分析（PHEWAS），转录组广泛的关联分析（TWA），遗传力估计，遗传相关性和一种我们称为多基因转录组的新方法风险评分（PTR）预测。所有这些分析通常在我们的实验室中进行，并且是使用大鼠，老鼠和人类的先前出版物的主题。