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Genomic regulatory sequence analysis for alcohol-related phenotypes

酒精相关表型的基因组调控序列分析

基本信息

批准号：
8131741
负责人：
Katherina Kechris-Mays
金额：
$ 13.03万
依托单位：
UNIVERSITY OF COLORADO DENVER
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-15 至 2013-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8131741
关键词：
Affect Alcohol consumption Alcohol dependence Alcohol-Related Disorders Alcoholism Alcohols Animal Model Animals Area Award Back Behavioral Bioinformatics Biological Biological Models Brain Characteristics Chemicals Code Communication Communities Complex Computational algorithm Consumption Data Data Sources Dependency Development Disease Dopamine Elements Environment Environmental Risk Factor Gene Cluster Gene Expression Gene Expression Regulation Genes Genetic Genetic Enhancer Element Genetic Polymorphism Genetic Variation Genomics Genotype Glutamates Goals Health Human Indiana Laboratories Learning Mammals Mentors Methodology Methods Modeling Mus Nature Neurobiology Neurons Neurotransmitters Nucleic Acid Regulatory Sequences Orthologous Gene Outcome Pathway interactions Pattern Pharmacology Phenotype Physiological Play Rattus Recombinant Inbred Strain Regulatory Element Research Research Personnel Rodent Role Sequence Analysis Serotonin System Techniques Training Transcriptional Regulation Transcriptional Silencer Elements Universities Withdrawal Symptom Work alcohol behavior alcohol exposure alcohol research alcohol sensitivity animal breeding base brain cell comparative genomics design experience genetic regulatory protein genetics of alcoholism genome-wide improved interest mammalian genome preference protein function rat genome receptor research study response skills theories trait

项目摘要

DESCRIPTION (provided by applicant): The development of alcoholism related traits is believed to be caused by both genetic and environmental factors, in addition to their interactions. Genetic variations associated with alcoholism related traits can affect several different mechanisms, including gene expression regulation. The goal of this work is to study mammalian model systems to identify genomic regulatory sequences that contribute to transcriptional changes in alcohol-related behaviors. Genome-wide exploration of regulatory sequences is difficult in mammals because of the small and degenerate nature of these elements and because of the complexity and size of mammalian genomes. Therefore, the proposed study will rely on evidence from multiple different data sources to help narrow the search for regulatory sequences. First, high-throughput gene expression data in addition to genotypic data on recombinant inbred strains will be analyzed to identify genes that show common regulatory patterns and are correlated with alcohol related phenotypes. Then, common sequences shared in the upstream and downstream regions of these genes will be identified as potential regulatory elements. Second, gene expression experiments on rat selected lines will be performed so that they can be compared with existing mouse studies on alcohol preference. To improve the search for potential regulatory elements, only common expression patterns and sequences shared between orthologous genes in the two rodent studies will be considered. This project is designed as a mentored research opportunity for the candidate to apply her prior experience and training in computational approaches for studying transcription regulation to alcohol research. The candidate will use the award period to develop the background and skills in pharmacology, mammalian systems and genomics necessary for this endeavor. The outcome of this project is to develop large scale bioinformatics methods for analyzing gene expression studies, genetic data and genomic sequences in model systems of alcohol related traits. The resulting methods and data will be made available to the alcohol research community at large.

描述（由申请人提供）：酗酒相关特征的发展被认为是由遗传和环境因素共同引起的，以及它们之间的相互作用。与酒精中毒相关的遗传变异可以影响几种不同的机制，包括基因表达调节。这项工作的目的是研究哺乳动物模型系统，以确定有助于酒精相关行为转录变化的基因组调控序列。哺乳动物的全基因组调控序列的探索是困难的，因为这些元素的小和退化的性质，因为哺乳动物基因组的复杂性和大小。因此，拟议的研究将依赖于来自多个不同数据源的证据来帮助缩小对调控序列的搜索范围。首先，将分析重组自交系株的高通量基因表达数据和基因型数据，以确定显示共同调控模式并与酒精相关表型相关的基因。然后，在这些基因的上游和下游区域共享的共同序列将被确定为潜在的调控元件。其次，将在选择的大鼠品系上进行基因表达实验，以便与现有的小鼠酒精偏好研究进行比较。为了更好地寻找潜在的调控元件，我们只考虑两种啮齿动物研究中同源基因之间共有的表达模式和序列。该项目旨在为候选人提供一个有指导的研究机会，将她之前在研究转录调控的计算方法方面的经验和训练应用于酒精研究。候选人将利用奖励期发展药理学、哺乳动物系统和基因组学方面的必要背景和技能。该项目的结果是开发大规模的生物信息学方法，用于分析酒精相关性状模型系统中的基因表达研究、遗传数据和基因组序列。由此产生的方法和数据将提供给整个酒精研究界。