Genetic pathways for impulsivity and drug reinforcement: DNA and transcriptome variation in mice
冲动和药物强化的遗传途径:小鼠 DNA 和转录组变异
基本信息
- 批准号:10176439
- 负责人:
- 金额:$ 54.81万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-09-15 至 2023-05-31
- 项目状态:已结题
- 来源:
- 关键词:AnimalsAntisense RNAAreaBehaviorBehavioralBioinformaticsBiologicalBiological AssayBiological ModelsBrainBrain regionCell physiologyClinicalCocaineCocaine AbuseCocaine DependenceCodeComplexDNAData SetDetectionDiseaseDissectionDrug ControlsDrug RegulationsDrug abuseEquationFoundationsGene ExpressionGenesGeneticGenetic studyGenotypeGoalsHeritabilityHybridsImpulsivityInbred Strains MiceInbreedingIncentivesInternationalIntravenousLaboratoriesLearningLinkMapsMedialMeiosisMessenger RNAModelingMolecular StructureMotivationMusNucleotidesNucleus AccumbensPathway AnalysisPathway interactionsPharmaceutical PreparationsPhenotypePlayPrefrontal CortexProductionQuantitative EvaluationsQuantitative Trait LociRNARNA EditingRNA SplicingRecombinant Inbred StrainRecombinantsRecording of previous eventsRegulatory PathwayResolutionResourcesRewardsRiskRoleSingle Nucleotide PolymorphismSiteStatistical Data InterpretationStructureSubstance abuse problemTechnologyTherapeuticTherapeutic InterventionTissuesTranscriptUntranslated RNAVariantWorkaddictionbasebehavioral phenotypingbrain tissueclinical phenotypecocaine exposurecocaine self-administrationdisease phenotypedrug reinforcementexperiencegene productgenetic variantgenome-widegenomic datainsightnovelphenotypic datapublic health relevancetooltraittranscriptometranscriptome sequencing
项目摘要
PROJECT DESCRIPTION
This project will chart with high-resolution the genetic pathways that give rise to defined clinical phenotypes
related to cocaine addiction. We will utilize the power of the hybrid mouse diversity panel (HMDP), combined
with high quality behavioral phenotyping and massive-scale RNA sequencing, to trace the interconnections
from DNA to RNA to clinical trait and provide layered information on the mechanisms of cocaine abuse. The
HMDP consists of 100 inbred and recombinant inbred strains and has a wide array of meiotic breakpoints. The
panel has been densely genotyped with more than 200,000 single nucleotide polymorphisms (SNPs), allowing
very fine mapping of quantitative trait loci (QTLs). Further, the HMDP is genetically stable and renewable and
can be assayed for multiple phenotypes, yielding cumulative biological information. We will expand our
previous HMDP-based studies of cocaine abuse-related traits by adding massive-scale RNA sequencing
(RNA-Seq), in order to detail the genetic control of the pathways to addiction. Our approach offers the distinct
advantage of mapping loci for known pathways as well as those involving variant and exotic RNA species. The
following aims are proposed: (1) We will quantitate intravenous self-administration of cocaine in HMDP mice.
This phenotype is regarded as being one of the most faithful models of cocaine abuse in animals and will allow
evaluation of QTLs that regulate addiction-related phenotypes. (2) We will perform RNA-Seq on two key areas
of the brain that play a role in the control of drug abuse, the medial prefrontal cortex (mPFC) and nucleus
accumbens (NAc) shell region. (3) We will analyze the combined datasets with powerful statistical tools to
understand the genetic regulation of drug abuse-related phenotypes. These studies will map genetic networks
and inter-tissue regulatory pathways for cocaine addiction and suggest new, highly specific therapeutic
strategies.
项目描述
该项目将以高分辨率绘制产生明确临床表型的遗传途径
与可卡因成瘾有关。我们将利用混合小鼠多样性面板 (HMDP) 的力量,结合
通过高质量的行为表型分析和大规模 RNA 测序来追踪相互联系
从 DNA 到 RNA 再到临床特征,并提供有关可卡因滥用机制的分层信息。这
HMDP 由 100 个自交系和重组自交系组成,并具有广泛的减数分裂断点。这
该小组已对超过 200,000 个单核苷酸多态性 (SNP) 进行了密集基因分型,允许
数量性状基因座 (QTL) 的精细定位。此外,HMDP 具有遗传稳定性和可再生性,
可以检测多种表型,产生累积的生物学信息。我们将扩大我们的
之前基于 HMDP 的可卡因滥用相关特征研究,通过添加大规模 RNA 测序
(RNA-Seq),以详细说明成瘾途径的遗传控制。我们的方法提供了独特的
绘制已知途径以及涉及变异和外来 RNA 物种的基因座的优势。这
提出以下目标:(1)我们将定量 HMDP 小鼠静脉内自我施用的可卡因。
这种表型被认为是动物中可卡因滥用最忠实的模型之一,并将允许
评估调节成瘾相关表型的 QTL。 (2)我们将在两个关键领域进行RNA-Seq
在控制药物滥用方面发挥作用的大脑的内侧前额叶皮层 (mPFC) 和神经核
伏隔核 (NAc) 壳区。 (3) 我们将使用强大的统计工具分析组合数据集
了解药物滥用相关表型的基因调控。这些研究将绘制遗传网络图
和可卡因成瘾的组织间调节途径,并提出新的、高度特异性的治疗方法
策略。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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{{ truncateString('ELEAZAR ESKIN', 18)}}的其他基金
RADX TECH PROJECT NO. 2320 - UNIVERSITY OF CALIFORNIA, LOS ANGELES - SWABSEQ
RADX 科技项目编号
- 批准号:
10505889 - 财政年份:2021
- 资助金额:
$ 54.81万 - 项目类别:
Computational Genomics Summer Institute and Mentoring Network
计算基因组学暑期学院和指导网络
- 批准号:
10613400 - 财政年份:2020
- 资助金额:
$ 54.81万 - 项目类别:
Undergraduate Research Experiences in Neurogenetics and Neurogenomics
神经遗传学和神经基因组学的本科研究经验
- 批准号:
9920370 - 财政年份:2019
- 资助金额:
$ 54.81万 - 项目类别:
Undergraduate Research Experiences in Neurogenetics and Neurogenomics
神经遗传学和神经基因组学的本科研究经验
- 批准号:
10533277 - 财政年份:2019
- 资助金额:
$ 54.81万 - 项目类别:
Undergraduate Research Experiences in Neurogenetics and Neurogenomics
神经遗传学和神经基因组学的本科研究经验
- 批准号:
10300047 - 财政年份:2019
- 资助金额:
$ 54.81万 - 项目类别:
Undergraduate Research Experience in Neuropsychiatric Genomics
神经精神基因组学本科研究经验
- 批准号:
9210653 - 财政年份:2016
- 资助金额:
$ 54.81万 - 项目类别:
Undergraduate Research Experience in Neuropsychiatric Genomics
神经精神基因组学本科研究经验
- 批准号:
9390070 - 财政年份:2016
- 资助金额:
$ 54.81万 - 项目类别:
Undergraduate Research Experience in Neuropsychiatric Genomics
神经精神基因组学本科研究经验
- 批准号:
9045435 - 财政年份:2016
- 资助金额:
$ 54.81万 - 项目类别:
Mathematical and Computational Approaches in High-Throughput Genomics Training
高通量基因组学训练中的数学和计算方法
- 批准号:
8935619 - 财政年份:2015
- 资助金额:
$ 54.81万 - 项目类别:
Mathematical and Computational Approaches in High-Throughput Genomics Training
高通量基因组学训练中的数学和计算方法
- 批准号:
9132317 - 财政年份:2015
- 资助金额:
$ 54.81万 - 项目类别:
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