Deep Sequencing of CNR1 Gene Network in Substance Dependence

物质依赖性中CNR1基因网络的深度测序

• 批准号: 7953433
• 负责人: LINGJUN ZUO
• 金额: $ 18.18万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-15 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7953433
• 关键词: Adult; Affect; African American; Alcohol dependence; American; Area; Bioinformatics; Biological Markers; Biological Neural Networks; Brain; Brain-Derived Neurotrophic Factor; Candidate Disease Gene; Childhood; Complex; Computer Simulation; DNA; DRD2 gene; Data; Development; Disease; Environment; Environmental Risk Factor; Etiology; European; Event; Faculty; Family; Frequencies; Funding; Future; Gene Cluster; Gene Targeting; Genes; Genetic; Genetic Transcription; Genome; Genotype; HTR3A gene; Human; Individual; Joints; K-Series Research Career Programs; Life; Linkage Disequilibrium; Maps; Mentors; Modeling; Molecular Genetics; Neurosciences; Output; Pharmaceutical Preparations; Population; Prevention; Prevention strategy; Psychiatry; Public Health; Reporting; Research; Research Personnel; Research Project Grants; Risk; Running; Sample Size; Sampling; Signal Transduction; Single Nucleotide Polymorphism; Statistical Methods; Substance Addiction; Technology; Testing; Time; Training; Universities; Variant; abstracting; analytical method; cannabinoid receptor; case control; cost; effective therapy; gene environment interaction; genetic variant; meetings; member; next generation; novel; protein function; protein structure; public health relevance; receptor; tool

DESCRIPTION (provided by applicant): D Deep sequencing of CNR1 gene network in substance dependence: Abstract This Mentored Research Career Development Award (K01) is to train Dr. Lingjun Zuo, a junior faculty member of Department of Psychiatry at Yale University, to become an independent investigator in the research field on genetics of substance dependence (SD). The trainings include three main areas: (1) advanced human molecular genetics, in particularly in "Solexa" sequencing and cannabinoid receptor 1 (CNR1) gene network; (2) neuroscience, in particularly in SD, brain neural networks and functional relationship between cannabinoid receptor and protein product of other SD candidate genes; and (3) bioinformatic and statistical analytical methods for high-throughput sequence data, gene network data as well as gene x environment interaction analysis. To acquire these trainings, Dr. Zuo's time will be allocated (1) to courses and seminars, (2) to meetings with the mentor and co-mentors, (3) to interactions with other experts, and mainly (4) to the proposed research project per se. The research plan will focus on deep sequencing of CNR1 gene network that consists of CNR1 and five other biologically related genes. Dr. Zuo proposes to identify the potential functional variants underlying SD in this gene network by (1) sequencing the targeted gene regions in a relatively big size of sample using next generation sequencing approach, and by (2) using multiple-gene model to investigate the joint effects of multiple functional variants, which might exert too weak individual effects to be detectable using single-gene model. This proposed study would be promising to elucidate the genetic variants in the CNR1 gene network underlying SD, which would make a major progress in the etiology of SD, and may also be helpful to develop novel and effective treatment and prevention strategies for SD. PUBLIC HEALTH RELEVANCE: Relevance to public health This proposed project will carefully study the effects of cannabinoid receptor 1 gene (CNR1) network on risk for substance dependence (SD) using the next generation deep sequencing technology, which will help us better understand the mechanism for the development of SD. The expected findings would significantly contribute to the improvement of public health.

描述(申请人提供)：物质依赖中CNR1基因网络的深度测序：摘要本指导研究事业发展奖(K01)旨在培养耶鲁大学精神病学系初级教员左凌军博士，成为物质依赖遗传学研究领域的独立研究员。培训包括三个主要领域：(1)先进的人类分子遗传学，特别是在“Solexa”测序和大麻素受体1(CNR1)基因网络方面；(2)神经科学，特别是在可持续发展领域，大脑神经网络和大麻素受体与其他可持续发展候选基因的蛋白质产物之间的功能关系；(3)高通量序列数据、基因网络数据以及基因x环境相互作用分析的生物信息学和统计分析方法。为了获得这些培训，左博士的时间将被分配给(1)课程和研讨会，(2)与导师和共同导师的会议，(3)与其他专家的互动，以及主要(4)拟议的研究项目本身。该研究计划将重点放在CNR1基因网络的深度测序上，该网络由CNR1和其他五个生物相关基因组成。左博士建议通过(1)使用下一代测序方法在相对较大的样本中对目标基因区域进行测序，并通过(2)使用多基因模型来研究多个功能变体的联合效应，这些功能变体可能发挥的个体效应太弱而无法用单基因模型来检测，从而识别这个基因网络中潜在的功能变异。本研究有望阐明SD患者CNR1基因网络中的遗传变异，为SD的病因学研究取得重大进展，并有助于开发新的有效的SD治疗和预防策略。 与公众健康相关：与公众健康相关这项拟议的项目将利用下一代深度测序技术仔细研究大麻素受体1基因(CNR1)网络对物质依赖风险(SD)的影响，这将有助于我们更好地了解SD的发生机制。预期的结果将大大有助于改善公共卫生。