NEUROBIOLOGY AND GENETICS OF PANIC, TS, AND OCD

恐慌、TS 和强迫症的神经生物学和遗传学

• 批准号: 2883324
• 负责人: JOEL GELERNTER
• 金额: $ 10.53万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-09-01 至 2002-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2883324
• 关键词: Tourette's syndrome; behavioral genetics; cell line; clinical research; dopamine receptor; gene mutation; human genetic material tag; human subject; linkage mapping; nucleic acid sequence; obsessive compulsive disorder; oligonucleotides; panic disorder; polymerase chain reaction

NEUROBIOLOGY AND GENETICS OF PANIC, TS, AND OCD. This is an application for an NIMH K02 (Independent Scientist) award. The goal of the proposal is to continue specialized training for the PI, a psychiatrist, in molecular and population genetics. The aims of the research are to (a) locate genes affecting risk for panic disorder by genetic linkage; (b) identify genes influencing risk for Tourette's syndrome and obsessive-compulsive disorder using the haplotype relative risk (HRR) family association method; (c) identify genes associated with specific phenotypes (recognized, eg, by imaging studies) within groups affected with illness using association methods; and (d) identify specific mutations associated with phenotype by mutational analysis and sequencing. Under some circumstances, genome scan- directed linkage studies are most useful in identifying genes predisposing to illness; under other circumstances, HRR studies may be more efficient. For very strong candidate gene hypotheses, mutational analysis may be employed directly. Preliminary results have been generated using all of these methods. For our panic disorder linkage project ("a"), we have obtained DNA from 201 individuals in 21 families, as of May 1995. We have used the HRR method to identify a genetic association between Tourette's syndrome and an allele at the D4 dopamine receptor locus ('b"). In the area of genotype/phenotype association, we have reported an association between cocaine-induced paranoia and dopamine transporter alleles; we have obtained preliminary data using SPECT imaging techniques regarding the relationship between alleles at the D2 dopamine receptor locus (DRD2) and brain D2 receptor density ("c". We propose to complete a genome scan for the panic disorder linkage project; attempt to identify other genes influencing risk for Tourette's syndrome and obsessive-compulsive disorder; and identify other genotype-phenotype relationships using imaging studies as a way to ascertain phenotype directly.

恐慌症、TS和强迫症的神经生物学和遗传学。这是一个应用程序 NIMH K02(独立科学家)奖。该提案的目标是 继续对精神病学家PI进行分子方面的专门培训 和种群遗传学。这项研究的目的是(A)定位基因 通过基因连锁影响恐慌症风险；(B)确定基因 影响多发性抽动症和强迫症的风险 使用单倍型相对风险(HRR)家庭关联法；(C) 识别与特定表型相关的基因(例如，通过 成像研究)在受疾病影响的群体内使用关联 方法；以及(D)通过以下方式确定与表型有关的特定突变 突变分析和测序。在某些情况下，基因组扫描- 定向连锁研究在识别易感基因方面最有用 在其他情况下，HRR研究可能更有效率。 对于非常强的候选基因假设，突变分析可能是 直接受雇。初步结果是使用所有 这些方法。对于我们的恐慌症联动项目(A)，我们有 截至1995年5月，从21个家庭的201个人身上获得了DNA。我们有 使用HRR方法确定多发性抽动症之间的遗传关联 综合征和D4多巴胺受体基因(‘b’)上的一个等位基因。 基因/表型关联的区域，我们已经报告了一个关联 在可卡因引起的偏执狂和多巴胺转运体等位基因之间；我们有 使用SPECT成像技术获得了关于 D2多巴胺受体基因座(DRD2)等位基因与 脑D2受体密度(“c”)。我们建议完成一项基因组扫描 恐慌症连锁项目；试图确定其他基因 影响多发性抽动症和强迫症的风险； 并使用成像研究确定其他基因-表型关系 作为一种直接确定表型的方法。