NEUROBIOLOGY AND GENETICS OF PANIC, TS, AND OCD

神经生物学和恐慌，TS和强迫症的遗传学。 这是一个应用程序 NIMH K 02（独立科学家）奖该提案的目的是 继续对PI进行专门培训，精神科医生，在分子 和群体遗传学。 研究的目的是（a）定位基因 通过遗传连锁影响惊恐障碍的风险;（B）鉴定基因 影响抽动秽语综合征和强迫症的风险 使用单倍型相对风险（HRR）家族关联方法;（c） 识别与特定表型相关的基因（例如， 影像学研究）在受疾病影响的人群中使用关联 方法;和（d）通过以下方法鉴定与表型相关的特定突变： 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， 疾病;在其他情况下，HRR研究可能更有效。 对于非常强的候选基因假设，突变分析可能是 直接雇用。 初步结果已产生使用所有 这些方法。 对于我们的恐慌症联系项目（“a”），我们有 截至1995年5月，从21个家庭的201个个体中获得了DNA。 我们有 使用HRR方法来确定图雷特氏症与 综合征和D4多巴胺受体基因座（“b”）的等位基因。 在 在基因型/表型关联方面，我们已经报道了一种关联， 可卡因引起的妄想症和多巴胺转运体等位基因之间的联系;我们有 使用SPECT成像技术获得了关于 D2多巴胺受体基因座（DRD 2）等位基因之间的关系， 脑D2受体密度（“c”. 我们建议完成基因组扫描， 恐慌症连锁项目;试图识别其他基因 影响抽动秽语综合征和强迫症的风险; 并通过成像研究确定其他基因型-表型关系 作为一种直接确定表型的方法。

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.