GENETICS OF A BEHAVIORAL DISORDER;TOURETTE SYNDROME (RG)

申请人的长期目标是更好地了解 遗传和环境因素在人类神经精神疾病中的作用 通过对特定疾病的研究，Gilles de la 图雷特综合征（TS）。最近的研究导致了几个值得注意的 我们对TS的理解有了进步：1）有更大范围的 表型表达比想象的（包括强迫症） .2）TS和相关疾病比其他疾病更常见。 以前曾被认为是;和3）障碍似乎是 作为常染色体显性遗传。此外，它的流行 它对那些受折磨的人的衰弱作用使这种综合症成为一种主要的 公共卫生问题。 了解TS的遗传学将对患者直接有益 关注其家庭中的复发;最终，澄清 TS的遗传学可以阐明其发病机制。数据收集已 已完成102个TS和对照系列。初步结果 对这些数据的分析重复了我们早期的发现， TS和OCD之间存在病因学关系， - TS和相关疾病的传播方式与 显性遗传在本申请中，我们建议研究 另外100个强迫症家庭和对照先证者， 可以更全面地描述关系的性质 TS和OCD之间的区别此外，收集遗传连锁的数据 将在5个TS先证者的多代大家族中进行研究， 持续期间内的关联数据将使我们能够证实我们的发现， 分离分析，并分离和表征任何遗传位点。 最后，一项对有TS风险的未受影响的幼儿的前瞻性研究 将扩大。四十名儿童和他们的父母已经 参加了这项研究。我们计划将样本量增加到50个。这 研究将有助于确定发病的重要“非遗传”因素， 这些新受试者样本的数据将 有助于确定与之相关的特定遗传和环境因素， TS及其相关行为的变量表达。 拟议的奖励将使申请人能够继续专注于 研究发展性精神病理学预计的专业增长 将允许家庭研究设计、前瞻性风险 研究，代谢评估和连锁研究使用RFLPS。这 结合起来应该为继续研究提供强有力的方法， 儿童期行为障碍

The long term objective of the applicant is a better understanding of the role of genetic and environmental factors in human neuropsychiatric disorders through the study of the specific disorder, Gilles de la Tourette's syndrome (TS). Recent research has led to several notable advances in our understanding of TS: 1) there is a greater range of phenotypic expression than was thought (including obsessive compulsive disorder (OCD));.2) TS and related conditions are much more common than had previously been considered; and 3) the disorder appears to be transmitted As an autosomal dominant trait. Furthermore, its prevalence and its debilitating effect on those afflicted makes the syndrome a major public health problem. Understanding the genetics of TS will be of direct benefit to patients concerned about recurrence in their families; ultimately, clarifying the genetics of TS may elucidate its pathogenesis. Data collection has been completed for 102 TS and control families. Results from preliminary analyses of these data replicated our earlier findings which suggested that there is an etiologic relationship between TS and OCD and that the mode of transmission of-TS and related-disorders is consistent with autosomal dominant inheritance. In this application we propose to study another 100 families of OCD and control probands so that it will be possible to characterize more completely the nature of the relationship between TS and OCD. Tn addition, data collection for a genetic linkage study in 5 large multigenerational families of TS probands will be continued. The linkage data will allow us to confirm our findings from segregation analyses and to isolate and characterize any genetic locus. Finally, a prospective study of young unaffected children at risk for TS will be expanded. Forty children and their parents have already been enrolled in the study. We plan to increase our sample size to 50. This study will help to identify "non-genetic" factors important for onset and manifestation of the disorder, Data from these new subject samples will help identify specific genetic and environmental factors associated with the variable expression of TS and related behaviors. The proposed award will enable the applicant to continue to focus on the study developmental psychopathology. The professional growth projected will allow continued integration of family study design, prospective risk research, metabolic assessment and-linkage studies using RFLPS. This combination should provide powerful methods for the continuing study of childhood behavioral disorders.