POPULATION GENETIC MAPPING OF TOURETTE SYNDROME

描述（改编自研究者摘要）：这是一项建议， 确定导致抽动秽语综合症的基因的染色体位置 (TS)是一种以运动和发声抽搐为特征的遗传性疾病。 他们 计划对两个遗传同质的种群进行研究， 在过去的几百年里迅速：中央谷的 哥斯达黎加（CR）和美国的德系犹太人。 TS 这些人群中的患者可能遗传了这种易感性， 一个或几个共同祖先的疾病。 TS基因将被映射， 搜索TS患者在血统上共享相同的基因组区域 (IBD)来自这些祖先;这些区域将包括TS基因，并且可能 两个群体之间的差异。 他们将通过以下方式搜索IBD区域： 随机抽样只受影响的个人和他们的父母从这些 孤立的人群。 研究样本将由个人组成 中度至重度TS患者，约100例CR患者和约200例 德系犹太人 诊断评估将包括对患者的访谈， 家庭成员和审查医疗记录;最终诊断将是 通过专家进行的“最佳估计”协商一致程序分配， 诊断TS。 将获得所有受试者的家谱， 只有当他们的大多数祖先来自目标地区时， 人口。 将使用分布在不同区域的标记物对样本进行基因分型。 整个基因组。 将对每个基因组区域中的IBD进行评价。 使用关联测试完成。 他们的计算机模拟能力 研究表明，在每项研究中检测到TS位点的概率很高 人群，即使TS在每个人群中的病因异质性 人口 一旦TS基因被定位，精细定位研究将开始， 导致定位克隆的努力。 此外，临床问题相关的 了解TS的原因和过程将使用 为PGM研究取样的患者。 他们已经完成了初步的 研究表明采样，诊断和基因分型的可行性 本提案所述的方法。 将通过以下方式促进取样： 正在进行的CR合作以及与几个TS中心的新合作 在美国

DESCRIPTION (Adapted from investigator's abstract): This is a proposal to identify the chromosomal location of genes responsible for Tourette Syndrome (TS), an inherited disorder characterized by motor and vocal tics. They plan studies of two genetically homogeneous populations that have expanded rapidly over the past few hundred years: that of the Central Valley of Costa Rica (CR) and that of Ashkenazi Jews in the United States. TS patients in these populations may have inherited a susceptibility to this disorder from one or a few common ancestors. TS genes will be mapped by searching for genomic regions that TS patients share identical by descent (IBD) from such ancestors; these regions will include the TS genes, and may differ between the two populations. They will search for IBD regions by randomly sampling only affected individuals and their parents from these isolated populations. The study sample will consist of individuals moderately to severely affected with TS, about 100 from CR and about 200 Ashkenazim. Diagnostic assessment will include interviews of patients and family members and review of medical records; final diagnoses will be assigned through a 'best estimate' consensus process conducted by experts in diagnosing TS. Genealogies will be obtained for all subjects, who will be included in the study only if most of their ancestors were from the target populations. The samples will be genotyped using markers distributed throughout the genome. Evaluation of IBD in each genome region will be accomplished using association tests. Their computer simulation power studies show a high probability of detecting TS loci in each study population, even if TS is etiologically heterogeneous within each population. Once TS genes are localized, fine-mapping studies will begin, leading to positional cloning efforts. Also, clinical questions relevant to understanding the cause and course of TS will be addressed using the patients sampled for the PGM studies. They have completed preliminary studies to show the feasibility of the sampling, diagnostic, and genotyping approaches described in this proposal. The sampling will be facilitated by ongoing collaborations in CR and new collaborations with several TS centers in the U.S.