POPULATION GENETIC MAPPING OF TOURETTE SYNDROME

描述(改编自调查人员摘要)：这是一项建议 确定Tourette综合征相关基因的染色体位置 (TS)，一种以运动和发声痉挛为特征的遗传性疾病。他们 对两个已扩大的遗传同质群体的计划研究 在过去的几百年里迅速地：中央山谷的 哥斯达黎加(CR)和在美国的德系犹太人。TS 这些人群中的患者可能遗传了这种易感性。 来自一个或几个共同祖先的紊乱。TS基因将通过以下方式定位 寻找TS患者血统相同的基因组区域 (IBD)来自这些祖先；这些区域将包括TS基因，并可能 两个群体之间的差异。他们将通过以下方式搜索IBD地区 只从受影响的个人及其父母中随机抽样 孤立的种群。研究样本将由个人组成 患有TS的患者中，约有100人受到中度至重度影响，约200人受到影响 阿什肯纳兹姆。诊断性评估将包括对患者和 家庭成员和医疗记录审查；最终诊断将是 通过专家在#年进行的“最佳估计”协商过程分配 诊断TS。将获得所有受试者的家谱，谁将是 只有当他们的大多数祖先来自目标时才包括在研究中 人口。样本将使用分发的标记进行基因分型 在整个基因组中。将对每个基因组区域的IBD进行评估 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基因座的可能性很高 群体，即使TS在每个群体中在病因上是不同的 人口。一旦TS基因定位，精细定位研究将开始， 导致了位置克隆的努力。此外，与以下方面相关的临床问题 了解TS的原因和过程将使用 对PGM研究的患者进行抽样。他们已经完成了预赛 表明抽样、诊断和基因分型的可行性的研究 本提案中所述的方法。抽样将通过以下方式提供便利 CR中的持续协作以及与多个TS中心的新协作 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.