Population Genetic Mapping of Tourette Syndrome

描述（由申请人提供）：这是一份旨在确定图雷特综合征（TS）遗传基础的竞争性续期申请。该项目基于全基因组群体遗传定位方法，即使用密集间隔、高度多态性的短串联重复（STR）标记来识别与TS连锁不平衡（LD）的区域。LD定位研究的重点是来自哥斯达黎加中央山谷（CVCR）孤立群体的独立确定的TS患者（及其父母）。PI和合作者一直在改进分析这种LD数据的方法。

DESCRIPTION (provided by applicant): This is an application for competitive renewal of a grant aimed at identifying the genetic basis of Tourette syndrome (TS). The project is based on a genomewide population genetic mapping approach, that is, using densely spaced, highly polymorphic short tandem repeat (STR) markers to identify regions of linkage disequilibrium (LD) with TS. The LD mapping study is focused on independently ascertained TS patients (and their parents) from the isolated population of the Central Valley of Costa Rica (CVCR). The PI and collaborators have been refining approaches for analyzing such LD data. During the previous award, we sampled probands and their parents from the CVCR and initiated a genomewide LD-screen. Preliminary analyses of genotype data suggest several possible localizations for TS susceptibility genes. In particular, strong LD with the TS phenotype was observed on chromosome 17q25, a region in which linkage to TS had previously been suggested by other groups. In the renewal of this grant, sample collection, genotyping and genome-wide LD mapping will be completed for the CVCR samples. Regions highlighted from the whole genome screen will be followed up in additional TS samples from the same population. Positive findings in the follow-up studies will be used as a guide to select genome regions for fine-mapping studies. These fine scale genotyping studies of the CVCR samples and samples from collaborators, using STRs and single nucleotide polymorphisms (SNPs), will be carried out to pinpoint the location of TS susceptibility genes. In the most promising of these regions we will screen candidate genes using existing SNPs as well as using SNPs that we will identify in the study samples. By the completion of the award, we aim to identify one or more sequence variants associated with TS susceptibility.