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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
3R01NS037484-10S1
Application #
7912566
Study Section
Mammalian Genetics Study Section (MGN)
Program Officer
Mamounas, Laura
Project Start
1998-04-30
Project End
2011-05-31
Budget Start
2009-09-30
Budget End
2011-05-31
Support Year
10
Fiscal Year
2009
Total Cost
$250,088
Indirect Cost
Name
University of California Los Angeles
Department
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
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Nag, Abhishek; Bochukova, Elena G; Kremeyer, Barbara et al. (2013) CNV analysis in Tourette syndrome implicates large genomic rearrangements in COL8A1 and NRXN1. PLoS One 8:e59061
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Scharf, Jeremiah M; Mathews, Carol A (2010) Copy number variation in Tourette syndrome: another case of neurodevelopmental generalist genes? Neurology 74:1564-5

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