Chromosome 5 and Gilles de la Tourette syndrome: Linkage in a large pedigree and association study of six candidates in the region

Authors

  • Nancy Laurin,

    1. Genetics and Development Division, Toronto Western Research Institute, University Health Network, Toronto, ON, Canada
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  • Karen G. Wigg,

    1. Genetics and Development Division, Toronto Western Research Institute, University Health Network, Toronto, ON, Canada
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  • Yu Feng,

    1. Genetics and Development Division, Toronto Western Research Institute, University Health Network, Toronto, ON, Canada
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  • Paul Sandor,

    1. Division of Brain, Imaging, and Behaviour Systems, Toronto Western Research Institute, University Health Network, Toronto, ON, Canada
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  • Cathy L. Barr

    Corresponding author
    1. Genetics and Development Division, Toronto Western Research Institute, University Health Network, Toronto, ON, Canada
    2. Program in Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, ON, Canada
    • Genetics and Development Division, Toronto Western Research Institute, 399 Bathurst St. MP14-302, Toronto, Ontario, Canada M5T 2S8.
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  • Please cite this article as follows: Laurin N, Wigg KG, Feng Y, Sandor P, Barr CL. 2008. Chromosome 5 and Gilles de la Tourette syndrome: Linkage in a large pedigree and association study of six candidates in the region. Am J Med Genet Part B 150B:95–103.

Abstract

Gilles de la Tourette Syndrome (TS) is a neuropsychiatric disorder characterized by both motor and vocal tics. In our previous genome scan for TS we identified evidence for linkage to the centromeric region of chromosome 5 in a single large family of 32 individuals with 10 family members with TS or chronic multiple tics (CMT). In this paper we report further analyses of the 5p-centromeric region in this pedigree. An additional 11 family members were identified and screened for TS. Using a set of 14 microsatellite markers we refined the linked region to a ∼28 Mb interval between the markers D5S1506 and D5S76. A set of six candidate genes located in this region were selected to be tested for genetic association with TS. These genes were GDNF, ITGA1, ISL1, FGF10, HCN1 and SLC1A3. The TDT statistic was used for the association tests in a sample of 171 independent nuclear families with 241 affected children with TS. We found no evidence for an association between TS and markers in these genes in this sample of families. This study represents the first efforts to narrow the linkage region in the extended pedigree and the first tests of candidate genes in the chromosome 5 region linked to TS. © 2008 Wiley-Liss, Inc.

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