Genotype and Phenotype Analysis in Large Extended Pedigrees with Tourette Syndrome and/or Tics

Grant Type
Grant Year
Institution Location
Institution Organization Name
University of Utah
Investigators Name
Lyon, Gholson J., MD, PhD

This research on Tourette syndrome (TS) and chronic tics will apply the newest genomic technologies to some large extended pedigrees collected in the state of Utah and surrounding areas. This will involve genetic mapping and exome sequencing of several large extended Tourette pedigrees, including ones with 65, 31 and 23 descendants. This research will include extensive phenotypic charac-terizations of these unique pedigrees with TS and other co-morbid conditions such as attention deficit hyperactivity disorder (ADHD) and Obsessive Compulsive Disorder (OCD). We plan to obtain dense genotyping using the Illumina 610K chip, with genotyping performed by our collaborator at the Children’s Hospital of Philadelphia, Hakon Hakonarson. We will perform standard linkage analysis, along with copy number variation (CNV) detection using available algorithms. We also plan to perform exome sequencing on carefully selected members of these pedigrees, giving us the ability to identify exonic mutations shared amongst affected members of the pedigree, and not found in unaffected members of the pedigree. This will likely identify candidate genes worth following up in other members of the pedigree and in unrelated cases. The overall goal will be to identify rare (or even private) mutations that cause TS within these families. This research may shed light on new biological pathways implicated in the disorder. Gholson J. Lyon, M.D., Ph.D.,Hilary Coon, Ph.D. University of Utah, Salt Lake City, UT Award: $73,818 Commentary: Tourette syndrome seems to run in families, but finding the gene has been difficult. In recent years, technology has advanced so much that we can now study most of the genes in any particular family. Because family members are more genetically similar than unrelated people, comparing genes from affected family members with unaffected family members is one of the most successful techniques for genetic discovery. However, there are two critical requirements for this type of research: 1) the families must be large enough for the genetic effect to be visible, and 2) the researchers must know how family members are related to each other. These critical components come together in Utah, where we propose to do this research. This award is funded by Ralph Ochsman and the Ochsman Foundation Tourette Association of America Inc. – Research Grant Award 2010-2011