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Whole-exome sequencing identifies genes associated with Tourette’s disorder in multiplex families

Authors: Xiaolong Cao; Yeting Zhang; Mohamed Abdulkadir; Li Deng; Thomas V. Fernandez; Blanca Garcia-Delgar; Julie Hagstrøm; +33 Authors

Whole-exome sequencing identifies genes associated with Tourette’s disorder in multiplex families

Abstract

Tourette's Disorder (TD) is a neurodevelopmental disorder (NDD) that affects about 0.7% of the population and is one of the most heritable NDDs. Nevertheless, because of its polygenic nature and genetic heterogeneity, the genetic etiology of TD is not well understood. In this study, we combined the segregation information in 13 TD multiplex families with high-throughput sequencing and genotyping to identify genes associated with TD. Using whole-exome sequencing and genotyping array data, we identified both small and large genetic variants within the individuals. We then combined multiple types of evidence to prioritize candidate genes for TD, including variant segregation pattern, variant function prediction, candidate gene expression, protein-protein interaction network, candidate genes from previous studies, etc. From the 13 families, 71 strong candidate genes were identified, including both known genes for NDDs and novel genes, such as HtrA Serine Peptidase 3 (HTRA3), Cadherin-Related Family Member 1 (CDHR1), and Zinc Finger DHHC-Type Palmitoyltransferase 17 (ZDHHC17). The candidate genes are enriched in several Gene Ontology categories, such as dynein complex and synaptic membrane. Candidate genes and pathways identified in this study provide biological insight into TD etiology and potential targets for future studies.

Keywords

Cadherin Related Proteins, Nerve Tissue Proteins, Medical and Health Sciences, Article, Tourette International Collaborative Genetics Study, Clinical Research, Exome Sequencing, Genetics, 2.1 Biological and endogenous factors, Humans, Family, Genetic Predisposition to Disease, Genetic Testing, Aetiology, Psychiatry, Human Genome, Psychology and Cognitive Sciences, Serine Endopeptidases, Neurosciences, Biological Sciences, Brain Disorders, Pedigree, Cadherin Related Proteins; Family; Genetic Predisposition to Disease/genetics; Humans; Nerve Tissue Proteins/genetics; Pedigree; Serine Endopeptidases; Tourette Syndrome/genetics; Whole Exome Sequencing, Biotechnology, Tourette Syndrome

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
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