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Open Access Research article

Genome-wide sequencing for the identification of rearrangements associated with Tourette syndrome and obsessive-compulsive disorder

Sean D Hooper1, Anna CV Johansson1, Christian Tellgren-Roth1, Eva-Lena Stattin2, Niklas Dahl1, Lucia Cavelier1* and Lars Feuk1

Author Affiliations

1 Department of Immunology, Genetics and Pathology, Rudbeck Laboratory and Science for Life Laboratory, Uppsala University, Uppsala 751 85, Sweden

2 Department of Medical Biosciences, Medical and Clinical Genetics, Umeå University, Umeå, Sweden

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BMC Medical Genetics 2012, 13:123  doi:10.1186/1471-2350-13-123

Published: 19 December 2012

Abstract

Background

Tourette Syndrome (TS) is a neuropsychiatric disorder in children characterized by motor and verbal tics. Although several genes have been suggested in the etiology of TS, the genetic mechanisms remain poorly understood.

Methods

Using cytogenetics and FISH analysis, we identified an apparently balanced t(6,22)(q16.2;p13) in a male patient with TS and obsessive-compulsive disorder (OCD). In order to map the breakpoints and to identify additional submicroscopic rearrangements, we performed whole genome mate-pair sequencing and CGH-array analysis on DNA from the proband.

Results

Sequence and CGH array analysis revealed a 400 kb deletion located 1.3 Mb telomeric of the chromosome 6q breakpoint, which has not been reported in controls. The deletion affects three genes (GPR63, NDUFA4 and KLHL32) and overlaps a region previously found deleted in a girl with autistic features and speech delay. The proband’s mother, also a carrier of the translocation, was diagnosed with OCD and shares the deletion. We also describe a further potentially related rearrangement which, while unmapped in Homo sapiens, was consistent with the chimpanzee genome.

Conclusions

We conclude that genome-wide sequencing at relatively low resolution can be used for the identification of submicroscopic rearrangements. We also show that large rearrangements may escape detection using standard analysis of whole genome sequencing data. Our findings further provide a candidate region for TS and OCD on chromosome 6q16.

Keywords:
Tourette syndrome; Paired end sequencing; Chromosomal translocation; Structural variations