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

BMC Medical Genetics

Research Article

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

[1] Department of Immunology, Genetics and Pathology, Rudbeck Laboratory and Science for Life Laboratory, Uppsala University, 751 85, Uppsala, Sweden;Department of Medical Biosciences, Medical and Clinical Genetics, Umeå University, Umeå, Sweden;

关键词: Tourette syndrome;    Paired end sequencing;    Chromosomal translocation;    Structural variations;   

DOI  :  10.1186/1471-2350-13-123

 received in 2012-05-23, accepted in 2012-12-13,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundTourette 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.MethodsUsing 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.ResultsSequence 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.ConclusionsWe 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.

【 授权许可】

Unknown   
© Hooper et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.