Meta-analysis of heterogeneous Down Syndrome data reveals consistent genome-wide dosage effects related to neurological processes

BMC Genomics

Research Article

Hans Lehrach¹  Anja Thormann¹  Ralf Herwig¹  Elisabeth Maschke-Dutz¹  Axel Rasche¹  Mireia Vilardell²  Luis A Pérez-Jurado³ 

[1] Department of Vertebrate Genomics, Max-Planck-Institute for Molecular Genetics, Ihnestr. 63-73, D-14195, Berlin, Germany;Department of Vertebrate Genomics, Max-Planck-Institute for Molecular Genetics, Ihnestr. 63-73, D-14195, Berlin, Germany;Unitat de Genètica, Universitat Pompeu Fabra, y CIBER de Enfermedades Raras (CIBERER), Parc de Recerca Biomèdica de Barcelona, C/Dr Aiguader, 88, 08003, Barcelona, Spain;Unitat de Genètica, Universitat Pompeu Fabra, y CIBER de Enfermedades Raras (CIBERER), Parc de Recerca Biomèdica de Barcelona, C/Dr Aiguader, 88, 08003, Barcelona, Spain;Programa de Medicina Molecular I Genetica, Hospital Vall d'Hebron, 08035, Barcelona, Spain;

关键词: Down Syndrome;    Dosage Effect;    Down Syndrome Patient;    HSA21 Gene;    Dosage Imbalance;   

DOI  :  10.1186/1471-2164-12-229

 received in 2010-12-02, accepted in 2011-05-11,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundDown syndrome (DS; trisomy 21) is the most common genetic cause of mental retardation in the human population and key molecular networks dysregulated in DS are still unknown. Many different experimental techniques have been applied to analyse the effects of dosage imbalance at the molecular and phenotypical level, however, currently no integrative approach exists that attempts to extract the common information.ResultsWe have performed a statistical meta-analysis from 45 heterogeneous publicly available DS data sets in order to identify consistent dosage effects from these studies. We identified 324 genes with significant genome-wide dosage effects, including well investigated genes like SOD1, APP, RUNX1 and DYRK1A as well as a large proportion of novel genes (N = 62). Furthermore, we characterized these genes using gene ontology, molecular interactions and promoter sequence analysis. In order to judge relevance of the 324 genes for more general cerebral pathologies we used independent publicly available microarry data from brain studies not related with DS and identified a subset of 79 genes with potential impact for neurocognitive processes. All results have been made available through a web server under http://ds-geneminer.molgen.mpg.de/.ConclusionsOur study represents a comprehensive integrative analysis of heterogeneous data including genome-wide transcript levels in the domain of trisomy 21. The detected dosage effects build a resource for further studies of DS pathology and the development of new therapies.

【 授权许可】

CC BY   
© Vilardell et al; licensee BioMed Central Ltd. 2011