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

Mireia Vilardell12*, Axel Rasche1, Anja Thormann1, Elisabeth Maschke-Dutz1, Luis A Pérez-Jurado23, Hans Lehrach1 and Ralf Herwig1*

Author Affiliations

1 Department of Vertebrate Genomics, Max-Planck-Institute for Molecular Genetics, Ihnestr. 63-73, D-14195 Berlin, Germany

2 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

3 Programa de Medicina Molecular I Genetica, Hospital Vall d'Hebron, 08035 Barcelona, Spain

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BMC Genomics 2011, 12:229  doi:10.1186/1471-2164-12-229

Published: 11 May 2011



Down 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.


We 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 webcite.


Our 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.