title: Meta-analysis of heterogeneous Down Syndrome data reveals consistent genome-wide dosage effects related to neurological processes.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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 http://ds-geneminer.molgen.mpg.de/.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Vertebrate Genomics, Max-Planck-Institute for Molecular Genetics, Berlin, Germany. nogales@molgen.mpg.de
authors.forename: Mireia
authors.initials: M
authors.lastname: Vilardell
authors.forename: Axel
authors.initials: A
authors.lastname: Rasche
authors.forename: Anja
authors.initials: A
authors.lastname: Thormann
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Maschke-Dutz
authors.forename: Luis A
authors.initials: LA
authors.lastname: Pérez-Jurado
authors.forename: Hans
authors.initials: H
authors.lastname: Lehrach
authors.forename: Ralf
authors.initials: R
authors.lastname: Herwig
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics; D004314:Down Syndrome / Q000235:genetics* / Q000378:metabolism; D018628:Gene Dosage / Q000235:genetics*; D020869:Gene Expression Profiling; D015894:Genome, Human / Q000235:genetics; D023281:Genomics / Q000379:methods*; D006801:Humans; D051379:Mice; D058977:Molecular Sequence Annotation; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D040901:Proteomics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D014157:Transcription Factors