title: Using transcription modules to identify expression clusters perturbed in Williams-Beuren syndrome.
abstract: The genetic dissection of the phenotypes associated with Williams-Beuren Syndrome (WBS) is advancing thanks to the study of individuals carrying typical or atypical structural rearrangements, as well as in vitro and animal studies. However, little is known about the global dysregulations caused by the WBS deletion. We profiled the transcriptomes of skin fibroblasts from WBS patients and compared them to matched controls. We identified 868 differentially expressed genes that were significantly enriched in extracellular matrix genes, major histocompatibility complex (MHC) genes, as well as genes in which the products localize to the postsynaptic membrane. We then used public expression datasets from human fibroblasts to establish transcription modules, sets of genes coexpressed in this cell type. We identified those sets in which the average gene expression was altered in WBS samples. Dysregulated modules are often interconnected and share multiple common genes, suggesting that intricate regulatory networks connected by a few central genes are disturbed in WBS. This modular approach increases the power to identify pathways dysregulated in WBS patients, thus providing a testable set of additional candidates for genes and their interactions that modulate the WBS phenotypes.
authors.affiliation: The Center for Integrative Genomics, Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland.
authors.forename: Charlotte N
authors.initials: CN
authors.lastname: Henrichsen
authors.forename: Gábor
authors.initials: G
authors.lastname: Csárdi
authors.forename: Marie-Thérèse
authors.initials: MT
authors.lastname: Zabot
authors.forename: Carmela
authors.initials: C
authors.lastname: Fusco
authors.forename: Sven
authors.initials: S
authors.lastname: Bergmann
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Merla
authors.forename: Alexandre
authors.initials: A
authors.lastname: Reymond
mesh_terms: D016022:Case-Control Studies; D002460:Cell Line; D020869:Gene Expression Profiling; D006801:Humans; D005810:Multigene Family; D014158:Transcription, Genetic; D018980:Williams Syndrome / Q000235:genetics*