{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T12:03:10Z","timestamp":1756382590107},"reference-count":37,"publisher":"The Company of Biologists","issue":"8","license":[{"start":{"date-parts":[[2020,9,2]],"date-time":"2020-09-02T00:00:00Z","timestamp":1599004800000},"content-version":"vor","delay-in-days":2631,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,8,15]]},"abstract":"<jats:title>Summary<\/jats:title>\n               <jats:p>Although approximately 50% of Down Syndrome (DS) patients have heart abnormalities, they exhibit an overprotection against cardiac abnormalities related with the connective tissue, for example a lower risk of coronary artery disease. A recent study reported a case of a person affected by DS who carried mutations in FBN1, the gene causative for a connective tissue disorder called Marfan Syndrome (MFS). The fact that the person did not have any cardiac alterations suggested compensation effects due to DS. This observation is supported by a previous DS meta-analysis at the molecular level where we have found an overall upregulation of FBN1 (which is usually downregulated in MFS). Additionally, that result was cross-validated with independent expression data from DS heart tissue. The aim of this work is to elucidate the role of FBN1 in DS and to establish a molecular link to MFS and MFS-related syndromes using a computational approach. To reach that, we conducted different analytical approaches over two DS studies (our previous meta-analysis and independent expression data from DS heart tissue) and revealed expression alterations in the FBN1 interaction network, in FBN1 co-expressed genes and FBN1-related pathways. After merging the significant results from different datasets with a Bayesian approach, we prioritized 85 genes that were able to distinguish control from DS cases. We further found evidence for several of these genes (47%), such as FBN1, DCN, and COL1A2, being dysregulated in MFS and MFS-related diseases. Consequently, we further encourage the scientific community to take into account FBN1 and its related network for the study of DS cardiovascular characteristics.<\/jats:p>","DOI":"10.1242\/bio.20134408","type":"journal-article","created":{"date-parts":[[2013,6,26]],"date-time":"2013-06-26T00:27:46Z","timestamp":1372206466000},"page":"771-778","source":"Crossref","is-referenced-by-count":3,"title":["An integrative computational analysis provides evidence for <i>FBN1<\/i>-associated network deregulation in trisomy 21"],"prefix":"10.1242","volume":"2","author":[{"given":"Mireia","family":"Vilardell","sequence":"first","affiliation":[{"name":"Department of Vertebrate Genomics, Max-Planck-Institute for Molecular Genetics, Ihnestrasse 63\u201373, D-14195 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergi","family":"Civit","sequence":"additional","affiliation":[{"name":"Department of Statistics, University of Barcelona, Avenida Diagonal 645, Barcelona, 08028, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ralf","family":"Herwig","sequence":"additional","affiliation":[{"name":"Department of Vertebrate Genomics, Max-Planck-Institute for Molecular Genetics, Ihnestrasse 63\u201373, D-14195 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2013,6,20]]},"reference":[{"key":"2021111216353898900_b1","doi-asserted-by":"crossref","first-page":"pp. 45","DOI":"10.1007\/978-0-387-71385-4","volume-title":"Bayesian Computation with R","author":"Albert","year":"2007"},{"key":"2021111216353898900_b2","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1038\/nrg1749","article-title":"Microarray data analysis: from disarray to consolidation and consensus.","volume":"7","author":"Allison","year":"2006","journal-title":"Nat. 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