An integrative computational analysis gives evidence for FBN1-connected community deregulation in trisomy 21 [Investigation Article]
1Division of Vertebrate Genomics, Max-Planck-Institute for Molecular Genetics, Ihnestrasse 63–73, D-14195 Berlin, Germany
twoOffice of Data, College of Barcelona, Avenida Diagonal 645, Barcelona, 08028, Spain
- ↵*Author for correspondence ( )
Although around fifty% of Down Syndrome (DS) clients have coronary heart abnormalities, they exhibit an overprotection towards
cardiac abnormalities connected with the connective tissue, for illustration a reduce danger of coronary artery disease. A recent examine
noted a scenario of a particular person influenced by DS who carried mutations in FBN1, the gene causative for a connective tissue condition known as Marfan Syndrome (MFS). The simple fact that the man or woman did not have
any cardiac alterations proposed payment outcomes because of to DS. This observation is supported by a prior DS meta-evaluation
at the molecular stage exactly where we have located an total upregulation of FBN1 (which is normally downregulated in MFS). In addition, that outcome was cross-validated with impartial expression data from
DS coronary heart tissue. The purpose of this operate is to elucidate the function of FBN1 in DS and to create a molecular url to MFS and MFS-associated syndromes making use of a computational strategy. To achieve that, we
executed distinct analytical approaches above two DS studies (our previous meta-investigation and unbiased expression info
from DS heart tissue) and exposed expression alterations in the FBN1 conversation network, in FBN1 co-expressed genes and FBN1-related pathways. Right after merging the significant outcomes from different datasets with a Bayesian method, we prioritized
eighty five genes that were ready to distinguish management from DS situations. We more located proof for a number of of these genes (47%),
this sort of as FBN1, DCN, and COL1A2, currently being dysregulated in MFS and MFS-connected diseases. As a result, we more inspire the scientific local community to get
into account FBN1 and its associated network for the study of DS cardiovascular attributes.
Author contributions M.V. experienced the thought and analysed the information. M.V. and H.W. contributed to the style of the investigation. M.V., H.W. and S.C. contributed
to the information interpretation and collaborated to prepare and edit the manuscript.
Competing passions The authors have no competing passions to declare.
- Acquired February 12, 2013.
- Acknowledged May 18, 2013.
- © 2013. Released by The Company of Biologists Ltd
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