Pathways systematically associated to Hirschsprung's disease.

Abstract : Despite it has been reported that several loci are involved in Hirschsprung's disease, the molecular basis of the disease remains yet essentially unknown. The study of collective properties of modules of functionally-related genes provides an efficient and sensitive statistical framework that can overcome sample size limitations in the study of rare diseases. Here, we present the extension of a previous study of a Spanish series of HSCR trios to an international cohort of 162 HSCR trios to validate the generality of the underlying functional basis of the Hirschsprung's disease mechanisms previously found. The Pathway-Based Analysis (PBA) confirms a strong association of gene ontology (GO) modules related to signal transduction and its regulation, enteric nervous system (ENS) formation and other processes related to the disease. In addition, network analysis recovers sub-networks significantly associated to the disease, which contain genes related to the same functionalities, thus providing an independent validation of these findings. The functional profiles of association obtained for patients populations from different countries were compared to each other. While gene associations were different at each series, the main functional associations were identical in all the five populations. These observations would also explain the reported low reproducibility of associations of individual disease genes across populations.
Type de document :
Article dans une revue
Orphanet Journal of Rare Diseases, BioMed Central, 2013, 8 (1), pp.187. 〈10.1186/1750-1172-8-187〉
Liste complète des métadonnées

Littérature citée [45 références]  Voir  Masquer  Télécharger
Contributeur : Ed. Bmc <>
Soumis le : vendredi 20 décembre 2013 - 17:12:00
Dernière modification le : mardi 10 avril 2018 - 12:34:01
Document(s) archivé(s) le : vendredi 21 mars 2014 - 09:19:12





Raquel Fernández, Marta Bleda, Berta Luzón-Toro, Luz García-Alonso, Stacey Arnold, et al.. Pathways systematically associated to Hirschsprung's disease.. Orphanet Journal of Rare Diseases, BioMed Central, 2013, 8 (1), pp.187. 〈10.1186/1750-1172-8-187〉. 〈inserm-00921630〉



Consultations de la notice


Téléchargements de fichiers