Pathways systematically associated to Hirschsprung's disease

Raquel M. Fernández, Marta Bleda, Berta Luzón-Toro, Luz García-Alonso, Stacey Arnold, Yunia Sribudiani, Claude Besmond, Francesca Lantieri, Betty Doan, Isabella Ceccherini, Stanislas Lyonnet, Robert Mw Hofstra, Aravinda Chakravarti, Guillermo Antiñolo, Joaquín Dopazo, Salud Borrego

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


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.

Original languageEnglish (US)
Article number187
JournalOrphanet journal of rare diseases
Issue number1
StatePublished - Dec 2 2013
Externally publishedYes

ASJC Scopus subject areas

  • Genetics(clinical)
  • Pharmacology (medical)


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