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Orphanet Journal of Rare Diseases
Published in: Orphanet Journal of Rare Diseases 1/2012

Open Access 01-12-2012 | Research

Four new loci associations discovered by pathway-based and network analyses of the genome-wide variability profile of Hirschsprung’s disease

Authors: Raquel Ma Fernández, Marta Bleda, Rocío Núñez-Torres, Ignacio Medina, Berta Luzón-Toro, Luz García-Alonso, Ana Torroglosa, Martina Marbà, Ma Valle Enguix-Riego, David Montaner, Guillermo Antiñolo, Joaquín Dopazo, Salud Borrego

Published in: Orphanet Journal of Rare Diseases | Issue 1/2012

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Abstract

Finding gene associations in rare diseases is frequently hampered by the reduced numbers of patients accessible. Conventional gene-based association tests rely on the availability of large cohorts, which constitutes a serious limitation for its application in this scenario. To overcome this problem we have used here a combined strategy in which a pathway-based analysis (PBA) has been initially conducted to prioritize candidate genes in a Spanish cohort of 53 trios of short-segment Hirschsprung’s disease. Candidate genes have been further validated in an independent population of 106 trios. The study revealed a strong association of 11 gene ontology (GO) modules related to signal transduction and its regulation, enteric nervous system (ENS) formation and other HSCR-related processes. Among the preselected candidates, a total of 4 loci, RASGEF1A, IQGAP2, DLC1 and CHRNA7, related to signal transduction and migration processes, were found to be significantly associated to HSCR. Network analysis also confirms their involvement in the network of already known disease genes. This approach, based on the study of functionally-related gene sets, requires of lower sample sizes and opens new opportunities for the study of rare diseases.
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Metadata
Title
Four new loci associations discovered by pathway-based and network analyses of the genome-wide variability profile of Hirschsprung’s disease
Authors
Raquel Ma Fernández
Marta Bleda
Rocío Núñez-Torres
Ignacio Medina
Berta Luzón-Toro
Luz García-Alonso
Ana Torroglosa
Martina Marbà
Ma Valle Enguix-Riego
David Montaner
Guillermo Antiñolo
Joaquín Dopazo
Salud Borrego
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Orphanet Journal of Rare Diseases / Issue 1/2012
Electronic ISSN: 1750-1172
DOI
https://doi.org/10.1186/1750-1172-7-103

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