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

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...

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Autores: Fernández, Raquel María, Bleda, Marta, Núñez-Torres, Rocío, Medina, Ignacio, Luzón-Toro, Berta, García-Alonso, Luz, Antiñolo Gil, Guillermo, Borrego, Salud
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2012
País:España
Institución:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/107860
Acceso en línea:https://hdl.handle.net/11441/107860
https://doi.org/10.1186/1750-1172-7-103
Access Level:acceso abierto
Palabra clave:HSCR
Pathway-based analysis
Network analysis
GWAS
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spelling Four new loci associations discovered by pathway-based and network analyses of the genome-wide variability profile of Hirschsprung’s diseaseFernández, Raquel MaríaBleda, MartaNúñez-Torres, RocíoMedina, IgnacioLuzón-Toro, BertaGarcía-Alonso, LuzAntiñolo Gil, GuillermoBorrego, SaludHSCRPathway-based analysisNetwork analysisGWASFinding 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.Instituto de Salud Carlos IIIMinistry of Economy and Competitiveness, Spain (PI1001290)GVA-FEDER (PROMETEO/2010/001)Consejeria de Innovación Ciencia y Empresa de la Junta de Andalucia (CTS-7447)Springer NatureCirugía2012info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11441/107860https://doi.org/10.1186/1750-1172-7-103reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésOrphanet Journal of Rare Diseases, 7 (1), 103.PI1001290PROMETEO/2010/001CTS-7447https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-7-103info:eu-repo/semantics/openAccessoai:idus.us.es:11441/1078602026-06-17T12:51:07Z
dc.title.none.fl_str_mv Four new loci associations discovered by pathway-based and network analyses of the genome-wide variability profile of Hirschsprung’s disease
title Four new loci associations discovered by pathway-based and network analyses of the genome-wide variability profile of Hirschsprung’s disease
spellingShingle Four new loci associations discovered by pathway-based and network analyses of the genome-wide variability profile of Hirschsprung’s disease
Fernández, Raquel María
HSCR
Pathway-based analysis
Network analysis
GWAS
title_short Four new loci associations discovered by pathway-based and network analyses of the genome-wide variability profile of Hirschsprung’s disease
title_full Four new loci associations discovered by pathway-based and network analyses of the genome-wide variability profile of Hirschsprung’s disease
title_fullStr Four new loci associations discovered by pathway-based and network analyses of the genome-wide variability profile of Hirschsprung’s disease
title_full_unstemmed Four new loci associations discovered by pathway-based and network analyses of the genome-wide variability profile of Hirschsprung’s disease
title_sort Four new loci associations discovered by pathway-based and network analyses of the genome-wide variability profile of Hirschsprung’s disease
dc.creator.none.fl_str_mv Fernández, Raquel María
Bleda, Marta
Núñez-Torres, Rocío
Medina, Ignacio
Luzón-Toro, Berta
García-Alonso, Luz
Antiñolo Gil, Guillermo
Borrego, Salud
author Fernández, Raquel María
author_facet Fernández, Raquel María
Bleda, Marta
Núñez-Torres, Rocío
Medina, Ignacio
Luzón-Toro, Berta
García-Alonso, Luz
Antiñolo Gil, Guillermo
Borrego, Salud
author_role author
author2 Bleda, Marta
Núñez-Torres, Rocío
Medina, Ignacio
Luzón-Toro, Berta
García-Alonso, Luz
Antiñolo Gil, Guillermo
Borrego, Salud
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Cirugía
dc.subject.none.fl_str_mv HSCR
Pathway-based analysis
Network analysis
GWAS
topic HSCR
Pathway-based analysis
Network analysis
GWAS
description 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.
publishDate 2012
dc.date.none.fl_str_mv 2012
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11441/107860
https://doi.org/10.1186/1750-1172-7-103
url https://hdl.handle.net/11441/107860
https://doi.org/10.1186/1750-1172-7-103
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Orphanet Journal of Rare Diseases, 7 (1), 103.
PI1001290
PROMETEO/2010/001
CTS-7447
https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-7-103
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Springer Nature
publisher.none.fl_str_mv Springer Nature
dc.source.none.fl_str_mv reponame:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
repository.mail.fl_str_mv
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