<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Fernández, Raquel M</style></author><author><style face="normal" font="default" size="100%">Bleda, Marta</style></author><author><style face="normal" font="default" size="100%">Luzón-Toro, Berta</style></author><author><style face="normal" font="default" size="100%">García-Alonso, Luz</style></author><author><style face="normal" font="default" size="100%">Arnold, Stacey</style></author><author><style face="normal" font="default" size="100%">Sribudiani, Yunia</style></author><author><style face="normal" font="default" size="100%">Besmond, Claude</style></author><author><style face="normal" font="default" size="100%">Lantieri, Francesca</style></author><author><style face="normal" font="default" size="100%">Doan, Betty</style></author><author><style face="normal" font="default" size="100%">Ceccherini, Isabella</style></author><author><style face="normal" font="default" size="100%">Lyonnet, Stanislas</style></author><author><style face="normal" font="default" size="100%">Hofstra, Robert Mw</style></author><author><style face="normal" font="default" size="100%">Chakravarti, Aravinda</style></author><author><style face="normal" font="default" size="100%">Antiňolo, Guillermo</style></author><author><style face="normal" font="default" size="100%">Dopazo, Joaquin</style></author><author><style face="normal" font="default" size="100%">Borrego, Salud</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Pathways systematically associated to Hirschsprung's disease.</style></title><secondary-title><style face="normal" font="default" size="100%">Orphanet J Rare Dis</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Orphanet J Rare Dis</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">Genetic Predisposition to Disease</style></keyword><keyword><style  face="normal" font="default" size="100%">Genotype</style></keyword><keyword><style  face="normal" font="default" size="100%">Hirschsprung Disease</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Male</style></keyword><keyword><style  face="normal" font="default" size="100%">Polymorphism, Single Nucleotide</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2013</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2013 Dec 02</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">8</style></volume><pages><style face="normal" font="default" size="100%">187</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;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. &lt;/p&gt;</style></abstract><custom1><style face="normal" font="default" size="100%">https://www.ncbi.nlm.nih.gov/pubmed/24289864?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Fernández, Raquel Ma</style></author><author><style face="normal" font="default" size="100%">Bleda, Marta</style></author><author><style face="normal" font="default" size="100%">Núñez-Torres, Rocío</style></author><author><style face="normal" font="default" size="100%">Medina, Ignacio</style></author><author><style face="normal" font="default" size="100%">Luzón-Toro, Berta</style></author><author><style face="normal" font="default" size="100%">García-Alonso, Luz</style></author><author><style face="normal" font="default" size="100%">Torroglosa, Ana</style></author><author><style face="normal" font="default" size="100%">Marbà, Martina</style></author><author><style face="normal" font="default" size="100%">Enguix-Riego, Ma Valle</style></author><author><style face="normal" font="default" size="100%">Montaner, David</style></author><author><style face="normal" font="default" size="100%">Antiňolo, Guillermo</style></author><author><style face="normal" font="default" size="100%">Dopazo, Joaquin</style></author><author><style face="normal" font="default" size="100%">Borrego, Salud</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Four new loci associations discovered by pathway-based and network analyses of the genome-wide variability profile of Hirschsprung's disease.</style></title><secondary-title><style face="normal" font="default" size="100%">Orphanet J Rare Dis</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Orphanet J Rare Dis</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">Genetic Predisposition to Disease</style></keyword><keyword><style  face="normal" font="default" size="100%">Genome-Wide Association Study</style></keyword><keyword><style  face="normal" font="default" size="100%">Genotype</style></keyword><keyword><style  face="normal" font="default" size="100%">Hirschsprung Disease</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Male</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2012</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2012 Dec 28</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">7</style></volume><pages><style face="normal" font="default" size="100%">103</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;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.&lt;/p&gt;</style></abstract><custom1><style face="normal" font="default" size="100%">https://www.ncbi.nlm.nih.gov/pubmed/23270508?dopt=Abstract</style></custom1></record></records></xml>