<?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%">Villalba-Benito, Leticia</style></author><author><style face="normal" font="default" size="100%">López-López, Daniel</style></author><author><style face="normal" font="default" size="100%">Torroglosa, Ana</style></author><author><style face="normal" font="default" size="100%">Casimiro-Soriguer, Carlos S.</style></author><author><style face="normal" font="default" size="100%">Luzón-Toro, Berta</style></author><author><style face="normal" font="default" size="100%">Fernández, Raquel María</style></author><author><style face="normal" font="default" size="100%">Moya-Jiménez, María José</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%">Genome-wide analysis of DNA methylation in Hirschsprung enteric precursor cells: unraveling the epigenetic landscape of enteric nervous system developmentAbstractBackgroundResultsConclusionsGraphic abstract</style></title><secondary-title><style face="normal" font="default" size="100%">Clinical Epigenetics</style></secondary-title><short-title><style face="normal" font="default" size="100%">Clin Epigenet</style></short-title></titles><dates><year><style  face="normal" font="default" size="100%">2021</style></year><pub-dates><date><style  face="normal" font="default" size="100%">Jan-12-2021</style></date></pub-dates></dates><urls><web-urls><url><style face="normal" font="default" size="100%">http://link.springer.com/article/10.1186/s13148-021-01040-6/fulltext.html</style></url></web-urls></urls><volume><style face="normal" font="default" size="100%">13</style></volume><language><style face="normal" font="default" size="100%">eng</style></language><issue><style face="normal" font="default" size="100%">1</style></issue></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%">Gui, Hongsheng</style></author><author><style face="normal" font="default" size="100%">Schriemer, Duco</style></author><author><style face="normal" font="default" size="100%">Cheng, William W</style></author><author><style face="normal" font="default" size="100%">Chauhan, Rajendra K</style></author><author><style face="normal" font="default" size="100%">Antiňolo, Guillermo</style></author><author><style face="normal" font="default" size="100%">Berrios, Courtney</style></author><author><style face="normal" font="default" size="100%">Bleda, Marta</style></author><author><style face="normal" font="default" size="100%">Brooks, Alice S</style></author><author><style face="normal" font="default" size="100%">Brouwer, Rutger W W</style></author><author><style face="normal" font="default" size="100%">Burns, Alan J</style></author><author><style face="normal" font="default" size="100%">Cherny, Stacey S</style></author><author><style face="normal" font="default" size="100%">Dopazo, Joaquin</style></author><author><style face="normal" font="default" size="100%">Eggen, Bart J L</style></author><author><style face="normal" font="default" size="100%">Griseri, Paola</style></author><author><style face="normal" font="default" size="100%">Jalloh, Binta</style></author><author><style face="normal" font="default" size="100%">Le, Thuy-Linh</style></author><author><style face="normal" font="default" size="100%">Lui, Vincent C H</style></author><author><style face="normal" font="default" size="100%">Luzón-Toro, Berta</style></author><author><style face="normal" font="default" size="100%">Matera, Ivana</style></author><author><style face="normal" font="default" size="100%">Ngan, Elly S W</style></author><author><style face="normal" font="default" size="100%">Pelet, Anna</style></author><author><style face="normal" font="default" size="100%">Ruiz-Ferrer, Macarena</style></author><author><style face="normal" font="default" size="100%">Sham, Pak C</style></author><author><style face="normal" font="default" size="100%">Shepherd, Iain T</style></author><author><style face="normal" font="default" size="100%">So, Man-Ting</style></author><author><style face="normal" font="default" size="100%">Sribudiani, Yunia</style></author><author><style face="normal" font="default" size="100%">Tang, Clara S M</style></author><author><style face="normal" font="default" size="100%">van den Hout, Mirjam C G N</style></author><author><style face="normal" font="default" size="100%">van der Linde, Herma C</style></author><author><style face="normal" font="default" size="100%">van Ham, Tjakko J</style></author><author><style face="normal" font="default" size="100%">van IJcken, Wilfred F J</style></author><author><style face="normal" font="default" size="100%">Verheij, Joke B G M</style></author><author><style face="normal" font="default" size="100%">Amiel, Jeanne</style></author><author><style face="normal" font="default" size="100%">Borrego, Salud</style></author><author><style face="normal" font="default" size="100%">Ceccherini, Isabella</style></author><author><style face="normal" font="default" size="100%">Chakravarti, Aravinda</style></author><author><style face="normal" font="default" size="100%">Lyonnet, Stanislas</style></author><author><style face="normal" font="default" size="100%">Tam, Paul K H</style></author><author><style face="normal" font="default" size="100%">Garcia-Barceló, Maria-Mercè</style></author><author><style face="normal" font="default" size="100%">Hofstra, Robert Mw</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Whole exome sequencing coupled with unbiased functional analysis reveals new Hirschsprung disease genes.</style></title><secondary-title><style face="normal" font="default" size="100%">Genome biology</style></secondary-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Hirschprung</style></keyword><keyword><style  face="normal" font="default" size="100%">Rare Disease</style></keyword><keyword><style  face="normal" font="default" size="100%">WES</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2017</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2017 Mar 08</style></date></pub-dates></dates><urls><web-urls><url><style face="normal" font="default" size="100%">http://genomebiology.biomedcentral.com/articles/10.1186/s13059-017-1174-6</style></url></web-urls></urls><volume><style face="normal" font="default" size="100%">18</style></volume><pages><style face="normal" font="default" size="100%">48</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">BACKGROUND: Hirschsprung disease (HSCR), which is congenital obstruction of the bowel, results from a failure of enteric nervous system (ENS) progenitors to migrate, proliferate, differentiate, or survive within the distal intestine. Previous studies that have searched for genes underlying HSCR have focused on ENS-related pathways and genes not fitting the current knowledge have thus often been ignored. We identify and validate novel HSCR genes using whole exome sequencing (WES), burden tests, in silico prediction, unbiased in vivo analyses of the mutated genes in zebrafish, and expression analyses in zebrafish, mouse, and human. RESULTS: We performed de novo mutation (DNM) screening on 24 HSCR trios. We identify 28 DNMs in 21 different genes. Eight of the DNMs we identified occur in RET, the main HSCR gene, and the remaining 20 DNMs reside in genes not reported in the ENS. Knockdown of all 12 genes with missense or loss-of-function DNMs showed that the orthologs of four genes (DENND3, NCLN, NUP98, and TBATA) are indispensable for ENS development in zebrafish, and these results were confirmed by CRISPR knockout. These genes are also expressed in human and mouse gut and/or ENS progenitors. Importantly, the encoded proteins are linked to neuronal processes shared by the central nervous system and the ENS. CONCLUSIONS: Our data open new fields of investigation into HSCR pathology and provide novel insights into the development of the ENS. Moreover, the study demonstrates that functional analyses of genes carrying DNMs are warranted to delineate the full genetic architecture of rare complex diseases.</style></abstract></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%">Gui, Hongsheng</style></author><author><style face="normal" font="default" size="100%">Schriemer, Duco</style></author><author><style face="normal" font="default" size="100%">Cheng, William W.</style></author><author><style face="normal" font="default" size="100%">Chauhan, Rajendra K.</style></author><author><style face="normal" font="default" size="100%">Antiňolo, Guillermo</style></author><author><style face="normal" font="default" size="100%">Berrios, Courtney</style></author><author><style face="normal" font="default" size="100%">Bleda, Marta</style></author><author><style face="normal" font="default" size="100%">Brooks, Alice S.</style></author><author><style face="normal" font="default" size="100%">Brouwer, Rutger W. W.</style></author><author><style face="normal" font="default" size="100%">Burns, Alan J.</style></author><author><style face="normal" font="default" size="100%">Cherny, Stacey S.</style></author><author><style face="normal" font="default" size="100%">Dopazo, Joaquin</style></author><author><style face="normal" font="default" size="100%">Eggen, Bart J. L.</style></author><author><style face="normal" font="default" size="100%">Griseri, Paola</style></author><author><style face="normal" font="default" size="100%">Jalloh, Binta</style></author><author><style face="normal" font="default" size="100%">Le, Thuy-Linh</style></author><author><style face="normal" font="default" size="100%">Lui, Vincent C. H.</style></author><author><style face="normal" font="default" size="100%">Luzón-Toro, Berta</style></author><author><style face="normal" font="default" size="100%">Matera, Ivana</style></author><author><style face="normal" font="default" size="100%">Ngan, Elly S. W.</style></author><author><style face="normal" font="default" size="100%">Pelet, Anna</style></author><author><style face="normal" font="default" size="100%">Ruiz-Ferrer, Macarena</style></author><author><style face="normal" font="default" size="100%">Sham, Pak C.</style></author><author><style face="normal" font="default" size="100%">Shepherd, Iain T.</style></author><author><style face="normal" font="default" size="100%">So, Man-Ting</style></author><author><style face="normal" font="default" size="100%">Sribudiani, Yunia</style></author><author><style face="normal" font="default" size="100%">Tang, Clara S. M.</style></author><author><style face="normal" font="default" size="100%">van den Hout, Mirjam C. G. N.</style></author><author><style face="normal" font="default" size="100%">van der Linde, Herma C.</style></author><author><style face="normal" font="default" size="100%">van Ham, Tjakko J.</style></author><author><style face="normal" font="default" size="100%">van IJcken, Wilfred F. J.</style></author><author><style face="normal" font="default" size="100%">Verheij, Joke B. G. M.</style></author><author><style face="normal" font="default" size="100%">Amiel, Jeanne</style></author><author><style face="normal" font="default" size="100%">Borrego, Salud</style></author><author><style face="normal" font="default" size="100%">Ceccherini, Isabella</style></author><author><style face="normal" font="default" size="100%">Chakravarti, Aravinda</style></author><author><style face="normal" font="default" size="100%">Lyonnet, Stanislas</style></author><author><style face="normal" font="default" size="100%">Tam, Paul K. H.</style></author><author><style face="normal" font="default" size="100%">Garcia-Barceló, Maria-Mercè</style></author><author><style face="normal" font="default" size="100%">Hofstra, Robert M. W.</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Whole exome sequencing coupled with unbiased functional analysis reveals new Hirschsprung disease genes</style></title><secondary-title><style face="normal" font="default" size="100%">Genome Biology</style></secondary-title><short-title><style face="normal" font="default" size="100%">Genome Biol</style></short-title></titles><dates><year><style  face="normal" font="default" size="100%">2017</style></year><pub-dates><date><style  face="normal" font="default" size="100%">Jan-12-2017</style></date></pub-dates></dates><urls><web-urls><url><style face="normal" font="default" size="100%">http://genomebiology.biomedcentral.com/articles/10.1186/s13059-017-1174-6http://link.springer.com/content/pdf/10.1186/s13059-017-1174-6.pdf</style></url></web-urls></urls><volume><style face="normal" font="default" size="100%">18</style></volume><language><style face="normal" font="default" size="100%">eng</style></language><issue><style face="normal" font="default" size="100%">1</style></issue></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%">Luzón-Toro, Berta</style></author><author><style face="normal" font="default" size="100%">Gui, Hongsheng</style></author><author><style face="normal" font="default" size="100%">Ruiz-Ferrer, Macarena</style></author><author><style face="normal" font="default" size="100%">Sze-Man Tang, Clara</style></author><author><style face="normal" font="default" size="100%">Fernández, Raquel M.</style></author><author><style face="normal" font="default" size="100%">Sham, Pak-Chung</style></author><author><style face="normal" font="default" size="100%">Torroglosa, Ana</style></author><author><style face="normal" font="default" size="100%">Kwong-Hang Tam, Paul</style></author><author><style face="normal" font="default" size="100%">Espino-Paisán, Laura</style></author><author><style face="normal" font="default" size="100%">Cherny, Stacey S.</style></author><author><style face="normal" font="default" size="100%">Bleda, Marta</style></author><author><style face="normal" font="default" size="100%">Enguix-Riego, María Del Valle</style></author><author><style face="normal" font="default" size="100%">Dopazo, Joaquin</style></author><author><style face="normal" font="default" size="100%">Antiňolo, Guillermo</style></author><author><style face="normal" font="default" size="100%">Garcia-Barceló, Maria-Mercè</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%">Exome sequencing reveals a high genetic heterogeneity on familial Hirschsprung disease</style></title><secondary-title><style face="normal" font="default" size="100%">Scientific Reports</style></secondary-title><short-title><style face="normal" font="default" size="100%">Sci Rep</style></short-title></titles><dates><year><style  face="normal" font="default" size="100%">2015</style></year><pub-dates><date><style  face="normal" font="default" size="100%">Jan-12-2015</style></date></pub-dates></dates><urls><web-urls><url><style face="normal" font="default" size="100%">http://www.nature.com/articles/srep16473http://www.nature.com/articles/srep16473.pdfhttp://www.nature.com/articles/srep16473.pdfhttp://www.nature.com/articles/srep16473</style></url></web-urls></urls><volume><style face="normal" font="default" size="100%">5</style></volume><language><style face="normal" font="default" size="100%">eng</style></language><issue><style face="normal" font="default" size="100%">1</style></issue></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%">Luzón-Toro, Berta</style></author><author><style face="normal" font="default" size="100%">Gui, Hongsheng</style></author><author><style face="normal" font="default" size="100%">Ruiz-Ferrer, Macarena</style></author><author><style face="normal" font="default" size="100%">Sze-Man Tang, Clara</style></author><author><style face="normal" font="default" size="100%">Fernández, Raquel M</style></author><author><style face="normal" font="default" size="100%">Sham, Pak-Chung</style></author><author><style face="normal" font="default" size="100%">Torroglosa, Ana</style></author><author><style face="normal" font="default" size="100%">Kwong-Hang Tam, Paul</style></author><author><style face="normal" font="default" size="100%">Espino-Paisán, Laura</style></author><author><style face="normal" font="default" size="100%">Cherny, Stacey S</style></author><author><style face="normal" font="default" size="100%">Bleda, Marta</style></author><author><style face="normal" font="default" size="100%">Enguix-Riego, María Del Valle</style></author><author><style face="normal" font="default" size="100%">Joaquín Dopazo</style></author><author><style face="normal" font="default" size="100%">Antiňolo, Guillermo</style></author><author><style face="normal" font="default" size="100%">Garcia-Barceló, Maria-Mercè</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%">Exome sequencing reveals a high genetic heterogeneity on familial Hirschsprung disease.</style></title><secondary-title><style face="normal" font="default" size="100%">Scientific reports</style></secondary-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">babelomics</style></keyword><keyword><style  face="normal" font="default" size="100%">Hirschprung</style></keyword><keyword><style  face="normal" font="default" size="100%">NGS</style></keyword><keyword><style  face="normal" font="default" size="100%">prioritization</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2015</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2015</style></date></pub-dates></dates><urls><web-urls><url><style face="normal" font="default" size="100%">http://www.nature.com/articles/srep16473</style></url></web-urls></urls><volume><style face="normal" font="default" size="100%">5</style></volume><pages><style face="normal" font="default" size="100%">16473</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">Hirschsprung disease (HSCR; OMIM 142623) is a developmental disorder characterized by aganglionosis along variable lengths of the distal gastrointestinal tract, which results in intestinal obstruction. Interactions among known HSCR genes and/or unknown disease susceptibility loci lead to variable severity of phenotype. Neither linkage nor genome-wide association studies have efficiently contributed to completely dissect the genetic pathways underlying this complex genetic disorder. We have performed whole exome sequencing of 16 HSCR patients from 8 unrelated families with SOLID platform. Variants shared by affected relatives were validated by Sanger sequencing. We searched for genes recurrently mutated across families. Only variations in the FAT3 gene were significantly enriched in five families. Within-family analysis identified compound heterozygotes for AHNAK and several genes (N = 23) with heterozygous variants that co-segregated with the phenotype. Network and pathway analyses facilitated the discovery of polygenic inheritance involving FAT3, HSCR known genes and their gene partners. Altogether, our approach has facilitated the detection of more than one damaging variant in biologically plausible genes that could jointly contribute to the phenotype. Our data may contribute to the understanding of the complex interactions that occur during enteric nervous system development and the etiopathology of familial HSCR.</style></abstract></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%">Luzón-Toro, Berta</style></author><author><style face="normal" font="default" size="100%">Bleda, Marta</style></author><author><style face="normal" font="default" size="100%">Navarro, Elena</style></author><author><style face="normal" font="default" size="100%">García-Alonso, Luz</style></author><author><style face="normal" font="default" size="100%">Ruiz-Ferrer, Macarena</style></author><author><style face="normal" font="default" size="100%">Medina, Ignacio</style></author><author><style face="normal" font="default" size="100%">Martín-Sánchez, Marta</style></author><author><style face="normal" font="default" size="100%">Gonzalez, Cristina Y</style></author><author><style face="normal" font="default" size="100%">Fernández, Raquel M</style></author><author><style face="normal" font="default" size="100%">Torroglosa, Ana</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%">Identification of epistatic interactions through genome-wide association studies in sporadic medullary and juvenile papillary thyroid carcinomas.</style></title><secondary-title><style face="normal" font="default" size="100%">BMC medical genomics</style></secondary-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">epistasis</style></keyword><keyword><style  face="normal" font="default" size="100%">GWAS</style></keyword><keyword><style  face="normal" font="default" size="100%">Thyroid cancer</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2015</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2015</style></date></pub-dates></dates><urls><web-urls><url><style face="normal" font="default" size="100%">http://bmcmedgenomics.biomedcentral.com/articles/10.1186/s12920-015-0160-7</style></url></web-urls></urls><volume><style face="normal" font="default" size="100%">8</style></volume><pages><style face="normal" font="default" size="100%">83</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">BACKGROUND: The molecular mechanisms leading to sporadic medullary thyroid carcinoma (sMTC) and juvenile papillary thyroid carcinoma (PTC), two rare tumours of the thyroid gland, remain poorly understood. Genetic studies on thyroid carcinomas have been conducted, although just a few loci have been systematically associated. Given the difficulties to obtain single-loci associations, this work expands its scope to the study of epistatic interactions that could help to understand the genetic architecture of complex diseases and explain new heritable components of genetic risk. METHODS: We carried out the first screening for epistasis by Multifactor-Dimensionality Reduction (MDR) in genome-wide association study (GWAS) on sMTC and juvenile PTC, to identify the potential simultaneous involvement of pairs of variants in the disease. RESULTS: We have identified two significant epistatic gene interactions in sMTC (CHFR-AC016582.2 and C8orf37-RNU1-55P) and three in juvenile PTC (RP11-648k4.2-DIO1, RP11-648k4.2-DMGDH and RP11-648k4.2-LOXL1). Interestingly, each interacting gene pair included a non-coding RNA, providing thus support to the relevance that these elements are increasingly gaining to explain carcinoma development and progression. CONCLUSIONS: Overall, this study contributes to the understanding of the genetic basis of thyroid carcinoma susceptibility in two different case scenarios such as sMTC and juvenile PTC.</style></abstract></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%">Luzón-Toro, Berta</style></author><author><style face="normal" font="default" size="100%">Bleda, Marta</style></author><author><style face="normal" font="default" size="100%">Navarro, Elena</style></author><author><style face="normal" font="default" size="100%">García-Alonso, Luz</style></author><author><style face="normal" font="default" size="100%">Ruiz-Ferrer, Macarena</style></author><author><style face="normal" font="default" size="100%">Medina, Ignacio</style></author><author><style face="normal" font="default" size="100%">Martín-Sánchez, Marta</style></author><author><style face="normal" font="default" size="100%">Gonzalez, Cristina Y.</style></author><author><style face="normal" font="default" size="100%">Fernández, Raquel M.</style></author><author><style face="normal" font="default" size="100%">Torroglosa, Ana</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%">Identification of epistatic interactions through genome-wide association studies in sporadic medullary and juvenile papillary thyroid carcinomas</style></title><secondary-title><style face="normal" font="default" size="100%">BMC Medical Genomics</style></secondary-title></titles><dates><year><style  face="normal" font="default" size="100%">2015</style></year><pub-dates><date><style  face="normal" font="default" size="100%">Dec</style></date></pub-dates></dates><urls><web-urls><url><style face="normal" font="default" size="100%">https://doi.org/10.1186/s12920-015-0160-7</style></url></web-urls></urls><volume><style face="normal" font="default" size="100%">8</style></volume><pages><style face="normal" font="default" size="100%">83</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">The molecular mechanisms leading to sporadic medullary thyroid carcinoma (sMTC) and juvenile papillary thyroid carcinoma (PTC), two rare tumours of the thyroid gland, remain poorly understood. Genetic studies on thyroid carcinomas have been conducted, although just a few loci have been systematically associated. Given the difficulties to obtain single-loci associations, this work expands its scope to the study of epistatic interactions that could help to understand the genetic architecture of complex diseases and explain new heritable components of genetic risk.</style></abstract></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 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%">Joaquín Dopazo</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 journal of rare diseases</style></secondary-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">GWAS</style></keyword><keyword><style  face="normal" font="default" size="100%">Hirschprung</style></keyword><keyword><style  face="normal" font="default" size="100%">network analysis</style></keyword><keyword><style  face="normal" font="default" size="100%">Pathway Based Analysis</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 2</style></date></pub-dates></dates><urls><web-urls><url><style face="normal" font="default" size="100%">http://www.ojrd.com/content/8/1/187/abstract</style></url></web-urls></urls><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%">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.</style></abstract></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 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%">Joaquín Dopazo</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 journal of rare diseases</style></secondary-title></titles><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><urls><web-urls><url><style face="normal" font="default" size="100%">http://www.ojrd.com/content/7/1/103/abstract</style></url></web-urls></urls><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%">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.</style></abstract></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>