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dc.contributor.authorToma, C.
dc.contributor.authorDiaz-Gay, M.
dc.contributor.authorSoares de Lima, Y.
dc.contributor.authorArnau-Collell, C.
dc.contributor.authorFranch-Exposito, S.
dc.contributor.authorMunoz, J.
dc.contributor.authorOvers, B.
dc.contributor.authorBonjoch, L.
dc.contributor.authorCarballal, S.
dc.contributor.authorOcana, T.
dc.contributor.authorCuatrecasas, M.
dc.contributor.authorDiaz de Bustamante, A.
dc.contributor.authorCastells, A.
dc.contributor.authorBujanda, L.
dc.contributor.authorCubiella Fernández, Joaquín 
dc.contributor.authorBalaguer, F.
dc.contributor.authorRodriguez-Alcalde, D.
dc.contributor.authorFullerton, J. M.
dc.contributor.authorCastellvi-Bel, S.
dc.date.accessioned2022-01-27T10:40:21Z
dc.date.available2022-01-27T10:40:21Z
dc.date.issued2019
dc.identifier.issn2155-384x
dc.identifier.otherhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6919450/pdf/ct9-10-e00100.pdfes
dc.identifier.urihttp://hdl.handle.net/20.500.11940/15961
dc.description.abstractOBJECTIVES: Serrated polyposis syndrome (SPS) is a complex disorder with a high risk of colorectal cancer for which the germline factors remain largely unknown. Here, we combined whole-exome sequencing (WES) and linkage studies in families with multiple members affected by SPS to identify candidate genes harboring rare variants with higher penetrance effects. METHODS: Thirty-nine affected subjects from 16 extended SPS families underwent WES. Genome-wide linkage analysis was performed under linear and exponential models. The contribution of rare coding variants selected to be highly pathogenic was assessed using the gene-based segregation test. RESULTS: A significant linkage peak was identified on chromosome 3p25.2-p22.3 (maxSNP = rs2293787; LODlinear = 2.311, LODexp = 2.11), which logarithm of the odds (LOD) score increased after fine mapping for the same marker (maxSNP = rs2293787; LODlinear = 2.4, LODexp = 2.25). This linkage signal was replicated in 10 independent sets of random markers from this locus. To assess the contribution of rare variants predicted to be pathogenic, we performed a family-based segregation test with 11 rare variants predicted to be deleterious from 10 genes under the linkage intervals. This analysis showed significant segregation of rare variants with SPS in CAPT7, TMEM43, NGLY1, and FBLN2 genes (weighted P value > 0.007). DISCUSSION: Protein network analysis suggested FBLN2 as the most plausible candidate genes for germline SPS predisposition. Etiologic rare variants implicated in disease predisposition may be identified by combining traditional linkage with WES data. This powerful approach was effective for the identification of a new candidate gene for hereditary SPS.en
dc.language.isoenges
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subject.meshGenetic Counseling*
dc.subject.meshExtracellular Matrix Proteins*
dc.subject.meshAdult*
dc.subject.meshMiddle Aged*
dc.subject.meshHumans*
dc.subject.meshYoung Adult*
dc.subject.meshCalcium-Binding Proteins*
dc.subject.meshAdenomatous Polyposis Coli*
dc.subject.meshGenetic Predisposition to Disease*
dc.subject.meshAged*
dc.subject.meshGenetic Linkage*
dc.titleIdentification of a Novel Candidate Gene for Serrated Polyposis Syndrome Germline Predisposition by Performing Linkage Analysis Combined With Whole-Exome Sequencingen
dc.typeArtigoes
dc.identifier.doi10.14309/ctg.0000000000000100
dc.identifier.pmid31703024
dc.identifier.sophos32698
dc.issue.number10es
dc.journal.titleClin Transl Gastroenteroles
dc.organizationServizo Galego de Saúde::Estrutura de Xestión Integrada (EOXI)::EOXI de Ourense, Verín e O Barco de Valdeorras - Complexo Hospitalario Universitario de Ourensees
dc.page.initiale00100es
dc.rights.accessRightsopenAccesses
dc.subject.decsligamiento genético*
dc.subject.decsconsejo genético*
dc.subject.decspoliposis adenomatosa del colon*
dc.subject.decsanciano*
dc.subject.decsproteínas de la matriz extracelular*
dc.subject.decsadulto joven*
dc.subject.decsmediana edad*
dc.subject.decshumanos*
dc.subject.decsadulto*
dc.subject.decspredisposición genética a la enfermedad*
dc.subject.decsproteínas de unión al calcio*
dc.subject.keywordCHUOes
dc.typefidesArtículo Originales
dc.typesophosArtículo Originales
dc.volume.number10es


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