Using linkage studies combined with whole-exome sequencing to identify novel candidate genes for familial colorectal cancer
dc.contributor.author | Toma, Claudio | |
dc.contributor.author | Díaz Gay, Marcos | |
dc.contributor.author | Franch Expósito, Sebastià | |
dc.contributor.author | Arnau Collell, Coral | |
dc.contributor.author | Overs, Bronwyn | |
dc.contributor.author | Muñoz, Jenifer | |
dc.contributor.author | Bonjoch, Laia | |
dc.contributor.author | Soares de Lima, Yasmin | |
dc.contributor.author | Ocaña, Teresa | |
dc.contributor.author | Cuatrecasas, Miriam | |
dc.contributor.author | Castells, Antoni | |
dc.contributor.author | Bujanda Fernández de Pierola, Luis | |
dc.contributor.author | Balaguer, Francesc | |
dc.contributor.author | Cubiella, Joaquín | |
dc.contributor.author | Caldés, Trinidad | |
dc.contributor.author | Fullerton, Janice M. | |
dc.contributor.author | Castellví Bel, Sergi | |
dc.date.accessioned | 2020-02-28T09:23:54Z | |
dc.date.available | 2020-02-28T09:23:54Z | |
dc.date.issued | 2019-11 | |
dc.identifier.citation | International Journal of Cancer 146(6) : 1568-1577 (2019) | es_ES |
dc.identifier.issn | 0020-7136 | |
dc.identifier.uri | http://hdl.handle.net/10810/41846 | |
dc.description.abstract | Colorectal cancer (CRC) is a complex disorder for which the majority of the underlying germline predisposition factors remain still unidentified. Here, we combined whole-exome sequencing (WES) and linkage analysis in families with multiple relatives affected by CRC to identify candidate genes harboring rare variants with potential high-penetrance effects. Forty-seven affected subjects from 18 extended CRC families underwent WES. Genome-wide linkage analysis was performed under linear and exponential models. Suggestive linkage peaks were identified on chromosomes 1q22-q24.2 (maxSNP = rs2134095; LODlinear = 2.38, LODexp = 2.196), 7q31.2-q34 (maxSNP = rs6953296; LODlinear = 2.197, LODexp = 2.149) and 10q21.2-q23.1 (maxSNP = rs1904589; LODlinear = 1.445, LODexp = 2.195). These linkage signals were replicated in 10 independent sets of random markers from each of these regions. To assess the contribution of rare variants predicted to be pathogenic, we performed a family-based segregation test with 89 rare variants predicted to be deleterious from 78 genes under the linkage intervals. This analysis showed significant segregation of rare variants with CRC in 18 genes (weighted p-value > 0.0028). Protein network analysis and functional evaluation were used to suggest a plausible candidate gene for germline CRC predisposition. Etiologic rare variants implicated in cancer germline predisposition may be identified by combining traditional linkage with WES data. This approach can be used with already available NGS data from families with several sequenced members to further identify candidate genes involved germline predisposition to disease. This approach resulted in one candidate gene associated with increased risk of CRC but needs evidence from further studies. | es_ES |
dc.description.sponsorship | Grant sponsor: "la Caixa" Foundation; Grant number: LCF/BQ/DI18/11660058; Grant sponsor: Agencia de Gestio d'Ajuts Universitaris i de Recerca; Grant numbers: 2018FI_B1_00213, GRPRE 2017SGR21, GRC 2017SGR653; Grant sponsor: Australian National Health and Medical Research; Grant numbers: 1063960, 1066177; Grant sponsor: COST (European Cooperation in Science and Technology); Grant number: CA17118; Grant sponsor: Departament d'Universitats, Recerca i Societat de la Informacio; Grant sponsor: Fondo de Investigacion Sanitaria/FEDER; Grant number: 17/00878; Grant sponsor: Fundacion Cientifica de la Asociacion Espanola contra el Cancer; Grant number: GCB13131592CAST; Grant sponsor: Generalitat de Catalunya, Salut; Grant number: PERIS SLT002/16/00398; Grant sponsor: Instituto de Salud Carlos III; Grant sponsor: Juan de la Cierva postdoctoral contract; Grant number: FJCI-2017-32593 | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Wiley | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/es/ | * |
dc.subject | colorectal cancer | es_ES |
dc.subject | whole-exome sequencing | es_ES |
dc.subject | linkage analysis | es_ES |
dc.subject | genetic predisposition to disease | es_ES |
dc.subject | copy number variants | es_ES |
dc.subject | rare variants | es_ES |
dc.subject | predisposition | es_ES |
dc.subject | mutation | es_ES |
dc.subject | genetics | es_ES |
dc.subject | pathway | es_ES |
dc.title | Using linkage studies combined with whole-exome sequencing to identify novel candidate genes for familial colorectal cancer | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. | es_ES |
dc.rights.holder | Atribución-NoComercial-SinDerivadas 3.0 España | * |
dc.relation.publisherversion | https://onlinelibrary.wiley.com/doi/full/10.1002/ijc.32683 | es_ES |
dc.identifier.doi | 10.1002/ijc.32683 | |
dc.departamentoes | Medicina | es_ES |
dc.departamentoeu | Medikuntza | es_ES |
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