Cytogenomic integrative network analysis of the critical region associated with Wolf-Hirschhorn Syndrome
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFRGS |
Texto Completo: | http://hdl.handle.net/10183/181591 |
Resumo: | Deletions in the 4p16.3 region are associated with Wolf-Hirschhorn syndrome (WHS), a contiguous gene deletion syndrome involving variable size deletions. In this study, we perform a cytogenomic integrative analysis combining classical cytogenetic methods, fluorescence in situ hybridization (FISH), chromosomal microarray analysis (CMA), and systems biology strategies, to establish the cytogenomic profile involving the 4p16.3 critical region and suggest WHS-related intracellular cell signaling cascades. The cytogenetic and clinical patient profiles were evaluated. We characterized 12 terminal deletions, one interstitial deletion, two ring chromosomes, and one classical translocation 4;8.CMAallowed delineation of the deletions, which ranged from3.7 to 25.6Mb with breakpoints from 4p16.3 to 4p15.33. Furthermore, the smallest region of overlapping (SRO) encompassed seven genes in a terminal region of 330 kb in the 4p16.3 region, suggesting a region of susceptibility to convulsions and microcephaly. Therefore, molecular interaction networks and topological analysis were performed to understand these WHS-related symptoms. Our results suggest that specific cell signaling pathways including dopamine receptor,NAD+nucleosidase activity, and fibroblast growth factoractivated receptor activity are associated with the diverse pathological WHS phenotypes and their symptoms. Additionally, we identified 29 hub-bottlenecks (H-B) nodes with a major role in WHS. |
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Corrêa, ThiagoMergener, RafaellaLeite, Júlio César LoguercioGalera, Marcial FrancisMoreira, Lília Maria de AzevedoVargas, José EduardoRiegel, Mariluce2018-09-01T02:55:15Z20182314-6141http://hdl.handle.net/10183/181591001067565Deletions in the 4p16.3 region are associated with Wolf-Hirschhorn syndrome (WHS), a contiguous gene deletion syndrome involving variable size deletions. In this study, we perform a cytogenomic integrative analysis combining classical cytogenetic methods, fluorescence in situ hybridization (FISH), chromosomal microarray analysis (CMA), and systems biology strategies, to establish the cytogenomic profile involving the 4p16.3 critical region and suggest WHS-related intracellular cell signaling cascades. The cytogenetic and clinical patient profiles were evaluated. We characterized 12 terminal deletions, one interstitial deletion, two ring chromosomes, and one classical translocation 4;8.CMAallowed delineation of the deletions, which ranged from3.7 to 25.6Mb with breakpoints from 4p16.3 to 4p15.33. Furthermore, the smallest region of overlapping (SRO) encompassed seven genes in a terminal region of 330 kb in the 4p16.3 region, suggesting a region of susceptibility to convulsions and microcephaly. Therefore, molecular interaction networks and topological analysis were performed to understand these WHS-related symptoms. Our results suggest that specific cell signaling pathways including dopamine receptor,NAD+nucleosidase activity, and fibroblast growth factoractivated receptor activity are associated with the diverse pathological WHS phenotypes and their symptoms. Additionally, we identified 29 hub-bottlenecks (H-B) nodes with a major role in WHS.application/pdfengBiomed research international. New York. Vol. 2018 2018), ID 5436187, 10 p.Síndrome de Wolf-HirschhornAnálise citogenéticaCromossomos humanos par 4Receptores dopaminérgicosFenótipoVariação biológica da populaçãoCytogenomic integrative network analysis of the critical region associated with Wolf-Hirschhorn SyndromeEstrangeiroinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFRGSinstname:Universidade Federal do Rio Grande do Sul (UFRGS)instacron:UFRGSORIGINAL001067565.pdfTexto completo (inglês)application/pdf2089036http://www.lume.ufrgs.br/bitstream/10183/181591/1/001067565.pdf32f03f5e87aca3ede153a761aca51b1dMD51TEXT001067565.pdf.txt001067565.pdf.txtExtracted Texttext/plain41835http://www.lume.ufrgs.br/bitstream/10183/181591/2/001067565.pdf.txt9f60af736c172bc231242f7a8864e9cdMD52THUMBNAIL001067565.pdf.jpg001067565.pdf.jpgGenerated Thumbnailimage/jpeg1817http://www.lume.ufrgs.br/bitstream/10183/181591/3/001067565.pdf.jpg86ae8c96233cc84abf2a8e8759093990MD5310183/1815912023-04-20 03:22:11.59944oai:www.lume.ufrgs.br:10183/181591Repositório de PublicaçõesPUBhttps://lume.ufrgs.br/oai/requestopendoar:2023-04-20T06:22:11Repositório Institucional da UFRGS - Universidade Federal do Rio Grande do Sul (UFRGS)false |
dc.title.pt_BR.fl_str_mv |
Cytogenomic integrative network analysis of the critical region associated with Wolf-Hirschhorn Syndrome |
title |
Cytogenomic integrative network analysis of the critical region associated with Wolf-Hirschhorn Syndrome |
spellingShingle |
Cytogenomic integrative network analysis of the critical region associated with Wolf-Hirschhorn Syndrome Corrêa, Thiago Síndrome de Wolf-Hirschhorn Análise citogenética Cromossomos humanos par 4 Receptores dopaminérgicos Fenótipo Variação biológica da população |
title_short |
Cytogenomic integrative network analysis of the critical region associated with Wolf-Hirschhorn Syndrome |
title_full |
Cytogenomic integrative network analysis of the critical region associated with Wolf-Hirschhorn Syndrome |
title_fullStr |
Cytogenomic integrative network analysis of the critical region associated with Wolf-Hirschhorn Syndrome |
title_full_unstemmed |
Cytogenomic integrative network analysis of the critical region associated with Wolf-Hirschhorn Syndrome |
title_sort |
Cytogenomic integrative network analysis of the critical region associated with Wolf-Hirschhorn Syndrome |
author |
Corrêa, Thiago |
author_facet |
Corrêa, Thiago Mergener, Rafaella Leite, Júlio César Loguercio Galera, Marcial Francis Moreira, Lília Maria de Azevedo Vargas, José Eduardo Riegel, Mariluce |
author_role |
author |
author2 |
Mergener, Rafaella Leite, Júlio César Loguercio Galera, Marcial Francis Moreira, Lília Maria de Azevedo Vargas, José Eduardo Riegel, Mariluce |
author2_role |
author author author author author author |
dc.contributor.author.fl_str_mv |
Corrêa, Thiago Mergener, Rafaella Leite, Júlio César Loguercio Galera, Marcial Francis Moreira, Lília Maria de Azevedo Vargas, José Eduardo Riegel, Mariluce |
dc.subject.por.fl_str_mv |
Síndrome de Wolf-Hirschhorn Análise citogenética Cromossomos humanos par 4 Receptores dopaminérgicos Fenótipo Variação biológica da população |
topic |
Síndrome de Wolf-Hirschhorn Análise citogenética Cromossomos humanos par 4 Receptores dopaminérgicos Fenótipo Variação biológica da população |
description |
Deletions in the 4p16.3 region are associated with Wolf-Hirschhorn syndrome (WHS), a contiguous gene deletion syndrome involving variable size deletions. In this study, we perform a cytogenomic integrative analysis combining classical cytogenetic methods, fluorescence in situ hybridization (FISH), chromosomal microarray analysis (CMA), and systems biology strategies, to establish the cytogenomic profile involving the 4p16.3 critical region and suggest WHS-related intracellular cell signaling cascades. The cytogenetic and clinical patient profiles were evaluated. We characterized 12 terminal deletions, one interstitial deletion, two ring chromosomes, and one classical translocation 4;8.CMAallowed delineation of the deletions, which ranged from3.7 to 25.6Mb with breakpoints from 4p16.3 to 4p15.33. Furthermore, the smallest region of overlapping (SRO) encompassed seven genes in a terminal region of 330 kb in the 4p16.3 region, suggesting a region of susceptibility to convulsions and microcephaly. Therefore, molecular interaction networks and topological analysis were performed to understand these WHS-related symptoms. Our results suggest that specific cell signaling pathways including dopamine receptor,NAD+nucleosidase activity, and fibroblast growth factoractivated receptor activity are associated with the diverse pathological WHS phenotypes and their symptoms. Additionally, we identified 29 hub-bottlenecks (H-B) nodes with a major role in WHS. |
publishDate |
2018 |
dc.date.accessioned.fl_str_mv |
2018-09-01T02:55:15Z |
dc.date.issued.fl_str_mv |
2018 |
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2314-6141 |
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001067565 |
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http://hdl.handle.net/10183/181591 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartof.pt_BR.fl_str_mv |
Biomed research international. New York. Vol. 2018 2018), ID 5436187, 10 p. |
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openAccess |
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