The role of ESCO2, SALL4 and TBX5 genes in the susceptibility to thalidomide teratogenesis
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFRGS |
Texto Completo: | http://hdl.handle.net/10183/204323 |
Resumo: | Thalidomide is widely used for several diseases; however, it causes malformations in embryos exposed during pregnancy. The complete understanding of the mechanisms by which thalidomide afects the embryo development has not yet been obtained. The phenotypic similarity makes TE a phenocopy of syndromes caused by mutations in ESCO2, SALL4 and TBX5 genes. Recently, SALL4 and TBX5 were demonstrated to be thalidomide targets. To understand if these genes act in the TE development, we sequenced them in 27 individuals with TE; we verifed how thalidomide afect them in human pluripotent stem cells (hPSCs) through a diferential gene expression (DGE) analysis from GSE63935; and we evaluated how these genes are functionally related through an interaction network analysis. We identifed 8 variants in ESCO2, 15 in SALL4 and 15 in TBX5. We compared allelic frequencies with data from ExAC, 1000 Genomes and ABraOM databases; eight variants were signifcantly diferent (p<0.05). Eleven variants in SALL4 and TBX5 were previously associated with cardiac diseases or malformations; however, in TE sample there was no association. Variant efect prediction tools showed 97% of the variants with potential to infuence in these genes regulation. DGE analysis showed a signifcant reduction of ESCO2 in hPSCs after thalidomide exposure. |
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Gomes, Julia do AmaralKowalski, Thayne WoycinckFraga, Lucas RosaMacedo, Gabriel SouzaSanseverino, Maria Teresa VieiraFaccini, Lavinia SchulerVianna, Fernanda Sales Luiz2020-01-15T04:16:23Z20192045-2322http://hdl.handle.net/10183/204323001103836Thalidomide is widely used for several diseases; however, it causes malformations in embryos exposed during pregnancy. The complete understanding of the mechanisms by which thalidomide afects the embryo development has not yet been obtained. The phenotypic similarity makes TE a phenocopy of syndromes caused by mutations in ESCO2, SALL4 and TBX5 genes. Recently, SALL4 and TBX5 were demonstrated to be thalidomide targets. To understand if these genes act in the TE development, we sequenced them in 27 individuals with TE; we verifed how thalidomide afect them in human pluripotent stem cells (hPSCs) through a diferential gene expression (DGE) analysis from GSE63935; and we evaluated how these genes are functionally related through an interaction network analysis. We identifed 8 variants in ESCO2, 15 in SALL4 and 15 in TBX5. We compared allelic frequencies with data from ExAC, 1000 Genomes and ABraOM databases; eight variants were signifcantly diferent (p<0.05). Eleven variants in SALL4 and TBX5 were previously associated with cardiac diseases or malformations; however, in TE sample there was no association. Variant efect prediction tools showed 97% of the variants with potential to infuence in these genes regulation. DGE analysis showed a signifcant reduction of ESCO2 in hPSCs after thalidomide exposure.application/pdfengScientific reports. London. Vol. 9, no. 1 (Aug. 2019), 11413, 11 p.TalidomidaGenesTeratogêneseGene ESCO2Gene SALL4Gene TBX5The role of ESCO2, SALL4 and TBX5 genes in the susceptibility to thalidomide teratogenesisEstrangeiroinfo: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:UFRGSTEXT001103836.pdf.txt001103836.pdf.txtExtracted Texttext/plain50539http://www.lume.ufrgs.br/bitstream/10183/204323/2/001103836.pdf.txt0b428a91465578e778ad8bf481cad645MD52ORIGINAL001103836.pdfTexto completo (inglês)application/pdf2281271http://www.lume.ufrgs.br/bitstream/10183/204323/1/001103836.pdf9a30665d0fa234ad905bb7b89b476938MD5110183/2043232022-06-23 04:42:46.99081oai:www.lume.ufrgs.br:10183/204323Repositório de PublicaçõesPUBhttps://lume.ufrgs.br/oai/requestopendoar:2022-06-23T07:42:46Repositório Institucional da UFRGS - Universidade Federal do Rio Grande do Sul (UFRGS)false |
dc.title.pt_BR.fl_str_mv |
The role of ESCO2, SALL4 and TBX5 genes in the susceptibility to thalidomide teratogenesis |
title |
The role of ESCO2, SALL4 and TBX5 genes in the susceptibility to thalidomide teratogenesis |
spellingShingle |
The role of ESCO2, SALL4 and TBX5 genes in the susceptibility to thalidomide teratogenesis Gomes, Julia do Amaral Talidomida Genes Teratogênese Gene ESCO2 Gene SALL4 Gene TBX5 |
title_short |
The role of ESCO2, SALL4 and TBX5 genes in the susceptibility to thalidomide teratogenesis |
title_full |
The role of ESCO2, SALL4 and TBX5 genes in the susceptibility to thalidomide teratogenesis |
title_fullStr |
The role of ESCO2, SALL4 and TBX5 genes in the susceptibility to thalidomide teratogenesis |
title_full_unstemmed |
The role of ESCO2, SALL4 and TBX5 genes in the susceptibility to thalidomide teratogenesis |
title_sort |
The role of ESCO2, SALL4 and TBX5 genes in the susceptibility to thalidomide teratogenesis |
author |
Gomes, Julia do Amaral |
author_facet |
Gomes, Julia do Amaral Kowalski, Thayne Woycinck Fraga, Lucas Rosa Macedo, Gabriel Souza Sanseverino, Maria Teresa Vieira Faccini, Lavinia Schuler Vianna, Fernanda Sales Luiz |
author_role |
author |
author2 |
Kowalski, Thayne Woycinck Fraga, Lucas Rosa Macedo, Gabriel Souza Sanseverino, Maria Teresa Vieira Faccini, Lavinia Schuler Vianna, Fernanda Sales Luiz |
author2_role |
author author author author author author |
dc.contributor.author.fl_str_mv |
Gomes, Julia do Amaral Kowalski, Thayne Woycinck Fraga, Lucas Rosa Macedo, Gabriel Souza Sanseverino, Maria Teresa Vieira Faccini, Lavinia Schuler Vianna, Fernanda Sales Luiz |
dc.subject.por.fl_str_mv |
Talidomida Genes Teratogênese Gene ESCO2 Gene SALL4 Gene TBX5 |
topic |
Talidomida Genes Teratogênese Gene ESCO2 Gene SALL4 Gene TBX5 |
description |
Thalidomide is widely used for several diseases; however, it causes malformations in embryos exposed during pregnancy. The complete understanding of the mechanisms by which thalidomide afects the embryo development has not yet been obtained. The phenotypic similarity makes TE a phenocopy of syndromes caused by mutations in ESCO2, SALL4 and TBX5 genes. Recently, SALL4 and TBX5 were demonstrated to be thalidomide targets. To understand if these genes act in the TE development, we sequenced them in 27 individuals with TE; we verifed how thalidomide afect them in human pluripotent stem cells (hPSCs) through a diferential gene expression (DGE) analysis from GSE63935; and we evaluated how these genes are functionally related through an interaction network analysis. We identifed 8 variants in ESCO2, 15 in SALL4 and 15 in TBX5. We compared allelic frequencies with data from ExAC, 1000 Genomes and ABraOM databases; eight variants were signifcantly diferent (p<0.05). Eleven variants in SALL4 and TBX5 were previously associated with cardiac diseases or malformations; however, in TE sample there was no association. Variant efect prediction tools showed 97% of the variants with potential to infuence in these genes regulation. DGE analysis showed a signifcant reduction of ESCO2 in hPSCs after thalidomide exposure. |
publishDate |
2019 |
dc.date.issued.fl_str_mv |
2019 |
dc.date.accessioned.fl_str_mv |
2020-01-15T04:16:23Z |
dc.type.driver.fl_str_mv |
Estrangeiro info:eu-repo/semantics/article |
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info:eu-repo/semantics/publishedVersion |
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http://hdl.handle.net/10183/204323 |
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2045-2322 |
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001103836 |
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http://hdl.handle.net/10183/204323 |
dc.language.iso.fl_str_mv |
eng |
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dc.relation.ispartof.pt_BR.fl_str_mv |
Scientific reports. London. Vol. 9, no. 1 (Aug. 2019), 11413, 11 p. |
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info:eu-repo/semantics/openAccess |
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openAccess |
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