The role of ESCO2, SALL4 and TBX5 genes in the susceptibility to thalidomide teratogenesis
Abstract 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 affects the embryo development has not yet been obtained. The phenotypic similarity makes TE a phenocopy o...
Guardado en:
| Autores principales: | , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Nature Portfolio
2019
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/47bc5eea5a014c35bbd8994693675834 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:47bc5eea5a014c35bbd8994693675834 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:47bc5eea5a014c35bbd89946936758342021-12-02T15:07:54ZThe role of ESCO2, SALL4 and TBX5 genes in the susceptibility to thalidomide teratogenesis10.1038/s41598-019-47739-82045-2322https://doaj.org/article/47bc5eea5a014c35bbd89946936758342019-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-47739-8https://doaj.org/toc/2045-2322Abstract 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 affects 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 verified how thalidomide affect them in human pluripotent stem cells (hPSCs) through a differential gene expression (DGE) analysis from GSE63935; and we evaluated how these genes are functionally related through an interaction network analysis. We identified 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 significantly different (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 effect prediction tools showed 97% of the variants with potential to influence in these genes regulation. DGE analysis showed a significant reduction of ESCO2 in hPSCs after thalidomide exposure.Julia do Amaral GomesThayne Woycinck KowalskiLucas Rosa FragaGabriel S. MacedoMaria Teresa Vieira SanseverinoLavínia Schuler-FacciniFernanda Sales Luiz ViannaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-11 (2019) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Julia do Amaral Gomes Thayne Woycinck Kowalski Lucas Rosa Fraga Gabriel S. Macedo Maria Teresa Vieira Sanseverino Lavínia Schuler-Faccini Fernanda Sales Luiz Vianna The role of ESCO2, SALL4 and TBX5 genes in the susceptibility to thalidomide teratogenesis |
| description |
Abstract 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 affects 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 verified how thalidomide affect them in human pluripotent stem cells (hPSCs) through a differential gene expression (DGE) analysis from GSE63935; and we evaluated how these genes are functionally related through an interaction network analysis. We identified 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 significantly different (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 effect prediction tools showed 97% of the variants with potential to influence in these genes regulation. DGE analysis showed a significant reduction of ESCO2 in hPSCs after thalidomide exposure. |
| format |
article |
| author |
Julia do Amaral Gomes Thayne Woycinck Kowalski Lucas Rosa Fraga Gabriel S. Macedo Maria Teresa Vieira Sanseverino Lavínia Schuler-Faccini Fernanda Sales Luiz Vianna |
| author_facet |
Julia do Amaral Gomes Thayne Woycinck Kowalski Lucas Rosa Fraga Gabriel S. Macedo Maria Teresa Vieira Sanseverino Lavínia Schuler-Faccini Fernanda Sales Luiz Vianna |
| author_sort |
Julia do Amaral Gomes |
| title |
The role of ESCO2, SALL4 and TBX5 genes in the susceptibility to thalidomide teratogenesis |
| 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 |
role of esco2, sall4 and tbx5 genes in the susceptibility to thalidomide teratogenesis |
| publisher |
Nature Portfolio |
| publishDate |
2019 |
| url |
https://doaj.org/article/47bc5eea5a014c35bbd8994693675834 |
| work_keys_str_mv |
AT juliadoamaralgomes theroleofesco2sall4andtbx5genesinthesusceptibilitytothalidomideteratogenesis AT thaynewoycinckkowalski theroleofesco2sall4andtbx5genesinthesusceptibilitytothalidomideteratogenesis AT lucasrosafraga theroleofesco2sall4andtbx5genesinthesusceptibilitytothalidomideteratogenesis AT gabrielsmacedo theroleofesco2sall4andtbx5genesinthesusceptibilitytothalidomideteratogenesis AT mariateresavieirasanseverino theroleofesco2sall4andtbx5genesinthesusceptibilitytothalidomideteratogenesis AT laviniaschulerfaccini theroleofesco2sall4andtbx5genesinthesusceptibilitytothalidomideteratogenesis AT fernandasalesluizvianna theroleofesco2sall4andtbx5genesinthesusceptibilitytothalidomideteratogenesis AT juliadoamaralgomes roleofesco2sall4andtbx5genesinthesusceptibilitytothalidomideteratogenesis AT thaynewoycinckkowalski roleofesco2sall4andtbx5genesinthesusceptibilitytothalidomideteratogenesis AT lucasrosafraga roleofesco2sall4andtbx5genesinthesusceptibilitytothalidomideteratogenesis AT gabrielsmacedo roleofesco2sall4andtbx5genesinthesusceptibilitytothalidomideteratogenesis AT mariateresavieirasanseverino roleofesco2sall4andtbx5genesinthesusceptibilitytothalidomideteratogenesis AT laviniaschulerfaccini roleofesco2sall4andtbx5genesinthesusceptibilitytothalidomideteratogenesis AT fernandasalesluizvianna roleofesco2sall4andtbx5genesinthesusceptibilitytothalidomideteratogenesis |
| _version_ |
1718388311231299584 |