Utilize este identificador para referenciar este registo:
https://hdl.handle.net/1822/57785
Título: | Identification of rare de novo epigenetic variations in congenital disorders |
Autor(es): | Barbosa, Mafalda Joshi, Ricky S. Garg, Paras Martin-Trujillo, Alejandro Patel, Nihir Jadhav, Bharati Watson, Corey T. Gibson, William Chetnik, Kelsey Tessereau, Chloe Mei, Hui De Rubeis, Silvia Reichert, Jennifer Lopes, Fátima Daniela Teixeira Vissers, Lisenka E. L. M. Kleefstra, Tjitske Grice, Dorothy E. Edelmann, Lisa Soares, Gabriela Maciel, P. Brunner, Han G. Buxbaum, Joseph D. Gelb, Bruce D. Sharp, Andrew J. |
Palavras-chave: | Adolescent Adult Case-Control Studies Child Child, Preschool Cohort Studies Congenital Abnormalities DNA Methylation Datasets as Topic Epigenomics Genome, Human Humans Infant Infant, Newborn Loss of Function Mutation Male Middle Aged Neurodevelopmental Disorders Sequence Analysis, DNA Sequence Analysis, RNA Young Adult Epigenesis, Genetic |
Data: | 2018 |
Editora: | Nature Research |
Revista: | Nature Communications |
Resumo(s): | Certain human traits such as neurodevelopmental disorders (NDs) and congenital anomalies (CAs) are believed to be primarily genetic in origin. However, even after whole-genome sequencing (WGS), a substantial fraction of such disorders remain unexplained. We hypothesize that some cases of ND-CA are caused by aberrant DNA methylation leading to dysregulated genome function. Comparing DNA methylation profiles from 489 individuals with ND-CAs against 1534 controls, we identify epivariations as a frequent occurrence in the human genome. De novo epivariations are significantly enriched in cases, while RNAseq analysis shows that epivariations often have an impact on gene expression comparable to loss-of-function mutations. Additionally, we detect and replicate an enrichment of rare sequence mutations overlapping CTCF binding sites close to epivariations, providing a rationale for interpreting non-coding variation. We propose that epivariations contribute to the pathogenesis of some patients with unexplained ND-CAs, and as such likely have diagnostic relevance. |
Tipo: | Artigo |
URI: | https://hdl.handle.net/1822/57785 |
DOI: | 10.1038/s41467-018-04540-x |
ISSN: | 2041-1723 |
Arbitragem científica: | yes |
Acesso: | Acesso aberto |
Aparece nas coleções: | ICVS - Artigos em revistas internacionais / Papers in international journals |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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Barbosa_etal_2018_epimutations.pdf | 2,57 MB | Adobe PDF | Ver/Abrir |