dc.creator | Chen, Zhongbo | es |
dc.creator | Zhang, David | es |
dc.creator | Reynolds, Regina H. | es |
dc.creator | Labrador-Espinosa, Miguel Á. | es |
dc.creator | Periñán Tocino, María Teresa | es |
dc.creator | Mir Rivera, Pablo | es |
dc.creator | Ryten, Mina | es |
dc.date.accessioned | 2022-11-03T15:14:07Z | |
dc.date.available | 2022-11-03T15:14:07Z | |
dc.date.issued | 2021-04-06 | |
dc.identifier.citation | Chen, Z., Zhang, D., Reynolds, R.H., Labrador-Espinosa, M.Á., Periñán Tocino, M.T., Mir Rivera, P. y Ryten, M. (2021). Human-lineage-specific genomic elements are associated with neurodegenerative disease and APOE transcript usage. Nature Communications, 12 (1), 2076. https://doi.org/10.1038/s41467-021-22262-5. | |
dc.identifier.issn | 2041-1723 | es |
dc.identifier.uri | https://hdl.handle.net/11441/138676 | |
dc.description.abstract | Knowledge of genomic features specific to the human lineage may provide insights into brain-related diseases. We leverage high-depth whole genome sequencing data to generate a combined annotation identifying regions simultaneously depleted for genetic variation (constrained regions) and poorly conserved across primates. We propose that these constrained, non-conserved regions (CNCRs) have been subject to human-specific purifying selection and are enriched for brain-specific elements. We find that CNCRs are depleted from protein-coding genes but enriched within lncRNAs. We demonstrate that per-SNP heritability of a range of brain-relevant phenotypes are enriched within CNCRs. We find that genes implicated in neurological diseases have high CNCR density, including APOE, highlighting an unannotated intron-3 retention event. Using human brain RNA-sequencing data, we show the intron-3-retaining transcript to be more abundant in Alzheimer’s disease with more severe tau and amyloid pathological burden. Thus, we demonstrate potential association of human-lineage-specific sequences in brain development and neurological disease. | es |
dc.format | application/pdf | es |
dc.format.extent | 13 p. | es |
dc.language.iso | eng | es |
dc.publisher | Nature Research | es |
dc.relation.ispartof | Nature Communications, 12 (1), 2076. | |
dc.rights | Atribución 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | Human-lineage-specific | es |
dc.subject | Genomic elements | es |
dc.subject | Neurodegenerative disease | es |
dc.subject | APOE transcript usage | es |
dc.title | Human-lineage-specific genomic elements are associated with neurodegenerative disease and APOE transcript usage | es |
dc.type | info:eu-repo/semantics/article | es |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Medicina | es |
dc.relation.publisherversion | https://www.nature.com/articles/s41467-021-22262-5 | es |
dc.identifier.doi | 10.1038/s41467-021-22262-5 | es |
dc.journaltitle | Nature Communications | es |
dc.publication.volumen | 12 | es |
dc.publication.issue | 1 | es |
dc.publication.initialPage | 2076 | es |