Please use this identifier to cite or link to this item: https://hdl.handle.net/20.500.12530/55720
Title: Human-lineage-specific genomic elements are associated with neurodegenerative disease and APOE transcript usage.
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Issue Date: 6-Apr-2021
Citation: Nat Commun.2021;(12)1:2076
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.
PMID: 33824317
URI: https://hdl.handle.net/20.500.12530/55720
Rights: openAccess
Appears in Collections:Fundaciones e Institutos de Investigación > FIIB H. U. Infanta Sofía y H. U. Henares > Artículos

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