Integrative functional genomic analysis of intron retention in human and mouse brain with Alzheimer's disease.
Alzheimers Dement
; 17(6): 984-1004, 2021 06.
Article
em En
| MEDLINE
| ID: mdl-33480174
ABSTRACT
Intron retention (IR) has been implicated in the pathogenesis of complex diseases such as cancers; its association with Alzheimer's disease (AD) remains unexplored. We performed genome-wide analysis of IR through integrating genetic, transcriptomic, and proteomic data of AD subjects and mouse models from the Accelerating Medicines Partnership-Alzheimer's Disease project. We identified 4535 and 4086 IR events in 2173 human and 1736 mouse genes, respectively. Quantitation of IR enabled the identification of differentially expressed genes that conventional exon-level approaches did not reveal. There were significant correlations of intron expression within innate immune genes, like HMBOX1, with AD in humans. Peptides with a high probability of translation from intron-retained mRNAs were identified using mass spectrometry. Further, we established AD-specific intron expression Quantitative Trait Loci, and identified splicing-related genes that may regulate IR. Our analysis provides a novel resource for the search for new AD biomarkers and pathological mechanisms.
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Base de dados:
MEDLINE
Assunto principal:
Autopsia
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Encéfalo
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Íntrons
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Genômica
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Modelos Animais de Doenças
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Doença de Alzheimer
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article