Title: Integrative functional genomic analysis of intron retention in human and mouse brain with Alzheimer's disease.

Authors: Li, Hong-Dong; Funk, Cory C; McFarland, Karen; Dammer, Eric B; Allen, Mariet; Carrasquillo, Minerva M; Levites, Yona; Chakrabarty, Paramita; Burgess, Jeremy D; Wang, Xue; Dickson, Dennis; Seyfried, Nicholas T; Duong, Duc M; Lah, James J; Younkin, Steven G; Levey, Allan I; Omenn, Gilbert S; Ertekin-Taner, Nilüfer; Golde, Todd E; Price, Nathan D

Published In Alzheimers Dement, (2021 Jun)

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.

PubMed ID: 33480174

MeSH Terms: No MeSH terms associated with this publication