Alternative splicing regulation of low-frequency genetic variants in exon 2 of trem2 in alzheimer’s disease by splicing-based aggregation
DC Field | Value | Language |
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dc.contributor.author | Han, Seonggyun | - |
dc.contributor.author | Na, Yirang | - |
dc.contributor.author | Koh, Insong | - |
dc.contributor.author | Nho, Kwangsik | - |
dc.contributor.author | Lee, Younghee | - |
dc.date.accessioned | 2022-07-06T13:21:40Z | - |
dc.date.available | 2022-07-06T13:21:40Z | - |
dc.date.created | 2021-11-22 | - |
dc.date.issued | 2021-09 | - |
dc.identifier.issn | 1661-6596 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/141022 | - |
dc.description.abstract | TREM2 is among the most well-known Alzheimer’s disease (AD) risk genes; however, the functional roles of its AD-associated variants remain to be elucidated, and most known risk alleles are low-frequency variants whose investigation is challenging. Here, we utilized a splicing-guided aggregation method in which multiple low-frequency TREM2 variants were bundled together to investigate the functional impact of those variants on alternative splicing in AD. We analyzed whole genome sequencing (WGS) and RNA-seq data generated from cognitively normal elderly controls (CN) and AD patients in two independent cohorts, representing three regions in the frontal lobe of the human brain: the dorsolateral prefrontal cortex (CN = 213 and AD = 376), frontal pole (CN = 72 and AD = 175), and inferior frontal (CN = 63 and AD = 157). We observed an exon skipping event in the second exon of TREM2, with that exon tending to be more frequently skipped (p = 0.0012) in individuals having at least one low-frequency variant that caused loss-of-function for a splicing regulatory element. In addition, genes differentially expressed between AD patients with high vs. low skipping of the second exon (i.e., loss of a TREM2 functional domain) were significantly enriched in immune-related pathways. Our splicing-guided aggregation method thus provides new insight into the regulation of alternative splicing of the second exon of TREM2 by low-frequency variants and could be a useful tool for further exploring the potential molecular mechanisms of multiple, disease-associated, low-frequency variants. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | MDPI | - |
dc.title | Alternative splicing regulation of low-frequency genetic variants in exon 2 of trem2 in alzheimer’s disease by splicing-based aggregation | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Koh, Insong | - |
dc.identifier.doi | 10.3390/ijms22189865 | - |
dc.identifier.scopusid | 2-s2.0-85114668573 | - |
dc.identifier.wosid | 000699871300001 | - |
dc.identifier.bibliographicCitation | International Journal of Molecular Sciences, v.22, no.18, pp.1 - 12 | - |
dc.relation.isPartOf | International Journal of Molecular Sciences | - |
dc.citation.title | International Journal of Molecular Sciences | - |
dc.citation.volume | 22 | - |
dc.citation.number | 18 | - |
dc.citation.startPage | 1 | - |
dc.citation.endPage | 12 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | Y | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Chemistry | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Chemistry, Multidisciplinary | - |
dc.subject.keywordPlus | RARE CODING VARIANTS | - |
dc.subject.keywordPlus | RISK | - |
dc.subject.keywordAuthor | Aggregation of low-frequency variants | - |
dc.subject.keywordAuthor | Alternative splicing | - |
dc.subject.keywordAuthor | Alzheimer’s disease | - |
dc.subject.keywordAuthor | Low-frequency variant | - |
dc.subject.keywordAuthor | TREM2 | - |
dc.identifier.url | https://www.mdpi.com/1422-0067/22/18/9865 | - |
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