Alternative Splicing Regulation of an Alzheimer’s Risk Variant in CLU
Clusterin (<i>CLU</i>) is one of the risk genes most associated with late onset Alzheimer’s disease (AD), and several genetic variants in <i>CLU</i> are associated with AD risk. However, the functional role of known AD risk genetic variants in <i>CLU</i> has been...
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MDPI AG
2020-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/19/7079 |
| _version_ | 1797552529331978240 |
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| author | Seonggyun Han Kwangsik Nho Younghee Lee |
| author_facet | Seonggyun Han Kwangsik Nho Younghee Lee |
| author_sort | Seonggyun Han |
| collection | DOAJ |
| description | Clusterin (<i>CLU</i>) is one of the risk genes most associated with late onset Alzheimer’s disease (AD), and several genetic variants in <i>CLU</i> are associated with AD risk. However, the functional role of known AD risk genetic variants in <i>CLU</i> has been little explored. We investigated the effect of an AD risk variant (rs7982) in the 5th exon of <i>CLU</i> on alternative splicing by using an integrative approach of brain-tissue-based RNA-Seq and whole genome sequencing data from Accelerating Medicines Partnership—Alzheimer’s Disease (AMP-AD). RNA-Seq data were generated from three regions in the temporal lobe of the brain—the temporal cortex, superior temporal gyrus, and parahippocampal gyrus. The rs7982 was significantly associated with intron retention (IR) of the 5th exon of <i>CLU</i>; as the number of alternative alleles (<i>G</i>) increased, the IR rates decreased more significantly in females than in males. Our results suggest a sex-dependent role of rs7982 in AD pathogenesis via splicing regulation. |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T16:02:23Z |
| publishDate | 2020-09-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-0e2f109e3acc4f7daed1065f90fdce1a2023-11-20T15:07:28ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-09-012119707910.3390/ijms21197079Alternative Splicing Regulation of an Alzheimer’s Risk Variant in CLUSeonggyun Han0Kwangsik Nho1Younghee Lee2Department of Biomedical Informatics, University of Utah School of Medicine, Salt Lake City, UT 84108, USADepartment of Radiology and Imaging Sciences and Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, IN 46202, USADepartment of Biomedical Informatics, University of Utah School of Medicine, Salt Lake City, UT 84108, USAClusterin (<i>CLU</i>) is one of the risk genes most associated with late onset Alzheimer’s disease (AD), and several genetic variants in <i>CLU</i> are associated with AD risk. However, the functional role of known AD risk genetic variants in <i>CLU</i> has been little explored. We investigated the effect of an AD risk variant (rs7982) in the 5th exon of <i>CLU</i> on alternative splicing by using an integrative approach of brain-tissue-based RNA-Seq and whole genome sequencing data from Accelerating Medicines Partnership—Alzheimer’s Disease (AMP-AD). RNA-Seq data were generated from three regions in the temporal lobe of the brain—the temporal cortex, superior temporal gyrus, and parahippocampal gyrus. The rs7982 was significantly associated with intron retention (IR) of the 5th exon of <i>CLU</i>; as the number of alternative alleles (<i>G</i>) increased, the IR rates decreased more significantly in females than in males. Our results suggest a sex-dependent role of rs7982 in AD pathogenesis via splicing regulation.https://www.mdpi.com/1422-0067/21/19/7079<i>CLU</i>Alzheimer’s diseasealternative splicingsQTLs |
| spellingShingle | Seonggyun Han Kwangsik Nho Younghee Lee Alternative Splicing Regulation of an Alzheimer’s Risk Variant in CLU International Journal of Molecular Sciences <i>CLU</i> Alzheimer’s disease alternative splicing sQTLs |
| title | Alternative Splicing Regulation of an Alzheimer’s Risk Variant in CLU |
| title_full | Alternative Splicing Regulation of an Alzheimer’s Risk Variant in CLU |
| title_fullStr | Alternative Splicing Regulation of an Alzheimer’s Risk Variant in CLU |
| title_full_unstemmed | Alternative Splicing Regulation of an Alzheimer’s Risk Variant in CLU |
| title_short | Alternative Splicing Regulation of an Alzheimer’s Risk Variant in CLU |
| title_sort | alternative splicing regulation of an alzheimer s risk variant in clu |
| topic | <i>CLU</i> Alzheimer’s disease alternative splicing sQTLs |
| url | https://www.mdpi.com/1422-0067/21/19/7079 |
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