Genome-wide Identification and Analysis of Splicing QTLs in Multiple Sclerosis by RNA-Seq Data
Multiple sclerosis (MS) is an autoimmune disease characterized by inflammatory demyelinating lesions in the central nervous system. Recently, the dysregulation of alternative splicing (AS) in the brain has been found to significantly influence the progression of MS. Moreover, previous studies demons...
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| Format: | Article |
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Frontiers Media S.A.
2021-11-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2021.769804/full |
| _version_ | 1830411580959883264 |
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| author | Yijie He Lin Huang Yaqin Tang Zeyuan Yang Zhijie Han |
| author_facet | Yijie He Lin Huang Yaqin Tang Zeyuan Yang Zhijie Han |
| author_sort | Yijie He |
| collection | DOAJ |
| description | Multiple sclerosis (MS) is an autoimmune disease characterized by inflammatory demyelinating lesions in the central nervous system. Recently, the dysregulation of alternative splicing (AS) in the brain has been found to significantly influence the progression of MS. Moreover, previous studies demonstrate that many MS-related variants in the genome act as the important regulation factors of AS events and contribute to the pathogenesis of MS. However, by far, no genome-wide research about the effect of genomic variants on AS events in MS has been reported. Here, we first implemented a strategy to obtain genomic variant genotype and AS isoform average percentage spliced-in values from RNA-seq data of 142 individuals (51 MS patients and 91 controls). Then, combing the two sets of data, we performed a cis-splicing quantitative trait loci (sQTLs) analysis to identify the cis-acting loci and the affected differential AS events in MS and further explored the characteristics of these cis-sQTLs. Finally, the weighted gene coexpression network and gene set enrichment analyses were used to investigate gene interaction pattern and functions of the affected AS events in MS. In total, we identified 5835 variants affecting 672 differential AS events. The cis-sQTLs tend to be distributed in proximity of the gene transcription initiation site, and the intronic variants of them are more capable of regulating AS events. The retained intron AS events are more susceptible to influence of genome variants, and their functions are involved in protein kinase and phosphorylation modification. In summary, these findings provide an insight into the mechanism of MS. |
| first_indexed | 2024-12-20T19:52:21Z |
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| id | doaj.art-fbe5d17d32d74d4a89b8c0f8660207de |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-20T19:52:21Z |
| publishDate | 2021-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-fbe5d17d32d74d4a89b8c0f8660207de2022-12-21T19:28:17ZengFrontiers Media S.A.Frontiers in Genetics1664-80212021-11-011210.3389/fgene.2021.769804769804Genome-wide Identification and Analysis of Splicing QTLs in Multiple Sclerosis by RNA-Seq DataYijie HeLin HuangYaqin TangZeyuan YangZhijie HanMultiple sclerosis (MS) is an autoimmune disease characterized by inflammatory demyelinating lesions in the central nervous system. Recently, the dysregulation of alternative splicing (AS) in the brain has been found to significantly influence the progression of MS. Moreover, previous studies demonstrate that many MS-related variants in the genome act as the important regulation factors of AS events and contribute to the pathogenesis of MS. However, by far, no genome-wide research about the effect of genomic variants on AS events in MS has been reported. Here, we first implemented a strategy to obtain genomic variant genotype and AS isoform average percentage spliced-in values from RNA-seq data of 142 individuals (51 MS patients and 91 controls). Then, combing the two sets of data, we performed a cis-splicing quantitative trait loci (sQTLs) analysis to identify the cis-acting loci and the affected differential AS events in MS and further explored the characteristics of these cis-sQTLs. Finally, the weighted gene coexpression network and gene set enrichment analyses were used to investigate gene interaction pattern and functions of the affected AS events in MS. In total, we identified 5835 variants affecting 672 differential AS events. The cis-sQTLs tend to be distributed in proximity of the gene transcription initiation site, and the intronic variants of them are more capable of regulating AS events. The retained intron AS events are more susceptible to influence of genome variants, and their functions are involved in protein kinase and phosphorylation modification. In summary, these findings provide an insight into the mechanism of MS.https://www.frontiersin.org/articles/10.3389/fgene.2021.769804/fullmultiple sclerosisalternative splicingRNA-seqsplicing quantitative trait locifunction analysis |
| spellingShingle | Yijie He Lin Huang Yaqin Tang Zeyuan Yang Zhijie Han Genome-wide Identification and Analysis of Splicing QTLs in Multiple Sclerosis by RNA-Seq Data Frontiers in Genetics multiple sclerosis alternative splicing RNA-seq splicing quantitative trait loci function analysis |
| title | Genome-wide Identification and Analysis of Splicing QTLs in Multiple Sclerosis by RNA-Seq Data |
| title_full | Genome-wide Identification and Analysis of Splicing QTLs in Multiple Sclerosis by RNA-Seq Data |
| title_fullStr | Genome-wide Identification and Analysis of Splicing QTLs in Multiple Sclerosis by RNA-Seq Data |
| title_full_unstemmed | Genome-wide Identification and Analysis of Splicing QTLs in Multiple Sclerosis by RNA-Seq Data |
| title_short | Genome-wide Identification and Analysis of Splicing QTLs in Multiple Sclerosis by RNA-Seq Data |
| title_sort | genome wide identification and analysis of splicing qtls in multiple sclerosis by rna seq data |
| topic | multiple sclerosis alternative splicing RNA-seq splicing quantitative trait loci function analysis |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2021.769804/full |
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