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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Autores principales:	Yijie He, Lin Huang, Yaqin Tang, Zeyuan Yang, Zhijie Han
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	multiple sclerosis alternative splicing RNA-seq splicing quantitative trait loci function analysis Genetics QH426-470
Acceso en línea:	https://doaj.org/article/fbe5d17d32d74d4a89b8c0f8660207de
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spelling	oai:doaj.org-article:fbe5d17d32d74d4a89b8c0f8660207de2021-11-12T05:32:04ZGenome-wide Identification and Analysis of Splicing QTLs in Multiple Sclerosis by RNA-Seq Data1664-802110.3389/fgene.2021.769804https://doaj.org/article/fbe5d17d32d74d4a89b8c0f8660207de2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fgene.2021.769804/fullhttps://doaj.org/toc/1664-8021Multiple 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.Yijie HeLin HuangYaqin TangZeyuan YangZhijie HanFrontiers Media S.A.articlemultiple sclerosisalternative splicingRNA-seqsplicing quantitative trait locifunction analysisGeneticsQH426-470ENFrontiers in Genetics, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	multiple sclerosis alternative splicing RNA-seq splicing quantitative trait loci function analysis Genetics QH426-470
spellingShingle	multiple sclerosis alternative splicing RNA-seq splicing quantitative trait loci function analysis Genetics QH426-470 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
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.
format	article
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
title	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_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_sort	genome-wide identification and analysis of splicing qtls in multiple sclerosis by rna-seq data
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/fbe5d17d32d74d4a89b8c0f8660207de
work_keys_str_mv	AT yijiehe genomewideidentificationandanalysisofsplicingqtlsinmultiplesclerosisbyrnaseqdata AT linhuang genomewideidentificationandanalysisofsplicingqtlsinmultiplesclerosisbyrnaseqdata AT yaqintang genomewideidentificationandanalysisofsplicingqtlsinmultiplesclerosisbyrnaseqdata AT zeyuanyang genomewideidentificationandanalysisofsplicingqtlsinmultiplesclerosisbyrnaseqdata AT zhijiehan genomewideidentificationandanalysisofsplicingqtlsinmultiplesclerosisbyrnaseqdata
_version_	1718431207252819968

Genome-wide Identification and Analysis of Splicing QTLs in Multiple Sclerosis by RNA-Seq Data

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