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Identification of human genetic variants controlling circular RNA expression
Circular RNAs (circRNAs) are abundant in eukaryotic transcriptomes and have been linked to various human disorders. However, understanding genetic control of circular RNA expression is in the early stages. Here we present the first integrated analysis of circRNAs and genome sequence variation from l...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6859849/ https://www.ncbi.nlm.nih.gov/pubmed/31519742 http://dx.doi.org/10.1261/rna.071654.119 |
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author | Ahmed, Ikhlak Karedath, Thasni Al-Dasim, Fatima M. Malek, Joel A. |
author_facet | Ahmed, Ikhlak Karedath, Thasni Al-Dasim, Fatima M. Malek, Joel A. |
author_sort | Ahmed, Ikhlak |
collection | PubMed |
description | Circular RNAs (circRNAs) are abundant in eukaryotic transcriptomes and have been linked to various human disorders. However, understanding genetic control of circular RNA expression is in the early stages. Here we present the first integrated analysis of circRNAs and genome sequence variation from lymphoblastoid cell lines of the 1000 Genomes Project. We identified thousands of circRNAs in the RNA-seq data and show their association with local single-nucleotide polymorphic sites, referred to as circQTLs, which influence the circRNA transcript abundance. Strikingly, we found that circQTLs exist independently of eQTLs with most circQTLs having no effect on mRNA expression. Only a fraction of the polymorphic sites are shared and linked to both circRNA and mRNA expression with mostly similar effects on circular and linear RNA. A shared intronic QTL, rs55928920, of HMSD gene drives the circular and linear expression in opposite directions, potentially modulating circRNA levels at the expense of mRNA. Finally, circQTLs and eQTLs are largely independent and exist in separate linkage disequilibrium (LD) blocks with circQTLs highly enriched for functional genomic elements and regulatory regions. This study reveals a previously uncharacterized role of DNA sequence variation in human circular RNA regulation. |
format | Online Article Text |
id | pubmed-6859849 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-68598492019-12-04 Identification of human genetic variants controlling circular RNA expression Ahmed, Ikhlak Karedath, Thasni Al-Dasim, Fatima M. Malek, Joel A. RNA Article Circular RNAs (circRNAs) are abundant in eukaryotic transcriptomes and have been linked to various human disorders. However, understanding genetic control of circular RNA expression is in the early stages. Here we present the first integrated analysis of circRNAs and genome sequence variation from lymphoblastoid cell lines of the 1000 Genomes Project. We identified thousands of circRNAs in the RNA-seq data and show their association with local single-nucleotide polymorphic sites, referred to as circQTLs, which influence the circRNA transcript abundance. Strikingly, we found that circQTLs exist independently of eQTLs with most circQTLs having no effect on mRNA expression. Only a fraction of the polymorphic sites are shared and linked to both circRNA and mRNA expression with mostly similar effects on circular and linear RNA. A shared intronic QTL, rs55928920, of HMSD gene drives the circular and linear expression in opposite directions, potentially modulating circRNA levels at the expense of mRNA. Finally, circQTLs and eQTLs are largely independent and exist in separate linkage disequilibrium (LD) blocks with circQTLs highly enriched for functional genomic elements and regulatory regions. This study reveals a previously uncharacterized role of DNA sequence variation in human circular RNA regulation. Cold Spring Harbor Laboratory Press 2019-12 /pmc/articles/PMC6859849/ /pubmed/31519742 http://dx.doi.org/10.1261/rna.071654.119 Text en © 2019 Ahmed et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society http://creativecommons.org/licenses/by/4.0/ This article, published in RNA, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Ahmed, Ikhlak Karedath, Thasni Al-Dasim, Fatima M. Malek, Joel A. Identification of human genetic variants controlling circular RNA expression |
title | Identification of human genetic variants controlling circular RNA expression |
title_full | Identification of human genetic variants controlling circular RNA expression |
title_fullStr | Identification of human genetic variants controlling circular RNA expression |
title_full_unstemmed | Identification of human genetic variants controlling circular RNA expression |
title_short | Identification of human genetic variants controlling circular RNA expression |
title_sort | identification of human genetic variants controlling circular rna expression |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6859849/ https://www.ncbi.nlm.nih.gov/pubmed/31519742 http://dx.doi.org/10.1261/rna.071654.119 |
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