Please use this identifier to cite or link to this item: doi:10.22028/D291-35401
Title: Genomic structural variations lead to dysregulation of important coding and non-coding RNA species in dilated cardiomyopathy
Author(s): Haas, Jan
Mester, Stefan
Lai, Alan
Frese, Karen S.
Sedaghat-Hamedani, Farbod
Kayvanpour, Elham
Rausch, Tobias
Nietsch, Rouven
Boeckel, Jes-Niels
Carstensen, Avisha
Völkers, Mirko
Dietrich, Carsten
Pils, Dietmar
Amr, Ali
Holzer, Daniel B.
Martins Bordalo, Diana
Oehler, Daniel
Weis, Tanja
Mereles, Derliz
Buss, Sebastian
Riechert, Eva
Wirsz, Emil
Wuerstle, Maximilian
Korbel, Jan O.
Keller, Andreas
Katus, Hugo A.
Posch, Andreas E.
Meder, Benjamin
Language: English
Title: EMBO Molecular Medicine
Volume: 10
Issue: 1
Pages: 107-120
Publisher/Platform: EMBOpress
Year of Publication: 2017
Free key words: cardiac transcriptome
dilated cardiomyopathy
expression quantitative trait locus
genomic structural variation
heart failure
DDC notations: 610 Medicine and health
Publikation type: Journal Article
Abstract: The transcriptome needs to be tightly regulated by mechanisms that include transcription factors, enhancers, and repressors as well as non-coding RNAs. Besides this dynamic regulation, a large part of phenotypic variability of eukaryotes is expressed through changes in gene transcription caused by genetic variation. In this study, we evaluate genome-wide structural genomic variants (SVs) and their association with gene expression in the human heart. We detected 3,898 individual SVs affecting all classes of gene transcripts (e.g., mRNA, miRNA, lncRNA) and regulatory genomic regions (e.g., enhancer or TFBS). In a cohort of patients (n = 50) with dilated cardiomyopathy (DCM), 80,635 non-protein-coding elements of the genome are deleted or duplicated by SVs, containing 3,758 long non-coding RNAs and 1,756 protein-coding transcripts. 65.3% of the SV-eQTLs do not harbor a significant SNV-eQTL, and for the regions with both classes of association, we find similar effect sizes. In case of deleted protein-coding exons, we find downregulation of the associated transcripts, duplication events, however, do not show significant changes over all events. In summary, we are first to describe the genomic variability associated with SVs in heart failure due to DCM and dissect their impact on the transcriptome. Overall, SVs explain up to 7.5% of the variation of cardiac gene expression, underlining the importance to study human myocardial gene expression in the context of the individual genome. This has immediate implications for studies on basic mechanisms of cardiac maladaptation, biomarkers, and (gene) therapeutic studies alike.
DOI of the first publication: 10.15252/emmm.201707838
Link to this record: urn:nbn:de:bsz:291--ds-354011
ISSN: 1757-4684
Date of registration: 4-Feb-2022
Description of the related object: Supplementary Information
Related object:
Faculty: M - Medizinische Fakultät
Department: M - Medizinische Biometrie, Epidemiologie und medizinische Informatik
Professorship: M - Univ.-Prof. Dr. Andreas Keller
Collections:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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