Matches in SemOpenAlex for { <https://semopenalex.org/work/W3033905089> ?p ?o ?g. }
- W3033905089 abstract "Rationale: Mitral valve prolapse (MVP) is a common valve disease that leads to mitral insufficiency, heart failure and sudden death. The identification of risk loci provided insight into its genetic architecture, although the causal variants and target genes need to be fully characterized. Objective: To establish the chromatin accessibility profiles and gene regulation specificities of human mitral valve and identify functional variants and target genes at MVP loci. Methods and Results: We mapped the open chromatin accessible regions in nuclei from 11 human mitral valves by an assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-Seq). Compared to the heart tissue and cardiac fibroblasts, we found that mitral valve-specific ATAC-Seq peaks were enriched near genes involved in extracellular matrix organization, chondrocyte differentiation, and connective tissue development. The most enriched motif in mitral valve-specific open chromatin peaks was for the nuclear factor of activated T cells (NFATC) family of transcription factors, involved in valve endocardial and interstitial cells formation. We also found that MVP-associated variants (p < 10-5) observed in the current MVP GWAS were significantly enriched (p<0.05) in mitral valve open chromatin peaks. Integration of the ATAC-Seq data with GWAS loci, extensive functional annotation, and gene reporter assay revealed plausible causal variants at two risk loci: rs6723013 at the IGFBP5/TNS1 locus and rs2641440 at the SMG6/SRR locus. Circular chromosome conformation capture followed by high-throughput sequencing provided evidence for several target genes, including SRR, HIC1, and DPH1 at the SMG6/SRR locus and further supported TNS1 as the most likely target gene on Chr2. Conclusions: Here we describe unprecedented genome-wide open chromatin profiles from human mitral valves that indicates specific gene regulation profiles, compared to the heart. We also report in vitro functional evidence for potential causal variants and target genes at MVP risk loci involving established and new biological mechanisms relevant to mitral valve disease." @default.
- W3033905089 created "2020-06-12" @default.
- W3033905089 creator A5004968672 @default.
- W3033905089 creator A5011729525 @default.
- W3033905089 creator A5013120513 @default.
- W3033905089 creator A5021039269 @default.
- W3033905089 creator A5028184651 @default.
- W3033905089 creator A5028260570 @default.
- W3033905089 creator A5028555797 @default.
- W3033905089 creator A5030107100 @default.
- W3033905089 creator A5031060731 @default.
- W3033905089 creator A5064095357 @default.
- W3033905089 creator A5083966673 @default.
- W3033905089 creator A5091433297 @default.
- W3033905089 date "2020-06-05" @default.
- W3033905089 modified "2023-10-03" @default.
- W3033905089 title "Characterization of genomic regulation profiles in human mitral valve whole tissue to annotate genetic risk loci for mitral valve prolapse" @default.
- W3033905089 cites W1531821806 @default.
- W3033905089 cites W1754892555 @default.
- W3033905089 cites W19217443 @default.
- W3033905089 cites W1969353942 @default.
- W3033905089 cites W1978684697 @default.
- W3033905089 cites W1982382856 @default.
- W3033905089 cites W1984054398 @default.
- W3033905089 cites W1991149014 @default.
- W3033905089 cites W2002254633 @default.
- W3033905089 cites W2005435367 @default.
- W3033905089 cites W2025389038 @default.
- W3033905089 cites W2035618305 @default.
- W3033905089 cites W2054184296 @default.
- W3033905089 cites W2076550209 @default.
- W3033905089 cites W2082392154 @default.
- W3033905089 cites W2098651180 @default.
- W3033905089 cites W2099327671 @default.
- W3033905089 cites W2099627334 @default.
- W3033905089 cites W2100566978 @default.
- W3033905089 cites W2112848098 @default.
- W3033905089 cites W2118953216 @default.
- W3033905089 cites W2126551936 @default.
- W3033905089 cites W2141298377 @default.
- W3033905089 cites W2141820415 @default.
- W3033905089 cites W2152885121 @default.
- W3033905089 cites W2155826575 @default.
- W3033905089 cites W2157780291 @default.
- W3033905089 cites W2157952888 @default.
- W3033905089 cites W2169451257 @default.
- W3033905089 cites W2266573952 @default.
- W3033905089 cites W2314625636 @default.
- W3033905089 cites W2334656801 @default.
- W3033905089 cites W2341651781 @default.
- W3033905089 cites W2439189013 @default.
- W3033905089 cites W2510973425 @default.
- W3033905089 cites W2604500500 @default.
- W3033905089 cites W2606675097 @default.
- W3033905089 cites W2750416916 @default.
- W3033905089 cites W2753167114 @default.
- W3033905089 cites W2770704374 @default.
- W3033905089 cites W2788090496 @default.
- W3033905089 cites W2886367104 @default.
- W3033905089 cites W2899606542 @default.
- W3033905089 cites W2900562943 @default.
- W3033905089 cites W2914465181 @default.
- W3033905089 cites W2915083598 @default.
- W3033905089 cites W2917207851 @default.
- W3033905089 cites W2921923541 @default.
- W3033905089 cites W2945038365 @default.
- W3033905089 cites W2952706635 @default.
- W3033905089 cites W2953622121 @default.
- W3033905089 cites W3002539048 @default.
- W3033905089 cites W3007967893 @default.
- W3033905089 doi "https://doi.org/10.1101/2020.06.04.20122010" @default.
- W3033905089 hasPublicationYear "2020" @default.
- W3033905089 type Work @default.
- W3033905089 sameAs 3033905089 @default.
- W3033905089 citedByCount "2" @default.
- W3033905089 countsByYear W30339050892020 @default.
- W3033905089 countsByYear W30339050892022 @default.
- W3033905089 crossrefType "posted-content" @default.
- W3033905089 hasAuthorship W3033905089A5004968672 @default.
- W3033905089 hasAuthorship W3033905089A5011729525 @default.
- W3033905089 hasAuthorship W3033905089A5013120513 @default.
- W3033905089 hasAuthorship W3033905089A5021039269 @default.
- W3033905089 hasAuthorship W3033905089A5028184651 @default.
- W3033905089 hasAuthorship W3033905089A5028260570 @default.
- W3033905089 hasAuthorship W3033905089A5028555797 @default.
- W3033905089 hasAuthorship W3033905089A5030107100 @default.
- W3033905089 hasAuthorship W3033905089A5031060731 @default.
- W3033905089 hasAuthorship W3033905089A5064095357 @default.
- W3033905089 hasAuthorship W3033905089A5083966673 @default.
- W3033905089 hasAuthorship W3033905089A5091433297 @default.
- W3033905089 hasBestOaLocation W30339050891 @default.
- W3033905089 hasConcept C104317684 @default.
- W3033905089 hasConcept C106208931 @default.
- W3033905089 hasConcept C111936080 @default.
- W3033905089 hasConcept C126322002 @default.
- W3033905089 hasConcept C135763542 @default.
- W3033905089 hasConcept C153209595 @default.
- W3033905089 hasConcept C2777543888 @default.
- W3033905089 hasConcept C2781030672 @default.
- W3033905089 hasConcept C54355233 @default.