{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Cocera-Ortega L"],"funding":["DCVA ARENA-PRIME Young Talent program","Netherlands Organisation for Health Research and Development"],"pagination":["4053"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9000197"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["23(7)"],"pubmed_abstract":["Long-QT syndrome type 1 (LQT1) is caused by mutations in <i>KCNQ1</i>. Patients heterozygous for such a mutation co-assemble both mutant and wild-type <i>KCNQ1</i>-encoded subunits into tetrameric Kv7.1 potassium channels. Here, we investigated whether allele-specific inhibition of mutant <i>KCNQ1</i> by targeting a common variant can shift the balance towards increased incorporation of the wild-type allele to alleviate the disease in human-induced pluripotent stem-cell-derived cardiomyocytes (hiPSC-CMs). We identified the single nucleotide polymorphisms (SNP) rs1057128 (G/A) in <i>KCNQ1</i>, with a heterozygosity of 27% in the European population. Next, we determined allele-specificity of short-hairpin RNAs (shRNAs) targeting either allele of this SNP in hiPSC-CMs that carry an LQT1 mutat"],"journal":["International journal of molecular sciences"],"pubmed_title":["shRNAs Targeting a Common <i>KCNQ1</i> Variant Could Alleviate Long-QT1 Disease Severity by Inhibiting a Mutant Allele."],"pmcid":["PMC9000197"],"funding_grant_id":["VENI 91616150","-"],"pubmed_authors":["Tijsen AJ","de Vries DK","Gepstein L","Pinto YM","Kamps SC","Verkerk AO","Huber I","Wilders R","Cocera-Ortega L","van den Bout A","Fabrizi B","van der Made I"],"additional_accession":[]},"is_claimable":false,"name":"shRNAs Targeting a Common <i>KCNQ1</i> Variant Could Alleviate Long-QT1 Disease Severity by Inhibiting a Mutant Allele.","description":"Long-QT syndrome type 1 (LQT1) is caused by mutations in <i>KCNQ1</i>. Patients heterozygous for such a mutation co-assemble both mutant and wild-type <i>KCNQ1</i>-encoded subunits into tetrameric Kv7.1 potassium channels. Here, we investigated whether allele-specific inhibition of mutant <i>KCNQ1</i> by targeting a common variant can shift the balance towards increased incorporation of the wild-type allele to alleviate the disease in human-induced pluripotent stem-cell-derived cardiomyocytes (hiPSC-CMs). We identified the single nucleotide polymorphisms (SNP) rs1057128 (G/A) in <i>KCNQ1</i>, with a heterozygosity of 27% in the European population. Next, we determined allele-specificity of short-hairpin RNAs (shRNAs) targeting either allele of this SNP in hiPSC-CMs that carry an LQT1 mutat","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Apr","modification":"2026-04-08T10:36:04.853Z","creation":"2025-02-19T01:10:59.497Z"},"accession":"S-EPMC9000197","cross_references":{"pubmed":["35409410"],"doi":["10.3390/ijms23074053"]}}