ArticlePLoS genetics2017
Positional cloning of quantitative trait nucleotides for blood pressure and cardiac QT-interval by targeted CRISPR/Cas9 editing of a novel long non-coding RNA.
Article in PLoS genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 33 citations in OpenAlex.
- Peptidylarginine deiminase 4 is a differential regulator of salt-sensitive and salt-resistant hypertension.iScience · 2026Article
- Harnessing the power of genomics in hypertension: tip of the iceberg?Cambridge prisms. Precision medicine · 2025Review
- Gene editing of angiotensin for blood pressure management.International journal of cardiology. Cardiovascular risk and prevention · 2024Article
- Genetic Modifications to Alter Blood Pressure Level.Biomedicines · 2022Review
- Recent Advances in the Production of Genome-Edited Rats.International journal of molecular sciences · 2022Review
- CRISPR/Cas9 Mediated Deletion of the Angiotensinogen Gene Reduces Hypertension: A Potential for Cure?Hypertension (Dallas, Tex. : 1979) · 2021Article
- Single Nucleotide Polymorphism ofHypertension (Dallas, Tex. : 1979) · 2020Article
- Rat models of human diseases and related phenotypes: a systematic inventory of the causative genes.Journal of biomedical science · 2020Review
- Long noncoding RNAs as novel players in the pathogenesis of hypertension.Hypertension research : official journal of the Japanese Society of Hypertension · 2020Review
- Modularity/non-cumulativity of quantitative trait loci on blood pressure.Journal of human hypertension · 2020Review
- Genetic predisposition for increased red blood cell distribution width is an early risk factor for cardiovascular and renal comorbidities.Disease models & mechanisms · 2020Article
- Animal Models of Hypertension: A Scientific Statement From the American Heart Association.Hypertension (Dallas, Tex. : 1979) · 2019Review
- QTL mapping of rat blood pressure loci on RNO1 within a homologous region linked to human hypertension on HSA15.PloS one · 2019Article
- Epigenetic Mechanisms and Hypertension.Hypertension (Dallas, Tex. : 1979) · 2018Review
- Article
- Noncoding RNAs in the Regulatory Network of Hypertension.Hypertension (Dallas, Tex. : 1979) · 2018Review
- A Strategy for Identifying Quantitative Trait Genes Using Gene Expression Analysis and Causal Analysis.Genes · 2017Review
- Towards Precision Medicine for Hypertension: A Review of Genomic, Epigenomic, and Microbiomic Effects on Blood Pressure in Experimental Rat Models and Humans.Physiological reviews · 2017Review
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Multiple GWAS studies have reported strong association of cardiac QT-interval to a region on HSA17. Interestingly, a rat locus homologous to this region is also linked to QT-intervals. The high resolution positional mapping study located the rat QT-interval locus to a <42.5kb region on RNO10. This region contained no variants in protein-coding sequences, but a prominent contiguous 19bp indel polymorphism was noted within a novel predicted long non-coding RNA (lncRNA), which we named as Rffl-lnc1. To assess the candidacy of this novel lncRNA on QT-interval, targeted CRISPR/Cas9 based genome-engineering approaches were applied on the rat strains used to map this locus. Targeted disruption of the rat Rffl-lnc1 locus caused aberrant, short QT-intervals and elevated blood pressure. Further, to specifically examine the significance of the 19bp polymorphism within the Rffl-lnc1 locus, a CRISPR/Cas9 based targeted knock-in rescue model was constructed by inserting the 19bp into the strain which contained the deletion polymorphism. The knock-in alleles successfully rescued the aberrant QT-interval and blood pressure phenotypes. Further studies revealed that the 19bp polymorphism was necessary and sufficient to recapitulate the phenotypic effect of the previously mapped <42.5kb rat locus. To our knowledge, this study is the first demonstration of a combination of both CRISPR/Cas9 based targeted disruption as well as CRISPR/Cas9 based targeted knock-in rescue approaches applied for a mammalian positional cloning study, which defines the quantitative trait nucleotides (QTNs) within a rat long non-coding RNA as being important for the pleiotropic regulation of both cardiac QT-intervals and blood pressure.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.