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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


Diseases of the cardiovascular system such as essential hypertension do not have a clear cause, but are known to run in families. The inheritance patterns of essential hypertension and other cardiac diseases suggest that they are not due to a single defective gene but instead are caused by multiple genetic defects that are inherited together in a patient. This complex inheritance makes it difficult to pinpoint the underlying defects. Here, we describe a panel of genetically-engineered rats, using which we have discovered a novel gene, which does not code for any protein, as a gene required for maintenance of normal blood pressure. Structural defects within this non-coding RNA cause hypertension and cardiac short-QT interval. Further, by performing genome surgery to correct the gene defect, we demonstrate the precise error in nucleotides that was inherited and caused hypertension and cardiac short-QT interval syndrome.


Vyšlo v časopise: 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. PLoS Genet 13(8): e32767. doi:10.1371/journal.pgen.1006961
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1006961

Souhrn

Diseases of the cardiovascular system such as essential hypertension do not have a clear cause, but are known to run in families. The inheritance patterns of essential hypertension and other cardiac diseases suggest that they are not due to a single defective gene but instead are caused by multiple genetic defects that are inherited together in a patient. This complex inheritance makes it difficult to pinpoint the underlying defects. Here, we describe a panel of genetically-engineered rats, using which we have discovered a novel gene, which does not code for any protein, as a gene required for maintenance of normal blood pressure. Structural defects within this non-coding RNA cause hypertension and cardiac short-QT interval. Further, by performing genome surgery to correct the gene defect, we demonstrate the precise error in nucleotides that was inherited and caused hypertension and cardiac short-QT interval syndrome.


Zdroje

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