Comparative and Functional Genomic Resource for Mechanistic Studies of Human Blood Pressure–Associated Single Nucleotide Polymorphisms
| Autor: | Mingyu Liang, Andrew S. Greene, Pengyuan Liu, Eugene Y. Liang, Sridhar Rao, Manoj K. Mishra, Aron M. Geurts, Paul L. Auer, Yong Liu |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
CCCTC-Binding Factor Linkage disequilibrium RNA Splicing Quantitative Trait Loci Blood Pressure Single-nucleotide polymorphism Genomics Computational biology Biology Polymorphism Single Nucleotide Proof of Concept Study Synteny Linkage Disequilibrium Article Mice 03 medical and health sciences Deep Learning 0302 clinical medicine Internal Medicine Animals Humans Genetic Predisposition to Disease RNA Messenger Nucleotide Motifs Models Genetic Human blood MicroRNAs Enhancer Elements Genetic 030104 developmental biology Haplotypes Mutagenesis Site-Directed Nucleic Acid Conformation RNA Long Noncoding Cell Adhesion Molecules 030217 neurology & neurosurgery Protein Binding Transcription Factors |
| Zdroj: | Hypertension |
| ISSN: | 1524-4563 0194-911X |
| DOI: | 10.1161/hypertensionaha.119.14109 |
| Popis: | The objective of the current study is to use comparative and functional genomic analysis to help to understand the biological mechanism mediating the effect of single nucleotide polymorphisms (SNPs) on blood pressure. We mapped 26 585 SNPs that are in linkage disequilibrium with 1071 human blood pressure–associated sentinel SNPs to 9447 syntenic regions in the mouse genome. Approximately 21.8% of the 1071 linkage disequilibrium regions are located at least 10 kb from any protein-coding gene. Approximately 300 blood pressure–associated SNPs are expression quantitative trait loci for a few dozen known blood pressure physiology genes in tissues including specific kidney regions. Blood pressure–associated sentinel SNPs are significantly enriched for expression quantitative trait loci for blood pressure physiology genes compared with randomly selected SNPs ( P P =4.90×10 −7 , Pearson χ 2 test). One example synonymous SNP rs9337951 was predicted to influence the secondary structure of its host mRNA JCAD (junctional cadherin 5 associated) and was experimentally validated to influence JCAD protein expression. These findings provide an extensive comparative and functional genomic resource for developing experiments to test the functional significance of human blood pressure–associated SNPs in human cells and animal models. |
| Databáze: | OpenAIRE |
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