Dec 16, 2014

Dynamic effects of genetic variation on gene expression revealed following hypoxic stress in cardiomyocytes

BioRxiv : the Preprint Server for Biology
Sean RuddyYoav Gilad

Abstract

One life-threatening outcome of cardiovascular disease is myocardial infarction, where cardiomyocytes are deprived of oxygen. To study inter-individual differences in response to hypoxia, we established an in vitro model of induced pluripotent stem cell-derived cardiomyocytes from 15 individuals. We measured gene expression levels, chromatin accessibility, and methylation levels in four culturing conditions that correspond to normoxia, hypoxia and short or long-term re-oxygenation. We characterized thousands of gene regulatory changes as the cells transition between conditions. Using available genotypes, we identified 1,573 genes with a cis expression quantitative locus (eQTL) in at least one condition, as well as 367 dynamic eQTLs, which are classified as eQTLs in at least one, but not in all conditions. A subset of genes with dynamic eQTLs is associated with complex traits and disease. Our data demonstrate how dynamic genetic effects on gene expression, which are likely relevant for disease, can be uncovered under stress.

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Mentioned in this Paper

Molecular Sequence Database
Exons
Genome
Genes
Nucleic Acid Sequencing
Gene Expression
Genomics
Sequencing
Analysis
Computer Program Package

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