New 3D map could support research into heart attacks, heart failure and heart rhythm disorders

31st July 2018

Researchers at The University of Chicago have developed a map of 3D interactions in cardiovascular disease. The innovative map will allow researchers to identify vital genes when investigating new treatments for heart attacks, heart rhythm disorders, and heart failure.

More than 500 genetic variants have been linked with increased risk of cardiovascular disease, with the majority located in ‘non-coding’ regions of the genome. This means they don’t code for a certain protein molecule and has been challenging for researchers as there was no way to understand genetic variations or to study their function until now.

Lead author Lindsey Montefiori said, “The strongest genetic signatures associated with complex human diseases, including many cardiovascular diseases, are actually located outside of genes, scattered throughout the vast 98 percent of the genome that is ‘non-coding’.

“What we think is happening is that these mutations affect the function of the ‘switches’ of genes, called enhancers, which determine where, when and to what level each gene should be turned on.”

It has recently become possible to map these enhancers to their target genes using a technique called high-resolution promoter capture, which uses the enhancer region as 'bait' to catch its target gene. The team added an extra step to this, so that they only 'captured' a region of the genome that contains coding genes. This enabled them to map each mutation to its target gene in human heart cells and examine the precise wiring of all the potential enhancers controlling each gene.

More than 10,000 genetic variations linked to CVD were identified, and the researchers found that 1999 of them make physical contact with 347 target genes. When these genes were studied further, it was identified that they were known for their roles in cardiac function

Robert Hall, Cardiomyopathy Support Nurse said: "This is a step forward in the further understanding of genetic cardiac conditions. It will be interesting to see how this research is applied to identifying further gene mutations associated with cardiomyopathy”