Victor Chang Group

Genetics Breakthrough

A better genetic test for heart disease

2 July 2018

Harnessing the power of DNA to detect deadly heart disease

In the largest patient study of its kind, a collaborative Australian investigation has put whole genome sequencing to the test, measuring its effectiveness as a first-line clinical diagnostic tool for dilated cardiomyopathy (DCM), an inherited heart disease.

After two decades of heart disease research and three years of genetic analysis, the study found there are clear benefits of using a whole genome sequencing test to help find the causes of cardiomyopathy. In particular, it is a sensitive, and more comprehensive test than is currently used clinically, and it provides rich additional information that is likely to be valuable in the future.

The research, conducted by scientists at the Victor Chang Cardiac Research Institute and the Garvan Institute of Medical Research through their collaborative National Cardiogenomics Program, looked at the entire genetic make-up of 42 patients with dilated cardiomyopathy (DCM). This inherited disease causes the heart to weaken and enlarge and can affect up to 1 in 500 Australians. It is also the most common reason for heart transplantation.

Diane Fatkin looking at a petri dish
“For families affected by cardiomyopathy, we are constantly seeking better ways to pinpoint those at risk of developing the disease at the earliest possible stage. That way we can begin treating the disease before symptoms develop,” said Professor Diane Fatkin, from the Victor Chang Cardiac Research Institute.

Using the whole genome test, which looks at a person’s entire DNA sequence, the scientists were able to find the genetic causes of more cases of dilated cardiomyopathy than the standard test, which only looks at a restricted set of heart disease genes.

“There has been a common misconception that whole genome sequencing wouldn’t pick up as many genetic variants as conventional genetic testing, but our evidence refutes this,” Professor Fatkin revealed.

“We found several genetic variants that had been completely missed by the panel sequencing test,” added Dr Mark Cowley from the Garvan Institute of Medical Research. “These included, for instance, a structural variation in an important cardiomyopathy gene.

“This is a genetic variant that hadn’t been described before. It’s a large-scale reorganisation of the DNA sequence, and is very likely to be diagnostic of cardiomyopathy. It’s difficult to pick up these kinds of change with any approach other than whole genome testing.”

Whole genome sequencing also yielded a wealth of untapped additional information from each participant, including many genetic variants that may be unrecognised causes of cardiomyopathy. Although the exact role of each of these variants in the development of disease isn’t yet understood, it is likely to become clearer over time, as more research is done and disease mechanisms are better understood.

Fatkin Laboratory Victor Chang Institute

Dr Cowley says the study has driven the development of sophisticated bioinformatic tools that unlock new kinds of information from the genome.

Dr Cowley adds, “As part of this research, we’ve developed new methods to uncover variants within the genome. We developed a new tool called ClinSV, which helps us to uncover structural variations within DNA sequences and will be valuable for genetic diagnosis, both in heart disease and other diseases.”

Considerable excitement surrounds the genomic revolution in healthcare, which promises care and treatment on the basis of a person’s unique DNA sequence: their genome. So far, though, whole genome sequencing has only been integrated into routine patient care in a select few instances.

“It’s hugely satisfying that we can now say to clinicians – yes, you should absolutely consider whole-genome sequencing as the test of choice in families at risk of developing cardiomyopathy. This is a real breakthrough and will play a major role in bringing genomic medicine into routine patient care,” Professor Fatkin concludes.

The research has just been published in Genetics in Medicine, the official journal of the American College of Medical Genetics and Genomics.


This work was made possible through the shared vision and support of Dr John Schubert AO (Chairman, Garvan) and Mr Matthew Grounds (Chairman, Victor Chang Cardiac Research Institute), and through crucial additional support from NSW Health via its Sydney Genomics Collaborative.

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Acknowledgement of Country

The Victor Chang Cardiac Research Institute acknowledges Traditional Owners of Country throughout Australia and recognises the continuing connection to lands, waters and communities. We pay our respect to Aboriginal and Torres Strait Islander cultures; and to Elders past and present.

Victor Chang Cardiac Research Institute - The Home of Heart Research for 30 Years