Genetic discovery could lead to better treatment of congenital heart disease

Baby wearing heart shaped band aid

One in every 100 babies is born with congenital heart disease (CHD), the major cause of death in newborns – however, the genetic cause of these developmental disorders is not fully understood, hindering the development of accurate prenatal genetic testing. 

Now researchers from Murdoch Children's Research Institute (MCRI) and Monash University have developed a way to determine which genes cause these cardiac abnormalities.  

The technique not only confirmed well-known CHD genes but also predicted more than 1,300 new genes not previously suspected in the disease. The research opens the way, in the future, for more accurate prenatal genetic testing for congenital heart disease. 

The collaborative study, published in Genome Biology, was co-led by Associate Professor Mirana Ramialison, Group Leader of MCRI's Transcriptomic and Bioinformatics group and Monash Australian Regenerative Medicine Institute's (ARMI) Systems Developmental Biology Laboratory, and Dr Travis Johnson, Head of Monash University's Drosophila Developmental Biology Research Group.

Lead author and ARMI Dr Hieu Nim said the current approach focused on screening genes that were present in the heart only. 

"This approach often overlooks genes that are present in other tissues as well, despite still playing important roles in heart development," he said.

Dr Nim said the trick was to mine genome databases to identify genes that were specifically 'switched on' in the heart. This process identified not only genes specific for the heart but genes that may also be associated with other organs such as the liver or kidney.  

Associate Professor Ramialison said the data could comprise many of the missing congenital heart disease genes, that have previously been discounted because they were not unique to the heart.

The researchers then used the "vinegar fly" testing model, which uses the genes of flies, to explore some of the functional impacts of these new genes. Researchers use the model because it is a well-established tool to understand the genetic mechanisms of many human diseases because about 75 per cent of human disease-causing genes are found in flies. 

Dr Johnson said the vinegar-fly studies revealed a long list of high-quality candidate genes for causing heart abnormalities in humans, giving real insight into just how susceptible this organ was to genetic mutations.

But he cautioned it may be some time before new candidate genes could provide more accurate pre-natal genetic testing for CHD.  

"We now need to conduct further studies on all of these genes to determine what they actually do, so it's early days, but we now have an excellent starting point, he said.

The collaborative study also involved researchers from the Children's Medical Research Institute in Sydney, the University of Melbourne, La Trobe University and the University of Copenhagen.