The CHD gene panel
As part of her PhD, Gillian Blue designed the first CHD gene panel using targeted next generation sequencing technology. This tool was used to screen 16 families in which multiple members were affected by CHD in order to identify the cause of the heart defects in the family. The CHD gene panel was able to identify the cause of CHD in 5 out of the 16 families (31%) and these findings were published in the esteemed Journal of the American College of Cardiology in December 2014 see publication list.
Wellcome Trust Genome-wide Association Study in congenital heart disease
This international collaboration used genome-wide technology to identify new genes involved in heart development. Our DNA Bank contributed 400 samples towards a total of 2000 samples analysed from the various research centres around the world. The study identified a region on chromosome 4p that was associated with an increased risk of developing atrial septal defects (ASDs). The findings of this study were published in the esteemed Journal, Nature Genetics in 2013 see publication list.
Congenital HEART and Environment/Epidemiological Database (CHeartED) is another international genome-wide association study that focussed specifically on the heart condition, Tetralogy of Fallot. Two regions on chromosomes 12q and 13q were found to be associated with Tetralogy of Fallot. The findings of this study were published in Human Molecular Genetics in 2013 see publication list.
Cardiovascular Research Network (CVRN)
The primary focus of the CVRN is on left-sided heart disease and we were involved in a number of sub-studies relating to genetic aspects thereof. We collaborated with Prof Diane Fatkin and Prof Richard Harvey from the Victor Chang Cardiac Research Institute to discover new genes involved in the development of hypoplastic left heart using exome sequencing. In We also collaborated with Prof Chris Semsarian at the Centenary Institute in Sydney, on a study of bicuspid aortic valve (BAV). This study sought to perform a comprehensive clinical and genetic investigation of individuals and families with BAV to identify novel genes with the view to improve diagnostics and risk stratification in families.
Somatic mutations in patients with congenital heart disease
Research suggested that mutations present in the DNA of the actual diseased heart tissue (somatic mutations) could explain certain types of CHD. We conducted a study on a small group of samples from our DNA Bank to investigate this further and concluded that somatic mutations were not a causal factor in our cohort.
Collaborations with Victor Chang Cardiac Research Institute
We have ongoing collaborations with world-renowned developmental biologist, Professor Richard Harvey from the Victor Chang Cardiac Research Institute. Numerous genes known to be involved in heart development have been analysed using samples from the Kids Heart Research DNA Bank and several rare mutations were identified. A study on the gene GATA4 identified two novel mutations associated with cardiac septal defects and in another study, mutations identified in the gene, TBX20, were the first to link this gene to human disease and the work culminated in a high profile publication in the American Journal of Human Genetics.
GATA4 mutations as a cause for CHD
Mutations in GATA4 have been associated with both familial and sporadic forms of CHD in the past. We investigated the pathogenic role of GATA4 in CHD by screening 357 unrelated patients with various forms of CHD. We identified two novel and two known mutations in patients with septal defects and thereby added to the spectrum of mutations associated with CHD.
During research into the immune processes and B-cell development, researcher Dr Fabienne Mackay at the Garvan Institute, serendipitously discovered an association between mutations in the gene encoding CXCR7 and the development of a specific type of CHD in a mouse model. The DNA Bank contributed 300 samples to successfully confirm this association with human CHD.