Genetics and Health

The Genetics and Health Team uses "omics" technologies, including:

• Genomics (studies of human genetic variation)
• Transcriptomics (global analysis of gene expression)
• Epigenetic profiling (how environment determines gene expression)
• Studies of the microbiome
• Metabolomics

These technologies allow us to look at all of our genes and metabolic products to find biomarkers of complex diseases like infections and diabetes, as well as identifying rare genetic variants causing single gene disorders.

In Australia, our current focus is on investigating the genetic basis to extreme outcomes like severe otitis media (ear infections) in children in a Western Australian Aboriginal population. Ear infections are the most common reason for young children to visit a doctor, and are a major cause of burst eardrums and hearing loss in Aboriginal children.

We are also interested in congenitally acquired diseases, including the outcomes of infections transmitted to babies in utero, as well as developmental anomalies such as hypospadias. Using exciting new data, our research is looking at how the genome interacts with environmental factors, resulting in changes to gene expression through epigenetic ("above genetics") mechanisms.

Our team is also leading international consortia that are using genetics and metabolomics to understand infections of resource-poor nations. We are especially focused on a disease called leishmaniasis which is present in India, Brazil and Sudan; and fevers caused by bacterial infections and malaria in Africa. Some of the major breakthroughs we have been involved in include determining the most important genetic risk factor for visceral leishmaniasis, and identifying diagnostic biomarkers to rapidly diagnose the cause of fever in African children.

Another project our team are leading is the SeqNextGen Project, which aims at improving the genetic diagnosis of all rare diseases in Western Australian children using Next Generation sequencing. In particular, we are aiming to develop better computational pipelines to pinpoint the disease-causing variants and, as part of the new initiative in precision medicine, we are developing laboratory-based tools to validate the genetic diagnosis.

Team Highlights

Our genome-wide association study for visceral leishmaniasis showed that the most important genetic risk factor, HLA-DRB1, lies at the heart of eliciting T cell immunity.  Results of further studies characterizing the specific epitopes presented to the immune system by protective versus risk-associated HLA-DRB1 Class II molecules appeared in the Journal of Immunology in April 2018.  This paper was highlighted in the editorial section of the journal as one of the top 10% of publications in Immunology. 

Genevieve Syn was awarded her PhD thesis.  One publication showing dysregulation of mitochondrial function was published in Frontiers in Cellular and Infection Microbiology in December 2017, another on a computational pipeline developed with Richard Francis to look for Toxoplasma proteins that target to the host cell nucleus was published in MIOC in May 2018.  A third publication showing epigenetic dysregulation of host dopamine and amyloid pathways in Toxoplasma infection was published in Infection, Genetics and Evolution in July 2018. 

The Otitis Media Microbiome project’s first publication appeared in BMC Microbiology in February 2018, based on work carried out by PhD student Rachael Lappan.  Two bacterial genera, Corynebacterium and Dolosigranulum, were shown to be associated with resistance to recurrent acute otitis media, paving the way for development of nasal probiotics.

By studying rare functional variants in an Aboriginal Australian population we were able to demonstrate that so-called pseudodeficiency alleles at arylsulphastase A are associated with hyptension and chronic renal disease in Aboriginal Australians.  This work was published in Scientific Reports in July 2018.