Functional Genomics in Gene Discovery and Clinical Practice

Translational Research Grants

$287,469 AUD

01/09/2018 → 30/08/2020

Carolyn Sue


Professor David Thorburn

Research Institution

Murdoch Children’s Research Institute

Project Name

Functional Genomics in Gene Discovery and Clinical Practice

Project Overview

Australian children with suspected mitochondrial disease (mito) will have the best possible opportunity to achieve a diagnosis, thanks to this project. Professor Thorburn and his team’s work will underpin ongoing sustainable provision of genomic and functional genomic testing.

Project Details

This project will focus on improving translation of genomics into optimal clinical practice by addressing the following issues:

  • Improved genomic diagnosis
  • Bridging the functional genomics translation gap

Despite the genomics revolution, about half of all children thought to have mito are not currently receiving a confirmed molecular diagnosis even when they have genomic sequencing of all their 20,000 genes. This is due to a number of reasons, one of which is that even when changes are found in a relevant gene, they have often not been linked to disease previously. Unless functional evidence can be provided, such variants remain a Variant of Uncertain Significance (VUS).

Professor Thorburn and his team will aim to bridge this evidence gap through providing a more sustainable mechanism for functional validation, and applying new genomic, transcriptomic and proteomic technologies to enable discovery of novel genetic causes of mito.

Disorders of mitochondrial oxidative phosphorylation (OXPHOS) affect at least 1/5000 births, corresponding to an expected minimum of 60 new cases each year in Australia, with up to half expected to present in childhood. Muscle histopathology and OXPHOS enzyme testing are effectively the only mitochondrial functional tests offered as diagnostic tests in Australia.

In order to provide evidence of causation, appropriate methods will be applied to children with probable or definite OXPHOS disorders and a VUS of likely clinical significance.

Professor Thorburn will collate an evidence base to meet the pathology requirements for additional functional genomic tests to be incorporated into clinical laboratory testing in Australia.