05 December 2016
A new Centre for Research Excellence, which aims to transform diagnosis and management of severe intellectual disability (also known as neurocognitive disorders) through genomics, is to be established in Australia. The Centre is one of six clinical Centres of Research Excellence (CREs) to receive funding from the NHMRC this year, and one of 14 Garvan-led proposals to be funded across the two most recent funding rounds.
The Centre’s team is led by Dr Tony Roscioli (Team Leader in Rare Disease Genomics at the Garvan Institute of Medical Research) and includes researchers and clinicians from across Australia, who together have internationally recognised expertise in neurogenetics research, genomics, bioinformatics, health economics and clinical practice. A full list of chief investigators is included below.
Neurocognitive disorders are one of the largest unmet challenges in Australian healthcare. They are common, with approximately 3000 children born annually with a moderate to severe neurocognitive disorder. In addition, these disorders have high management costs and recur frequently within families.
Despite the significant unmet need for treatments for neurocognitive disorders, it has been very difficult to make a gene diagnosis in these disorders, and to develop effective therapies. This is because neurocognitive disorders are remarkably genetically diverse: more than 1200 genes have so far been associated with them, and it is estimated that over 1000 more are yet to be identified.
Dr Roscioli says that we are at the beginning of an exciting time in the diagnosis of neurocognitive disorders and in the development of therapies:
"In the past, we relied on clinical diagnosis and single gene-by-gene tests to diagnose neurocognitive disorders, which were only partially successful. Now, through the new CRE, we propose to transform diagnosis of neurocognitive disorders through the application of whole genome sequencing," Dr Roscioli says.
Whole genome sequencing is a laboratory technique used to determine the order of the DNA bases across the entire genome — including all of our 20,000+ genes and the regions between them.
"Because so many genes have been associated with neurocognitive disorders, whole genome sequencing is a faster, more successful and more cost-effective approach to genetic diagnosis for affected families. Through whole genome sequencing, we can look, at once, at all 1200 genes known to be associated with neurocognitive disorders – and we have already tripled the current diagnostic rate in people with moderate and severe neurocognitive disorders from 15-20% to over 60%, as well as identifying new genes not previously known to be associated with such disorders."
"This substantial increase in the rate of diagnosis will have a positive impact on many families across Australia. For a child to receive a genetic diagnosis early in life is a powerful thing: it gives parents an explanation of what caused the disorder, often a new non-inherited change with a very low chance of happening again. A specific diagnosis also helps families and doctors to plan for the future healthcare needs of children with neurocognitive disorders – and makes access to resources easier."
Beyond the transformation in the diagnosis of neurocognitive disorders, the new CRE also aims to:
- Understand how newly identified genetic variants contribute to disease;
- Bring together genomic information and clinical information, including 3D analysis of facial shape, so as to identify neurocognitive disorder subgroups that could respond differently to treatment;
- Investigate health economic models to contribute to policies to maximize resources for families and
- Investigate pharmacological treatment options across the identified subgroups.
An important strength of the CRE will be its engagement with Genomics England, the organisation leading the UK’s 100,000 Genomes Project. The Head of Genomics England, Professor Mark Caulfield, is an associate investigator in the CRE. Through Genomics England, and under the auspices of the CRE’s team will extend the impact of genomic data by searching for further families with the same or similar unique mutations on a global scale
The CRE’s activities will complement an ongoing philanthropic initiative of Garvan and Liverpool Hospital (Sydney) to improve diagnosis rates for children with intellectual disability through the provision of whole genome sequencing and analysis.
Professor John Mattick, Executive Director of Garvan, says, "The Garvan Institute is one of the leading centres of human genome sequencing and clinical genomics in the world, with wonderful partnerships such as this around the nation and the world. Genome sequencing will not only transform the lives and care of individuals and families with genetic disorders, but will also change healthcare for the whole population."
The chief investigators in the CRE team are as follows:
CIA: Doctor Tony Roscioli
CIB: Professor Jozef Gecz
CIC: Doctor Michael Field
CID: Professor Deborah Schofield
CIE: Doctor Michael Buckley
CIF: Professor Kathryn North
CIG: Associate Professor Marcel Dinger
CIH: Professor John Christodoulou
CII: Professor David Amor
CIJ: Associate Professor Gareth Baynam
*Image by courtesy of Massachusetts General Hospital and Draper Labs [Public domain], via Wikimedia Commons