One of the key challenges in the interpretation of WGS for the diagnosis of inherited disease is in the discrimination of a single or small number of disease-causing variants from large numbers of non-disease causing variants.
To facilitate accurate diagnosis of and discovery of new genetic variants underpinning disease, the Medical Genome Reference Bank (MGRB) Program will sequence and analyse the genomes from ~4,000 healthy, older individuals to create a high quality database that is depleted of damaging genetic variants.
Funded by the NSW State Government, the MGRB leverages the Illumina Hiseq X Ten sequencing platform at the Garvan Institute’s Kinghorn Centre for Clinical Genomics (KCCG). Participants in the 45 and Up (Sax Institute) and ASPirin in Reducing Events in the Elderly (ASPREE) (Monash University) studies will be sequenced to provide a resource of lasting value for national and international health and medical researchers.
This database will maximise the efficiency of disease-specific genomic analyses by acting as a powerful filter to distinguish between pathogenic and population genetic variation:
- clinically for Mendelian disorders; and
- in research, for population cohort studies focused on the common diseases affecting our community.
There is additional value in leveraging this cohort to understand the genetics of healthy aging. As our population ages, understanding the genetic basis for healthy aging will complement a medical genomics focus on common diseases.
The MGRB will generate an unprecedented amount of genomic information. It will promote and encourage significant scientific discovery by employing a hierarchical data management system to maintain participant privacy and confidentiality, whilst maximizing research and clinical usage of the database.
The development of the database began in early 2016 and information about the first 1200 sequences was launched on 16 December, 2016. It promises to provide the ideal background for the future of genomic research in Australia.
This project will involve sequencing the genomes of healthy older adults from two existing cohorts: the 45 and Up Study and the ASPirin in Reducing Events in the Elderly (ASPREE) Study. The 45 and Up study, which is coordinated by the Sax Institute in Sydney, is the largest ongoing study of healthy aging in the Southern Hemisphere. The ASPREE Study (coordinated by Monash University) is an international clinical trial to determine whether daily low-dose aspirin improves quality of life for older people around the world.
This project is being undertaken in collaboration with the NSW Health Office for Health and Medical Research.
Scientific Advisory Committee
- Prof Leslie Burnett (Chair): Consultant Clinical Pathologist, NSW Health Pathology, South Eastern Area Laboratory Services
- Prof David Thomas: Director of The Kinghorn Centre for Clinical Genomics
- Prof Peter Donnelly: Director of the Wellcome Trust Centre for Human Genetics, Oxford
- Prof Peter Visscher: Professor and Chair of Quantitative Genetics at the University of Queensland
- Dr Lee Taylor: Associate Director of Epidemiology and Statistics in the Centre for Epidemiology and Evidence.