The Medical Genome Reference Bank as a population control for germline variants in colorectal and prostate cancer

Research Opportunity
PhD, Masters by Research, Honours, Master of Biomedical Science
Number of Honour Places Available
Clinical Pathology
Group Leader Email Number Webpage
Dr Bernard Pope Personal web page
Primary Supervisor Email Number Webpage
A/Prof Daniel Buchanan 0385597004 Personal web page

Project Details

Rare germline DNA variants play an important role in the risk of developing many kinds of cancer. However, the genetic factors influencing the inherited component of cancer risk remain poorly understood. Addressing the "missing heritability" of cancer risk, many cancer research projects are employing whole genome sequencing (WGS) to interrogate the genetic make-up of individuals at very high resolution, however this also yields large numbers of rare variants that can be difficult to interpret in isolation. Population control groups can provide estimations of the prevalence and distribution of DNA variants and can therefore yield useful insights into disease association of individual variants and disease-related genes/pathways. Currently the most widely used population control data is provided by the Genome Aggregation Database (gnomAD [1]) containing DNA sequence data for 138,632 individuals (15,496 WGS). While gnomAD is a key resource, it has a number of characteristics which limit its use as a population control for cancer studies: * Limited to single nucleotide variants (SNVs) and small insertions and deletions (INDELs).
* Phenotype information about individuals is mostly unavailable.
* Genotype information for many individuals in the data set is unavailable.
* As an aggregation of other data sets, including disease-specific cohorts, and mixtures of ethnicities, the data is prone to hidden biases.
We believe that the Medical Genome Reference Bank (MGRB [2]) provides a unique opportunity to address this issue in an Australian context, due to its large size and selection of individuals who are healthy at relatively advanced age. Such individuals are, for example, unlikely to be carriers of highly penetrant, inherited cancer-predisposition mutations.
In this project, we propose to use the MGRB as a population control for germline variants in our colorectal and prostate cancer studies. Specifically, we propose to compare the frequency and distribution of germline DNA variants between cohorts of colorectal and prostate cancer patients (including cancer subtypes) against the individuals within the MGRB. We aim to be comprehensive in our consideration of variant types including SNVs, INDELs, copy number variants (CNVs), structural variants (SVs), and microsatellite polymorphisms from both nuclear and mitochondrial DNA.

Faculty Research Themes


School Research Themes

Cancer in Medicine

Research Opportunities

PhD, Masters by Research, Honours, Master of Biomedical Science
Students who are interested in joining this project will need to consider their elegibility as well as other requirements before contacting the supervisor of this research

Graduate Research application

Honours application

Key Contact

For further information about this research, please contact a supervisor.


Clinical Pathology

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