Differences in our genes determine not just our gender and how we look, but are also major determinants of our health and risk of disease.
Current Laboratory Members
Professor Matt Brown: Dr Gethin Thomas, Dr Patrick Danoy, Dr Emma Duncan, Dr Evgeny Glazov, Ms Johanna Hadler, Ms Katie Cremin, Ms Leanne Brooks, Ms Kate Addison, Ms Linda Bradbury, Ms Janelle McFarlane, Ms Karena Pryce, Ms Ran Duan, Mr Stuart Davidson. Dr Fernando Santos and Dr Kate Lowings (visiting).
Identifying genes that cause diseases provides us with basic information about the underlying factors involved in disease, informing further research about the disease process, as well as potentially leading to the development of new therapies and diagnostic tests. Breakthroughs in genetics research approaches over the last two years have greatly improved our capacity to identify genes causing common diseases.
Our group is working on identifying the genes that cause common forms of arthritis (ankylosing spondylitis and rheumatoid arthritis), osteoporosis, multiple sclerosis and cervical cancer, as well as taking findings from genetic studies, and researching how the genes identified cause the diseases concerned. These are all common conditions affecting large numbers of Australians and for which better treatments are desperately needed.
Current Research Projects
Genomewide association analysis of common human diseases 
The risk of developing many common human diseases is determined by genes. Until recently, identifying those genes was a nearly impossible task. The development of genomewide association study approaches in which hundreds of thousands of single nucleotide polymorphisms (SNPs) are studied in thousands of cases and healthy controls, has revolutionised this field. Our group is extremely active in this cutting-edge area. We are currently performing genomewide association studies in ankylosing spondylitis, multiple sclerosis and osteoporosis, and will shortly also be studying cervical cancer. In each of these diseases we expect to identify novel genes and genetic regions involved in the development of the disease, providing vital information for biologists as to definite components of the jigsaw of elements that lead to human disease.
Ankylosing Spondylitis (AS)
We are the main genetics centre for the Australo-Anglo-American Spondyloarthritis Consortium (TASC) that is funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases to perform genetic and epidemiology studies in AS. In collaboration with the Wellcome Trust Case Control Consortium, of which we are also partners, our groups identified in 2007 the genes IL23R and ARTS1 as being associated with AS causation. We are using genomewide association methods to identify new disease associated genes. We are also characterising gene-expression profiles in AS, and using that in combination with the genetic data to identify further disease-associated genes and to investigate the mechanism of their association.
Dr Gethin Thomas within our group works with mouse models of AS, and in human samples, to investigate the mechanisms underlying the genetic associations observed.
Osteoporosis
Osteoporosis and bone fractures are a major cause of morbidity and mortality worldwide. We are the genetics hub of the Australian Osteoporosis Genetics Consortium, a group of leading Australian investigators involved in osteoporosis genetics research. This group includes: Professor John Eisman (Garvan Institute of Medical Research, Sydney), Professor Graeme Jones (Menzies Research Institute, Hobart), Professor Geoff Nicholson (Barwon Health Service, Geelong), Professor Richard Prince (Sir Charles Gairdner Hospital, Perth),
Professor John Wark (Royal Melbourne Hospital, Melbourne), Dr David Evans (University of Bristol, Bristol, England), and Professor André Uitterlinden (Rotterdam, Holland).
This group aims to identify genes associated with bone mineral density by studying cases with extreme high or low bone density, a powerful and efficient gene-mapping method. We are also involved in the European Union funded ‘Genetic Factors for Osteoporosis’ (GEFOS) study, a large international group coordinating genetics research in osteoporosis and bone fragility, and will work to translate findings from other populations to the Australian setting.
We are also partners in a program of mouse mutagenesis based in Harwell, England, developing new models of bone and joint disease. These models will be used to investigate mechanisms by which genetic mutations can cause disease, and to identify new pathways causing disease.
Multiple Sclerosis
In collaboration with the ANZGene Consortium we have performed a genomewide association study of the major neurological disease, multiple sclerosis (MS). This study was published in June 2009 in the journal Nature Genetics, and identified two regions which are associated with susceptibility to MS. We are now working on those regions to pinpoint the disease causing genes, using our next-generation sequencer.
Cervical Cancer
In collaboration with Professor Ian Frazer, we are working with an international team to perform a genomewide association study in cervical cancer. Cervical cancer is caused by infection with human papillomavirus (HPV), but genetic factors play a major role in determining those who go on to develop cancer. Identifying the genes involved may allow the development of tests to predict those at highest risk of cervical cancer, and to the development of novel therapies for those affected.
Rheumatoid Arthritis
Rheumatoid arthritis (RA) is the most common form of inflammatory arthritis world-wide. We are working with Professor Huji Xu (Second Military Medical University, Shanghai, China) to study genes involved in both RA and ankylosing spondylitis in Han Chinese. Because of the major differences in genetic makeup of white Europeans and Han Chinese, these studies have the potential to identify genetic effects not observed in Europeans, and to assist in pinpointing key disease associated variants.
Next-Generation Sequencing 
Having identified disease associated regions, we then need to characterise the region fully, to identify all common and rare genetic variants at the locus, and then test these to identify the key associated variants. Funded by the Australian Cancer Research Foundation, we have recently purchased an Illumina Solexa next-generation sequencer for this form of study. This sequencer will be used for resequencing projects to identify genes involved in mono- and polygenic diseases, and for gene-expression studies in cancer and autoimmune diseases.
Professor Brown is currently offering postgraduate projects in his laboratory. Click here for more information.