Microarray-targeted Candidate Gene Approach To Finding Ovarian Cancer Susceptibility Genes
Funder
National Health and Medical Research Council
Funding Amount
$612,933.00
Summary
We propose that subtle, heritable changes in the expression or function of genes that are switched off, or on, early in the development of ovarian tumours, may predispose the individual to ovarian cancer. We will are carry out a large study of the most common subtype of ovarian adenocarcinoma, serous invasive tumors, in order to identify genes that affect a woman's risk of ovarian cancer. Identification of women at elevated risk for ovarian cancer on the basis of their genotype will allow them t ....We propose that subtle, heritable changes in the expression or function of genes that are switched off, or on, early in the development of ovarian tumours, may predispose the individual to ovarian cancer. We will are carry out a large study of the most common subtype of ovarian adenocarcinoma, serous invasive tumors, in order to identify genes that affect a woman's risk of ovarian cancer. Identification of women at elevated risk for ovarian cancer on the basis of their genotype will allow them to be targeted for screening, and for intervention studies, as well as providing fundamental insight into the etiology of ovarian cancer.Read moreRead less
Genetic Variation Of Mitochondrial Complex I: Its Role In Rare And Common Diseases
Funder
National Health and Medical Research Council
Funding Amount
$628,415.00
Summary
Our bodies convert food into energy in tiny cellular power plants called mitochondria. Each year about 50 Australian children inherit disorders of mitochondrial energy generation. The most severe disorders cause infant death, while others cause degenerative diseases in later life, particularly affecting brain and muscle. In most cases we lack effective treatments. The genetic causes of mitochondrial disorders are incredibly diverse, with over 70 disease genes known. Some are located on the uniqu ....Our bodies convert food into energy in tiny cellular power plants called mitochondria. Each year about 50 Australian children inherit disorders of mitochondrial energy generation. The most severe disorders cause infant death, while others cause degenerative diseases in later life, particularly affecting brain and muscle. In most cases we lack effective treatments. The genetic causes of mitochondrial disorders are incredibly diverse, with over 70 disease genes known. Some are located on the unique mitochondrial DNA we inherit only from our mothers. Many more genes await discovery. This grant focuses on the most common energy generation disorder, known as Complex I deficiency. Complex I requires 46 separate components to be assembled together in order to work properly, but mutations in the 46 genes encoding these components only seem to explain disease in about half of all patients. Our aim is to identify new disease genes and to determine whether some patients have mutations in two different genes that interact to cause disease, rather than in a single gene. We will use a number of methods to pinpoint where in the genome the causative genes are located and then home in on the exact changes in the genes that cause disease. Identifying these genes will allow us to improve future diagnosis and prevention of mitochondrial disease. We will also generate mice in which one of the Complex I genes has been knocked out. These mice will allow us to better understand the basic disease mechanisms that link gene changes to disease. Understanding the basic biology may allow us to develop new methods of treatment. The mouse models will also be useful for trialling new treatments and for investigating the role of milder mitochondrial problems in common diseases such as diabetes and Parkinson disease. Any new treatments could potentially have wide application.Read moreRead less
Australian Heritage: constructing the first Aboriginal reference genome. This project aims to use DNA sequencing technologies to generate the first complete and accurate Aboriginal genomes, along with maps of genomic variation around Australia. It will combine a range of advanced analytical methods to integrate past and present indigenous genetic diversity from human populations around the world into a new pan-human reference genome. This project will lead to a step change in our understanding o ....Australian Heritage: constructing the first Aboriginal reference genome. This project aims to use DNA sequencing technologies to generate the first complete and accurate Aboriginal genomes, along with maps of genomic variation around Australia. It will combine a range of advanced analytical methods to integrate past and present indigenous genetic diversity from human populations around the world into a new pan-human reference genome. This project will lead to a step change in our understanding of global human genomic variants and provide a range of new targets relevant to medical biology, while significantly improving our knowledge of human genetic history and its consequences in the modern day.Read moreRead less
The genomic landscape of speciation in hominins and other taxa. This project will develop a new analytical framework to build detailed genomic maps of speciation genes across different taxa, to determine whether observed speciation is the result of background selection and demography alone, or whether there are actual barriers to gene flow and introgressed DNA. The model will provide novel insights into the mechanistic basis of speciation, specifically whether a common set of genes or pathways a ....The genomic landscape of speciation in hominins and other taxa. This project will develop a new analytical framework to build detailed genomic maps of speciation genes across different taxa, to determine whether observed speciation is the result of background selection and demography alone, or whether there are actual barriers to gene flow and introgressed DNA. The model will provide novel insights into the mechanistic basis of speciation, specifically whether a common set of genes or pathways are central to the speciation process. The framework will be developed using the large genomic datasets available across a range of plant and animal species. Applying the model to a modern human population dataset will elucidate the role introgressed DNA from Denisovan and Neanderthals has played in shaping human evolutionary history and may provide novel insights into the genetic basis of disease.Read moreRead less
RNA-based analysis for prediction of islet death in diabetes. Death of insulin-producing cells is a common feature in diabetes. Presently, a blood glucose test remains the only blunt instrument to diagnose diabetes. The RNA-based analysis for prediction of islet death in diabetes (RAPID) study links with eight clinical trials to test this newly developed non-invasive assay for predicting diabetes. Early diagnosis will help to reduce diabetic complications in later life.