Development And Evaluation Of Statistical Methods And Software For Analysis Of Complex Genetic Disease Data
Funder
National Health and Medical Research Council
Funding Amount
$1,250,371.00
Summary
What are the major factors underpinning complex genetic diseases like diabetes, bipolar disorder or cancer? To answer this question new tools are needed, including software for mining the human genome with interactions between the genome and environment being incorporated. This is our focus. It will form the basis of a superior understanding of the overall process leading to disease and hence better predictions with important ramifications for new treatments and health care planning.
Genetic Associations Of Early Retinal Pathologic Phenotypes: Data Pooling And Meta-analyses Of Multiple Populations
Funder
National Health and Medical Research Council
Funding Amount
$736,481.00
Summary
We aim to use data already collected from multiple population-based studies to investigate the likely pathogeneses of early retinal phenotypes that are either markers for cardiovascular risk or precursors of a blinding condition. Understanding if there are genetic susceptibilities for these phenotypes, and if so, how they together with environmental exposures jointly influence the occurrence of the diseases may be key to reduce the burden from cardiovascular disease and blindness.
A Population-based Family Study Of Filaggrin Mutations And Allergic Disease Risk In Australia
Funder
National Health and Medical Research Council
Funding Amount
$308,584.00
Summary
It is biologically plausible that the association of known environmental risk factors for asthma may be different for genetically susceptible individuals. Few studies have examined the interaction between genetic and environmental factors. that have not considered genetic susceptibility are estimating an average risk of asthma across all genotypes in the population which may not be relevant for a particular sub-group.
Novel Statistical Methods For The Analysis Of Meausred Genetic And Environmental Risk Factors In Twin Studies
Funder
National Health and Medical Research Council
Funding Amount
$478,314.00
Summary
Studies on twins are an important way to determine whether the risk of disease is likely to be influenced by genetic factors but have traditionally focussed on unmeasured factors. New epidemiological studies measure thousands of genetic variants on many participants. This project will extend methods for analysing data within and between twin pairs to determine whether risk factors are likely to be causal and therefore should be the subject of further designed studies based on intervention.
Many recent gene mapping efforts have focused on population based approaches instead of previously used family based approaches. One of the limiting factors with population based approaches is the cost of the technology - each participant must be evaluated (or genotyped) for hundreds of thousands of genetic markers. The cost can be reduced by using an approach which pools individuals together for genotyping, with statistical models used to deal with the problems that this creates.
Novel Statistical Methods For Genetic Epidemiology
Funder
National Health and Medical Research Council
Funding Amount
$481,505.00
Summary
We are in the midst of a genomics revolution that is transforming epidemiology, medicine and drug discovery. However, the scarcity of sophisticated statistical techniques to deal with the complicated problems inherent in genetic investigations of complex diseases is currently the critical factor limiting the success of human gene discovery programs. Statistical genetic methodology is currently one of the fastest developing areas of epidemiology. In information-intensive' areas such as genetic ep ....We are in the midst of a genomics revolution that is transforming epidemiology, medicine and drug discovery. However, the scarcity of sophisticated statistical techniques to deal with the complicated problems inherent in genetic investigations of complex diseases is currently the critical factor limiting the success of human gene discovery programs. Statistical genetic methodology is currently one of the fastest developing areas of epidemiology. In information-intensive' areas such as genetic epidemiology, genomics, and proteomics, there is a high demand for data analysis and statistical skills. WA has some world class expertise in statistical science, both in academia and in industry. However, this expertise has not yet been applied in a system way to genetic data analysis. We propose to undertake advanced methodological research in statistical genetics and bioinformatics, to produce easy-to-use and accessible software tools and resources that allow methodological advances to be accessed by the Australian research community, and to apply our new methods and tools both to specific disease research and to the developing human genome epidemiology (HuGE) enterprise in WA. These new initiatives in methodological research will draw together a number of currently separate research strands and will provide new tools and resources that will allow applied Australian programs to improve the efficiency of their research into the causes of important. Methodological development in both bioinformatics and statistical genetics are recognized international areas of need.Read moreRead less
Statistical Analyses Of Breast Cancer Risks For Australian BRCA1 And BRCA2 Mutation Carriers
Funder
National Health and Medical Research Council
Funding Amount
$424,628.00
Summary
About 10 years ago two genes, called BRCA1 and BRCA2, were discovered. The normal function of these genes is to prevent breast and other cancers from developing. All people have two copies of each gene, one inherited from their mother and one from their father. Women who have inherited a fault in one copy are at increased risk of breast and ovarian cancer. There has been considerable controversy about what their actual cancer risks are, especially about how those risks might depend on their age. ....About 10 years ago two genes, called BRCA1 and BRCA2, were discovered. The normal function of these genes is to prevent breast and other cancers from developing. All people have two copies of each gene, one inherited from their mother and one from their father. Women who have inherited a fault in one copy are at increased risk of breast and ovarian cancer. There has been considerable controversy about what their actual cancer risks are, especially about how those risks might depend on their age. We have already conducted studies on this and have developed the necessary statistical methods to address these issues by analysing data from the families in which there are faulty genes. In this study we propose to use two large Australian studies, one of families with multiple-cases of breast cancer (Kathleen Cuningham Consortium for Research on Familial Breast Cancer; kConFab) and the other of the families of women with breast cancer chosen, irrespective of their family cancer histories, through the Victorian and NSW Cancer Registries (Australian Breast Cancer Family Study; ABCFS). A large amount of work has already been conducted to identify these families and test them for faults in BRCA1 and BRCA2. There are over 350 families who carry faults, making this one of the largest studies of its type in the world. We will check the cancer histories of these families and determine which members have, or are likely to have, inherited a faulty gene. We will then estimate the breast and ovarian cancer risks accurately, and with much more precision, than has been done previously. We will also use these large datasets to develop a simple method to identify which Australian women are most likely to carry a fault in BRCA1 or BRCA2, based on their personal and family cancer histories. This study will assist genetic counsellors inform Australian women who consider mutation testing for BRCA1 and BRCA2 about their cancer risks, and help make breast cancer genetics more cost effective.Read moreRead less
Fainting (syncope) is a common disorder leading to blackouts, which can cause injury. Breath-holding is a related problem in younger children also resulting in blackouts. Both of these conditions can run in families but little is known about what causes these events. We will study large families to identify the genes underlying these common phenomena. This will deepen our understanding of patterns of inheritance, improve genetic counseling, and lead to better diagnostic and treatment options.
Mapping Of Genetic Traits In Experimental Models Using Databases
Funder
National Health and Medical Research Council
Funding Amount
$237,750.00
Summary
The project aims to detect genes that influence human traits. These traits could be a disease such as diabetes or they may be much less sinister, representing hearing range as an example. Many of these traits are difficult to detect because they are governed by many genes which may also interact with the environment to influence the trait. In order to detect genes in these traits we would like to simplify the complex interactions by eliminating the environment as a potential cause or concentrati ....The project aims to detect genes that influence human traits. These traits could be a disease such as diabetes or they may be much less sinister, representing hearing range as an example. Many of these traits are difficult to detect because they are governed by many genes which may also interact with the environment to influence the trait. In order to detect genes in these traits we would like to simplify the complex interactions by eliminating the environment as a potential cause or concentrating on a particular population where the incidence appears to be much greater. In human populations we have no control over the environmental exposures and we cannot restrict their movements. For this reason many genetic studies have been conducted in mice. Many strains of mice have been generated. Their environment can be strictly controlled, enabling a much better identification of disease genes. Since mice and humans share much of their genome they also share many of their genes and are often afflicted by the same diseases. Thus if we identify genes in mice we have a very good chance of identifying the equivalent human genes. The completion of sequencing for the human genome is being closely followed by the completion of the mouse genome, precisely because mice have been used for over 100 years for genetic studies. The data generated from these sequencing efforts and prior genetic studies is now accumulating in vast databases. These databases of DNA information can be used to map genes for traits. The idea is to determine the trait measurement for many mice in different strains and compare these trait levels to the DNA state (genotype) of markers in the genome of the strains. If these are associated it indicates that the marker is situated close to a gene influencing the trait. This narrows the search considerably. Without this strategy we would have the daunting task of identifiying trait genes from many thousands of potential candidates.Read moreRead less
Comprehensive Assessment Of Genetic And Environmental Risk Factors For Melanoma: A Population-based Family Study
Funder
National Health and Medical Research Council
Funding Amount
$150,679.00
Summary
Excessive sunlight can cause melanoma, a serious type of skin cancer. However, there are other factors including a person's genetic make-up that are thought to put some people at higher risk. Many 'healthy' people have small changes in their genes that might make them more likely to develop melanoma. We need to know more about these genetic factors. Our study will investigate how particular small genetic changes influence a person's likelihood of developing melanoma.