Investigation Of The Role Of Epimutation In Programming Of Obseity And Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$333,669.00
Summary
Substantial evidence indicates that in utero environment influences the risk of developing some diseases later in life; this is known as fetal programming. We hypothesize that the in utero environment alters epigenetic marks in the fetus and changes gene expression, leading to disease later in life. We will investigate epigenetic changes in mice born to obese mothers. Better understanding of the mechanisms underlying fetal programming will result in improved administration of public health.
Genome-wide Association Study For Genes That Determine Environmental Sensitivity In Cardiovascular Disease Risk
Funder
National Health and Medical Research Council
Funding Amount
$287,321.00
Summary
There are many known lifestyle and environmental influences for the development of cardiovascular disease. But are there genes that control how susceptible an individual is to these environmental influences? Discovery of such genes could have far greater implications for the prevention and treatment of disease than genes which simply affect levels of the trait. This project will identify genes that affect the environmental susceptibility for cardiovascular disease risk factors.
Variation And Inheritance Of Retrotransposon Epigenotype In The Mouse
Funder
National Health and Medical Research Council
Funding Amount
$355,500.00
Summary
It is often assumed that traits in humans and other mammals are a product primarily of information encoded in the sequence of DNA, with some contribution from the environment. However, there is clear evidence that traits may vary widely between individuals with precisely the same DNA, such as identical twins, even in circumstances where environmental differences are negligible. This variation can be produced by epigenetic factors chemical changes or protein binding to DNA that alter the way gene ....It is often assumed that traits in humans and other mammals are a product primarily of information encoded in the sequence of DNA, with some contribution from the environment. However, there is clear evidence that traits may vary widely between individuals with precisely the same DNA, such as identical twins, even in circumstances where environmental differences are negligible. This variation can be produced by epigenetic factors chemical changes or protein binding to DNA that alter the way genes are used. Epigenetic factors can be passed from one generation to the next like the DNA itself, and this can make it difficult to know if a trait is encoded in the DNA itself or is epigenetic. We have found that some epigenetic traits in mice are caused by retrotransposons, which are parasitic elements that reside in and among genes, and can reproduce themselves, but do not have any known function (nearly half the human genome is made up of retrotransposons). Retrotransposons are generally kept silent by epigenetic factors, but may sometimes become active; when they do they may disturb normal patterns of gene activity and cause changes in traits and even disease. Much variation in humans may thus be due to variation in the epigenetic state (epigenotype) of retrotransposons. We propose to investigate variation and inheritance of epigenotype in mice, focussing on retrotransposons. We will use simple methods to compare epigenotype of a number of retrotransposons in genetically identical mice, and we will ask if any differences we find are heritable. We will also investigate the resetting of epigenotype the point in development when epigenetic factors are cleared and reset. We suspect that this occurs in early development. These studies may reveal a system of variation and inheritance with rules completely different from those found by Mendel, which may have a pervasive influence on traits, including sporadic diseases in humans.Read moreRead less
Common Fragile Site Genes: Function And Contribution To Cancer Cell Biology
Funder
National Health and Medical Research Council
Funding Amount
$474,597.00
Summary
Common fragile sites are regions on human chromosomes that everybody has. These regions are much more sensitive to damage from agents in the environment (including the diet) than other regions in human chromosomes - so when damage does occur it is more likely to occur at these fragile sites. Many of the most sensitive fragile sites have large genes that span them. We need to understand the function of these genes to see how their disruption can contribute to cancer.
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.
Cleavage Methods Of Mutation Detection: Improvement And Application In Cardiovascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,044,349.00
Summary
Genes contain the information to build our body and keep it operating normally. These genes are inherited from our parents and number around 100,000. Faults in these genes can cause inherited diseases such as cystic fibrosis, cancers and common disorders such as Asthma and diabetes. These genes need detecting so that particular genes can be identified as causing the disease and also so that patients can have their disease properly diagnosed so that proper therapy and information can be given to ....Genes contain the information to build our body and keep it operating normally. These genes are inherited from our parents and number around 100,000. Faults in these genes can cause inherited diseases such as cystic fibrosis, cancers and common disorders such as Asthma and diabetes. These genes need detecting so that particular genes can be identified as causing the disease and also so that patients can have their disease properly diagnosed so that proper therapy and information can be given to the patients. In future similar changes (but changes not causing disease) may be searched for in patients to overcome the side effects of drugs. Our centre specializes in the methods of detecting faults and their application. Two of our methods are being used around the world and one is being sold as simple kit. These methods still have drawbacks and the work proposed is to overcome some of these. We propose to apply our and other methods to faults in genes which have recently been shown to cause diseases of the artery. This is an exciting new development that shows that this disease is similar to cancer. We are fortunate to have attracted Dr Paula Bray from the laboratory which discovered this. This new finding needs to be studied in more detail and may identify life-style factors which cause coronary heart disease. Our studies will also assist in gene therapy when it becomes available.Read moreRead less