Imaging Genetics In Schizophrenia And Bipolar Disorder: Adjudicating Neurocognitive Endophenotypes
Funder
National Health and Medical Research Council
Funding Amount
$569,873.00
Summary
Schizophrenia and bipolar disorder share some common genes and cognitive deficits, yet manifest differently in terms of symptom expression, illness course, and functional impact. This research tests the assertion that genes implicated as common to these conditions may code for impairments in prefrontal cognitive and sub-cortical emotion processing. We also examine whether between-diagnosis distinctions in these brain responses may be mediated by hypothalamic-pituitary-adrenal axis functioning.
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.
Mapping EQTL To Dissect The Genetic Basis Of Complex Trait Variation
Funder
National Health and Medical Research Council
Funding Amount
$719,525.00
Summary
People vary in traits such as height and blood pressure and in their susceptibility to common disease. Part of these differences between individuals is because of their genetic make-up. This research is about understanding which of the genes are involved in common variation and how they work. In particular, the researchers investigate if variation in DNA sequence causes genes to be expressed more or less and how gene expression affects risk of disease.
Molecular Basis Of Transgenerational Epigenetic Inheritance In Mammals
Funder
National Health and Medical Research Council
Funding Amount
$477,965.00
Summary
While it has long been recognised that it is not just DNA, but chromosomes, that are passed from the gametes to the embryo, the non-DNA component was thought to carry no information with respect to the offspring's ultimate phenotype. However, there is now evidence that the non-DNA component, the epigenetic component, can play a role in the inheritance of phenotype in mammals. This study will attempt to determine the molecular nature of this phenomenon.
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
Linkage And Sequence Analysis Of A Locus On The X Chromosome That Contributes To Population Variation In Blood Pressure
Funder
National Health and Medical Research Council
Funding Amount
$458,080.00
Summary
High blood pressure is a prominent risk factor for heart attack and stroke which kill over 30,000 Australians each year. Blood pressure is determined by the combination of inherited predisposition and lifestyle factors such as diet. Understanding these combinations offers new opportunities for reducing the incidence of cardiovascular disease. We have discovered recently that genes on the sex chromosome known as chromosome X appear to be linked with high blood pressure. Building on this basic obs ....High blood pressure is a prominent risk factor for heart attack and stroke which kill over 30,000 Australians each year. Blood pressure is determined by the combination of inherited predisposition and lifestyle factors such as diet. Understanding these combinations offers new opportunities for reducing the incidence of cardiovascular disease. We have discovered recently that genes on the sex chromosome known as chromosome X appear to be linked with high blood pressure. Building on this basic observation, we shall extend our studies to place the findings beyond reasonable doubt. We shall investigate the gene sequences in this region of the X chromosome to discover what changes in the DNA code might lead to high blood pressure and how this might happen. Our studies capitalise on the recent release of the draft sequence of the entire human genome. These investigations in almost 800 healthy volunteer families have the potential to provide new opportunities for prevention and treatment of cardovascular disease.Read moreRead less
Linkage And Association Analyses Of A Locus On Chromosome 4 That Contributes To Population Variation In HDL Cholesterol
Funder
National Health and Medical Research Council
Funding Amount
$372,562.00
Summary
High-density lipoprotein (HDL) cholesterol is also known as good cholesterol becuase it helps remove cholesterol from the body. Many studies have shown that the higher one's HDL cholesterol, the less likely is the development of hardening of the arteries and heart attack. The important questions are what controls HDL cholesterol levels and how could we make them higher? We know that lifestyle and genetics are important. Smoking and lack of exercise are known to reduce HDL cholesterol, while mode ....High-density lipoprotein (HDL) cholesterol is also known as good cholesterol becuase it helps remove cholesterol from the body. Many studies have shown that the higher one's HDL cholesterol, the less likely is the development of hardening of the arteries and heart attack. The important questions are what controls HDL cholesterol levels and how could we make them higher? We know that lifestyle and genetics are important. Smoking and lack of exercise are known to reduce HDL cholesterol, while moderate alcohol intake increases HDL cholesterol. However, genetic factors are very important determinants, but have remained obscure. Through our recent discovery in the Victorian Family Heart Study (VFHS), we located a region on chromosome 4 that influences plasma level of HDL cholesterol. Further testing has confirmed and refined our genetic target - a gene somewhere in this region that controls HDL cholesterol levels. The next step is to find the culprit gene and the DNA sequences that explain why some people have high and others low HDL cholesterol levels. We have the advantage of a large and well characterised group of volunteers and the very latest molecular techniques to track down the gene. Few other groups internationally have our resources or are as advanced in their research. This study will have significant implications for the development of effective and targeted strategies for detection, prevention and treatment of cardiovascular disease.Read moreRead less