Investigating Genetic Determinants Of Absence Epilepsy In A Polygenic Rat Model
Funder
National Health and Medical Research Council
Funding Amount
$458,481.00
Summary
The underlying genetic causes of idiopathic generalised epilepsies (IGE) are still largely unknown. In an animal model of IGE we have discovered novel genetic abnormalities an ion channel. This proposal will build upon these novel findings to examine the role these abnormalities have in determining the absence epilepsy phenotype and this work has the potential to provide vital information regarding the mechanisms by which this gene contributes to an IGE seizure phenotype.
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
Uncovering The Aetiology Of Myopia Through Identification Of Refraction And Ocular Biometric Genes
Funder
National Health and Medical Research Council
Funding Amount
$697,786.00
Summary
Myopia or short-sightedness affects 1 in 4 people in the Western world and is a major source of uncorrected vision loss, as well as blindness. This proposal aims to identify genes in myopia using a new technique called genome wide association. We will apply this technique to individuals collected through a population based Eye study to allow us to identify these genes. The outcomes of this work will allow us to identify high risk individuals as well as develop new measures to prevent myopia.
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
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
Towards An Etiological Understanding Of The Comorbidity Of Psychiatric Disorders
Funder
National Health and Medical Research Council
Funding Amount
$997,883.00
Summary
Pyschiatric disorders are common disorders with both genetic and environmental etilogy. The disorders are characterised both by significant overlap of symptoms and by significant heterogenity of symptoms within disorders. The availability of genome-wide genotypes allows us, for the first time, to investigate co-morbidity directly at the molecular level. Understanding the nature of co-morbidity between disorders nay be an important key to effective treatment.
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.
How Important Is Collagen Destruction In Arthritis? A Study With Collagenase-resistant Knockin Mice
Funder
National Health and Medical Research Council
Funding Amount
$529,723.00
Summary
Aggecan and collagen are important structural molecules in cartilage. Together they allow cartilage to bear weight and resist compression. In arthritis, collagen is degraded by collagenases and aggrecan is degraded by aggrecanases. Aggrecan loss is a feature of cartilage disease. Early aggrecan loss is well documented and usually precedes clinical symptoms, suggesting that it is the initiating step in cartilage pathology. Aggrecan loss precedes collagen damage in explant culture, however it is n ....Aggecan and collagen are important structural molecules in cartilage. Together they allow cartilage to bear weight and resist compression. In arthritis, collagen is degraded by collagenases and aggrecan is degraded by aggrecanases. Aggrecan loss is a feature of cartilage disease. Early aggrecan loss is well documented and usually precedes clinical symptoms, suggesting that it is the initiating step in cartilage pathology. Aggrecan loss precedes collagen damage in explant culture, however it is not known whether inhibiting aggrecanases is sufficient to block cartilage damage long-term. In contrast, other studies suggest that aggrecan is only lost after damage to the collagen scaffold. These studies propose that clipping of the collagen scaffold may initiate aggrecan release; with progressive degeneration and collagen clipping, more aggrecan is lost, until ultimately the scaffold is severely damaged and aggrecan is severely depleted. Cartilage can only withstand a limited degree of collagen degradation and any significant damage to the network is widely considered to be irreparable. It is unclear what role aggrecanases and collagenases have in initiating and perpetuating cartilage damage. We have mice with aggrecan resistant to aggrecanases and mice with inactive aggrecanase. We will also create mice with collagen resistant to collagenase. We will use these mice to determine the contribution of collagenases and aggrecanases to the initiation and progression of cartilage damage, in three models of joint disease. We will identify differences in time of disease onset, rate of disease progression and disease severity. The results will show whether one or both activities is important for the initiation and progression of joint disease. This will reveal whether single or combination therapies are required for the management of arthritis. The research will inform the pharmaceutical industry on directions for the development of new drugs to prevent joint disease.Read moreRead less
Epilepsy is the name of a group of disorders where seizures occur. 5% of people will have at least one seizure. Seizures accompanied by fever (febrile) are common in early childhood. Most forms of epilepsy and febrile seizures have an inherited component. Progress in finding genes for common forms of epilepsy has been slow, probably because they are due to the interaction of a number of genes. Four genes for rare epilepsies with single gene inheritance have been identified. These genes code for ....Epilepsy is the name of a group of disorders where seizures occur. 5% of people will have at least one seizure. Seizures accompanied by fever (febrile) are common in early childhood. Most forms of epilepsy and febrile seizures have an inherited component. Progress in finding genes for common forms of epilepsy has been slow, probably because they are due to the interaction of a number of genes. Four genes for rare epilepsies with single gene inheritance have been identified. These genes code for subunits of ion channels in cells. We study families where many individuals have seizures and carefully diagnose the seizures types. This work has resulted in the description of 5 new inherited epilepsies and led to discovery of 3 of the 4 known genes. The most important new inherited epilepsy is Generalized Epilepsy with Febrile Seizures Plus (GEFS+). GEFS+ accounts for many children with febrile seizures restricted to early childhood, or where seizures continue into mid-childhood. GEFS+ families may contain an individual with severe generalized epilepsy with intellectual disability. In a Tasmanian family with GEFS+, we found a gene defect in the sodium channel of nerve cells in the brain. We plan to study more families with GEFS+. We believe that specific severe childhood epilepsies may occur in families with GEFS+. If so, then the underlying cause of these serious disorders may be gene defects of GEFS+. Finding such genes will help to understand the basis of seizures and ultimately lead to targeted therapies. The second major focus of our work on GEFS+ is to use family studies to understand how different types of seizures are inherited, and to gain insights into the gene interactions underlying common epilepsies. We plan to study isolated cases of GEFS+ for the gene defects found in families. This strategy will reveal whether the same genes are important in the genetics of the common epilepsies.Read moreRead less
The Future Of Tobacco Control: Exploring The Feasibility, Acceptability And Cost-effectiveness Of New Policy Directions
Funder
National Health and Medical Research Council
Funding Amount
$495,752.00
Summary
We will examine the practical feasibility, ethical and public acceptability, and likely cost effectiveness of a number of different ways of reducing tobacco smoking and the harm caused by smoking in Australia. These policy options will include: (1) more restrictive policies towards tobacco products (such as prohibiting tobacco smoking and creating a government monopoly on the manufacture and supply of tobacco); (2) encouraging smokers to switch from smoking cigarettes to less harmful ways of usi ....We will examine the practical feasibility, ethical and public acceptability, and likely cost effectiveness of a number of different ways of reducing tobacco smoking and the harm caused by smoking in Australia. These policy options will include: (1) more restrictive policies towards tobacco products (such as prohibiting tobacco smoking and creating a government monopoly on the manufacture and supply of tobacco); (2) encouraging smokers to switch from smoking cigarettes to less harmful ways of using nicotine, such as using nicotine patches or gum ; (3) using new biotechnologies to improve smokers chances of quitting (e.g. genetic screening of smokers to select the most effective way of helping them to stop smoking and vaccinating ex-smokers against the effects of nicotine); and (4) new biotechnologies that may prevent nonsmokers from beginning to smoke (e.g. vaccinating nonsmokers against the effects of nicotine) or reduce the chances of their developing tobacco-related diseases (e.g. screening the population for genes that predict an increased susceptibility to nicotine dependence and tobacco-related diseases). The project will provide important information that will assist government in formulating policies to reduce the rate of cigarette smoking in the Australian population below current levels.Read moreRead less