Physiological Genomic Analysis Of Lvm-1 - A Genetic Locus That Determines Left Ventricular Mass
Funder
National Health and Medical Research Council
Funding Amount
$356,540.00
Summary
As many as one in ten healthy individuals have big hearts. Careful scientific investigation has revealed that the bigger one's heart, the greater the risk of dying from cardiovascular disease. This is true even in the absence of known causes of heart disease. Unlike high blood pressure or cholesterol, the size of the heart is not easily measured and enlargement often goes undetected. We were among the first internationally to discover genetic clues to enlarged hearts. We identified regions on ra ....As many as one in ten healthy individuals have big hearts. Careful scientific investigation has revealed that the bigger one's heart, the greater the risk of dying from cardiovascular disease. This is true even in the absence of known causes of heart disease. Unlike high blood pressure or cholesterol, the size of the heart is not easily measured and enlargement often goes undetected. We were among the first internationally to discover genetic clues to enlarged hearts. We identified regions on rat chromosomes that harbour the gene or genes that influence heart size. The aim of these studies is to identify the exact gene responsible and to understand how that gene produces its effects. The experiments involve testing DNA samples already obtained from many hundreds of rats and breeding animals to study the consequences of the genetic abnormality in greater detail. The experiments are critical steps towards the prevention of big hearts and their complications in humans. In time, genetic tests will offer earlier detection and facilitate targeted and tailored treatments.Read moreRead less
Australian Genomewide Association Study In Osteoporosis
Funder
National Health and Medical Research Council
Funding Amount
$882,722.00
Summary
Osteoporosis is a common condition in which bone strength is reduced due to reduced amount and quality of bone. Reduced bone strength means an increased risk of fracture. Osteoporotic fractures occur in 1 in 2 women and 1 in 3 men in their lifetime, and the likelihood of suffering osteoporotic fracture increases with age. Most of the risk of developing osteoporosis is genetic, but few of the genes involved have been identified. Our goal is to identify those genes.
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
Linkage Disequilibrium Mapping And Positional Cloning For Gene Identification In Osteoporotic Families
Funder
National Health and Medical Research Council
Funding Amount
$330,500.00
Summary
Osteoporosis is a common chronic disease with associated pain, loss of function and death. Patients with the disease commonly experience spine, hip or wrist fracture. Fracture of vertebrae may result in chronic back pain and deformity. Respiratory and digestive health are then also compromised. In comparison, hip fracture may lead to a need for surgery, reduced mobility and institutionalization. In view of improved general community health and increased longevity, the incidence of this disease a ....Osteoporosis is a common chronic disease with associated pain, loss of function and death. Patients with the disease commonly experience spine, hip or wrist fracture. Fracture of vertebrae may result in chronic back pain and deformity. Respiratory and digestive health are then also compromised. In comparison, hip fracture may lead to a need for surgery, reduced mobility and institutionalization. In view of improved general community health and increased longevity, the incidence of this disease and the drain on public health funding will continue to increase substantially in coming years. Presently the cost in Australia is $7.5 billion per annum. Instituting effective prevention strategies is essential. This project aims to contribute to this goal by identifying a major gene(s) involved in disease susceptibility. The term osteoporosis covers a number of heterogeneous syndromes including juvenile osteoporosis, secondary osteoporosis (e.g. corticosteroid induced) and postmenopausal osteoporosis. In this later broad grouping there is evidence of a strong familial association. Previous work has shown that a family history of fracture increases your risk of fracture more than four fold. Furthermore, studies in twins have persistently shown that bone mineral density, the largest risk factor for osteoporotic fracture, is strongly inherited. This data confirms a genetic basis for the disease in some individuals. We have completed two whole genome screen projects and genetic linkage analysis in the families studied has highlighted four regions of the genome, which may harbour genes involved in the disease process. In this project we will fine map these regions and identify the genes that are responsible for the observed linkage. We will use a technique called positional cloning to discover the identity of the gene(s) and will characterise how genetic variation (polymorphism) in the gene leads to reduced bone mass and osteoporotic fracture.Read moreRead less
Genetic And Environmental Determinants Of Tobacco And Alcohol Use Trajectories Into Adulthood:a Prospective Twin Study.
Funder
National Health and Medical Research Council
Funding Amount
$172,875.00
Summary
Problems associated with the long-term use of tobacco and the abuse of alcohol permeate society. The development of effective programs for both the prevention and cessation of tobacco use and alcohol abuse requires an understanding of the natural history of the use of these substances. Most studies of the natural history of tobacco and alcohol use have followed individuals through secondary school and into the early 20s. These studies tell us about the psychosocial influences on these behaviours ....Problems associated with the long-term use of tobacco and the abuse of alcohol permeate society. The development of effective programs for both the prevention and cessation of tobacco use and alcohol abuse requires an understanding of the natural history of the use of these substances. Most studies of the natural history of tobacco and alcohol use have followed individuals through secondary school and into the early 20s. These studies tell us about the psychosocial influences on these behaviours but not about the role of genes on initiation and escalation of substance use. Yet recent advances in the neurophysiology of nicotine and alcohol receptivity and molecular genetics research suggest that genes play at least some role in determining the use of alcohol and tobacco. This proposal is for funding to continue a study designed to investigate the natural histories of alcohol and tobacco use among a sample of 1400 young Australian twins from adolescence to adulthood (early 30s). The study involves a telephone survey of these twins about their smoking and drinking behaviours, and among other things, their attitudes about smoking and drinking, the use of tobacco and alcohol by family and friends and presence of smoking bans at home and work. Because this study explicitly examines the influence of social and psychological factors on tobacco and alcohol use we will be able to determine the relative contribution of genes and psychosocial factors in tobacco and alcohol use. The proposed study is unique in its use of twins, its longitudinal design and its integration of genetics into psychosocial models of behaviour. The results of this study will help to clarify the role of genes in the development of tobacco use and alcohol abuse. Importantly the results of this study will help to identify those social and psychological factors that increase the likelihood of a genetically susceptible individual becoming dependent on nicotine and-or abusing alcohol.Read moreRead less
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.
Risk Factors Associated With The Expansion Of CGG Repeat Sequences In The FMR1 (fragile X) Gene: A Study In Tasmania
Funder
National Health and Medical Research Council
Funding Amount
$246,020.00
Summary
This study will identify the risk factors that lie in an individual's DNA profile for a disease called fragile X syndrome. This disease is the most common form of intellectual disability that runs in families caused by an unusual form of change in a particular gene called FMR1, whereby a very short sequence of DNA in a gene expands by repeating itself to such an extent that once it reaches a certain size the whole gene stops working and the disease occurs. The expansion in the gene is not unifor ....This study will identify the risk factors that lie in an individual's DNA profile for a disease called fragile X syndrome. This disease is the most common form of intellectual disability that runs in families caused by an unusual form of change in a particular gene called FMR1, whereby a very short sequence of DNA in a gene expands by repeating itself to such an extent that once it reaches a certain size the whole gene stops working and the disease occurs. The expansion in the gene is not uniform across the generations, and only occurs when passed on from the mother to her offspring. However, many females carrying only a short sequence may pass on, for unknown reasons, either a large expanded sequence leading to disease, or one similar in size to her own. This complexity in the progression of the number of CGG repeats means that there is a relatively large number of mothers, ~1 in 300, who are quite normal but at risk of having an affected offspring. The factors that trigger this expansion in the DNA are presently not well understood, but a number of genetic markers in the FMR1 gene have been implicated. This study will assess the contribution of an array of these genetic markers in determining the risk of expansion of the short repeat from mother to offspring and hence the risk of fragile X. Conducting this study in Tasmania has two advantages. First, by having access to genealogical records that permit the linking of fragile X families we shall be able to identify common predisposing factors of fragile X more accurately. Second, by testing the whole population with intellectual disability in one State of manageable size we shall obtain an unbiased estimate of the prevalence of fragile X.Read moreRead less
Investigating The Role Of Pigmentation Pathway Genes In Moliness And Melanoma Risk
Funder
National Health and Medical Research Council
Funding Amount
$943,545.00
Summary
Melanoma is an important cause of death in Australia and our generally light pigmentation in a geographical area of high sun exposure is a major factor in this. Our research increasingly points to certain pigmentation genes having a direct biochemical influence on cancer risk in addition to their risk via pigmentation. Understanding how the genes that deternine skin, hair and eye colour act to modify moliness and melanoma risk is important for public health prevention schemes.
A large mole (melanocytic nevi) count is the strongest known risk factor for melanoma. An understanding of the factors governing naevus development may therefore lead to important insights into the etiology of melanoma. We shall carry out molecular genetic analysis of DNA samples collected from twins and their parents with the aim of identifying major genes affecting moliness, pigmentation and other risk factors for melanoma. The importance of this study is that it will significantly advance our ....A large mole (melanocytic nevi) count is the strongest known risk factor for melanoma. An understanding of the factors governing naevus development may therefore lead to important insights into the etiology of melanoma. We shall carry out molecular genetic analysis of DNA samples collected from twins and their parents with the aim of identifying major genes affecting moliness, pigmentation and other risk factors for melanoma. The importance of this study is that it will significantly advance our understanding of the relationship between moliness and melanoma risk and may lead to new therapeutic interventions.Read moreRead less
A Genome Wide Association Study For Alcohol And Nicotine Addiction Susceptibility Genes
Funder
National Health and Medical Research Council
Funding Amount
$872,816.00
Summary
Alcohol and nicotine addiction are major public health problems within Australia. As well as the personal and economic costs associated with dependence, there is a wide range of downstream health effects from heavy drinking and smoking. This is a proposal for a genome wide association study to systematically screen and identify genetic variants within the Australian population that affects an individual's liability to developing alcohol addiction, nicotine addiction or both.