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
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
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
Identifying genes causing thermal evolution of ectotherm body size. Cold-blooded animals increase in body size as they are found in populations at greater distances from the equator. These patterns are due to populations adapting to temperature. The aim of this project is to identify the genes involved in this adaptation process. We will do this by taking advantage of a well-studied body size cline in the vinegar fly on the east coast of Australia, and by building on an international collaborati ....Identifying genes causing thermal evolution of ectotherm body size. Cold-blooded animals increase in body size as they are found in populations at greater distances from the equator. These patterns are due to populations adapting to temperature. The aim of this project is to identify the genes involved in this adaptation process. We will do this by taking advantage of a well-studied body size cline in the vinegar fly on the east coast of Australia, and by building on an international collaboration between a leading UK and two Australian research groups. In doing so we will provide an explanation at the molecular level for one of the great unresolved phenomena in biology: why do cold-blooded animals get bigger in the cold? The research also leads to the potential to manipulate body size in animals.Read moreRead less
A Genomic Dissection of Natural Adaptation in Mate Recognition. Adaptation is a fundamental area of evolutionary biology but we know surprisingly little about its underlying genetic basis. As a process, adaptation poses several challenges for Australian society including bacterial evolution of resistance to antibiotics, HIV resistance to antiviral medications and the evolution of pesticide resistance in agricultural pests. This study will use a model system and genomic tools to test theoretical ....A Genomic Dissection of Natural Adaptation in Mate Recognition. Adaptation is a fundamental area of evolutionary biology but we know surprisingly little about its underlying genetic basis. As a process, adaptation poses several challenges for Australian society including bacterial evolution of resistance to antibiotics, HIV resistance to antiviral medications and the evolution of pesticide resistance in agricultural pests. This study will use a model system and genomic tools to test theoretical models of the genetic basis of adaptation. This integrative approach will enhance Australia's research profile in genomics and evolutionary biology. The project will provide emerging scientists with skills in areas including genomics, molecular biology, evolutionary biology and agricultural genetics.Read moreRead less
Maximising knowledge from dense SNP (single nucleotide polymorphisms) data using multi-locus analysis. The genomics revolution has made it possible to measure thousands of DNA variants in individuals. This information can be used in many ways, including to find genes that cause variation between individuals in a population and to estimate the size of the population in the past. Our study will lead an analysis method that will extract more information out of such data. This will improve the effi ....Maximising knowledge from dense SNP (single nucleotide polymorphisms) data using multi-locus analysis. The genomics revolution has made it possible to measure thousands of DNA variants in individuals. This information can be used in many ways, including to find genes that cause variation between individuals in a population and to estimate the size of the population in the past. Our study will lead an analysis method that will extract more information out of such data. This will improve the efficiency of gene mapping methods, including applications in humans for traits related to productive ageing and a healthy start to life, will allow the estimation of genetic relatedness and genetic variation in natural populations, and will lead to more efficient selection programs in agricultural populations.Read moreRead less
Intra-genomic conflict and the evolution of sexually selected traits. The dynamics of sexual selection may prevent the simultaneous optimization of traits shared by the sexes, or of different traits within each sex. This proposal focuses on the consequences of these conflicts for phenotypic and genomic evolution. First, I will compare selection acting on a sexually dimorphic trait in males and females. Second, I will use artificial selection to create a novel sexually dimorphic trait, and track ....Intra-genomic conflict and the evolution of sexually selected traits. The dynamics of sexual selection may prevent the simultaneous optimization of traits shared by the sexes, or of different traits within each sex. This proposal focuses on the consequences of these conflicts for phenotypic and genomic evolution. First, I will compare selection acting on a sexually dimorphic trait in males and females. Second, I will use artificial selection to create a novel sexually dimorphic trait, and track the evolutionary response. Third, I will investigate the link between two important fitness traits: body size and ageing rate. This work will enhance important on-going research in the laboratory of Robert Brooks (UNSW).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.
Drosophila Quantitative Genomics. This research proposal will be a key element in the emerging program in evolutionary and ecological functional genomics at the University of Queensland. Our studies utilize modern genomics approaches to address diverse national priorities from conservation of biological resources in the face of climate change, to understanding how genetic history contributes to drug susceptibility. The research will contribute to the intellectual foundation upon which rigorous ....Drosophila Quantitative Genomics. This research proposal will be a key element in the emerging program in evolutionary and ecological functional genomics at the University of Queensland. Our studies utilize modern genomics approaches to address diverse national priorities from conservation of biological resources in the face of climate change, to understanding how genetic history contributes to drug susceptibility. The research will contribute to the intellectual foundation upon which rigorous environmental and biomedical research is built. Social impact will be seen in the training of a new generation of integrative genome biologists, and the shaping of attitudes toward the role of genetics in human biology.Read moreRead less
The Maintenance of Genetic Variation by Antagonistic Sexual Selection. The principle outcomes of my proposed research are fundamental knowledge, training of young scientists and the improvement of Australia's research capacity and profile. My research will have a major impact on two major branches of evolutionary biology that are seldom integrated - sexual selection and quantitative genetics. My research will enable me to establish myself as an independent researcher. Moreover, my collaborations ....The Maintenance of Genetic Variation by Antagonistic Sexual Selection. The principle outcomes of my proposed research are fundamental knowledge, training of young scientists and the improvement of Australia's research capacity and profile. My research will have a major impact on two major branches of evolutionary biology that are seldom integrated - sexual selection and quantitative genetics. My research will enable me to establish myself as an independent researcher. Moreover, my collaborations with one of the leading research laboratories in the UK, will teach me several modern techniques that I can disseminate to Australian students participating on the proposed project.Read moreRead less