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
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.
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
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
Why is most of the genetic variance for complex traits undetected by large powerful screens of common variants? The genomics revolution has made it possible to measure thousands of DNA variants in individuals. These variants have been associated with phenotypic outcomes in a range of species. Paradoxically, even very large studies have only accounted for a fraction of the resemblance between relatives that we know exist. Our study will test three specific hypotheses to explain this paradox. A be ....Why is most of the genetic variance for complex traits undetected by large powerful screens of common variants? The genomics revolution has made it possible to measure thousands of DNA variants in individuals. These variants have been associated with phenotypic outcomes in a range of species. Paradoxically, even very large studies have only accounted for a fraction of the resemblance between relatives that we know exist. Our study will test three specific hypotheses to explain this paradox. A better understanding about the genetic architecture for complex traits 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 lead to more efficient selection programs in agricultural populations and will inform us with respect to past evolutionary events.Read moreRead less
Development of molecular markers for resistance to blackleg disease (Leptosphaeria maculans) in canola. Canola (Brassica napus) is a valuable oil seed crop grown in many parts of the world and contributes annually $A450 million to the Australian economy. The overall aim of this project is to develop molecular markers for blackleg resistance using Australian germplasm along with evaluation in Australian disease nurseries which are regarded worlwide to develop the highest levels of disease pressu ....Development of molecular markers for resistance to blackleg disease (Leptosphaeria maculans) in canola. Canola (Brassica napus) is a valuable oil seed crop grown in many parts of the world and contributes annually $A450 million to the Australian economy. The overall aim of this project is to develop molecular markers for blackleg resistance using Australian germplasm along with evaluation in Australian disease nurseries which are regarded worlwide to develop the highest levels of disease pressure. Once molecular marker systems are developed and evaluated, they will be applied to facilitate the selection of Nugrain's (Industry Partner) canola breeding programs. Any molecular markers and QTL developed for Australian cultivars would find commercial application in breeding programmes.Read moreRead less
Breaking selective constraints: is Hsp90 a capacitor of evolutionary change? Gene action and expression can be modulated by genetic mechanisms. If a general mechanism controlling gene expression exists that can be easily manipulated it has the potential to allow animal and plant breeders to quickly produce and select for new characters of agricultural importance without relying on transgenics and long-term breeding programs. It would also assist in the development of tools for identifying and de ....Breaking selective constraints: is Hsp90 a capacitor of evolutionary change? Gene action and expression can be modulated by genetic mechanisms. If a general mechanism controlling gene expression exists that can be easily manipulated it has the potential to allow animal and plant breeders to quickly produce and select for new characters of agricultural importance without relying on transgenics and long-term breeding programs. It would also assist in the development of tools for identifying and detecting genes that increase susceptibility to human diseases, such as cancer, that are only expressed under certain conditions environmental. I intend to determine whether the protein Hsp90 represents a general mechanism controlling gene expression. Read moreRead less
Adaptive evolution of mutual mate preferences in nature. Working at the interface of evolution, genetics and the environment, our research combines top scientists from Australia and abroad to seek a comprehensive understanding of the origins of biodiversity, and the evolution of new species. Such knowledge is essential if we wish to predict, and hopefully minimise, the loss of biodiversity through human-mediated environmental change. Using a native Australian insect, we are investigating the evo ....Adaptive evolution of mutual mate preferences in nature. Working at the interface of evolution, genetics and the environment, our research combines top scientists from Australia and abroad to seek a comprehensive understanding of the origins of biodiversity, and the evolution of new species. Such knowledge is essential if we wish to predict, and hopefully minimise, the loss of biodiversity through human-mediated environmental change. Using a native Australian insect, we are investigating the evolutionary consequences of the choice individuals make when selecting a mate. In addition to its role in the origin and maintenance of biodiversity, these choices can have fundamental effects on adaptation to changing environments and the long-term persistence of endangered populations.Read moreRead less