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Research Topic : genetic polymorphisms
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  • Funded Activity

    Functional And Genetic Analysis Of PHF11, A New Gene Associated With Atopic Dermatitis And Asthma

    Funder
    National Health and Medical Research Council
    Funding Amount
    $483,261.00
    Summary
    Atopic dermatitis, or eczema, is an increasingly common severe allergic condition affecting the skin that afflicts up to 30% of all Australian children. Eczema has significant financial impact on families as well on the health and well being of the affected child. The majority of asthmatics are also allergic, explaining why many children who suffer from eczema often go on to develop asthma as well. A familial history of asthma or eczema is an important risk factors for a child developing the dis .... Atopic dermatitis, or eczema, is an increasingly common severe allergic condition affecting the skin that afflicts up to 30% of all Australian children. Eczema has significant financial impact on families as well on the health and well being of the affected child. The majority of asthmatics are also allergic, explaining why many children who suffer from eczema often go on to develop asthma as well. A familial history of asthma or eczema is an important risk factors for a child developing the disorder, meaning that allergy is to a large extent determined by the genes we inherit from our parents. Our genes consist of four different building blocks, called nucleotides, which are identified by four letters: A, G, C and T. Each gene has a specific spelling of these four letters, although between any two people there will invariably be small single letter differences in the way a gene is spelt. Normally, these differences have no effect. In an allergic individual, however, these differences do have an effect. Identifying differences in the way a gene is spelt and why this should lead to eczema or asthma is a major research goal. In the past several years a number of genes have been identified that play an important role in allergy and we have recently identified a spelling difference in a new gene that we believe is important in the allergic response of eczema and asthma. At the moment, we can only guess how this gene might work. We know it is expressed in cells of our immune system that are important in allergy. We also suspect it might be an on or off switch for other genes important for allergy. This project will test these ideas and show how differences in the way this gene is spelt lead to differences in how this gene works. This will be important in adding another piece to the puzzle of how genes control allergy and could lead to better and earlier treatment of these disorders with improved health for affected children as well as adults.
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    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.
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    Novel Statistical Methods For The Analysis Of Meausred Genetic And Environmental Risk Factors In Twin Studies

    Funder
    National Health and Medical Research Council
    Funding Amount
    $478,314.00
    Summary
    Studies on twins are an important way to determine whether the risk of disease is likely to be influenced by genetic factors but have traditionally focussed on unmeasured factors. New epidemiological studies measure thousands of genetic variants on many participants. This project will extend methods for analysing data within and between twin pairs to determine whether risk factors are likely to be causal and therefore should be the subject of further designed studies based on intervention.
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    Funded Activity

    The Interaction Of LPS Pathway Genes With Pre-natal And Early Exposure To LPS And Allergens Predicts Atopy At Age One

    Funder
    National Health and Medical Research Council
    Funding Amount
    $381,263.00
    Summary
    The poor understanding of the cause of asthma has made prevention strategies unsuccessful. This study will provide valuable data for understanding the interactions between exposure to environmental stimuli and LPS pathway genes on the development of allergy and asthma in infants. As environmental modifications and dietary interventions during pregnancy are being investigated, the findings from the proposed study will be important in guiding prevention practices of allergic diseases.
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    Funded Activity

    A Population-based Family Study Of Filaggrin Mutations And Allergic Disease Risk In Australia

    Funder
    National Health and Medical Research Council
    Funding Amount
    $308,584.00
    Summary
    It is biologically plausible that the association of known environmental risk factors for asthma may be different for genetically susceptible individuals. Few studies have examined the interaction between genetic and environmental factors. that have not considered genetic susceptibility are estimating an average risk of asthma across all genotypes in the population which may not be relevant for a particular sub-group.
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    Funded Activity

    Identification Of Novel Genes Influencing Development Of Type 2 Diabetes

    Funder
    National Health and Medical Research Council
    Funding Amount
    $558,920.00
    Summary
    Type 2 diabetes is usually associated with obesity and is often part of a wider disturbance affecting an individual's energy metabolism. The number of affected people with type 2 diabetes has trebled since 1981 in Australia and is still increasing. Apart from individual suffering, this presents a major public health burden for the country (approx $3 billion annually). Currently available lifestyle based and pharmaceutical therapies are inadequate to control the increasing numbers of affected ind .... Type 2 diabetes is usually associated with obesity and is often part of a wider disturbance affecting an individual's energy metabolism. The number of affected people with type 2 diabetes has trebled since 1981 in Australia and is still increasing. Apart from individual suffering, this presents a major public health burden for the country (approx $3 billion annually). Currently available lifestyle based and pharmaceutical therapies are inadequate to control the increasing numbers of affected individuals. Unfortunately the cause of disease is poorly understood, although genetic factors are known to be important, in other words it runs in the family. This project proposes to identify some of these factors (genes) and how they contribute to the disease. Using molecular flags on the DNA (like DNA fingerprinting) we have previously found that a small region on chromosome 12 is likely to carry one or more of these disease genes. But there are over 100 genes in the region. To help choose the most likely candidates first for testing, we have developed an automated computer database searching program ranked the genes based on what is already known about them. We have also taken a large number of physiological measures in a large group of people. Some of these measures are controlled by the same chromosome 12 region - thus to improve our chances of finding the genes quickly we will look at those that change the most between people with diabetes and people without diabetes. In this project we shall investigate the 20 genes most likely affect diabetes based on changes in physiological measures and what is already known about them. A successful finding means we will know more about the mechanism of disease development and be able to better develop new therapies for treatment and prevention. If none of these genes are the culprit, we would continue examination of the next set of genes likely to be involved and so on until we are successful.
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    Funded Activity

    Inflammation, Genes And Atherosclerosis

    Funder
    National Health and Medical Research Council
    Funding Amount
    $287,970.00
    Summary
    Atherosclerotic vascular disease cause considerable morbidity, mortality and use of health services in Australia. Current known risk factors explain approximately half of all cardiovascular diseases. The search for new risk factors is therefore a high priority. Evidence suggests that chronic inflammation is closely involved in the process of atherosclerosis and its clinical complications. This study aims to determine if sensitive serum markers of inflammation and gene-environment interactions th .... Atherosclerotic vascular disease cause considerable morbidity, mortality and use of health services in Australia. Current known risk factors explain approximately half of all cardiovascular diseases. The search for new risk factors is therefore a high priority. Evidence suggests that chronic inflammation is closely involved in the process of atherosclerosis and its clinical complications. This study aims to determine if sensitive serum markers of inflammation and gene-environment interactions that affect inflammation will predict the extent and progression of carotid atherosclerosis in an Aboriginal and a non Aboriginal community population and in patients with premature coronary heart disease. This study should provide a greater understanding of the mechanisms involved in the development and progression of atherosclerosis. It is likely that we will find that some inflammatory markers and candidate gene polymorphisms will help identify individuals at increased cardiovascular risk, and who require earlier treatment to prevent disease. In particular, it would focus on preventive therapies that reduce atherosclerosis through anti-inflammatory targets. This study represents a crucial step towards improving our understanding of the aetiology of cardiovascular diseases, and in developing new ways to prevent heart disease and stroke. Progress in these areas will likely have significant public health benefits
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    Funded Activity

    Predictors Of Treatment Outcomes Following Anti-vascular Endothelial Growth Factor (VEGF) Therapy For Neovascular AMD.

    Funder
    National Health and Medical Research Council
    Funding Amount
    $240,277.00
    Summary
    Age-related macular degeneration (AMD) is the most common cause of severe, irreversible loss of vision amongst elderly populations in the developed world. Bleeding in the retina destroys central vision. New treatments have been developed to stop this bleeding. However not all patients benefit equally, with some still losing vision. This project aims to investigate what determines how well an individual responds to treatment, in particular, how genes might influence the response.
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    Funded Activity

    Genetic Polymorphisms In Genes Controlling Innate Immunity As Risk Factors For Childhood Acute Lymphoblastic Leukaemia

    Funder
    National Health and Medical Research Council
    Funding Amount
    $241,500.00
    Summary
    For some time now, researchers have speculated that the development of childhood leukaemia is related to exposure to an infectious agent. However, a causal pathogen is yet to be identified. Recent studies have shown that the initial recognition of microbes as they enter the human body is determined by a group of receptors, toll-like receptors (TLRs), which selectively bind to essential components of these pathogens. This process allows the body to respond immediately to microbial invasion; a pro .... For some time now, researchers have speculated that the development of childhood leukaemia is related to exposure to an infectious agent. However, a causal pathogen is yet to be identified. Recent studies have shown that the initial recognition of microbes as they enter the human body is determined by a group of receptors, toll-like receptors (TLRs), which selectively bind to essential components of these pathogens. This process allows the body to respond immediately to microbial invasion; a process which is vital during early childhood, when clonal expansion of antibodies and other host defences is inadequate. It is becoming increasingly apparent that this innate immune response is not just the first line of defence but a necessary event for the development of an adaptive immune response. We propose that the innate immune system of children carrying TLR gene variants may be less effective at detecting the presence of microbial pathogens in the environment. We hypothesize that by dampening the stimulation of innate immunity in early childhood, TLR gene variants may indirectly cause a dysfunction in the maturation of a child's immune system and increase the chance of a pre-leukaemic clone emerging, leading to the development of childhood leukaemia.
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    Funded Activity

    Neurogenic Mechanisms Of Cardiovascular Risk In The Metabolic Syndrome: Benefits Of Lifestyle Interventions

    Funder
    National Health and Medical Research Council
    Funding Amount
    $328,194.00
    Summary
    One in four adult Australians has the 'metabolic syndrome' (MetS), a clustering of metabolic and heart disease risk factors associated with abdominal obesity. Sympathetic nervous system (SNS) activity is increased in the MetS resulting in enhanced release of the stress hormone 'noradrenaline' . This project will examine the biological and genetic determinants of enhanced SNS activity and the benefits of lifestyle interventions (weight loss, weight loss maintenance and aerobic exercise).
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