Fine Mapping Of Genes Underlying Asthma And Eosinophilia
Funder
National Health and Medical Research Council
Funding Amount
$278,000.00
Summary
Asthma is the fourth most common chronic disease in Australia, and is increasing in incidence. Genetic factors are known to be important modifiers of disease risk, and several genes have been reported in the literature as being involved in either causing asthma or altering response to therapy. Immunoglobulin E (IgE) level and eosinophil count are two factors known to be increased in the blood of asthmatics. In two studies by our group, one of asthma in families, the other of healthy adolescent t ....Asthma is the fourth most common chronic disease in Australia, and is increasing in incidence. Genetic factors are known to be important modifiers of disease risk, and several genes have been reported in the literature as being involved in either causing asthma or altering response to therapy. Immunoglobulin E (IgE) level and eosinophil count are two factors known to be increased in the blood of asthmatics. In two studies by our group, one of asthma in families, the other of healthy adolescent twins, we showed these measures to be genetically linked to two different regions in the genome. Closer examination of these regions found several genes that might be responsible for the linkage. In the present study, we plan to test which of these candidate genes actually causes elevated IgE level or eosinophil count. The approach is to compare the frequency of a putative gene in a child expressing that phenotype to that in their parents. Each child receives one copy of a gene from the father, and one from the mother, making up a complete genotype (two possibly different versions or alleles of the gene). Since each parent transmitted only one allele to the child, the remaining allele from each parent can be used to create a normal control genotype, that is guaranteed to come from the same ethnic background as the asthmatic child. Therefore, we will collect replacement blood samples in those familes where all the previously DNA has been used up in our earlier study. We will extract DNA, and measure the genotypes of parents and children at the 6 genes in our two regions that we think most likely to be involved in eosinophil count or IgE level. This family based test will allow us to decide which genes are genuinely associated with asthma in our population. We will also test if these genes interact with other genes thought to be asthma risk factors. Identification of novel genes involved in asthma will help understand and ultimately treat this condition.Read moreRead less
Delivering On The GWAS Promise: From Genetic Discoveries To Novel Drug Targets For Asthma
Funder
National Health and Medical Research Council
Funding Amount
$697,605.00
Summary
The aim of this study is to identify new drug targets for asthma. This is important because for 6 in 10 asthma patients, current treatments do not adequately control disease symptoms and so these individuals are at a higher risk of having severe exacerbations. I propose that identifying asthma risk genes represents our best chance to identify novel drug targets for asthma. In this study, I will identify new asthma risk genes and test whether blocking these genes can alleviate disease symptoms.
Centre Of Research Excellence In Pulmonary And Environmental Medicine.
Funder
National Health and Medical Research Council
Funding Amount
$2,007,200.00
Summary
This Centre will study inhalational lung diseases, ie diseases caused by substances such as asbestos, cigarette smoke, air pollutants and allergens. Australia has of the highest incidences in the world of at least 2 of the diseases to be studied, asbestos- and allergen-induced lung diseases. These two alone are estimated to cost the Australian economy over $100 million -yr and $1 billion respectively in direct health costs plus loss of productivity and compensation. Furthermore COPD on of our ot ....This Centre will study inhalational lung diseases, ie diseases caused by substances such as asbestos, cigarette smoke, air pollutants and allergens. Australia has of the highest incidences in the world of at least 2 of the diseases to be studied, asbestos- and allergen-induced lung diseases. These two alone are estimated to cost the Australian economy over $100 million -yr and $1 billion respectively in direct health costs plus loss of productivity and compensation. Furthermore COPD on of our other major areas of interest is the 4th leading cause of death in males and conservatively costs the economy over one billion dollars per year as well as being the leading cause of disability in the elderly. It is predicted that COPD will be the 4th most common disease worldwide by 2020. As such this area of study is important for Australia and internationally and any advances will deliver major economic and health benefits. We will study the role of blood and sputum tests in the diagnosis, monitoring, screening and management of lung diseases caused by asbestos, cigarette smoke, air pollutants and allergens ie. mesothelioma, asthma, COPD and lung cancer. We will apply modern DNA 'gene chip' methods to study the pathogenesis of these diseases and help us to identify new treatment targets. This will also be used to guide genetic searches for polymorphism's, spliced variants and DNA modification(epigentics) in COPD and lung cancer. Genetic studies of sensitivity to air pollution will be used to define at risk patients We will also evaluate how the method of cell death that occurs during some therapies eg. in cancer and allergy-asthma, might alter how the body responds and thus help us develop novel therapeutic strategies for these diseases. This research program should lead to new tests and treatments and at the same time promote the training of a new generation of young researchers in this field and so ensure that the work continues long termRead moreRead less
I am a clinical researcher determining: a) the role of altered airway structure, particularly airway smooth muscle and extracellular matrix, in asthma and COPD; and b) the prevalence of, and risk factors for, respiratory disease in general populations.