A Genome-wide Association Study In 2000 Glaucoma Cases With Matched Controls Using Equimoloar DNA Pools
Funder
National Health and Medical Research Council
Funding Amount
$610,267.00
Summary
Glaucoma is a common cause of loss of vision worldwide but we are unable to predict which people are at high risk of blindness. We aim to discover the genetic risk factors for glaucoma. We will use cutting edge genetic technology to assess the whole genome in thousands of patients with glaucoma. We hope to identify important new glaucoma genes, which could lead to the development of diagnostic tests and treatments which will provide the most cost-efficient ways to prevent glaucoma blindness.
Identifying Rare Genetic Variants Conferring Susceptibility To Multiple Sclerosis
Funder
National Health and Medical Research Council
Funding Amount
$293,898.00
Summary
Recently there has been success in identifying common genetic variants that confer susceptibility to multiple sclerosis. The variants that have been discovered so far have modest effects on risk of disease, and only explain a small proportion of familial aggregation of disease. In this study we aim to identify rarer genetic variants that have stronger effects on risk of disease, using new statistical methods and new methods to sequence very large amounts of DNA.
New High-risk Variants For Colorectal Cancer: The Post-GWAS Era
Funder
National Health and Medical Research Council
Funding Amount
$710,105.00
Summary
Our aim is to discover new genes that greatly increase bowel cancer risk. If we can identify these carriers we may be able to prevent them getting cancer. By studying DNA related to bowel cancer, using a novel family design, we will identify families most likely to carry the new genes. We will focus genetic testing, using new techniques, to look for mutations in these prioritised families. Identified mutations will be tested in a 3,500 bowel cancer cases to see how important they are.
Fine Mapping Of A Significant Linkage Region For Endometriosis
Funder
National Health and Medical Research Council
Funding Amount
$518,250.00
Summary
Endometriosis is a common disorder affecting up to 10% of women. In this condition, a special type of tissue that normally lines the inside of the womb (the 'endometrium') starts to grow outside the womb, mostly in the pelvis (lower abdomen). Common symptoms are severe pelvic pain, menstrual problems and infertility. The disease has a major impact on women's health, relationships, productivity and life choices. The mechanisms that cause endometriosis are not well understood. Genetic factors infl ....Endometriosis is a common disorder affecting up to 10% of women. In this condition, a special type of tissue that normally lines the inside of the womb (the 'endometrium') starts to grow outside the womb, mostly in the pelvis (lower abdomen). Common symptoms are severe pelvic pain, menstrual problems and infertility. The disease has a major impact on women's health, relationships, productivity and life choices. The mechanisms that cause endometriosis are not well understood. Genetic factors influence a woman's risk of developing endometriosis and finding genes and pathways leading to this disease would be a major advance. This will help design better approaches for the diagnosis, prevention and treatment of endometriosis. Since 1996, nearly 4,000 women with endometriosis plus their families have joined our genetic study. This includes around 1,000 families with two or more sisters who both have the disease. We have looked at the DNA from these sisters and found significant evidence for a gene or genes affecting endometriosis on one chromosome. No one else has linked this location with endometriosis. We are now focusing our efforts in the laboratory on this area, which contains approximately 250 genes. The aim of our new project is to study genes in the region in more detail to pinpoint the gene or genes responsible for risk of endometriosis.Read moreRead less
Defining The Mechanism Of Melanoma And Naevus Risk On Chromosome 9p21
Funder
National Health and Medical Research Council
Funding Amount
$523,448.00
Summary
Melanoma is a common cancer. In 2001, 8,885 Australians were diagnosed with melanoma and 1074 died from the disease. We identified markers on chromosome 9 associated with increased melanoma risk. Our aim is to explore this region in detail to identify the genes and pathways affected. Understanding genetic risk factors for melanoma will help to identify individuals in the population at most risk, how that risk can be modified and whether targeted surveillance could identify early stage disease.
The Role Of Genomic Copy Number Variation In Regulation Of Bone Disease Phenotypes
Funder
National Health and Medical Research Council
Funding Amount
$438,600.00
Summary
We have been working to identify quantitative trait loci for key clinical traits relevant to osteoporosis, for the past 15 years, with substantial success. We recently completed a Genome Wide Association Study and identified 20 loci with strong evidence for a role in the regulation of key bone disease phenotypes. In this project we will extend that highly acclaimed research to study genomic copy number variation and define the role of those genetic variants in osteoporosis.
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
P.gingivalis GroEL And HSP60 Specific T Cells In Periodontal And Cardiovascular Diseases
Funder
National Health and Medical Research Council
Funding Amount
$619,500.00
Summary
Cardiovascular diseases are the major cause of death in adults in most developed and many developing countries. In recent years there has been accumulating evidence that chronic infections such as Helicobacter pylori and Chlamydia pneumoniae are associated with cardiovascular diseases. Chronic inflammatory periodontal diseases are among the most common chronic infections with over one million Australians at risk of losing their teeth. Poor dental health and in particular chronic periodontitis is ....Cardiovascular diseases are the major cause of death in adults in most developed and many developing countries. In recent years there has been accumulating evidence that chronic infections such as Helicobacter pylori and Chlamydia pneumoniae are associated with cardiovascular diseases. Chronic inflammatory periodontal diseases are among the most common chronic infections with over one million Australians at risk of losing their teeth. Poor dental health and in particular chronic periodontitis is now consistently being associated with a number of other diseases and conditions including cardiovascular disease. In some studies the relationship between periodontal disease and cardiovascular disease is stronger than that for other risk factors such as smoking and high cholesterol. Periodontitis results from the inflammatory response to dental plaque. One of the major pathogens identified in dental plaque is P.gingivalis. Heat shock proteins (HSP) are expressed by cells on exposure to various forms of stress including temperature and injury. They participate in physiological processes such as the assembly, transport and protection of proteins from breakdown. There is a remarkable conservation in the structure of heat shock genes and HSP across species. Many pathogens including P.gingivalis bear antigens that are similar to human HSPand cross reactivity during infection may result in disease such as atherosclerosis. This study aims to test the hypothesis that cross reactivity between the bacterial antigens and HSP may explain the mechanism of the association between periodontal disease and cardiovascular disease. This would have a significant impact on the treatment of both periodontal and cardiovascular disease.Read moreRead less