Identification And Characterisation Of Novel Mouse Models For Recessively Inherited Deafness.
Funder
National Health and Medical Research Council
Funding Amount
$504,750.00
Summary
Hearing loss affects 10% of Australians. Approximately 1 in 1000 children is born deaf. Another 1 in 1000 people develops hearing loss by adulthood. A progressive hearing impairment occurs with age so that more than 50% of people over the age of 75 have a substantial hearing loss. The financial, social and personal costs of deafness are significant. Deafness is caused by environmental and- or inherited factors. Environmental risk factors include premature birth, infections and exposure to loud n ....Hearing loss affects 10% of Australians. Approximately 1 in 1000 children is born deaf. Another 1 in 1000 people develops hearing loss by adulthood. A progressive hearing impairment occurs with age so that more than 50% of people over the age of 75 have a substantial hearing loss. The financial, social and personal costs of deafness are significant. Deafness is caused by environmental and- or inherited factors. Environmental risk factors include premature birth, infections and exposure to loud noise. Inherited factors include changes (mutations) in one of many genes whose products are essential for normal hearing. In the majority of children and young people with a hearing impairment the underlying cause is genetic. It is also thought that genetic predisposition frequently contributes to the early onset and the severity of age-related hearing loss. However, it has been difficult to identify the genes causing deafness, and as a consequence we know relatively little about what these genes do. The mouse ear is very similar to the human ear and in this application we propose to use mice to identify and study deafness genes. Australia has a unique resource of mice that are being especially bred to uncover genetic diseases. We have shown that 1 in a 1,000 of these mice have a genetic hearing loss similar to that found in most newborns and young people. These mice therefore provide us with an exceptional opportunity to discover novel deafness genes, which again will provide us with more information about how we hear. We will investigate why changes in these genes causes hearing loss and this information will allow us to determine in detail how genetic and environmental factors lead to hearing loss in young and old. The results will immediately allow us to offer earlier diagnosis and better counselling to affected families, and in the longer term we believe our research will enable us to develop improved or novel treatments to delay or prevent deafness.Read moreRead less
I am a clinician-scientist and endocrinologist most interested in clinical problems associated with bone, in particular the highly heritable disease of osteoporosis. I hope by studying genetic determinants of bone mass to determine the key genes involved, with the long term aim of informing the development of novel therapies for this common, painful and disabling disease.
Fine Scale Mapping And Identification Of The IBD1 Gene On Chromsosome 16
Funder
National Health and Medical Research Council
Funding Amount
$483,849.00
Summary
One of the greatest challenges facing contemporary gastroenterology is to understand the causes of the inflammatory bowel diseases (IBD). Studies on the prevalence, incidence and cost of IBD indicate that these diseases have considerable impact in Australia. On average, patients lose more than 13 days from work each year, and in hospital, IBD in-patients accounted for 7% of total admissions and 10% of total bed days at an average cost of $2600 per admission. We estimate that there may be more th ....One of the greatest challenges facing contemporary gastroenterology is to understand the causes of the inflammatory bowel diseases (IBD). Studies on the prevalence, incidence and cost of IBD indicate that these diseases have considerable impact in Australia. On average, patients lose more than 13 days from work each year, and in hospital, IBD in-patients accounted for 7% of total admissions and 10% of total bed days at an average cost of $2600 per admission. We estimate that there may be more than 10,000 Australians who suffer from IBD. The existence of a genetic predisposition to IBD is now well established, and there is strong evidence that the disease is complex, resulting from the interaction of a number of different genes. To date, one genetic localisation on chromosome 16 has been established in several different populations, and we have confirmed the importance of this localisation in the Australian population. We will further refine the localisation by fine scale mapping in the pericentromeric region of chromosome 16 by identifying and studying the inheritance of novel markers in the region. We will then identify and characterise the gene itself using several complementary appoaches that rely on differences at the molecular level between disease and normal tissue. This work is part of the international effort to identify all IBD susceptibility genes. Once that is achieved, approaches to explaining the interactions between the genes, their protein products and environmental triggers can be determined. Only when the mechanisms of these interactions are understood will the expectation of rational therapies based on an understanding of disease aetiology be possible.Read moreRead less
Genome-wide Association Studies Of Biomedical Traits And Endophenotypes For Complex Disease
Funder
National Health and Medical Research Council
Funding Amount
$295,804.00
Summary
The burden of common complex diseases, such as cardiovascular disease is substantial to the health care system. These diseases are caused by genes and environments as well as their interactions. The proposed project will identify genes affecting the susceptibility of individuals to complex diseases. Discovery of such genes will be important for their diagnosis, prevention and treatment and may serve as an important resource for future personalized medicine.
Glaucoma is the second leading cause of blindness in the world affecting approximately 70 million people. Glaucoma can occur at any age but the commonest type occurs in middle to old age. The disease has a genetic basis and can be inherited. As a result we have been studying the genetics of the disease in two large families from Tasmania. We hope to identify the genes involved in disease causation using a number of genetic techniques. Once mutations in a disease gene have been identified from af ....Glaucoma is the second leading cause of blindness in the world affecting approximately 70 million people. Glaucoma can occur at any age but the commonest type occurs in middle to old age. The disease has a genetic basis and can be inherited. As a result we have been studying the genetics of the disease in two large families from Tasmania. We hope to identify the genes involved in disease causation using a number of genetic techniques. Once mutations in a disease gene have been identified from affected individuals we will then be in a position to look for mutations in other family members and identify those individuals at risk of developing disease. Improvements in our understanding of how these genes are involved in disease causation will allow us to offer diagnostic testing to the wider community and develop better therapeutic interventions for treatment.Read moreRead less
A Genome Wide Association Study For Endometriosis Susceptibility Genes
Funder
National Health and Medical Research Council
Funding Amount
$946,750.00
Summary
Endometriosis is a common condition that affects up to 10% of women. Symptoms are severe pelvic pain, menstrual problems and infertility with major impacts on women's lives and relationships. Since 1996, 4,000 affected women plus their families have joined our genetic study. Our aim is to conduct a genome wide search to identify genes contributing to endometriosis. This knowledge will ultimately lead to better diagnosis and treatment for the millions of women who suffer the disease.
Genes Controlling The Development Of Lung Disease In Normal And Cystic Fibrosis Mice.
Funder
National Health and Medical Research Council
Funding Amount
$362,582.00
Summary
Patients with cystic fibrosis have a lethal predisposition to bacterial infection which causes irreversible lung disease. It is clear that even when patients carry the same mutation in the defective gene (CFTR), genetic background influences the course of the disease. Very little is known of the nature of these other genes and this proposal will identify those genes which influence the response of the CF lung to pathogens and in doing so may indicate novel therapeutic strategies.
Many recent gene mapping efforts have focused on population based approaches instead of previously used family based approaches. One of the limiting factors with population based approaches is the cost of the technology - each participant must be evaluated (or genotyped) for hundreds of thousands of genetic markers. The cost can be reduced by using an approach which pools individuals together for genotyping, with statistical models used to deal with the problems that this creates.
Histone H3.3 Dynamics At The Telomere In Pluripotent Embryonic Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$571,977.00
Summary
The telomere is required for the protection of the chromosome ends. Telomere loses its repeat during each cell division, so telomere shorthening is one of the mechanisms underlying organismal aging as critically short telomeres induce chromosome instability and cell death. Defective telomeres can also result in genetic diseases and development of cancers. Here, we propose to study the mechanism that operates to ensure continual telomere renewal without senescence in embryonic stem cells.