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.
The Role Of GRHL-3, A Mammalian Homologue Of Drosophila Grainyhead, In Neural Tube Development
Funder
National Health and Medical Research Council
Funding Amount
$496,500.00
Summary
Spina bifida and anencephaly are two common human congenital malformations that form part of a wide spectrum of mutations known collectively as neural tube defects (NTDs). Patients with the most severe form of spina bifida have a failure of the vertebral column and skin to close over the spinal cord and therefore suffer from limb paralysis and marked bladder and bowel dysfunction. Infants with anencephaly have an open cranial vault and failure of normal brain development and die within the first ....Spina bifida and anencephaly are two common human congenital malformations that form part of a wide spectrum of mutations known collectively as neural tube defects (NTDs). Patients with the most severe form of spina bifida have a failure of the vertebral column and skin to close over the spinal cord and therefore suffer from limb paralysis and marked bladder and bowel dysfunction. Infants with anencephaly have an open cranial vault and failure of normal brain development and die within the first few hours of life. These abnormalities occur frequently (1-1000 live births) and are a direct result of failure of the neural tube to close during embryogenesis. NTDs are influenced by both environmental and genetic factors. The best characterised environmental factor is the dietary supplement folate, which when administered before conception results in a reduction in the incidence of spina bifida. The genetic complexity is evidenced by the array of mouse genetic mutations that give rise to NTDs. One of these mouse mutations, known as Curly tail (ct), has served as the major animal model of human NTDs. This is because the ct mice are resistant to folate administration (like most of the cases of spina bifida currently seen in patients) and because the mice seem to have normal development in virtually all other organ systems. Ironically, the genetic mutation that causes the curly tail phenotype has remained undiscovered for over 50 years. We have now identified the gene mutated in the curly tail mice. This gene is highly conserved in humans suggesting that it will play a similar role in neural tube development in man. The gene, known as GRHL-3, is a descendant of a fly gene critical for development of the nervous system in that organism. The studies we propose here will examine the developmental pathways involved in normal neural tube closure in mice and humans and will impact on our understanding of these devastating congenital malformations.Read moreRead less
Epilepsy is the name of a group of disorders where seizures occur. 5% of people will have at least one seizure. Seizures accompanied by fever (febrile) are common in early childhood. Most forms of epilepsy and febrile seizures have an inherited component. Progress in finding genes for common forms of epilepsy has been slow, probably because they are due to the interaction of a number of genes. Four genes for rare epilepsies with single gene inheritance have been identified. These genes code for ....Epilepsy is the name of a group of disorders where seizures occur. 5% of people will have at least one seizure. Seizures accompanied by fever (febrile) are common in early childhood. Most forms of epilepsy and febrile seizures have an inherited component. Progress in finding genes for common forms of epilepsy has been slow, probably because they are due to the interaction of a number of genes. Four genes for rare epilepsies with single gene inheritance have been identified. These genes code for subunits of ion channels in cells. We study families where many individuals have seizures and carefully diagnose the seizures types. This work has resulted in the description of 5 new inherited epilepsies and led to discovery of 3 of the 4 known genes. The most important new inherited epilepsy is Generalized Epilepsy with Febrile Seizures Plus (GEFS+). GEFS+ accounts for many children with febrile seizures restricted to early childhood, or where seizures continue into mid-childhood. GEFS+ families may contain an individual with severe generalized epilepsy with intellectual disability. In a Tasmanian family with GEFS+, we found a gene defect in the sodium channel of nerve cells in the brain. We plan to study more families with GEFS+. We believe that specific severe childhood epilepsies may occur in families with GEFS+. If so, then the underlying cause of these serious disorders may be gene defects of GEFS+. Finding such genes will help to understand the basis of seizures and ultimately lead to targeted therapies. The second major focus of our work on GEFS+ is to use family studies to understand how different types of seizures are inherited, and to gain insights into the gene interactions underlying common epilepsies. We plan to study isolated cases of GEFS+ for the gene defects found in families. This strategy will reveal whether the same genes are important in the genetics of the common epilepsies.Read moreRead less
MINIMAL RESIDUAL DISEASE IN ACUTE LYMPHOBLASTIC LEUKAEMIA
Funder
National Health and Medical Research Council
Funding Amount
$455,204.00
Summary
This project will study the extremely small numbers of leukaemic cells which are found in patients who are apparently healthy, but which sometimes lead to relapse. Very sensitive methods for measuring and studying low levels of leukaemic cells will be developed and used. To develop new better treatments in the long term, we will study why current treatment sometimes fails to eradicate the leukaemia, leading to patients relapsing. Clinicians currently need to obtain samples of bone marrow to asse ....This project will study the extremely small numbers of leukaemic cells which are found in patients who are apparently healthy, but which sometimes lead to relapse. Very sensitive methods for measuring and studying low levels of leukaemic cells will be developed and used. To develop new better treatments in the long term, we will study why current treatment sometimes fails to eradicate the leukaemia, leading to patients relapsing. Clinicians currently need to obtain samples of bone marrow to assess leukaemia, and the research will show whether this needs to be continued, or whether, with sensitive tests, samples of blood can be used instead. The study will involve collaboration with clinicians throughout Australia and overseas.Read moreRead less