Blood Biomarkers For The Diagnosis Of Pre-clinical Alzheimer’s Disease Employing The Dominantly Inherited Alzheimer Network Cohort
Funder
National Health and Medical Research Council
Funding Amount
$1,125,804.00
Summary
Alzheimer’s disease (AD) is the most common form of dementia and yet a postmortem examination serves as the only definitive diagnosis. The current proposal seeks to investigate alterations in biochemical profiles of individuals who will develop Alzheimer’s disease due to an inherited mutation, against family members who are non-carriers of the mutation, to identify AD related blood changes which can contribute towards the development of a diagnostic blood test for the disease.
Genetic Determinants Of Inherited Optic Neuropathies
Funder
National Health and Medical Research Council
Funding Amount
$249,750.00
Summary
Glaucoma is a slowly progressive visual disorder of the optic nerves often but not always associated with elevated pressure in the eyes. There is a strong genetic component. It is estimated to affect in excess of 60 million people worldwide with more than 6 million of those blind in both eyes. It is the second commonest cause of visual impairment in the developed world, and is present in up to 10% of the population by age 90. Numbers of affected patients in Australia are expected to double in th ....Glaucoma is a slowly progressive visual disorder of the optic nerves often but not always associated with elevated pressure in the eyes. There is a strong genetic component. It is estimated to affect in excess of 60 million people worldwide with more than 6 million of those blind in both eyes. It is the second commonest cause of visual impairment in the developed world, and is present in up to 10% of the population by age 90. Numbers of affected patients in Australia are expected to double in the next 30 years. Current methods of early detection and treatment are often inadequate, and associated visual loss is irreversible. There is a strong need for greater understanding of the disease process and new strategies to prevent and treat visual loss. Two less common causes of untreatable optic nerve blindness are Leber Hereditary Optic Neuropathy (LHON) and autosomal dominant optic atrophy (ADOA) which occur in younger age groups than most cases of glaucoma, and hence sufferers may experience substantial physical, emotional and economic hardship. Over a 10 year period we have seen large numbers of patients with all three eye conditions and have developed a powerful study to determine the genes which cause optic nerve blindness and their relative importance. The research is gathering momentum and the genetics of all 3 conditions are now partly understood. This project seeks to analyse a new major glaucoma gene (Optineurin) in our Australian population and to try to understand the way in which a number of genes interact to cause blindness in some patients but not others. This work will lead to greater understanding of these causes of blindness and is likely to lead to new screening tests to know who is at most risk, and the opportunity to develop and test new treatments targeted to the underlying genetic problem.Read moreRead less
Investigating The Use Of Bone Marrow Transplantation To Study And Treat Polycystic Kidney Disease
Funder
National Health and Medical Research Council
Funding Amount
$349,250.00
Summary
Polycystic kidney disease (PKD) is a common genetic condition that causes fluid filled cysts to form in the kidney. In many cases, these cysts lead to kidney failure. Once the kidneys fail irreversibly, the only treatments available are dialysis and kidney transplantation. Dialysis to remove waste products from the blood is time consuming and does not completely replace all functions of the kidney. Kidney transplantation is limited by the availability of donor organs. At present, there are no re ....Polycystic kidney disease (PKD) is a common genetic condition that causes fluid filled cysts to form in the kidney. In many cases, these cysts lead to kidney failure. Once the kidneys fail irreversibly, the only treatments available are dialysis and kidney transplantation. Dialysis to remove waste products from the blood is time consuming and does not completely replace all functions of the kidney. Kidney transplantation is limited by the availability of donor organs. At present, there are no reliable ways to prevent the onset or slow the progression of PKD. The kidney consists of a complex system of tubules and ducts. PKD causes the cells that make up these tubules and ducts to grow uncontrollably and form cysts. We are using mice to study how mutations affect the mechanisms that control cell growth in the kidney and cause PKD. Bone marrow cells can move to the kidney and repair it after damage. We will test if bone marrow cells carrying a PKD mutation can cause PKD when transplanted into a healthy mouse. This will help us learn how mutations cause PKD in humans. We will also see if normal bone marrow can prevent disease when transplanted into a mutant mouse that spontaneously develops PKD. This experiment may lay the basis for a way to treat human PKD.Read moreRead less
Oxidative Phosphorylation Regulation And Neuroprotection In Optic Neuropathies
Funder
National Health and Medical Research Council
Funding Amount
$430,231.00
Summary
We have shown clear differences in the mitochodria, cellular organelles that generate energy, between optic atrophy patients who have good vision and those of patients who have poor vision. We believe that these changes represent a compensation mechanisms that preserves mitochondrial energy production and protects optic nerve cells. This study will characterize these differences further with the aim of identfying new treatments for preventing nerve loss and preserving vision.
RNA-based Expanded Repeat Pathogenic Pathway In Neurodegenerative Diseases
Funder
National Health and Medical Research Council
Funding Amount
$595,153.00
Summary
Many important human genetic diseases (incl Huntington’s Disease) are due to a common mutation mechanism with some similarities in clinical outcome (late in life nerve cell loss). For these diseases it is still not known what mechanism is responsible for causing the disease. This is essential in order to delay onset, slow progression or effect cure. We will test a mechanism for disease pathology that we have identified in a simple model organism and seen evidence of its activity in human disease
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
Mapping EQTL To Dissect The Genetic Basis Of Complex Trait Variation
Funder
National Health and Medical Research Council
Funding Amount
$719,525.00
Summary
People vary in traits such as height and blood pressure and in their susceptibility to common disease. Part of these differences between individuals is because of their genetic make-up. This research is about understanding which of the genes are involved in common variation and how they work. In particular, the researchers investigate if variation in DNA sequence causes genes to be expressed more or less and how gene expression affects risk of disease.
Determining The Impact Of Inherited Epigenetic Information On Development And Disease
Funder
National Health and Medical Research Council
Funding Amount
$511,691.00
Summary
Recent observations show that the environment in which you live can alter disease susceptibility in your children, without altering the sequence of your genes. This is due to epigenetic mechanisms which control the way the DNA is interpreted. In this study we will study the potential for epigenetic mechanisms to affect sperm production and impact characteristics and disease in the next generation.
Evaluation of the optic nerve head (optic disc) is important in the diagnosis of various eye diseases, including glaucoma. The influence of genetics on the shape of the optic disc is not well understood because shape is difficult to measure. Using a novel method of shape analysis, this study will examine optic disc shape in populations of Australian twins and individuals with optic nerve disease. It will contribute to the genetic understanding of the optic nerve head and related disorders.