Understanding The Causes Of Childhood Congenital Anomalies Of The Kidney And Urinary Tract
Funder
National Health and Medical Research Council
Funding Amount
$609,748.00
Summary
Congenital anomalies of the kidney and urinary tract (CAKUT) is a common cause of renal failure in children. The majority of patients with CAKUT do not know the underlying cause of their renal anomalies. In this proposal we will characterise the developmental events that are perturbed in three mouse models of CAKUT and identify the causal gene responsible in each mouse model. We will translate this information to the clinic by screening patients with CAKUT for mutations in these newly identified ....Congenital anomalies of the kidney and urinary tract (CAKUT) is a common cause of renal failure in children. The majority of patients with CAKUT do not know the underlying cause of their renal anomalies. In this proposal we will characterise the developmental events that are perturbed in three mouse models of CAKUT and identify the causal gene responsible in each mouse model. We will translate this information to the clinic by screening patients with CAKUT for mutations in these newly identified genes.Read moreRead less
High Resolution Mapping Of Genomic Regions Implicated In Migraine
Funder
National Health and Medical Research Council
Funding Amount
$392,545.00
Summary
Migraine is a frequent, debilitating and painful disorder that affects a significant proportion of the population. Using the diagnostic criteria of the international Headache Society, the prevalence of migraine has been estimated to be approximately 12%, with a recent study in the United States showing that migraine affects 4% of children, 6% of men and 18% of women. The aetiology of migraine is unknown and there are no laboratory based diagnostic tests to identify those who suffer from the diso ....Migraine is a frequent, debilitating and painful disorder that affects a significant proportion of the population. Using the diagnostic criteria of the international Headache Society, the prevalence of migraine has been estimated to be approximately 12%, with a recent study in the United States showing that migraine affects 4% of children, 6% of men and 18% of women. The aetiology of migraine is unknown and there are no laboratory based diagnostic tests to identify those who suffer from the disorder. Clinical diagnosis is currently based on patient symptom descriptions, with individual symptoms being shown to vary with age. Migraine is believed to have a genetic basis with specific environmental factors, such as particular foods, hormonal levels and fatigue, being capable of inducing attacks in predisposed individuals. Migraine shows strong familial aggregation with about 50% of those affected, having another close relative also affected with the disorder. At present the number of genes involved in the disorder is unknown and have not been identified. Recent studies in our laboratory have localised two migraine genes, one to chromosome 19 and the other to the X chromosome. More recently we have also found evidence for a third gene on chromosome 1. This study is aimed at fine scale mapping analysis of these three chromosomal regions in order to pinpoint the location of migraine genes. Our ultimate aim is to identify the molecular causes of this disorder. This would have important implications to both the diagnosis and treatment of migraine.Read moreRead less
Functional Characterisation Of Genetic Risk Variants For ADHD: From Association To Biology
Funder
National Health and Medical Research Council
Funding Amount
$526,816.00
Summary
ADHD is a prevalent behavioural disorder affecting a substantial proportion of the Australian public. Functional characterization of ADHD susceptibility genes will enhance our knowledge of the neurobiology and revolutionise the drug treatment of the disorder
A Genomic Approach Towards An Understanding Of Clonal Evolution And Disease Progression In Multiple Myeloma
Funder
National Health and Medical Research Council
Funding Amount
$671,689.00
Summary
Cancer development is associated with changes in the genetic composition of the cell. These changes involve the loss/gain of genetic material and/or changes in gene expression. Using sophisticated technology, we will define the changes in the genes that are associated with the transition from a benign to a malignant cancer state. We will examine this process in the blood cancer, multiple myeloma, in order to identify new treatment targets for this incurable disease.
It is now well established that there are genetic factors contributing to risk of depression but it is far from clear what these are and how they interact with environmental risk factors such as stressful life events (SLE) and poor social support (SS). A recent, highly cited paper has claimed that those carrying a particular genotype at the sertonin transporter gene are much more badly affected by stressful life events than other genotypes, and that this puts these people at much higher risk of ....It is now well established that there are genetic factors contributing to risk of depression but it is far from clear what these are and how they interact with environmental risk factors such as stressful life events (SLE) and poor social support (SS). A recent, highly cited paper has claimed that those carrying a particular genotype at the sertonin transporter gene are much more badly affected by stressful life events than other genotypes, and that this puts these people at much higher risk of depression. If true, this could have important practical implications for preventative mental health, in identifying those at greatest risk if depression and counselling them to avoid stressful situations. However, success in replicating this finding has been mixed, and this is possibly because another important risk factor, social support, has not been taken into account. We have DNA samples from over 5000 twins who have been assessed for depression and risk factors including SLE and SS. This will give us unprecedented power to estimate the importance of the genotype x environment interaction. We shall also type other genes that have been implicated in depression and check for interactions with life events and social support. Our results will inform preventative strategies in mental health practice.Read moreRead less
Molecular And Clinico-pathological Investigation Of Congenital Myopathies
Funder
National Health and Medical Research Council
Funding Amount
$743,290.00
Summary
Congenital myopathies are inherited disorders causing muscle weakness from birth. Some types lead to early death of the affected child, while others are compatible with life to adulthood. Like any disease of childhood, the congenital myopathies cause considerable trauma to the families concerned. Couples at risk of having another affected child frequently wait for prenatal diagnosis to become available for their particular disease before attempting to have further children. However, prenatal dia ....Congenital myopathies are inherited disorders causing muscle weakness from birth. Some types lead to early death of the affected child, while others are compatible with life to adulthood. Like any disease of childhood, the congenital myopathies cause considerable trauma to the families concerned. Couples at risk of having another affected child frequently wait for prenatal diagnosis to become available for their particular disease before attempting to have further children. However, prenatal diagnosis is only possible once the gene causing a disorder and the mutation in an individual family are identified. In the past, the Laboratories collaborating in this project, the Molecular Neurogenetics Laboratory, Australian Neuromuscular Research Institute, Perth, and the Neurogenetics Research Unit, New Children s Hospital, Sydney, have identified disease genes for congenital myopathies. Prenatal diagnosis is now possible for families whose disease-causing mutation is identified. However the genetic cause of many of the congenital myopathies remains unknown. DNA and other samples have been sent to the Laboratories from around the world, making us reference centres for congenital myopathy research. Part one of the project is to study these and Australasian samples, to identify other congenital myopathy genes. This will help families who currently cannot have prenatal diagnosis. Finding the genes also increases understanding of the diseases by clarifying which proteins are involved. In part two of the project we shall study the mutated proteins, to try to unravel how the gene mutations cause the diseases. The third part of the project is to reevaluate the highly variable muscle pathology in congenital myopathies in cases where the disease gene is now known, in order to investigate genotype-phenotype correlations. Understanding the pathologic basis of the congenital myopathies will ultimately allow us to begin to think rationally about possible treatments.Read moreRead less