Using High-throughput Genomics To Reveal The Deleterious Genetic Changes That Underlie Paediatric Leukoencephalopathies
Funder
National Health and Medical Research Council
Funding Amount
$1,003,712.00
Summary
There has been an explosion of high-throughput DNA sequencing technologies in the past five years, which have the potential to completely revolutionise medicine and scientific research. Here we present a series of studies showing the successful application of this technology to children with genetic disorders of the central nervous system. This proposal seeks to expand this study to a large cohort of similarly affected paediatric patients.
Diagnosis Of Inherited Genetic Disorders Using DNA Reference Standards
Funder
National Health and Medical Research Council
Funding Amount
$690,820.00
Summary
Whole genome sequencing can diagnose mutations that cause inherited disease, however, errors during sequencing and analysis can result in incorrect diagnosis. We propose to develop synthetic DNA standards that mirror important disease-associated mutations. These DNA standards are then added directly of a patient DNA sample and act as internal controls during sequencing and analysis to provide more accurate and reliable diagnosis.
A Study Of The Role Of Voltage-gated Potassium Channels In The Process Of Phototransduction, In The Setting Of Photoreceptor Sensitivity Levels And Response Times, And In The Progression Of A Distinctive Form Of Inherited Retinal Dystrophy
Funder
National Health and Medical Research Council
Funding Amount
$360,371.00
Summary
Inherited retinal disease is a major cause of blindness but the genetic basis is extremely heterogeneous. One such disorder, cone dystrophy with supernormal rod ERG, arises from mutations in KCNV2 that encodes a potassium voltage-gated channel protein. The objective of the project is to use animal models of the disease to determine the role of this channel protein in normal visual function and to assess the impact of loss of function on retinal development and function.
Defining The Leukaemogenic Mechanism For GATA2 T354M, A New Predisposing Mutation In Familial MDS/AML
Funder
National Health and Medical Research Council
Funding Amount
$631,883.00
Summary
A successful approach for identification of cancer genes has been to study the 5-10% of cases occurring in families with inherited predisposition to develop cancer. Unlike solid tumours, few cancer-causing mutations are known for haematological cancers. We have found a new mutation in 3 families in a gene (GATA2) not previously associated with familial acute myeloid leukaemia. We will explore how this mutation causes leukaemia to help better understand the more common non-inherited leukaemias.
Development Of A Bioinformatic Tool For The Rapid Identification Of Candidate Disease Genes
Funder
National Health and Medical Research Council
Funding Amount
$436,367.00
Summary
Candidate disease gene prediction systems assist geneticists by using biological data to suggest genes likely to be causative of diseases in regions of the genome delineated by genetic studies. This area has been enabled by completion of the Human Genome Project and increased availability of high-throughput experimental data and sophisticated bioinformatic tools. Identification of disease genes will contribute to an understanding of disease, as well as its prevention, diagnosis, and treatment.
Balance disorders are very common, but particularly in those conditions that involve the brain 'balance centres' are often difficult for doctors to diagnose. When diseases are difficult to diagnose, then recommending helpful treatment is particularly challenging. We will use a group of specialized tests to better understand these balance conditions in order to help patients receive accurate diagnoses and therefore, better treatment.
Clinical And Neurobiological Predictors Of Onset Of Major Mental Disorders (mania, Psychosis, Severe Depression), And Associated Functional Impairment, In Adolescent And Young Adult Twins: A Prospective Longitudinal Study
Funder
National Health and Medical Research Council
Funding Amount
$1,356,103.00
Summary
The Brisbane Twin Study is a prospective twin study tracking the real-time developmental trajectories of the onset of anxiety, mood, psychotic or substance misuse disorders through adolescence and young adulthood. This unique study has now reached the point where reassessment (after 20 years) can be performed. We will now determine the extent to which outcomes are predicted by neurobiological and genetic markers. This information is critical to prevention or early intervention strategies.
Dopamine-2 Receptor Antibody In Movement And Psychiatric Disorders
Funder
National Health and Medical Research Council
Funding Amount
$415,783.00
Summary
Autoimmune movement and psychiatric disorders are a common cause of neurological disability young adults and adolescents. We have identified a subgroup of patients whose disease is associated with an autoimmune reaction. Our study will identify the earliest immune responses against the brain in children with autoimmune movement and psychiatric disorders. Identifying these early immune responses will allow early and directed treatments to prevent disability and death in the future.
Multivariate Whole Genome Estimation And Prediction Analysis Of Genomics Data Applied To Psychiatric Disorders
Funder
National Health and Medical Research Council
Funding Amount
$639,582.00
Summary
We have made major contributions to the development of statistical methods applied to data from the international Psychiatric Genomics Consortium. Major new data sets will soon become available, with immense sample sizes (100,000s) and more extensive clinical and environmental data. We will develop and apply novel statistical analyses of these data, to answer fundamental questions about the genetic basis of psychiatric disorders and the interplay of genetic and environmental risk factors.
Epigenetic Impacts Of Paternal Experience On Offspring Anxiety And Cognition: Molecular Mediators And Therapeutic Targets
Funder
National Health and Medical Research Council
Funding Amount
$681,162.00
Summary
Stress and physical activity are two of the major lifestyle factors impacting on human health, including brain disorders. We have recently discovered that stress and exercise in male mice can impact the phenotype of offspring. We will study molecules in the sperm of these fathers, and in the brains of offspring to understand the mechanisms involved. There is evidence that lifestyle factors in men prior to conception impact on their children and this research has major public health implications.