Twin and family studies show schizophrenia has a genetic basis. Attempts to find and characterise the underlying genes have not been successful so far. A main reason for this is that insufficient attention has been paid to the complexity of the underlying genetic architecture of the disorder. The pathway from genes to symptoms of schizophrenia is likely to involve elementary processes at neuronal and neural circuitry levels that vary between individuals and this variation is reflected in a grade ....Twin and family studies show schizophrenia has a genetic basis. Attempts to find and characterise the underlying genes have not been successful so far. A main reason for this is that insufficient attention has been paid to the complexity of the underlying genetic architecture of the disorder. The pathway from genes to symptoms of schizophrenia is likely to involve elementary processes at neuronal and neural circuitry levels that vary between individuals and this variation is reflected in a graded susceptibility to schizophrenia. During the last three years we have recruited a large number of families with at least one family member diagnosed with schizophrenia. The proband and all participating first-degree relatives have been assessed with a neurocognitive test battery including measures of sustained attention, working memory, speed of information processing, auditory verbal learning and executive function. Analysis of the neurocognitive data on this sample produced strong evidence that several measures are altered in patients with schizophrenia and a proportion of their asymptomatic first-degree relatives compared to unrelated normal controls. In the study we will systematically search the human genome for DNA markers linked to these measures. This will set the stage for the systematic search and characterisation of the underlying genes. This will allow us to better understand the predisposition to develop schizophrenia. In the individual case it is likely that this vulnerability results from a high-risk combination of a number of relatively common alleles which contribute to basic neural processes.Read moreRead less
The Mechanisms Of Infection Of Bronchial Epithelial Cells By Human And Avian Influenza Viruses In Chronic Airways Disease
Funder
National Health and Medical Research Council
Funding Amount
$395,559.00
Summary
Influenza is an important infection that causes disease every year in the Australian population. People with lung disease are at particular risk to its effects. The ability of the virus to grow in birds and change its appearance to our immune system allows this virus to cause severe disease every year. We will examine the immune response to this virus in human cells, comparing this response to human and bird strains of the virus and see why subjects with lung disease are more susceptible.
Developing And Applying Biologically Plausible Statistical Models For Normal And Non-normal Family Data
Funder
National Health and Medical Research Council
Funding Amount
$339,700.00
Summary
Although molecular and computing advances have enabled more detailed investigations of inherited diseases and the ability to fit realistic statistical models to these data, limitations still exist when analysing family data. Often only basic statistical analyses are performed, due to the lack of understanding of complexities within the data and-or inability of researchers to fit appropriate statistical models. These factors have hampered the search for genes and environmental factors influencing ....Although molecular and computing advances have enabled more detailed investigations of inherited diseases and the ability to fit realistic statistical models to these data, limitations still exist when analysing family data. Often only basic statistical analyses are performed, due to the lack of understanding of complexities within the data and-or inability of researchers to fit appropriate statistical models. These factors have hampered the search for genes and environmental factors influencing common diseases. This project aims to develop novel, biologically realistic statistical models for investigation of common, complex diseases, such as heart disease and cancer, in families. These models will incorporate both measured and unmeasured genetic and environmental factors, and will be applicable to both normally distributed and non-normally distributed traits. Model fitting will use computer-intensive simulation techniques. Application of the models to data from two large pre-existing studies of international renown, the Victorian Family Heart Study and the Australian Prostate Cancer Family Study, will enable a better understanding of the genetic and environmental factors influencing heart disease and cancer. The models will also be applicable to many other studies of diseases which use data from families, and allow more accurate and useful information to be obtained from data. Software will also be made freely available to other researchers. This will ultimately translate into better outcomes from familial genetic research, and eventually, better prevention, detection, and treatment of the diseases.Read moreRead less