Clinical Genetic Phenotyping Of Autism Spectrum Disorders
Funder
National Health and Medical Research Council
Funding Amount
$582,114.00
Summary
Individuals with autism spectrum disorders (ASD) have difficulty with communication, social interaction and intellectual disability. The cause is generally not known although most cases have a genetic basis involving multiple genes and possibly environmental factors. We will study families of children with ASD and carefully characterize features related to ASD in family members. This will help us to understand how ASD is inherited and serve as the basis for the discovery of autism genes.
Identification And Characterisation Of Novel Genes For Congenital Cataract
Funder
National Health and Medical Research Council
Funding Amount
$432,750.00
Summary
Cataracts are the leading cause of blindness worldwide. The term describes a clouding of the lens which may lead to visual impairment. Congenital cataracts (present at birth) are less common than age-related cataract but the lifelong impact on vision can be severe, with a third of patients remaining legally blind. Late complications such as aphakic glaucoma may be blinding. We have shown that congenital cataracts are often inherited and have performed a population-based study in South-Eastern Au ....Cataracts are the leading cause of blindness worldwide. The term describes a clouding of the lens which may lead to visual impairment. Congenital cataracts (present at birth) are less common than age-related cataract but the lifelong impact on vision can be severe, with a third of patients remaining legally blind. Late complications such as aphakic glaucoma may be blinding. We have shown that congenital cataracts are often inherited and have performed a population-based study in South-Eastern Australia over the past 5 years to determine the causative genes. A large number of families have been involved in the study and solid progress has been made in identifying mutations in cataract genes and understanding what effect these may have on the patient's prognosis. We have recently identified a new gene in a large Australian family with a syndrome of cataract, mental retardation and teeth problems. This syndrome, known as Nance-Horan syndrome was originally described in Australia 30 years ago and we have worked with the original family to find the exact gene responsible. We already know that this gene causes the same syndrome in other families and in this project we will examine whether it can cause cataract without the other features or mental retardation without cataract. We will perform a series of experiments to learn what this gene does and how it causes the disease. We have also selected 3 other very interesting families with congenital cataracts for further study as we either know already or strongly suspect that they will enable us to identify further new genes for cataract, and in one case mental retardation. Our work in other diseases indicates that understanding the genes in severe young onset cases can give valuable clues to the causes of age-related forms and may in the future enable new ways to prevent and treat the commonest cause of worldwide blindness.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
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.
A Study Of The Molecular Epidemiology And Virulence Determinants Of Enterovirus 71 Strains From The Asia-Pacific Region
Funder
National Health and Medical Research Council
Funding Amount
$286,325.00
Summary
In this study, we aim to understand the reasons for the emergence of epidemics of severe neurological disease due to enterovirus 71 (EV71) in young children of the Asia-Pacific region since 1997, and to develop strategies for disease prevention. EV71 is a human enterovirus closely related to the polioviruses. Most infections with EV71 are trivial, however, they may occasionally result in severe disease, including brainstem encephalitis with a high mortality and acute flaccid paralysis similar to ....In this study, we aim to understand the reasons for the emergence of epidemics of severe neurological disease due to enterovirus 71 (EV71) in young children of the Asia-Pacific region since 1997, and to develop strategies for disease prevention. EV71 is a human enterovirus closely related to the polioviruses. Most infections with EV71 are trivial, however, they may occasionally result in severe disease, including brainstem encephalitis with a high mortality and acute flaccid paralysis similar to poliomyelitis. There has been a large increase in EV71 epidemic activity throughout the Asia-Pacific region since 1997, including a large epidemic in Perth, Western Australia in 1999. These epidemics have resulted in many deaths and cases of severe neurological disability. In view of the severity of EV71 neurological disease and the lack of effective treatments, our research effort needs to focus on prevention through public health surveillance and vaccine development. The major aims of our study are two-fold: 1. To study the origin and evolution of EV71 in the Asia-Pacific region using molecular techniques and to use this information to implement surveillance in Australia and Southeast Asia. It is anticipated that improved surveillance will provide early warning of impending epidemics. 2. To understand the molecular basis of virulence of EV71, with emphasis on the ability of virus to cause severe disease of the central nervous system. This study will have two goals: a. To identify the human cellular receptor of EV71. The ultimate goal of this research will be the development of a small animal model of EV71 encephalitis by constructing a transgenic mouse expressing the human cellular receptor for EV71. b. To construct an infectious cDNA clone of EV71 and to develop genetically defined attenuated strains by mutagenesis of the infectious clone. Mutant strains of EV71 will be tested for replication and virulence in newborn mice and in human neuroblastoma cells.Read moreRead less
LONGITUDINAL STUDY OF BEHAVIOUR AND EMOTIONAL PROBLEMS IN YOUNG PEOPLE WITH INTELLECTUAL DISABILITIES
Funder
National Health and Medical Research Council
Funding Amount
$761,790.00
Summary
Families caring for young people with intellectual disabilities face major burdens of care if the young person also has serious behaviour problems. These behaviour problems are also costly for our community. This project is intended to assist young people and their carers by providing new information about the factors contributing to these behaviour problems and how they develop over time. The project makes use of an internationally unique follow up study which has followed a group of young peop ....Families caring for young people with intellectual disabilities face major burdens of care if the young person also has serious behaviour problems. These behaviour problems are also costly for our community. This project is intended to assist young people and their carers by providing new information about the factors contributing to these behaviour problems and how they develop over time. The project makes use of an internationally unique follow up study which has followed a group of young people aged 4-18 for the last eight years. The young people are now entering a critical age band facing many changes in their lives such as the possibility of independent living, work challenges, as well as a search for new social relationships and day activities in the post-school period. Also they face increased risk for mental health problems which most commonly emerge in this age group, particularly psychosis and depression. This project promises to determine how the young people cope with these challenges and what steps our community needs to make to assist them and their families to reach an optimal adjustment.Read moreRead less
A Longitudinal Study Of Psychopathology In People With Intellectual Disability
Funder
National Health and Medical Research Council
Funding Amount
$999,803.00
Summary
This project will further develop the research opportunities of an internationally unique 15 year follow up study of the mental health of young Australians with ID. We have shown that this group has 2-3 times the risk of suffering serious emotional and behavioural problems that are an added heavy burden on the individual, their family and carers and the community. These problems often are not recognised but are as common as schizophrenia in the community. The study will continue to use a combina ....This project will further develop the research opportunities of an internationally unique 15 year follow up study of the mental health of young Australians with ID. We have shown that this group has 2-3 times the risk of suffering serious emotional and behavioural problems that are an added heavy burden on the individual, their family and carers and the community. These problems often are not recognised but are as common as schizophrenia in the community. The study will continue to use a combination of questionnaire survey and in depth interviews of the young adults and their families or carers to track the course of their mental health. The study commenced in 1990 with nearly 1000 young people with ID aged 4-18 years and their progress has been reviewed every 2-3 years in over 75% of the original group. During the next 5 years we plan to follow their mental health during the critical stage of young adult life. During this time there is the greatest risk of mental illnesses such as depression and schizophrenia and the stresses of adjusting to new daily occupations, independent living or residential care and social contact away from the family. We will be able to study the specific emotional and behavioural problems faced by young adults with the main known causes of ID such as Down, Fragile X, Prader Willi and William Syndromes, as well as those who have autism. The great benefit of a long term follow up study is that it allows us to study the links between earlier family environmental, psychological and biological factors and subsequent mental health problems. We can also demonstrate the impact that mental illness in a young person with ID has on the family and parental mental health. The findings have implications for better diagnosis, improved care and management, early intervention and prevention of these common severe and under recognized mental health problems in this disadvantaged group of young Australians and their families and carers.Read moreRead less
Identifying Target Genes For Novel Anti-epileptic Therapies In The Mouse
Funder
National Health and Medical Research Council
Funding Amount
$469,802.00
Summary
Epilepsy is a disease which affects 2-4% of the population. There are a wide range of drugs available to treat the condition but there is consistently 30-40% of patients who do not respond well to any of these drugs and who continue to have seizures. The reason that there are no drugs available for these people is that most of the drugs available have been designed along the same principles. A new set of principles is needed to develop new drugs which will be able to treat those people not respo ....Epilepsy is a disease which affects 2-4% of the population. There are a wide range of drugs available to treat the condition but there is consistently 30-40% of patients who do not respond well to any of these drugs and who continue to have seizures. The reason that there are no drugs available for these people is that most of the drugs available have been designed along the same principles. A new set of principles is needed to develop new drugs which will be able to treat those people not responding to current therapy. This project is designed to identify new biologic pathways which may be interrupted with drugs to prevent seizures in people with epilepsy. This project uses a procedure to induce mutations into genes in mice and then screens for mice which do not seize when challenged with a drug which generates seizures in mice. Genetic studies will identify the mutated genes and these will be used as potential targets for new therapies or will identify new biological pathway which should expand the use of future anti-epileptic drugs.Read moreRead less
A Population-based Family Study Of Filaggrin Mutations And Allergic Disease Risk In Australia
Funder
National Health and Medical Research Council
Funding Amount
$308,584.00
Summary
It is biologically plausible that the association of known environmental risk factors for asthma may be different for genetically susceptible individuals. Few studies have examined the interaction between genetic and environmental factors. that have not considered genetic susceptibility are estimating an average risk of asthma across all genotypes in the population which may not be relevant for a particular sub-group.
Markers Of Androgen Action, Genetic Variation And Prostate Cancer Risk
Funder
National Health and Medical Research Council
Funding Amount
$798,907.00
Summary
This proposal aim to follow up evidence from a number of studies that genetic and non-genetic markers of hormonal action in different periods of a man's life are associated with prostate cancer risk using a collection of three large, independent epidemiologic studies on prostate cancer named the Prostate Cancer Program. A principal objective is to collect exposure data on acne and digit ratio, and genotype cases and controls across the studies of the Prostate Cancer Program for common genetic va ....This proposal aim to follow up evidence from a number of studies that genetic and non-genetic markers of hormonal action in different periods of a man's life are associated with prostate cancer risk using a collection of three large, independent epidemiologic studies on prostate cancer named the Prostate Cancer Program. A principal objective is to collect exposure data on acne and digit ratio, and genotype cases and controls across the studies of the Prostate Cancer Program for common genetic variants in 4 candidate genes in the hormonal pathway. The established risk factors for prostate cancer are only age, race and family history. We anticipate that this project will cast light on the role of hormones in prostate cancer and that we will identify new markers of risk of prostate cancer and markers of disease aggressiveness. These outcomes will help us identifying men who are at risk for prostate cancer to target screening and surveillance, and plan prevention strategies. Furthermore, they will also form the basis for research on treatment targets.Read moreRead less