Morphological And Spectroscopic Study Of Monozygotic Twins Discordant For Epilepsy
Funder
National Health and Medical Research Council
Funding Amount
$139,079.00
Summary
Understanding the causes of epilepsies is essential for treatment and prevention. In many people with epilepsy the cause is not obvious and is frequently attributed to events at birth or minor head injuries. It is clear that these factors are generally not important. There is increasing evidence that subtle changes in brain structure, reflecting developmental or maturational abnormalities, may be the cause of these epilepsies. Such subtle changes can be detected by novel magnetic resonance imagi ....Understanding the causes of epilepsies is essential for treatment and prevention. In many people with epilepsy the cause is not obvious and is frequently attributed to events at birth or minor head injuries. It is clear that these factors are generally not important. There is increasing evidence that subtle changes in brain structure, reflecting developmental or maturational abnormalities, may be the cause of these epilepsies. Such subtle changes can be detected by novel magnetic resonance imaging strategies. However, due to individual differences of brain morphology, the significance of such subtle changes can be disputed. Monozygotic twins have an increased similarity of their brain morphology. Therefore, analysis of monozygotic twins where only one twin is affected with epilepy, is a powerful way to characterize significant brain abnormalities. This will provide novel information on the causes of epilepsy relevant to the general population.Read moreRead less
Environmental Influences In The Establishment Of The Epigenetic Landscape In Children
Funder
National Health and Medical Research Council
Funding Amount
$695,097.00
Summary
The DNA in each of our cells does not exist alone, it is packaged into complex structures called chromosomes, through association with many different proteins. The distribution of these proteins varies along the length of a chromosome depending on the type of cell and this phenomenon is called 'epigenetics', literally meaning 'above the DNA'. Epigenetic analysis is the study of how proteins and other molecules can change the activity of a gene without changing the DNA sequence. All of our cells ....The DNA in each of our cells does not exist alone, it is packaged into complex structures called chromosomes, through association with many different proteins. The distribution of these proteins varies along the length of a chromosome depending on the type of cell and this phenomenon is called 'epigenetics', literally meaning 'above the DNA'. Epigenetic analysis is the study of how proteins and other molecules can change the activity of a gene without changing the DNA sequence. All of our cells use epigenetic changes to help control how they grow and develop. Evidence suggests a direct link between diet and environmental influences on our epigenetic profile. Recent research has traced the origins of many of the health problems of adult life back to the earliest periods of development _ to the time spent in the womb and the first few years of life. If we are born with a low birth weight, we are more likely to get sick later in life. Overwhelming evidence exists that the environment in the womb is critical for a healthy birth weight (and health in later life) and it is thought that epigenetics may be the missing link between this environment, low birth weight, and therefore health in later life. In addition, mounting evidence supports a general link between epigenetic de-regulation and predisposition to disease. However, the timing and the overall contribution of environmental- genetic influences to the establishment of faulty epigenetic markings remain largely unknown. Twins are the best model to study this link as they share similar (but not identical environments) and some share identical genetic makeup. Using twins, Dr Jeffrey Craig and his team will investigate the factors in the prenatal environment that modify specific cells, leading to low birth weight and increase disease risk later in life. They predict that this occurs via specific changes in gene activity caused by epigenetic disruption.Read moreRead less
Genetic Regulation Of Hip Geometry, Structure And Fracture
Funder
National Health and Medical Research Council
Funding Amount
$403,625.00
Summary
Osteoporotic hip fracture is common in the elderly and a major cause of hospitalization. Hip fracture may lead to surgery, chronic reduced mobility, loss of function, institutionalization or death. The term osteoporosis covers a heterogeneous syndrome including juvenile, secondary (e.g. corticosteroid induced) and postmenopausal osteoporosis. This later broad grouping shows evidence of a strong familial association. Previous work has shown that a family history of fracture increases the risk of ....Osteoporotic hip fracture is common in the elderly and a major cause of hospitalization. Hip fracture may lead to surgery, chronic reduced mobility, loss of function, institutionalization or death. The term osteoporosis covers a heterogeneous syndrome including juvenile, secondary (e.g. corticosteroid induced) and postmenopausal osteoporosis. This later broad grouping shows evidence of a strong familial association. Previous work has shown that a family history of fracture increases the risk of fracture by more than four fold. Furthermore, studies in twins have persistently shown that phenotypes such as bone mineral density (BMD), broadband ultrasound attenuation of bone and hip structural indices are strongly inherited. This confirms a genetic basis for the disease in some individuals. Community health in general has improved substantially in Australia in the past four decades and this has resulted in increased longevity. In contrast, the incidence of hip fracture and the resulting drain on public health funding continues to increase rapidly. Presently the cost of osteoporosis in Australia is $7.5 billion per annum. Hip fracture accounts for the majority of these costs. Instituting effective prevention strategies is essential. This project aims to contribute to one of Australia's National Research Pritoities by improving understanding about the way in which inherited aspects of hip geometry and structure contribute to the hip fracture susceptibility. We have successfully completed genome screen projects studying genetic linkage in the families to localize genes regulating BMD in the past. However, BMD is only one of a number of relevant phenotypes. In relation to hip fracture, geometry and structure are thought to be particularly important. In this project we will make use of existing resources to advance studies of both genetic linkage and association to examine fundamental issues related to hip facture.Read moreRead less
ADHD And Comorbidity: Implications For Clinical Practice And Molecular Genetics
Funder
National Health and Medical Research Council
Funding Amount
$284,878.00
Summary
ADHD is emerging as the most common, controversial childhood behavioural problem. Previously we have shown that much of the confusion may lie in the fact that ADHD is inherited as a continuum throughout the entire population, only some people having such a strong genetic potential that they warrant the label ADHD. The threshold to achieve this label is partly a community one, leading to the argument over who should be labelled and treated. This grant goes further in examining the possibility tha ....ADHD is emerging as the most common, controversial childhood behavioural problem. Previously we have shown that much of the confusion may lie in the fact that ADHD is inherited as a continuum throughout the entire population, only some people having such a strong genetic potential that they warrant the label ADHD. The threshold to achieve this label is partly a community one, leading to the argument over who should be labelled and treated. This grant goes further in examining the possibility that there is more than one type of ADHD. Some ADHD children have other behavioural problems such as conduct disorder or learning problems. Some have problems throughout their lives while others grow out of it. In Australia we are unique in having developed the most extensive twin databases world-wide and have already studied aspects of ADHD both in the children and their parents. In this grant we shall explore whether there are distinct genetic types of ADHD, characterised not just by their ADHD symptoms but also by the other behavioural problems they experience and by what happens as they grow-up. Such information is invaluable in developing a treatment program dealing with all aspects of the ADHD and also addresses the question of what will happen as they get older. No other study internationally has such extensive data to address these key questions., vital both to clinicians and families. Given the significant genetic component to ADHD, the next possibility is to find the genes involved in the different types. Knowing what these genes do may help in the development of medications more targeted to specific patterns of problems. Recently genes have been identified which may be involved in specific types of ADHD, as well as genes involved in associated problems such as reading disability and substance abuse. This study offers the potential to clearly identify the role of these genes and so assist in improved diagnosis and treatment interventions.Read moreRead less