Bipolar affective disorder (BP), or manic-depressive illness, is a major cause of disability and mortality worldwide. It has a lifetime prevalence of about 1% and suicide risk of about 20%. The disorder is characterised by episodes of mania or hypomania and depression, appearing in varying succession, with or without intermission. Twin, family, and adoptive studies point to a strong genetic component leading to the development of bipolar disorder, with a heritability of the order of 80%. Yet the ....Bipolar affective disorder (BP), or manic-depressive illness, is a major cause of disability and mortality worldwide. It has a lifetime prevalence of about 1% and suicide risk of about 20%. The disorder is characterised by episodes of mania or hypomania and depression, appearing in varying succession, with or without intermission. Twin, family, and adoptive studies point to a strong genetic component leading to the development of bipolar disorder, with a heritability of the order of 80%. Yet the identification of the genetic basis of the disease has proved exceedingly difficult, with numerous studies producing no definitive data. The lack of convincing results has been interpreted as an indication of complex genetic mechanisms and underlying differences between affected families and ethnic groups. Genetically isolated populations, where most individuals descend from a small number of founders, are believed to hold great potential for understanding the genetic basis of complex diseases, such as bipolar disorder. Affected subjects in such populations are likely to share the same predisposing genes, making these genes easier to identify. During the last 10 years, we have been involved in the study of bipolar disorder in one such population, with very promising results. In this project, we propose to take the research further by collecting more affected families, confirming the current positive findings and narrowing down the search to a small region, possibly a single gene. If successful, the study will be a major breakthrough which, by identifying a molecular pathway and disease mechanism, will contribute valuable and generally valid information on the biological basis of mood disorders.Read moreRead less
Molecular dissection of the effects of alpha-actinin-3 deficiency on normal variation in skeletal muscle function. We will study the mechanisms by which a common genetic variant influences muscle bulk, muscle strength and the metabolic efficiency of muscle in the general population. Common genetic variants that influence skeletal muscle function have major potential public health implications as they are likely to influence individuals' response to exercise and diet, and to contribute to suscept ....Molecular dissection of the effects of alpha-actinin-3 deficiency on normal variation in skeletal muscle function. We will study the mechanisms by which a common genetic variant influences muscle bulk, muscle strength and the metabolic efficiency of muscle in the general population. Common genetic variants that influence skeletal muscle function have major potential public health implications as they are likely to influence individuals' response to exercise and diet, and to contribute to susceptibility to common diseases such as obesity, diabetes, and the loss of muscle strength in the elderly. In addition, the identification of genetic factors that influence muscle bulk in vertebrates has implications for breeding programs in sheep and cattle and may provide commercial benefit to the livestock industry.Read moreRead less
Regulation And Role Of Transcription At The Centromere.
Funder
National Health and Medical Research Council
Funding Amount
$737,801.00
Summary
Every human cell has 46 chromosomes. Chromosomes are structures that carry genes in all our cells. The centromere is an essential component of a chromosome. It controls the process of cell division, and it ensures the equal division of the duplicated chromosomes. Defects in centromere function can result in various genetic diseases and development of cancers. The structure of the centromere is unique and its properties are determined by an array of proteins and other as yet unknown factors that ....Every human cell has 46 chromosomes. Chromosomes are structures that carry genes in all our cells. The centromere is an essential component of a chromosome. It controls the process of cell division, and it ensures the equal division of the duplicated chromosomes. Defects in centromere function can result in various genetic diseases and development of cancers. The structure of the centromere is unique and its properties are determined by an array of proteins and other as yet unknown factors that bind to it. In our preliminary work, we have demonstrated that a novel non-protein component in the form of RNA (which are expressed products of genes) is essential for the binding of key proteins to the centromere. The presence and importance of such an RNA component has not been previously suspected and represents an exciting new mechanism that help to determine the functional and structural integrity of the centromere. In this project, we propose to study the details of this RNA and to define how this RNA-related mechanism operates to ensure the proper assembly and function of the centromere during cell division.Read moreRead less
Discovering genes which modify human physical performance: a means of developing healthier life styles & novel athletic training programs. The aim of this multicentred study (University of Sydney, Australian National University, Australian Institute of Sport) is to find genes in the cardiac and musculoskeletal systems that are involved in modifying human physical performance. From this knowledge, it is proposed to develop novel physical training programs in our national sporting institutions ba ....Discovering genes which modify human physical performance: a means of developing healthier life styles & novel athletic training programs. The aim of this multicentred study (University of Sydney, Australian National University, Australian Institute of Sport) is to find genes in the cardiac and musculoskeletal systems that are involved in modifying human physical performance. From this knowledge, it is proposed to develop novel physical training programs in our national sporting institutions based on an individual's genetic information. In the broader community, knowledge of genes which contribute to the normal and healthy functioning of the cardiac and musculoskeletal systems will be invaluable in understanding and preventing breakdowns in these body systems.Read moreRead less