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
Identifying Novel Genes Causing Cytochrome C Oxidase (COX) Deficiency
Funder
National Health and Medical Research Council
Funding Amount
$426,917.00
Summary
Our bodies convert food into energy in tiny cellular power plants called mitochondria. Each year about 50 Australian children inherit disorders of mitochondrial energy generation. The most severe disorders cause infant death, while others cause degenerative diseases in later life, particularly affecting brain and muscle. In most cases we lack effective treatments. The genetic causes of mitochondrial disorders are incredibly diverse, with over 70 disease genes known. Some are located on the uniqu ....Our bodies convert food into energy in tiny cellular power plants called mitochondria. Each year about 50 Australian children inherit disorders of mitochondrial energy generation. The most severe disorders cause infant death, while others cause degenerative diseases in later life, particularly affecting brain and muscle. In most cases we lack effective treatments. The genetic causes of mitochondrial disorders are incredibly diverse, with over 70 disease genes known. Some are located on the unique mitochondrial DNA we inherit only from our mothers. Many more genes await discovery. This study focuses on the mitochondrial disorder cytochrome c oxidase (COX) deficiency, for which we have diagnosed 80 Australian patients. COX requires 13 separate components to be assembled together in order to work properly, but mutations in the genes encoding these components are not present in most patients. We believe that the most common problems will be in genes involved in assembling the components rather than in the components themselves. We will use a number of methods to pinpoint where in the genome the disease genes are located. A key to our strategy is identifying patients likely to have mutations in the same gene. We have identified two such groups, and will do studies that involving fusing two cell lines together to confirm they have the same disorder. We will then perform genetic mapping to look for regions of similarity in the genome using DNA (SNP) chips. We will test how well the genes in such regions are expressed, whether we can correct the problem in cultured skin cells by introducing a healthy copy of that chromosome, and look for gene mutations. Identifying these genes will allow us to improve future diagnosis and prevention and may allow us to develop new methods of treatment. Milder mitochondrial problems also contribute to a range of more common diseases such as diabetes and Alzheimer disease, so any new treatments could potentially have wide applicationRead moreRead less
A comparative genomics approach to understanding host-endosymbiont interactions. Australia's unique ecosystems are vulnerable to invasion by exotic pests that threaten agriculture and human health. The bacterial symbiont Wolbachia is found in many major pests of agricultural and medical importance. Our results will give insights into how Wolbachia spreads into host populations and improve its use as a tool to impair insect transmission of disease, e.g. as an agent to carry genes into an insect p ....A comparative genomics approach to understanding host-endosymbiont interactions. Australia's unique ecosystems are vulnerable to invasion by exotic pests that threaten agriculture and human health. The bacterial symbiont Wolbachia is found in many major pests of agricultural and medical importance. Our results will give insights into how Wolbachia spreads into host populations and improve its use as a tool to impair insect transmission of disease, e.g. as an agent to carry genes into an insect population that limit disease transmission. Our results will also make fundamental contributions to understanding host-parasite evolution, host-parasite communication, and insect developmental processes, and will be of interest to a large international community of researchers in this field. Read moreRead less
Australian Laureate Fellowships - Grant ID: FL200100068
Funder
Australian Research Council
Funding Amount
$3,328,974.00
Summary
Australian wild animals: environmental change and quantitative genomics. This project aims to determine the effects of changing environments on wild animal populations across Australia. By combining recent advances in genomic technology with a consortium of fourteen long-term studies of mammals, birds and reptiles, it aims to quantify the genetic basis of life-history variation and the potential for evolutionary adaptation in the wild. The project will generate a comprehensive understanding of t ....Australian wild animals: environmental change and quantitative genomics. This project aims to determine the effects of changing environments on wild animal populations across Australia. By combining recent advances in genomic technology with a consortium of fourteen long-term studies of mammals, birds and reptiles, it aims to quantify the genetic basis of life-history variation and the potential for evolutionary adaptation in the wild. The project will generate a comprehensive understanding of the genetic consequences of environmental change, population decline, inbreeding and disease in natural environments. The expected benefits include a coordinated network for long-term wild animal studies in Australia, advanced quantitative skills training, and knowledge transfer for wildlife management and conservation.Read moreRead less
Estimation of non-additive genetic variance for complex traits using genome-wide single nucleotide polymorphyisms and sequence data. Finding genes for traits of importance in agriculture, ecology and human health depends on understanding the genetic basis of these traits. This project will investigate whether variation in traits in humans, cattle and wild sheep are influenced by gene-gene interactions.
The genetic architecture and evolution of quantitative traits. Most important traits are controlled by many genes and by the environment, however there is little knowledge of how many genes are involved in these complex traits and what their effects are. This project will describe the number of genes and their effects for complex traits in humans and livestock and explain how these genes evolve.
Rapid mapping of genes for complex traits. This project will develop a new resource that will allow rapid identification of genes controlling complex traits. This world-leading resource will improve knowledge of diseases like diabetes and neurological diseases.
Methods to infer dense genomic information from sparsely genotyped populations. Prediction of phenotype based on DNA polymorphisms or sequence has important applications such as prediction of disease risk in human medicine and prediction of genetic value in plant or animal breeding. This project will enhance precision and lower the cost of association studies leading to substantial increase in accuracy of such predictions. This will allow more effective genetic improvement, particularly of diff ....Methods to infer dense genomic information from sparsely genotyped populations. Prediction of phenotype based on DNA polymorphisms or sequence has important applications such as prediction of disease risk in human medicine and prediction of genetic value in plant or animal breeding. This project will enhance precision and lower the cost of association studies leading to substantial increase in accuracy of such predictions. This will allow more effective genetic improvement, particularly of difficult but important traits such as disease resistance, reduced green-house gas emissions and product quality. The same methods can be extended to improve genetic improvement in plants and better prediction of human disease risk. Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE210100549
Funder
Australian Research Council
Funding Amount
$417,328.00
Summary
Adaptive evolution and its demographic consequences today. This project aims to provide the first test of whether the rate of adaptative genetic evolution has changed in the recent decades, to quantify how much recent genetic evolution helps animal populations survive, and to increase the ability to study on-going genetic evolution in Australian wildlife. The project is of major significance as many species are currently threatened, or invading, due to rapid environmental changes, in particular ....Adaptive evolution and its demographic consequences today. This project aims to provide the first test of whether the rate of adaptative genetic evolution has changed in the recent decades, to quantify how much recent genetic evolution helps animal populations survive, and to increase the ability to study on-going genetic evolution in Australian wildlife. The project is of major significance as many species are currently threatened, or invading, due to rapid environmental changes, in particular climate change. The anticipated outcome of the project is to deliver new methods, establish a network of international and national collaborators and improve the ability to measure and to forecast how Australian animals adapt to rapidly changing environments.Read moreRead less
Genetic architecture and evolution of complex traits across populations. Most human traits have a genetic component and display substantial diversity within and among populations. How natural selection changes and maintains genetic variation in human traits is a long-standing question in evolution that the proposed project aims to answer. Using innovative statistical methods and largest genomic “big” datasets ever across populations of different ancestral backgrounds, this project expects to gen ....Genetic architecture and evolution of complex traits across populations. Most human traits have a genetic component and display substantial diversity within and among populations. How natural selection changes and maintains genetic variation in human traits is a long-standing question in evolution that the proposed project aims to answer. Using innovative statistical methods and largest genomic “big” datasets ever across populations of different ancestral backgrounds, this project expects to generate new knowledge on the roles of natural selection in shaping the genetic variation in traits and identify key factors that drive the differentiation of human populations. These outcomes will significantly improve our understanding on the evolution of human traits and adaptation of populations to changing environments.Read moreRead less