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
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
Mutational genetic variance and the fitness optimum. Mutation and selection are ubiquitous forces in nature, but we do not understand how genetic variation produced by mutation is maintained in the presence of selection that depletes it. The recent discovery of apparent stabilising selection on traits with high levels of genetic variation provides a new approach to understanding this paradox.
Discovery Early Career Researcher Award - Grant ID: DE200100425
Funder
Australian Research Council
Funding Amount
$409,364.00
Summary
Genetic and Molecular Consequences of Non-Random Mating in Humans. This project aims to develop and apply novel statistical methods to quantify the effects on a large number of complex traits of two forms of non-random mating in humans, that is inbreeding and assortative mating. The innovation in this proposal lies in integrating multi-level phenotypes with next-generation sequencing data collected in more than half a million study participants. Expected outcomes of this research include advance ....Genetic and Molecular Consequences of Non-Random Mating in Humans. This project aims to develop and apply novel statistical methods to quantify the effects on a large number of complex traits of two forms of non-random mating in humans, that is inbreeding and assortative mating. The innovation in this proposal lies in integrating multi-level phenotypes with next-generation sequencing data collected in more than half a million study participants. Expected outcomes of this research include advanced analytical methods to perform this integration and dissection of the biological consequences of non-random mating in humans at an unprecedented phenotypically detailed scale. The benefit of this project will be to identify new drivers of mate choice that can contribute to economic, health and social inequalities. Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE140100958
Funder
Australian Research Council
Funding Amount
$394,112.00
Summary
Understanding how shared between-sex genetic variance constrains the evolution of sexual dimorphism. Differences between males and females in the expression of shared traits have been of lasting interest to biologists. One fundamental question, which is as yet poorly understood, regards the extent to which a common genome restricts the independent evolution of the sexes. This project proposes a novel way of examining the degree to which the shared genetic architecture restricts the evolution of ....Understanding how shared between-sex genetic variance constrains the evolution of sexual dimorphism. Differences between males and females in the expression of shared traits have been of lasting interest to biologists. One fundamental question, which is as yet poorly understood, regards the extent to which a common genome restricts the independent evolution of the sexes. This project proposes a novel way of examining the degree to which the shared genetic architecture restricts the evolution of the sexes and the costs this imposes on population fitness. The results from the proposed experiments will give a clearer picture of how current measures reflect the true genetic constraint imposed on the sexes from a shared genetic architecture.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
Characterising inheritance patterns of whole genome DNA methylation. This project aims to characterise epigenetic diversity and inheritance patterns in whole genome sequencing data from a unique human population. The project will employ the well-characterised Norfolk Island genetic isolate, cost-effective whole genome bisulphite sequencing technologies and advanced bioinformatics pipelines and statistical models. It will involve cross-discipline collaboration between human geneticists, epigeneti ....Characterising inheritance patterns of whole genome DNA methylation. This project aims to characterise epigenetic diversity and inheritance patterns in whole genome sequencing data from a unique human population. The project will employ the well-characterised Norfolk Island genetic isolate, cost-effective whole genome bisulphite sequencing technologies and advanced bioinformatics pipelines and statistical models. It will involve cross-discipline collaboration between human geneticists, epigeneticists, statistical geneticists and bioinformaticians. This project will advance our understanding of the interaction of genetics and epigenetics and their relationship to diversity and inheritance in humans.Read moreRead less