The role of X-chromosome inactivation in quantitative trait variation. This project aims to develop methods and software that can be applied to genetic and genomic studies in animal breeding, wildlife protection, and humans. X-chromosome inactivation (XCI) is an important biological phenomenon but its effect on quantitative trait variation remains largely unknown. This project aims to develop novel statistical methods to estimate the X-linked genetic variance and the proportion that escapes XCI, ....The role of X-chromosome inactivation in quantitative trait variation. This project aims to develop methods and software that can be applied to genetic and genomic studies in animal breeding, wildlife protection, and humans. X-chromosome inactivation (XCI) is an important biological phenomenon but its effect on quantitative trait variation remains largely unknown. This project aims to develop novel statistical methods to estimate the X-linked genetic variance and the proportion that escapes XCI, and identify trait-associated genetic variants affected and not affected by XCI. The methods would then be applied to large datasets from genome-wide association studies for a large number of traits. Project outcomes may enable us to better understand the role of XCI in quantitative trait variation and gene expression in humans and animals.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.
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.
Alternative Splicing in the Mouse Transcriptome. Although the human genome completion is cause for excitement we do not have any firm indication of precisely how many protein-coding genes exist in a mammalian genome. We have even less indication of the extent to which these genes generate alternative gene products, through a process termed alternative splicing. The detection and sequencing of these full-length alternative gene products is the focus of this application. This application details t ....Alternative Splicing in the Mouse Transcriptome. Although the human genome completion is cause for excitement we do not have any firm indication of precisely how many protein-coding genes exist in a mammalian genome. We have even less indication of the extent to which these genes generate alternative gene products, through a process termed alternative splicing. The detection and sequencing of these full-length alternative gene products is the focus of this application. This application details the opportunity to participate in the identification of the full transcriptome of the mouse and is part of a collaborative effort with The RIKEN Genome Sciences Center in Japan.Read moreRead less
A genomic approach to understanding the maintenance of genetic variation under sexual selection. Using a model Australian species, this project will dissect the linkages between DNA sequence variation, gene expression, phenotypic traits and fitness in a natural population. Data will facilitate powerful tests of evolutionary processes thought to maintain genetic variation in complex traits.
The contribution of pleiotropic mutation to genetic variation and evolution. This project aims to provide an in-depth characterization of pleiotropic effects across many traits, including fitness, in an outbred population of the fly, Drosophila serrata. The potential for one gene to affect many traits, pleiotropy, has been recognised for over 100 years. Pleiotropy is expected to underlie diverse biological phenomena, including evolution and age-related human diseases. Despite this, the contribut ....The contribution of pleiotropic mutation to genetic variation and evolution. This project aims to provide an in-depth characterization of pleiotropic effects across many traits, including fitness, in an outbred population of the fly, Drosophila serrata. The potential for one gene to affect many traits, pleiotropy, has been recognised for over 100 years. Pleiotropy is expected to underlie diverse biological phenomena, including evolution and age-related human diseases. Despite this, the contribution of pleiotropy to variation among individuals in appearance and in fitness remains poorly understood. By measuring the extent of pleiotropy and its fitness consequences, this project aims to advance understanding of how mutation and selection shape genetic variation and evolutionary potential in natural populations.Read moreRead less
Resolving genomic sexual conflicts via sexually dimorphic gene expression. Using powerful genomic technology this project aims to assess the strength of regulatory constraints between males and females and determine whether cis-regulatory mutations help to resolve them. Sex-differences in traits like morphology, behaviour and disease susceptibility often involve sex-differences in the regulation of gene expression. To achieve optimal performance, males and females must express their genes at dif ....Resolving genomic sexual conflicts via sexually dimorphic gene expression. Using powerful genomic technology this project aims to assess the strength of regulatory constraints between males and females and determine whether cis-regulatory mutations help to resolve them. Sex-differences in traits like morphology, behaviour and disease susceptibility often involve sex-differences in the regulation of gene expression. To achieve optimal performance, males and females must express their genes at different levels. Theory and data suggest that for some genes this is not possible, and that males and females could each achieve higher performance if gene regulation became genetically uncoupled between them. It has been suggested that cis-regulatory mutations may be important for resolving regulatory incompatibilities within the genome.Read moreRead less
The genetics of ageing in human populations. This project aims to test whether genetic differences among individuals influence changes in cognition and physiological function in later life. Differences among individuals, in terms of distinct changes in their physiology as they age, lead to differences in their susceptibility to negative later-life outcomes and ultimately to differences in lifespan. Using a combination of genomic techniques, novel data analysis methods, and the largest dataset of ....The genetics of ageing in human populations. This project aims to test whether genetic differences among individuals influence changes in cognition and physiological function in later life. Differences among individuals, in terms of distinct changes in their physiology as they age, lead to differences in their susceptibility to negative later-life outcomes and ultimately to differences in lifespan. Using a combination of genomic techniques, novel data analysis methods, and the largest dataset of its kind, the project intends to identify the genomic regions and biochemical pathways associated with these changes, and to test for genetic associations between early-life reproduction and later-life outcomes. This is crucial to understanding, predicting and managing transitions across different human life stages.Read moreRead less
A new paradigm of gene regulation - implications in embryogenesis and disease. The proposed analysis of a new paradigm of gene regulation will provide a new key to understanding genome function and inform some of the most compelling biological issues of our time such as stem cell biology, tissue and organ regeneration and genetic programming. The insights and technologies developed in this program will be widely applicable in biotechnological and pharmacogenomic research in Australia and worldwi ....A new paradigm of gene regulation - implications in embryogenesis and disease. The proposed analysis of a new paradigm of gene regulation will provide a new key to understanding genome function and inform some of the most compelling biological issues of our time such as stem cell biology, tissue and organ regeneration and genetic programming. The insights and technologies developed in this program will be widely applicable in biotechnological and pharmacogenomic research in Australia and worldwide, and assert Australia's leadership in this area of research.Read moreRead less