Genetical Genomics of Mutational Variance. Mutation is the ultimate source of all genetic variation. Understanding the nature of mutation, its frequency, the distribution of effects, and the forces of selection that remove mutational load from populations is therefore a central concern of genetics. The accumulation of mutational load both in endangered species and human populations, where the natural forces of selection tend not to operate, has the potential to create serious problems in these p ....Genetical Genomics of Mutational Variance. Mutation is the ultimate source of all genetic variation. Understanding the nature of mutation, its frequency, the distribution of effects, and the forces of selection that remove mutational load from populations is therefore a central concern of genetics. The accumulation of mutational load both in endangered species and human populations, where the natural forces of selection tend not to operate, has the potential to create serious problems in these populations. The goal is to understand what types of mutations are targeted by selection at the gene expression level and why.Read moreRead less
The Genomic Dimensionality of the Response to Natural Selection. Many future advances in agriculture and medicine, as well as an understanding of adaptive evolution in natural and pest populations will require discovering the genes that regulate the expression of complex traits. Microarray technology is at the forefront of modern genomics, but despite its promise, is currently restricted in its utility by significant analytical problems associated with the analysis of the large number of gene ex ....The Genomic Dimensionality of the Response to Natural Selection. Many future advances in agriculture and medicine, as well as an understanding of adaptive evolution in natural and pest populations will require discovering the genes that regulate the expression of complex traits. Microarray technology is at the forefront of modern genomics, but despite its promise, is currently restricted in its utility by significant analytical problems associated with the analysis of the large number of gene expression profiles and their interpretation. Analytical approaches will be developed that will substantially enhance the ability of transcriptional profiling to effectively uncover key genes underlying important phenotypes of interest across the biological and medical sciences.Read moreRead less
Drosophila Quantitative Genomics. This research proposal will be a key element in the emerging program in evolutionary and ecological functional genomics at the University of Queensland. Our studies utilize modern genomics approaches to address diverse national priorities from conservation of biological resources in the face of climate change, to understanding how genetic history contributes to drug susceptibility. The research will contribute to the intellectual foundation upon which rigorous ....Drosophila Quantitative Genomics. This research proposal will be a key element in the emerging program in evolutionary and ecological functional genomics at the University of Queensland. Our studies utilize modern genomics approaches to address diverse national priorities from conservation of biological resources in the face of climate change, to understanding how genetic history contributes to drug susceptibility. The research will contribute to the intellectual foundation upon which rigorous environmental and biomedical research is built. Social impact will be seen in the training of a new generation of integrative genome biologists, and the shaping of attitudes toward the role of genetics in human biology.Read moreRead less
Statistical Methods for Discovering Ribonucleic acids (RNAs) contributing to human diseases and phenotypes. Identifying the causative genetic factors involved in quantitative phenotypes and diseases is a major goal of biology in the 21st century and beyond. A crucial step towards this goal is identifying and classifying the functional non-protein-coding Ribonucleic acids (RNAs) encoded in the human genome. This project will make major contributions to international efforts in this area by identi ....Statistical Methods for Discovering Ribonucleic acids (RNAs) contributing to human diseases and phenotypes. Identifying the causative genetic factors involved in quantitative phenotypes and diseases is a major goal of biology in the 21st century and beyond. A crucial step towards this goal is identifying and classifying the functional non-protein-coding Ribonucleic acids (RNAs) encoded in the human genome. This project will make major contributions to international efforts in this area by identifying RNA molecules that contribute to quantitative phenotypes including susceptibility to disease. As such, it will directly benefit fundamental science via the discovery and classification of new molecules. Indirectly, it will lead to breakthroughs in biology, and consequently to major medical and pharmaceutical advances in the diagnosis and treatment of genetic disease.Read moreRead less
Dissecting the shared genetic architecture of psychiatric and psychological traits with application to prediction of genetic risk. Identification of the early phase of psychiatric disorders is considered critical for early intervention which is the essence of prevention. At present, the main obstacle to targeted early intervention strategies in psychiatric disorders is the non-specific nature of early stage symptoms. Many psychiatric disorders present with symptoms of depressed mood and anxiety ....Dissecting the shared genetic architecture of psychiatric and psychological traits with application to prediction of genetic risk. Identification of the early phase of psychiatric disorders is considered critical for early intervention which is the essence of prevention. At present, the main obstacle to targeted early intervention strategies in psychiatric disorders is the non-specific nature of early stage symptoms. Many psychiatric disorders present with symptoms of depressed mood and anxiety in the early stages, yet best intervention treatments are dependent on the final (unknown) diagnosed disorder. Prediction of genetic risk is likely to make an important contribution for identification of individuals at risk of specific psychiatric disorders so that the best early intervention treatment can be administered. Read moreRead less
The Genetic Basis of Differences Between the Sexes. Improved medical interventions against genetic disorders like cancer are made possible by advances in fundamental understanding of gene function and, especially, genetic mechanisms (like genomic imprinting) that are directly implicated in these disorders. Furthermore, an understanding of environmental effects within and across generations is vital in an age of global climate change. Recent theory and evidence suggest that research on sexually d ....The Genetic Basis of Differences Between the Sexes. Improved medical interventions against genetic disorders like cancer are made possible by advances in fundamental understanding of gene function and, especially, genetic mechanisms (like genomic imprinting) that are directly implicated in these disorders. Furthermore, an understanding of environmental effects within and across generations is vital in an age of global climate change. Recent theory and evidence suggest that research on sexually dimorphic traits may hold a key to a better understanding of these phenomena. The proposed research will strengthen Australia's position as leader in evolutionary genetics, enhance knowledge of native fauna, and improve our understanding of biological phenomena that affect human health. Read moreRead less
Does developmental noise have an epigenetic basis? One's ultimate phenotype is the result of a combination of genotype and environment, and includes a poorly understood component termed ?developmental noise?. The molecular basis of developmental noise remains unknown, but it appears to be established in early development and to be retained for the life of the organism. We propose that the molecular basis of developmental noise is the epigenetic state of the genome. The stochastic nature of th ....Does developmental noise have an epigenetic basis? One's ultimate phenotype is the result of a combination of genotype and environment, and includes a poorly understood component termed ?developmental noise?. The molecular basis of developmental noise remains unknown, but it appears to be established in early development and to be retained for the life of the organism. We propose that the molecular basis of developmental noise is the epigenetic state of the genome. The stochastic nature of the establishment of epigenetic state, combined with its heritability during mitosis, provides all the essential components for developmental noise. If our hypothesis proves correct, our work will have a major impact on the understanding of one of the most basic concepts in genetics.Read moreRead less