Genome-wide Association Studies Of Biomedical Traits And Endophenotypes For Complex Disease
Funder
National Health and Medical Research Council
Funding Amount
$295,804.00
Summary
The burden of common complex diseases, such as cardiovascular disease is substantial to the health care system. These diseases are caused by genes and environments as well as their interactions. The proposed project will identify genes affecting the susceptibility of individuals to complex diseases. Discovery of such genes will be important for their diagnosis, prevention and treatment and may serve as an important resource for future personalized medicine.
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.
This study investigates how much an individual's genes and environment account for the wide variation in brain structure and function. Using brain imaging we examine in what way the connectivity of the brain of identical and non-identical twins is the same or different from that of their co-twin, and carry out analysis of their DNA to identify some of the genes involved. This will provide fundamental information on genetic mechanisms influencing variation in brain structure and function.
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.
Identifying Resistance Mechanisms Of Targeted BRAF Inhibitors In Metastatic Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$379,015.00
Summary
Late-stage melanoma is an aggressive skin cancer for which traditional treatment strategies such as chemotherapy are ineffective. Recently, a new class of targeted drugs (BRAF inhibitors) has become the standard of care for a subset of melanoma patients; however, long term treatment success is complicated by drug resistance. This study will identify the causes of resistance with the purpose to improve targeted drug strategies and increase survival rates for late-stage melanoma patients.
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
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