Constructing Control Samples For The Australian And Other Populations: Improving Power And False Positive Rates In The Next Generation Of Genetic Association Studies With A Focus On Controlling For Fine-scale Population Structure In DNA Sequence Data
Funder
National Health and Medical Research Council
Funding Amount
$283,447.00
Summary
Individuals who live near each other tend to be more similar genetically than individuals who live in different parts of the world. One reason is that they share more of their genetic ancestry. There can be very subtle differences in patterns of genetic variation even within countries. Accounting for these subtle differences can be important for studies of the genetic basis of diseases. We will develop novel statistical methods to control for these genetic differences in disease studies.
Methods And Software Tool For Complex Trait Analyses Using Multi-omics Data
Funder
National Health and Medical Research Council
Funding Amount
$573,999.00
Summary
This project aims to develop methods to disentangle the contribution of people’s difference in DNA sequence, DNA methylation, and gene expression to their difference in characteristics (including risks to diseases), and to utilise these information to predict disease risks of different people. This project also aims to develop a versatile and efficient computer software to implement the methods being proposed in this project, as well as all other commonly used methods in the research community.
Identifying Mitochondrial Genome Variants Associated With Familial Migraine Susceptibility
Funder
National Health and Medical Research Council
Funding Amount
$443,273.00
Summary
New therapeutic targets for migraine are desperately needed. Although studies have identified some migraine genes there remains considerable underlying genetic variation to be characterised. This study aims to identify functional variants in the mitochondrial genome that contribute to migraine susceptibility, utilising the isolated Norfolk Island population. Outcomes will determine the significance of the variants identified, potentially leading to new diagnostics.
Identifying Novel Gene Mutations For Molecular Diagnosis Of Familial Hemiplegic Migraine
Funder
National Health and Medical Research Council
Funding Amount
$623,460.00
Summary
This proposal aims to identify novel FHM genes by undertaking an NGS screen of the whole exome of 209 FHM patient samples. We will test the pathological relevance of detected novel mutations by functional analysis in human cell models and using patient-specific stem cell techniques. Using whole genome NGS technology to identify novel mutations will assist in the design and development of a comprehensive NGS approach to diagnose and differentiate this severe neurological disorder.
The Molecular And Biological Roles Of Growth Inhibiting Chromatin Binding Proteins
Funder
National Health and Medical Research Council
Funding Amount
$814,843.00
Summary
Our previous work has led to the identification of mutations underlying human birth defects. Similarly, our proposed work will identify a new gene as potentially mutated in human heart defects. We will determine its overlapping functions with a related gene and elucidate their roles in embryonic development and cancer.
Statistical Analyses Of Whole Genome Genotype Data To Better Understand Psychiatric Disorders
Funder
National Health and Medical Research Council
Funding Amount
$543,755.00
Summary
Until now, determining an overlapping genetic aetiology between disorders, required large study cohorts of family records. Here we will use genome-wide genotypes available on independent case-control samples to estimate a shared genetic aetiology directly from the molecular data. In this way we will explore previously intractable questions, such as the relationship between rheumatoid arthritis in people with schizophrenia, a well-recognised epidemiological puzzle.
Identification And Characterisation Of A Novel Genetic Signature At The 5p15 Region Associated With Risk Of Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$610,974.00
Summary
We have recently replicated the genetic association of a region (5p15) with the risk of prostate cancer in Australian men. We now seek to identify the precise genetic variant behind this association, and the functional role of these novel gene/s and variants in disease pathology. Our results will provide a foundation for the development of sensitive and readily applicable lab-based screening tools to be used clinically and will also provide impetus for drug-targeted research by furthering our un ....We have recently replicated the genetic association of a region (5p15) with the risk of prostate cancer in Australian men. We now seek to identify the precise genetic variant behind this association, and the functional role of these novel gene/s and variants in disease pathology. Our results will provide a foundation for the development of sensitive and readily applicable lab-based screening tools to be used clinically and will also provide impetus for drug-targeted research by furthering our understanding on this multifactorial disease.Read moreRead less
Identifying Regulators Of The DNA Damage Response And Tumourigenesis Using C. Elegans
Funder
National Health and Medical Research Council
Funding Amount
$514,367.00
Summary
By the age of 85, one in two men and one in three women in Australia will develop cancer. Regrettably, not all cancers respond to current therapies. Recently a new mechanism that prevents certain cancers from responding to chemotherapy has been identified, involving a protein called HIPK. We are using a simple model system, the nematode Caenorhabditis elegans, to discover ways in which this block to successful cancer treatment can be overcome, with the view to developing new therapeutic agents.
Translation Of PALB2 Genetic Information Into Breast Cancer Clinical Genetic Services
Funder
National Health and Medical Research Council
Funding Amount
$423,081.00
Summary
Today in Australia women attending clinical genetics services and receiving genetic counselling due to a personal and/or family history of breast cancer are not considered for testing of PALB2 despite mounting evidence that the risk of breast cancer in mutation carriers is at least as high as the risk for BRCA2 mutation carriers. This project will provide the evidence base to support the incorporation of PALB2 gene testing into routine clinical genetics services both in Australia and around the ....Today in Australia women attending clinical genetics services and receiving genetic counselling due to a personal and/or family history of breast cancer are not considered for testing of PALB2 despite mounting evidence that the risk of breast cancer in mutation carriers is at least as high as the risk for BRCA2 mutation carriers. This project will provide the evidence base to support the incorporation of PALB2 gene testing into routine clinical genetics services both in Australia and around the world.Read moreRead less
Genomic Signposts, High-resolution Sequencing And Novel Genes In Eye Disease
Funder
National Health and Medical Research Council
Funding Amount
$333,694.00
Summary
Blindness is a very distressing sensory loss. Hereditary eye disorders account for the vision impairment in at least one-third of people who are registered as blind. These disorders cause blindness from a young age and work productivity is significantly impaired. This project will identify novel genetic factors in blinding eye disorders. Identifying these genetic factors will lead to better early detection methods for people and improved treatments to prevent the blindness.