Development And Evaluation Of Statistical Methods And Software For Analysis Of Complex Genetic Disease Data
Funder
National Health and Medical Research Council
Funding Amount
$1,250,371.00
Summary
What are the major factors underpinning complex genetic diseases like diabetes, bipolar disorder or cancer? To answer this question new tools are needed, including software for mining the human genome with interactions between the genome and environment being incorporated. This is our focus. It will form the basis of a superior understanding of the overall process leading to disease and hence better predictions with important ramifications for new treatments and health care planning.
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.
Fine Mapping Of Genes Underlying Asthma And Eosinophilia
Funder
National Health and Medical Research Council
Funding Amount
$278,000.00
Summary
Asthma is the fourth most common chronic disease in Australia, and is increasing in incidence. Genetic factors are known to be important modifiers of disease risk, and several genes have been reported in the literature as being involved in either causing asthma or altering response to therapy. Immunoglobulin E (IgE) level and eosinophil count are two factors known to be increased in the blood of asthmatics. In two studies by our group, one of asthma in families, the other of healthy adolescent t ....Asthma is the fourth most common chronic disease in Australia, and is increasing in incidence. Genetic factors are known to be important modifiers of disease risk, and several genes have been reported in the literature as being involved in either causing asthma or altering response to therapy. Immunoglobulin E (IgE) level and eosinophil count are two factors known to be increased in the blood of asthmatics. In two studies by our group, one of asthma in families, the other of healthy adolescent twins, we showed these measures to be genetically linked to two different regions in the genome. Closer examination of these regions found several genes that might be responsible for the linkage. In the present study, we plan to test which of these candidate genes actually causes elevated IgE level or eosinophil count. The approach is to compare the frequency of a putative gene in a child expressing that phenotype to that in their parents. Each child receives one copy of a gene from the father, and one from the mother, making up a complete genotype (two possibly different versions or alleles of the gene). Since each parent transmitted only one allele to the child, the remaining allele from each parent can be used to create a normal control genotype, that is guaranteed to come from the same ethnic background as the asthmatic child. Therefore, we will collect replacement blood samples in those familes where all the previously DNA has been used up in our earlier study. We will extract DNA, and measure the genotypes of parents and children at the 6 genes in our two regions that we think most likely to be involved in eosinophil count or IgE level. This family based test will allow us to decide which genes are genuinely associated with asthma in our population. We will also test if these genes interact with other genes thought to be asthma risk factors. Identification of novel genes involved in asthma will help understand and ultimately treat this condition.Read moreRead less
Investigating The Interplay Of Gene And Environment In Childhood And Adolescent Mental Health
Funder
National Health and Medical Research Council
Funding Amount
$386,298.00
Summary
Mental health and substance use disorders account for 60-70% of the overall disease burden among young Australians. This research aims to fully explore the gene-environment interplay in childhood and adolescent mental health. The potential outcomes of this research include: improved understanding of genetic and environmental architecture for single disorder, and the high comorbidity between disorders; guidance for personalised intervention based on one’s genetic background.
Atopic dermatitis (AD) or atopic eczema is the third condition making up the atopic triad (asthma, hayfever and eczema). It usually has its onset before two years of age. It is common, affecting approximately 10% of Australian children and 7% of Australian adults, and is increasing in prevalence. As with asthma, genes are known to be important in its causation, and several different genes have been reported to be involved by different investigators. These findings are not always repeatable in di ....Atopic dermatitis (AD) or atopic eczema is the third condition making up the atopic triad (asthma, hayfever and eczema). It usually has its onset before two years of age. It is common, affecting approximately 10% of Australian children and 7% of Australian adults, and is increasing in prevalence. As with asthma, genes are known to be important in its causation, and several different genes have been reported to be involved by different investigators. These findings are not always repeatable in different countries or ethnic groups. One, the mast cell chymase gene seems to be associated with AD in Japan, but not in Australia or Italy. However, this gene may be responsible only for AD where total serum Immunoglobulin E is low, roughly 20% of all AD. Therefore, the previous studies may not have included enough cases of this subtype to reliably detect the association. The present study aims to test all the published genes in two panels of families: one where both AD and asthma or hayfever are present in the family (180 families), the second where AD alone is present (100 families). We will also test for genetic linkage to particular regions of the genome, where the specific gene is yet to be identified, and for newly discovered gene variants in these regions that may be associated with AD. Confirming and refining the nature of genes involved in the causation of AD is useful for the basic understanding of biochemical pathways to disease and ultimately to the design of drugs to interfere with these pathways.Read moreRead less
Clinical Genetic Phenotyping Of Autism Spectrum Disorders
Funder
National Health and Medical Research Council
Funding Amount
$582,114.00
Summary
Individuals with autism spectrum disorders (ASD) have difficulty with communication, social interaction and intellectual disability. The cause is generally not known although most cases have a genetic basis involving multiple genes and possibly environmental factors. We will study families of children with ASD and carefully characterize features related to ASD in family members. This will help us to understand how ASD is inherited and serve as the basis for the discovery of autism genes.
Dissecting Genetic Variation For Human Complex Diseases And Traits
Funder
National Health and Medical Research Council
Funding Amount
$135,821.00
Summary
Understanding the pattern of inheritance for human common diseases such as cancers, obesity, diabetes and mental illness, is of key importance for disease diagnosis, treatment and prevention. In this project, we will develop statistical methods and software tools to analyse DNA and clinical data to better understand the genetic basis of human common diseases and to predict a person�s risk of developing disease.
Discovery And Analysis Of Vertebrate Intestinal Development Genes That May Play A Role In Colon Cancer
Funder
National Health and Medical Research Council
Funding Amount
$376,613.00
Summary
Colorectal cancer (CRC) causes more cancer deaths in Australia than any other cancer. While early detection improves survival rate, nearly half of all CRC patients succumb to the disease within five years. In general, metastatic CRC is resistant to chemotherapy and radiotherapy and new therapies are required. An increased knowledge of the processes that contribute to the malignant state is likely to suggest new targets for treatment. CRC, like all cancer, is the result of genetic abnormalities ( ....Colorectal cancer (CRC) causes more cancer deaths in Australia than any other cancer. While early detection improves survival rate, nearly half of all CRC patients succumb to the disease within five years. In general, metastatic CRC is resistant to chemotherapy and radiotherapy and new therapies are required. An increased knowledge of the processes that contribute to the malignant state is likely to suggest new targets for treatment. CRC, like all cancer, is the result of genetic abnormalities (mutations) that are acquired over the course of a lifetime. Together the mutated genes produce changes in cell behaviour in processes such as growth, migration, angiogenesis (the ability to attract a blood supply) and cell death. All of these processes are active during normal development of a vertebrate organism, but are generally shutdown in the adult state, except in cancer. In this study we will analyse a group of genes that we have recently shown to be indispensable for normal intestinal development in zebrafish. Zebrafish are small tropical fish that are used frequently for genetic studies. They are very closely related to mammals and it has been shown that the genetic pathways that control the development of this animal are highly conserved in fish and mammals. Importantly, the genetic pathways that lead to cancer in humans are also strikingly similar in zebrafish. Our experiments will use mouse models to discover whether the zebrafish genes we have identified can lead to cancer when they are aberrantly expressed in the intestines of mice. Any genes that are found to contribute to the development of cancer in these models could become potential new targets for cancer therapy.Read moreRead less