A large mole (melanocytic nevi) count is the strongest known risk factor for melanoma. An understanding of the factors governing naevus development may therefore lead to important insights into the etiology of melanoma. We shall carry out molecular genetic analysis of DNA samples collected from twins and their parents with the aim of identifying major genes affecting moliness, pigmentation and other risk factors for melanoma. The importance of this study is that it will significantly advance our ....A large mole (melanocytic nevi) count is the strongest known risk factor for melanoma. An understanding of the factors governing naevus development may therefore lead to important insights into the etiology of melanoma. We shall carry out molecular genetic analysis of DNA samples collected from twins and their parents with the aim of identifying major genes affecting moliness, pigmentation and other risk factors for melanoma. The importance of this study is that it will significantly advance our understanding of the relationship between moliness and melanoma risk and may lead to new therapeutic interventions.Read moreRead less
Investigating The Role Of Pigmentation Pathway Genes In Moliness And Melanoma Risk
Funder
National Health and Medical Research Council
Funding Amount
$943,545.00
Summary
Melanoma is an important cause of death in Australia and our generally light pigmentation in a geographical area of high sun exposure is a major factor in this. Our research increasingly points to certain pigmentation genes having a direct biochemical influence on cancer risk in addition to their risk via pigmentation. Understanding how the genes that deternine skin, hair and eye colour act to modify moliness and melanoma risk is important for public health prevention schemes.
Fine Mapping Of The ADH Region For Alcohol Metabolism, Use And Dependence
Funder
National Health and Medical Research Council
Funding Amount
$215,690.00
Summary
It is widely known that alcohol use and alcohol dependence can cause many social problems and morbidity. We know that social and and cultural factors can affect the possibility of becoming alcohol dependent. We also know that inheritance plays a major role in the risk of becoming dependent upon alcohol. Two inherited causes or genes have already been identified as causing some people to avoid alcohol and so have less chance of becoming dependent upon it. Clues as to why this happens come from wh ....It is widely known that alcohol use and alcohol dependence can cause many social problems and morbidity. We know that social and and cultural factors can affect the possibility of becoming alcohol dependent. We also know that inheritance plays a major role in the risk of becoming dependent upon alcohol. Two inherited causes or genes have already been identified as causing some people to avoid alcohol and so have less chance of becoming dependent upon it. Clues as to why this happens come from what happens to alcohol following a drink. The body detoxifies itself of alcohol in the liver. There it is converted to very highly toxic acetaldehyde and this is normally rapidly removed by a protein called aldehyde dehydrogenase. Some people do not have a normally functioning form of this protein and cannot remove the acetaldehyde from their bodies. They suffer unpleasant side effects such as nausea, facial flushing and sickness. Consequently they learn by experience to avoid alcohol use and are less likely to develop dependence. We now know that even people with a normally inherited form of aldehyde dehydrogenase can have a lowered risk of dependence. The rate at which our livers convert alcohol to actetaldehyde is also a key factor. Those who are inherently quick at this process again learn to avoid alcohol, others are more at risk. The hypothesis will be tested with a unique set of twins who have provided us with detailed information on how quickly they detoxify alcohol and of their drinking habits for over 20 years. Collectively they will enable us to determine if there is a major genetic influence on alcohol use and dependence that is caused by inter-individual differences in a gene for alcohol metabolism. The DNA of these twins will be used to locate mutations that we predict have a common effect upon our measures of alcohol detoxification, drinking habits and risk of alcoholism.Read moreRead less
Mapping Of Genetic Traits In Experimental Models Using Databases
Funder
National Health and Medical Research Council
Funding Amount
$237,750.00
Summary
The project aims to detect genes that influence human traits. These traits could be a disease such as diabetes or they may be much less sinister, representing hearing range as an example. Many of these traits are difficult to detect because they are governed by many genes which may also interact with the environment to influence the trait. In order to detect genes in these traits we would like to simplify the complex interactions by eliminating the environment as a potential cause or concentrati ....The project aims to detect genes that influence human traits. These traits could be a disease such as diabetes or they may be much less sinister, representing hearing range as an example. Many of these traits are difficult to detect because they are governed by many genes which may also interact with the environment to influence the trait. In order to detect genes in these traits we would like to simplify the complex interactions by eliminating the environment as a potential cause or concentrating on a particular population where the incidence appears to be much greater. In human populations we have no control over the environmental exposures and we cannot restrict their movements. For this reason many genetic studies have been conducted in mice. Many strains of mice have been generated. Their environment can be strictly controlled, enabling a much better identification of disease genes. Since mice and humans share much of their genome they also share many of their genes and are often afflicted by the same diseases. Thus if we identify genes in mice we have a very good chance of identifying the equivalent human genes. The completion of sequencing for the human genome is being closely followed by the completion of the mouse genome, precisely because mice have been used for over 100 years for genetic studies. The data generated from these sequencing efforts and prior genetic studies is now accumulating in vast databases. These databases of DNA information can be used to map genes for traits. The idea is to determine the trait measurement for many mice in different strains and compare these trait levels to the DNA state (genotype) of markers in the genome of the strains. If these are associated it indicates that the marker is situated close to a gene influencing the trait. This narrows the search considerably. Without this strategy we would have the daunting task of identifiying trait genes from many thousands of potential candidates.Read moreRead less
Validation And Replication Of Genes Associated With Common Human Disease Using Australian Twin Families
Funder
National Health and Medical Research Council
Funding Amount
$921,224.00
Summary
The European Network for Genetic and Genomic Epidemiology (ENGAGE) aims to translate the wealth of data emerging from large-scale research efforts in molecular epidemiology into information of direct relevance to future advances in clinical medicine. ENGAGE will do this through the integration of very large datasets already available from a substantial number of large and well-characterised samples. The resulting ENGAGE resource will represent a research investment >€100M (>AU$160M) and pr ....The European Network for Genetic and Genomic Epidemiology (ENGAGE) aims to translate the wealth of data emerging from large-scale research efforts in molecular epidemiology into information of direct relevance to future advances in clinical medicine. ENGAGE will do this through the integration of very large datasets already available from a substantial number of large and well-characterised samples. The resulting ENGAGE resource will represent a research investment >€100M (>AU$160M) and provide unprecedented power to discover disease and trait susceptibility genes. QIMR will contribute 12,000 twins for ENGAGE joint analyses and provide analytical expertise in the analysis of disease and genetic data related to lifestyle and metabolic traits, with particular emphasis on cardiovascular disease, type 2 diabetes and migraine risk factors. Our laboratory will also perform vital further genetic studies to establish the causal relationship between the genetic variants concerned and the traits of interest. Most importantly, our direct participation will allow the translation of these findings into the Australian population and clinical arena.Read moreRead less
Linkage Disequilibrium Mapping And Positional Cloning For Gene Identification In Osteoporotic Families
Funder
National Health and Medical Research Council
Funding Amount
$330,500.00
Summary
Osteoporosis is a common chronic disease with associated pain, loss of function and death. Patients with the disease commonly experience spine, hip or wrist fracture. Fracture of vertebrae may result in chronic back pain and deformity. Respiratory and digestive health are then also compromised. In comparison, hip fracture may lead to a need for surgery, reduced mobility and institutionalization. In view of improved general community health and increased longevity, the incidence of this disease a ....Osteoporosis is a common chronic disease with associated pain, loss of function and death. Patients with the disease commonly experience spine, hip or wrist fracture. Fracture of vertebrae may result in chronic back pain and deformity. Respiratory and digestive health are then also compromised. In comparison, hip fracture may lead to a need for surgery, reduced mobility and institutionalization. In view of improved general community health and increased longevity, the incidence of this disease and the drain on public health funding will continue to increase substantially in coming years. Presently the cost in Australia is $7.5 billion per annum. Instituting effective prevention strategies is essential. This project aims to contribute to this goal by identifying a major gene(s) involved in disease susceptibility. The term osteoporosis covers a number of heterogeneous syndromes including juvenile osteoporosis, secondary osteoporosis (e.g. corticosteroid induced) and postmenopausal osteoporosis. In this later broad grouping there is evidence of a strong familial association. Previous work has shown that a family history of fracture increases your risk of fracture more than four fold. Furthermore, studies in twins have persistently shown that bone mineral density, the largest risk factor for osteoporotic fracture, is strongly inherited. This data confirms a genetic basis for the disease in some individuals. We have completed two whole genome screen projects and genetic linkage analysis in the families studied has highlighted four regions of the genome, which may harbour genes involved in the disease process. In this project we will fine map these regions and identify the genes that are responsible for the observed linkage. We will use a technique called positional cloning to discover the identity of the gene(s) and will characterise how genetic variation (polymorphism) in the gene leads to reduced bone mass and osteoporotic fracture.Read moreRead less
Physiological Genomic Analysis Of Lvm-1 - A Genetic Locus That Determines Left Ventricular Mass
Funder
National Health and Medical Research Council
Funding Amount
$356,540.00
Summary
As many as one in ten healthy individuals have big hearts. Careful scientific investigation has revealed that the bigger one's heart, the greater the risk of dying from cardiovascular disease. This is true even in the absence of known causes of heart disease. Unlike high blood pressure or cholesterol, the size of the heart is not easily measured and enlargement often goes undetected. We were among the first internationally to discover genetic clues to enlarged hearts. We identified regions on ra ....As many as one in ten healthy individuals have big hearts. Careful scientific investigation has revealed that the bigger one's heart, the greater the risk of dying from cardiovascular disease. This is true even in the absence of known causes of heart disease. Unlike high blood pressure or cholesterol, the size of the heart is not easily measured and enlargement often goes undetected. We were among the first internationally to discover genetic clues to enlarged hearts. We identified regions on rat chromosomes that harbour the gene or genes that influence heart size. The aim of these studies is to identify the exact gene responsible and to understand how that gene produces its effects. The experiments involve testing DNA samples already obtained from many hundreds of rats and breeding animals to study the consequences of the genetic abnormality in greater detail. The experiments are critical steps towards the prevention of big hearts and their complications in humans. In time, genetic tests will offer earlier detection and facilitate targeted and tailored treatments.Read moreRead less
A Genome Wide Association Study For Alcohol And Nicotine Addiction Susceptibility Genes
Funder
National Health and Medical Research Council
Funding Amount
$872,816.00
Summary
Alcohol and nicotine addiction are major public health problems within Australia. As well as the personal and economic costs associated with dependence, there is a wide range of downstream health effects from heavy drinking and smoking. This is a proposal for a genome wide association study to systematically screen and identify genetic variants within the Australian population that affects an individual's liability to developing alcohol addiction, nicotine addiction or both.
Identifying Endophenotypes For Eating Disorders And Their Relationship To Specific Genotypes And Environments
Funder
National Health and Medical Research Council
Funding Amount
$507,419.00
Summary
Around 15% of Australian women will have an eating disorder at some time in their life, and half of these will experience significant levels of depression and suicidality. The current project seeks to build better models of the initiation and maintenance of eating disorders that can inform development of effective treatments, with identification of genes and environments that predict the various components that define eating disorders (i.e., behaviours, temperaments and cognitive flexibility).
Quantitative genetics of Eucalyptus globulus. Eucalypt plantations in Australia have expanded rapidly over the last decade. With increasing market competition from overseas plantations for both pulp and solid wood products, Australia must maintain a competitive edge through efficiencies in production and product quality. Breeding and deployment of genetically superior planting stock is part of the solution. With global climate chance and requirements for re-afforestation in drier zones, there ....Quantitative genetics of Eucalyptus globulus. Eucalypt plantations in Australia have expanded rapidly over the last decade. With increasing market competition from overseas plantations for both pulp and solid wood products, Australia must maintain a competitive edge through efficiencies in production and product quality. Breeding and deployment of genetically superior planting stock is part of the solution. With global climate chance and requirements for re-afforestation in drier zones, there is an increasing requirement to genetically improve drought tolerance. This project will provide genetic information and strategies to back Eucalyptus globulus breeding and deployment programs for traditional as well as drier environments. Read moreRead less