Australian Genomewide Association Study In Osteoporosis
Funder
National Health and Medical Research Council
Funding Amount
$882,722.00
Summary
Osteoporosis is a common condition in which bone strength is reduced due to reduced amount and quality of bone. Reduced bone strength means an increased risk of fracture. Osteoporotic fractures occur in 1 in 2 women and 1 in 3 men in their lifetime, and the likelihood of suffering osteoporotic fracture increases with age. Most of the risk of developing osteoporosis is genetic, but few of the genes involved have been identified. Our goal is to identify those genes.
The Identification Of Male Meiosis Genes Using A New Mouse Line And Human Genome Scans For Gene Copy Number Variations
Funder
National Health and Medical Research Council
Funding Amount
$604,793.00
Summary
Infertility affects 1 in 25 Australian men and meiosis is a key process in male fertility, yet we know very little about the mechanisms that control it. We will use a new point mutant mouse model of meisois failure to identify a novel regulator of male fertility. Further, we hypothesize that changes in gene copy number will lead to meiosis arrest and infertility in some men. Such variations will be assessed through a whole genome scan of a unique set of infertile men.
Effects Of Nevogenesis Susceptibility Genes And Phenotypic Correlation With Dermoscopic Characteristics Of Nevi
Funder
National Health and Medical Research Council
Funding Amount
$554,099.00
Summary
Melanoma is a form of skin cancer that arises from the cells that produce pigment and is a major public health issue in Australia. We will examine the relationship between the form, structure and colour of existing types of moles and their subsequent risk of developing into melanoma. This will be the first study to combine dermoscopy, a non-invasive examination technique, with DNA tests of the genes that determine skin, hair and eye colour, aiding in the early prediction and diagnosis of skin ca ....Melanoma is a form of skin cancer that arises from the cells that produce pigment and is a major public health issue in Australia. We will examine the relationship between the form, structure and colour of existing types of moles and their subsequent risk of developing into melanoma. This will be the first study to combine dermoscopy, a non-invasive examination technique, with DNA tests of the genes that determine skin, hair and eye colour, aiding in the early prediction and diagnosis of skin cancer.Read moreRead less
Twin and family studies show schizophrenia has a genetic basis. Attempts to find and characterise the underlying genes have not been successful so far. A main reason for this is that insufficient attention has been paid to the complexity of the underlying genetic architecture of the disorder. The pathway from genes to symptoms of schizophrenia is likely to involve elementary processes at neuronal and neural circuitry levels that vary between individuals and this variation is reflected in a grade ....Twin and family studies show schizophrenia has a genetic basis. Attempts to find and characterise the underlying genes have not been successful so far. A main reason for this is that insufficient attention has been paid to the complexity of the underlying genetic architecture of the disorder. The pathway from genes to symptoms of schizophrenia is likely to involve elementary processes at neuronal and neural circuitry levels that vary between individuals and this variation is reflected in a graded susceptibility to schizophrenia. During the last three years we have recruited a large number of families with at least one family member diagnosed with schizophrenia. The proband and all participating first-degree relatives have been assessed with a neurocognitive test battery including measures of sustained attention, working memory, speed of information processing, auditory verbal learning and executive function. Analysis of the neurocognitive data on this sample produced strong evidence that several measures are altered in patients with schizophrenia and a proportion of their asymptomatic first-degree relatives compared to unrelated normal controls. In the study we will systematically search the human genome for DNA markers linked to these measures. This will set the stage for the systematic search and characterisation of the underlying genes. This will allow us to better understand the predisposition to develop schizophrenia. In the individual case it is likely that this vulnerability results from a high-risk combination of a number of relatively common alleles which contribute to basic neural processes.Read moreRead less
This study investigates how much an individual's genes and environment account for the wide variation in brain structure and function. Using MRI we will examine in what way a twin's brain is the same or different from that of their co-twin, and carry out analysis of their DNA to identify some of the many genes influencing the structure and function of the brain. The study will provide fundamental information on genetic mechanisms influencing variation in brain structure and function.
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
ADHD Grown-up: Genetic And Environmental Determinants Of The Adult Outcomes Of Childhood ADHD And Comorbid Conditions
Funder
National Health and Medical Research Council
Funding Amount
$289,542.00
Summary
ADHD remains a controversial issue especially in adulthood. There are many related behavioural problems including substance abuse, anxiety, depression, and personality disorders. Australia is such a focus for twin research that many twin families have taken part in several studies of different aspects of mental health over the years. This grant allows us to link the various datasets to create a unique longitudinal genetic resource and to examine the longterm outcomes.
Functional Variants Of RUNX2 Related To Bone Density
Funder
National Health and Medical Research Council
Funding Amount
$451,938.00
Summary
Bone density and osteoporosis have a genetic component. Identifying genes that are involved in determining bone density may permit advances in controlling osteoporosis. We have identified a variant in a gene called RUNX2 that is related to bone density high enough to protect individuals four fold against Colle's fracture, the common wrist fracture seen in women. This variant is highly correlated with changes in the second promoter of RUNX2, such that the high bone density form appears to be the ....Bone density and osteoporosis have a genetic component. Identifying genes that are involved in determining bone density may permit advances in controlling osteoporosis. We have identified a variant in a gene called RUNX2 that is related to bone density high enough to protect individuals four fold against Colle's fracture, the common wrist fracture seen in women. This variant is highly correlated with changes in the second promoter of RUNX2, such that the high bone density form appears to be the ancestral form of this gene. We now need to know how this change in this promoter alters bone density and we are following up on observations that other important transcription factors bind to the variable site in the promoter. Furthermore, we have assembled a large collection of samples from people who have had extensive measures of bone density and arthritis in order to accurately measure the impact of this gene on bone density, osteoarthritis and bone fracture. In addition, some people with bone fracture at the hip, or low bone density, have mutations in this gene. Such mutations in a region called the Q-repeat are rather common, 1-200 people are carriers. Our data show that these mutant proteins are not as efficient at their task of regulating other genes. We now want to know how this occurs in a molecular sense, since it is known that the Runx2 protein resides in the nucleus of the cell and interacts with many other regulators. This part of the project is being done with one of the world experts on gene regulation in bone cells. Since RUNX2 is a master regulator of the cells that make bone, this gives hope that it may be possible to alter bone formation through this master regulator.Read moreRead less
High scorers on the personality trait neuroticism are at greatly increased risk of major depression and other neurotic disorders. Neuroticism is a personality trait that shows considerable stability over adulthood. It has a strong genetic basis and it seems that the same genes also determine risk of depression, anxiety and other neuroses. By selecting twins and sibs extremely discordant and concordant (EDAC) for neuroticism we can greatly reduce the cost and increase the power to find genes infl ....High scorers on the personality trait neuroticism are at greatly increased risk of major depression and other neurotic disorders. Neuroticism is a personality trait that shows considerable stability over adulthood. It has a strong genetic basis and it seems that the same genes also determine risk of depression, anxiety and other neuroses. By selecting twins and sibs extremely discordant and concordant (EDAC) for neuroticism we can greatly reduce the cost and increase the power to find genes influencing depression. Questionnaire responses and interviews from 15,027 Australian twins and 11,389 of their family members were reviewed to identify individuals with neuroticism scores in the top and bottom 10%. These individuals were invited to participate in a structured psychiatric interview by telephone, and to give a blood sample. Participation and DNA sampling rates were high and there was minimal evident participation bias. DNA was collected from 2,926 individuals from 884 families including 1,333 EDAC sibling pairs and over 795 parents. A preliminary genome scan on one third of this sample yields several linkage peaks suggesting genes of major effect that appear to replicate findings in similar studies conducted in Holland and England. Given these results it is highly desirable that we obtain a genome scan on the remainder of selected extreme sample. Another one third of this sample is currently being genotyped in America and here we request funds to genotype the remaining third. .If we are successful in identifying genes underlying neuroticism, we will also be able to analyse their contribution to depression and anxiety. This could lead to better drug treatments.Read moreRead less