Characterization Of A Novel Human X-linked Gene RBMX, A Candidate For X-linked Mental Retardation
Funder
National Health and Medical Research Council
Funding Amount
$356,870.00
Summary
We recently discovered a novel gene (which we have called RBMX for RNA-binding protein, X chromosome) on the human X chromosome. Its function is quite unknown, but it is active in all tissues, and it has changed very little in evolution, so we think it must have an important function in human development. Genes with a similar sequence bind to RNA and convert it to its final active form, so RBMX may have a similar role. Other RNA-binding proteins are active in the brain, so we suspect that RBMX m ....We recently discovered a novel gene (which we have called RBMX for RNA-binding protein, X chromosome) on the human X chromosome. Its function is quite unknown, but it is active in all tissues, and it has changed very little in evolution, so we think it must have an important function in human development. Genes with a similar sequence bind to RNA and convert it to its final active form, so RBMX may have a similar role. Other RNA-binding proteins are active in the brain, so we suspect that RBMX may be involved in brain development and learning. The RBMX gene is also interesting because it has a copy called RBMY on the human Y chromosome, which is thought to have a critical (unknown) function in sperm production. Of particular note is our finding that RBMX maps to the long arm of the human X chromosome at Xq26. This is a region that contains several inherited mental retardation syndromes called X linked mental retardation (XLMR) which are carried by females and manifest in males. At least eight XLMR syndromes have been mapped to human Xq26. Several of the syndromes have characteristic skeletal and facial abnormalities, as well as a range of other anomalies.. We will completely characterise the human RBMX gene. As well as giving us fresh clues to its function, this will allow us to make a mouse strain that lacks the gene (knockout) so we can see whether it is critical for life, and if it is involved in brain development and learning. Identification of an XLMR gene coding for an RNA binding protein will shed light on the role of RNA metabolism in the brain, and the effect of disruptions of RNA processing on mental function. We will then screen the RBMX gene in families with XLMR syndromes, to look for RBMX mutations in patients which may cause XLMR. If mutations in RBMX cause one or more XMLR phenotypes, it will be possible to use this knowledge to diagnose the condition and detect carriers.Read moreRead less
Identification Of Telomere-specific Recombination Pathways
Funder
National Health and Medical Research Council
Funding Amount
$540,075.00
Summary
Human cells stop to grow when the natural ends of chromosomes become too short. One way of how cancer cells evade this growth arrest is by using a copy-mechanism to extend short chromosome ends. Ironically, this copy mechanism is usually used by cells to keep the structure of chromosomes intact in order to prevent mutations that cause cancer. Here we will study a novel protein that contributes to the copy mechanism at short chromosome ends, but not as much in normal mutation prevention.
A Genome-wide Linkage Study Of Schizophrenia In A Large Sample From Tamil Nadu, India
Funder
National Health and Medical Research Council
Funding Amount
$500,000.00
Summary
A Study of Schizophrenia in Tamil Nadu, India. The cause of schizophrenia is unknown, but there is good evidence that genes play a role. Geneticists do not fully understand how the disease is inherited, but it is very complex, and several interacting genes as well as environmental factors are probably involved. We have been recruiting families with at least two siblings with schizophrenia from a number of communities-casts in Tamil Nadu. We plan to recruit a total of 400 affected sibling familie ....A Study of Schizophrenia in Tamil Nadu, India. The cause of schizophrenia is unknown, but there is good evidence that genes play a role. Geneticists do not fully understand how the disease is inherited, but it is very complex, and several interacting genes as well as environmental factors are probably involved. We have been recruiting families with at least two siblings with schizophrenia from a number of communities-casts in Tamil Nadu. We plan to recruit a total of 400 affected sibling families, together with 400 trio families (both parents, plus their affected child). A genome-wide scan of the genetic code in all individuals will be conducted to identify chromosomal regions linked to schizophrenia. This is the first necessary step toward identifying schizophrenia susceptibility genes. If one or more genes are discovered, this will greatly improve our understanding of this disease. It will also stimulate the search for similar genes in other samples world-wide, including Australia where schizophrenia costs $2.5 billion annually in terms of treatment and loss of employment. With such a discovery, it may be possible to find better treatments that correct the basic cause of the illness and identify factors that protect against the illness.Read moreRead less
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
Supporting The Australian Arm Of The International Tobacco Policy Evaluation Study
Funder
National Health and Medical Research Council
Funding Amount
$752,250.00
Summary
An international treaty, the Framework Convention on Tobaaco Control, is scheduled to be agreed on and ratified over the coming year. This will provide huge impetus to the development and implementation of new tobacco control policies. This project is part of a large international study designed to provide the best possible scientific evaluation of tobacco control policies that are introduced in the participating countries. This project will ensure that Australia continues to be one of the count ....An international treaty, the Framework Convention on Tobaaco Control, is scheduled to be agreed on and ratified over the coming year. This will provide huge impetus to the development and implementation of new tobacco control policies. This project is part of a large international study designed to provide the best possible scientific evaluation of tobacco control policies that are introduced in the participating countries. This project will ensure that Australia continues to be one of the countries studied. This will maximise the benefits to Austraia of the larger study, not only in providing quality scientific evaluations of the impact of new Australian policies, but also providing evidence to assess the generalisability to Australia of policies adopted in other participating countries . The study will help us understand how policies impact on smokers (their main target). Tobacco policies may not achieve their aims because smokers may respond to them in unanticipated ways. Understanding actual effects helps identify policies that work, and also helps to revise policies that fail (partly or in full). It is at least as important to understand the impacts of policies that affect millions as it is to understand interventions that only touch small numbers.Read moreRead less
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.
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.