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
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
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
A Genetic Study Of Schizophrenia In The Brahmin Of Tamil Nadu
Funder
National Health and Medical Research Council
Funding Amount
$267,226.00
Summary
The cause of schizophrenia is unknown, but there is good evidence that genes play a role. Geneticists do not fully understand how it is inherited, but it is very complex, and several interacting genes as well as environmental factors are probably involved. Societies such as Australia are genetically diverse because people from many different ethnic groups have intermarried. To detect susceptibility genes in this type of population, we must study very large patient samples. Alternatively, we can ....The cause of schizophrenia is unknown, but there is good evidence that genes play a role. Geneticists do not fully understand how it is inherited, but it is very complex, and several interacting genes as well as environmental factors are probably involved. Societies such as Australia are genetically diverse because people from many different ethnic groups have intermarried. To detect susceptibility genes in this type of population, we must study very large patient samples. Alternatively, we can study genetically homogenous patient samples, found in isolated gene-pool populations. One such population is the Brahmin people in Tamil Nadu, a south-eastern state of India. The Brahmin are descended from the Aryan peoples who migrated into southern India 2000 years ago. In the Hindu caste system, Brahmin are the highly educated priest class, and enjoy a privileged position in society. Traditionally, marriages among the Brahmin of Tamil Nadu have been prearranged, with a preference for first-cousin marriages. As well as this cultural and historical evidence, genetic marker studies confirm that this population is a suitable genetic isolate. In this project, genetic material (DNA) will be collected from Brahmin schizophrenic patients and their families. Diagnostic data, detailed family data, and blood samples will be gathered from 90-100 extended families, each containing two or more ill individuals. Analysis of their genetic code will enable a search for possible schizophrenia susceptibility genes and a systematic search for a mutation. If found, this will greatly improve our understanding of schizophrenia, and stimulate the search for similar genes in other samples world-wide, including Australia where schizophrenia costs $3 billion annually in terms of treatment and lost jobs. If schizophrenia genes can be found, it may be possible to find better treatments that correct the basic causes of the illness and identify factors that protect against the illness.Read moreRead less
Novel Statistical Methods For Genetic Epidemiology
Funder
National Health and Medical Research Council
Funding Amount
$481,505.00
Summary
We are in the midst of a genomics revolution that is transforming epidemiology, medicine and drug discovery. However, the scarcity of sophisticated statistical techniques to deal with the complicated problems inherent in genetic investigations of complex diseases is currently the critical factor limiting the success of human gene discovery programs. Statistical genetic methodology is currently one of the fastest developing areas of epidemiology. In information-intensive' areas such as genetic ep ....We are in the midst of a genomics revolution that is transforming epidemiology, medicine and drug discovery. However, the scarcity of sophisticated statistical techniques to deal with the complicated problems inherent in genetic investigations of complex diseases is currently the critical factor limiting the success of human gene discovery programs. Statistical genetic methodology is currently one of the fastest developing areas of epidemiology. In information-intensive' areas such as genetic epidemiology, genomics, and proteomics, there is a high demand for data analysis and statistical skills. WA has some world class expertise in statistical science, both in academia and in industry. However, this expertise has not yet been applied in a system way to genetic data analysis. We propose to undertake advanced methodological research in statistical genetics and bioinformatics, to produce easy-to-use and accessible software tools and resources that allow methodological advances to be accessed by the Australian research community, and to apply our new methods and tools both to specific disease research and to the developing human genome epidemiology (HuGE) enterprise in WA. These new initiatives in methodological research will draw together a number of currently separate research strands and will provide new tools and resources that will allow applied Australian programs to improve the efficiency of their research into the causes of important. Methodological development in both bioinformatics and statistical genetics are recognized international areas of need.Read moreRead less
Detection Of Susceptibility Genes For Multiple Sclerosis
Funder
National Health and Medical Research Council
Funding Amount
$589,073.00
Summary
Multiple sclerosis is one of the most common chronic diseases of the nervous system. It usually starts in young adulthood and continues with episodes of severe disability from which partial recovery leads in many patients to difficulties with walking, balance, speech, bladder control and other neurologic functions. The disease inflicts a severe burden on both patients and the community. There is currently no preventive treatment and therapy is expensive (interferon at $20,000 p.a.) and of limite ....Multiple sclerosis is one of the most common chronic diseases of the nervous system. It usually starts in young adulthood and continues with episodes of severe disability from which partial recovery leads in many patients to difficulties with walking, balance, speech, bladder control and other neurologic functions. The disease inflicts a severe burden on both patients and the community. There is currently no preventive treatment and therapy is expensive (interferon at $20,000 p.a.) and of limited benefit in stopping further damage and of no benefit in reversing existing damage. New treatments will come through a full understanding of how the immune system attacks the brain to cause MS. There is a strong inherited component in MS and the discovery of the genes responsible should speed up the quest to understand the cause of the disease. The proposed studies involve international collaboration co-ordinated from Cambridge University, UK, in which the entire human genome will be screened looking for the MS genes using world s best available technology. Funding of this grant will allow Australia an equal seat at the table for this collaboration involving 17 countries. No individual country can recruit enough patients and hence this international effort is essential. It is expected that the understanding of the cause of MS will lead to new treatments that are effective and with low side effects.Read moreRead less
Use Of Expression Profiling To Identify Genes Influencing Cardiovascular Risk In The Norfolk Island Population Isolate
Funder
National Health and Medical Research Council
Funding Amount
$697,409.00
Summary
This study will use a unique population isolate from Norfolk Island. We aim to identify genes that play a role in cardiovascular disease risk. Norfolk has a population of ~1200 permanent residents, most of whom are direct descendents of 18th century English Bounty mutineers and Polynesian women. We will undertake gene expression mapping to identify genomic loci that influence cardiovascular disease using samples from this population isolate.