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
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