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Determining the functional significance of non-coding DNA variants in genes for complex traits involving gene-environmental interactions


To identify non-protein coding DNA changes in genes that interact with the environment using 2 models – sporadic amyotrophic lateral sclerosis for the vulnerability to environmental toxins and elite athletes for exercise-related hypoxic response using a combined in silico approach and cell culture experiment.


Associate Professor Bing Yu.

Research location

Camperdown - Central Clinical School

Program type



Our recent genetic association studies suggest that genes involved in heavy metal detoxification in patients with sporadic amyotrophic lateral sclerosis (SALS) differ significantly from normal controls. In a second model involving elite endurance athletes, we have identified a very strong association between the epithelial PAS domain-containing protein 1 gene (EPAS1) and human endurance-type performance. These results are consistent with environmental factors such as toxin exposure and training exerting their effects on the development of complex traits through interactions with different forms of a gene. DNA variants can modify an environmental stimulus in either a susceptible or protective direction. As demonstrated in our studies: (1) certain forms of the metal-responsive transcription factor gene (MTF1) can make individuals more susceptible to SALS after exposure to heavy metals in the environment, and (2) elite athletes with unique EPAS1 haplotypes will be more efficient in responding to hypoxia during an intensive endurance competition. This project will be focused on searching for and characterisation of the non-protein coding DNA variants using in silico and in vitro experimental approaches. Demonstration of an impaired MTF1 would support a causal role for environmental toxins in SALS. Understanding of the different abilities to cope with hypoxia has significant impact on ageing or cardiovascular disease. Ultimately the project findings will lead to the identification of at-risk populations to environmental toxins or hypoxia-susceptible individuals, and provides potential targets for new therapeutics.

Additional information

The PhD student will be involved in in silico analysis as “dry” laboratory work as well as traditional “wet” experimental components such as minigene construction, transfection, RT-PCR and transcript characterization. The student will also have opportunities to be involved in SNP genotyping and gain experience in many cutting-edge techniques in the Molecular Genetics laboratory and SUPAMAC. Possible areas for PhD topics:

  1. Determining the functional significance of a “silent” mutation in amyotrophic lateral sclerosis
  2. Search for functional non-coding DNA variant(s) in EPAS1 that is(are) associated with endurance performance in elite athletes

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Opportunity ID

The opportunity ID for this research opportunity is 17