This web page was produced as an assignment for Genetics 564, an undergraduate course at UW-Madison
What is gene expression and How do we use it?
While every cell in our body has the same DNA, the parts of it that are transcribed into RNA is dependent on many factors including tissue type, disease conditions, medications, stress, and food intake just to name a few. All of the RNA transcripts in a cell make up its transcriptome. By studying changes in the genes transcribed or their levels of transcription, we can predict how the resultant protein product may be affected. An example of how gene expression could be used to study obesity is shown in Figure 1. [1]
Gene expression can be tested using a number of tools. The most common tool to study a transcriptome is a microarray. This technique can be used to look at the expression of thousands of genes in a given tissue or cell under a certain disease condition. A microarray tutorial can be found here. [2] The results from microarray experiments can be found in the Gene Expression Omnibus (GEO) database. Using this database you can search for a specific gene, such as tubby, as well as disease condition, such as obesity, and view their gene expression microarray experiments.
Gene expression profiles of tubby
There are many microarray experimental results available in the GEO database following a search for tubby. One interesting experiment found that fluoxetine (more commonly known as Prozac) leads to greatly reduced tubby expression in the hippocampus (Figure 2). [3] Another experiment showed that much higher levels of tubby are found in adult peripheral blood as compared to cord blood in endothelial progenitor cells (Figure 3). [4] Through a search of GEO Datasets for obesity, several sets of results are available.
While the results shown on this page in no way include all of the data about tubby and obesity that can be found in the GEO databases, the noted results do provide some potential avenues of further inquiry. The effect of fluoxetine (prozac), (an antidepressant that promotes proliferation and and survival of neurons in the hippocampus) on tubby provides evidence that dopamine may play a role in regulating tubby. The results in figure 3 also indicate that tubby may play different roles in utero than in adult animals. Analyzing the effect of different obesity disease states on tub expression would also be a another line of future inquiry. These are just a few examples of potential avenues of research for tubby that could be found using GEO results.
RNA interference as a tool to study gene expression
RNA interference, more commonly known as RNAi, allows for the study of genes by determining what happens when their RNA transcripts are reduced. RNAi is carried out by introducing double stranded RNAs of the gene of interest that are cut into small pieces by an enzyme called Dicer. These small fragments then tell the cell's RNAi machinery to destroy any RNA transcripts that match the fragment sequence, preventing the RNA from being translated into proteins. [5]
RNA interference and tubby
Through a search of FLIGHT, Wormbase, and the RNAi Database several RNAi studies have been performed in both C. elegans and fruit flies that have helped to begin to decipher the tubby mechanism. Knockdown of tubby using RNAi has led to similar phenotypes as those seen in tubby mice, strengthening the hypothesis that tubby is responsible for normal weight maintenance and fat accumulation.The availability of these screens and the potential to knockdown other genes thought to function with tubby by RNAi makes these organisms good potential model organisms. [6,7,8]
references
Cover Photo Credit
[1] Genetic Science Learning Center. "Measuring Gene Expression." University of Utah Health Sciences, accessed 24 April 2014.
[2] Genetic Science Learning Center. "DNA Microarray." University of Utah Health Sciences, accessed 4 May 2014.
[3] Fluoxetine effect on the hippocampus. GEO database, accessed 4 May 2014.
[4] Endothelial progenitor cells from cord blood and adult peripheral blood. GEO database, accessed 4 May 2014.
[5] National Institute of General Medical Sciences. RNA Interference Fact Sheet, accessed 9 May 2014.
[6] FLIGHT. v. 2.0. King tubby.
[7] WormBase. Tub-1 (gene).
[8] RNAi database. tub-1 RNAi experiments.
[1] Genetic Science Learning Center. "Measuring Gene Expression." University of Utah Health Sciences, accessed 24 April 2014.
[2] Genetic Science Learning Center. "DNA Microarray." University of Utah Health Sciences, accessed 4 May 2014.
[3] Fluoxetine effect on the hippocampus. GEO database, accessed 4 May 2014.
[4] Endothelial progenitor cells from cord blood and adult peripheral blood. GEO database, accessed 4 May 2014.
[5] National Institute of General Medical Sciences. RNA Interference Fact Sheet, accessed 9 May 2014.
[6] FLIGHT. v. 2.0. King tubby.
[7] WormBase. Tub-1 (gene).
[8] RNAi database. tub-1 RNAi experiments.
Site created by Rachael Baird.
Genetics 564 Assignment, Spring 2014
University of Wisconsin-Madison
Last Updated: 5-10-14
Genetics 564 Assignment, Spring 2014
University of Wisconsin-Madison
Last Updated: 5-10-14