Candidate Gene Strategy

Perhaps you are interested in the cause of obesity because, as an avid hamster-owner, you have observed that two closely related strains of hamsters are dramatically different weights as adults. You think that perhaps you have found a great comparative model for obesity. You could compare the thin hamsters to the obese hamsters. But here you get stuck. What, exactly, should you compare to narrow down the possible reasons for obesity? There are many different ways to begin thinking about and researching the underlying cause of the difference between the two strains. In one sense, organisms are little more than a collection of metabolic and biochemical pathways, so one way to approach this question is to ask about the underlying rate of gene expression of the genes that make up the key metabolic pathways. For example, the energy to run an organism comes from the metabolic pathway known as glycolysis. The enzymes that make up this pathway are well known (see the metabolic pathway map). You might hypothesize that one or more of the enzymes of the glycolytic pathway show a different activity level in the two strains of hamster. If you select one or more key genes, you can perform experiments to provide evidence that will help you determine whether the glycolytic pathway is in fact involved. After reading up on glycolysis, and delving into the literature, you have identified glucokinase as a good "candidate" gene that plays a key role in glycolysis. If you can compare the genes in both hamster strains, you might identify whether their DNA or protein sequence is identical or different, or whether the overall expression levels are the same or different.

If glycolysis is running more quickly in the thin strain than the obese strain, then that might be a cause of obesity. Glucokinase is a good choice of a gene to help you determine this.

What are some of the criteria for a good candidate gene? The main one is that it must be a good "indicator" for a specific biological process. Glucokinase is a good indicator for glycolysis.

Scientists use candidate genes in a strategy to uncover the underlying biological processes that are occuring in an organism. High fever in a human might be the result of an immune response. A good candidate gene might be IL-6, which is known to induce a strong immune response in humans.

Your choice of candidate genes is completely dependent upon the biology. If you want to know why corals bleach, you might choose to focus on identifying patterns of gene expression in bleaching and non-bleaching corals. Based on the coral literature that you have read so far, what underlying biological pathways or processes do you think might play a role in the bleaching response? Which candidate genes do you think might be good ones to examine?

You are ready to move on to learning about the strategies for finding the gene sequences of known genes, that you can then use to search out the coral/Aiptasia homologs.