This web page was produced as an assignment for Genetics 564, an undergraduate capstone course at UW-Madison.
What is chemical genetics?
Chemical genetics is the study of gene function through the medium of chemicals. This process takes an indirect approach to analysis of gene function, through two processes referred to as forward and reverse chemical genetics. Forward chemical genetics works through the addition of chemicals and analysis of phenotype in order to understand how a chemical effects a gene function. Reverse chemical genetics works by screening a protein with many different chemicals that could stimulate or limit its function. These processes can both contribute to further knowledge of a gene and its associated proteins. (1)
ABCA4 Chemical Genetics
Figure 2: Structure of Retinol
Retinol and retinol derivatives build up in the eye of those with nonfunctional ABCA4. Along with this link to retinol buildup, ABCA4 is also responsible for visual perception and retina homeostasis. There are many chemicals that are known to be associated with these processes that could effect the displayed ABCA4 phenotype, however none have been so far found. (2)
Discussion
While currently there are no known chemicals to induce ABCA4 negative or recover ABCA4 positive phenotypes, further testing could uncover such a substance. Zebrafish could operate as a model species to test retinol metabolism, retina homeostasis, and visual perception related chemicals upon, given its similar ABCA4 phenotypes and many years of experience being used in chemical screens. (3)
References
1. Walsh, D. P., & Chang, Y.-T. (2006). Chemical Genetics†. Chemical Reviews, 106(6), 2476–2530. https://doi.org/10.1021/cr0404141
2. Beharry, S., Zhong, M., & Molday, R. S. (2004). N-Retinylidene-phosphatidylethanolamine Is the Preferred Retinoid Substrate for the Photoreceptor-specific ABC Transporter ABCA4 (ABCR). Journal of Biological Chemistry, 279(52), 53972–53979. https://doi.org/10.1074/jbc.m405216200
3. Rennekamp, A. J., & Peterson, R. T. (2015). 15 years of zebrafish chemical screening. Current Opinion in Chemical Biology, 24, 58–70. https://doi.org/10.1016/j.cbpa.2014.10.025
2. Beharry, S., Zhong, M., & Molday, R. S. (2004). N-Retinylidene-phosphatidylethanolamine Is the Preferred Retinoid Substrate for the Photoreceptor-specific ABC Transporter ABCA4 (ABCR). Journal of Biological Chemistry, 279(52), 53972–53979. https://doi.org/10.1074/jbc.m405216200
3. Rennekamp, A. J., & Peterson, R. T. (2015). 15 years of zebrafish chemical screening. Current Opinion in Chemical Biology, 24, 58–70. https://doi.org/10.1016/j.cbpa.2014.10.025