Science Buddies: "Ask an Expert"

Hi,
I'm doing "Drugs & Genetics: Why Do Some People Respond to Drugs Differently than Others?" for my science project. My drug is fluorouracil. I had the hypothesis: 'If the drug fluorouracil is tested, then the allele mutation will be an exon with no amino acid change.' I don't think this makes any sense, since it doesn't hypothesize how exactly that allele mutation will make the drug interact differently with a person. I think I am confused as to what exactly I am supposed to be hypothesizing, and how an allele mutation will make the drug interact differently with someone. I would appreciate it if someone could give me some advice or help.

Hi Mona,

This is a great project and a good introduction to using online databases for research.

You did not give me enough information to answer your question. When you went to the PharmGKB site, what genes were listed where mutations have been reported to alter the response to fluorouracil (FU)? What proteins do these genes encode? What kinds of mutations are known and what does the mutation do? Some mutations might make cells more sensitive to FU while others might make them resistant.

Please post again with the results from your PharmGKB search and we will be able to help you.

Sybee

The genes I got were SLC22A7, ABCG2, ABCC4, DYPS, and UMPS. One specific allele in ABCG2 is rs2231142 (exon that changes from a polar, uncharged amino acid to a positively charged amino acid), and it is associated with increased reduction in low-density lipoprotein cholesterol (LDL-C) level as was written on PharmGKB

Have you done a search for these genes to find out if they can be linked to changes in FU responsiveness? If some of the genes have specific mutations that alter a protein involved in FU activity then they might be ones to take a closer look at.

I don't know how familiar you are with genetics and the types of mutations and what they do, so I would suggest that you take a look at the wiki on mutation: https://en.wikipedia.org/wiki/Mutation

and this video from Bozeman Science: https://www.youtube.com/watch?v=eDbK0cxKKsk

When you have more questions, post again and we will help you figure out what a particular mutation may be doing.

Sybee