Science Buddies: "Ask an Expert"

Hi,
I did the "From Genes to Genetic Diseases: What Kinds of Mutations Matter?" project, but the results are confusing me. First I did it with the CFTR gene suggested, and I understand that the alleles that are non-pathogenic either do not change the amino acid produced by the codon, or change it to an amino acid with the same electric charge. The ones that are pathogenic change the amino acid produced by the codon to one with a different electric charge, with few exceptions.

However, when I redid this experiment with alleles of the APP gene (one of the genes responsible for Alzheimer's), the pathogenic alleles changed the electric charge of the amino acid just a bit more than half of the time, and even that might be the result of me wanting to confirm my hypothesis. Why is this? I have a feeling I'm missing something.

Thank you in advance!

Hi Abby,

This is a really interesting project! https://www.sciencebuddies.org/science- ... p007.shtml

It's great that you recognized a pattern of mutation in the pathogenic genes for CFTR. But electric charge is not the only thing that can affect protein folding. Take another look at the amino acid changes you saw in the pathogenic mutations for the APP gene. Maybe the changes had to do with the size of the new amino acid, or a change in a special property of the amino acid. For example, cysteine is able to form disulfide bonds, which stabilize protein conformation. If a cysteine is replaced (or replaces another amino acid), that can have an effect on the final 3D conformation of the protein.

I would take another look, and look for any amino acid change with the pathogenic mutations. Then you can consider how those changes affected the final protein.

Please post again (in this same thread) if you have more questions.

Heather

Thank you so much for the answer!
I'll try what you suggested tonight. One more question though: could the function of the protein affect what amino acid properties cause it to become pathogenic? For example, the CFTR gene encodes a protein that transports negatively charged particles across cell membranes, so the electric charge of the amino acids that compose it is more important than in the APP gene?

Hi Abby,

Yes, that is very good thinking! If the function of a protein is to interact with charged particles, then the charge will be extremely important. Many proteins need to interact with receptors, and in that case the 3-dimensional shape of the protein can be very important. The shape determines the active site of a protein, and the amino acids in the active site are very important. However, sometimes changing the amino acids at another site causes the protein to fold incorrectly, which can also change the shape of the active site.\

Here is some information on protein folding, to help you with your background information.
http://en.wikipedia.org/wiki/Protein_folding
http://fold.it/portal/info/science

This site has information related to protein folding and Alzheimer's:
http://www.nature.com/horizon/proteinfo ... sease.html

Remember to look for a pattern in your particular results, which you may be able to relate to protein folding or some other characteristic of Alzheimer's disease.

I hope that helps!

Heather