SIFT/PolyPhen
Links:
Exome Variant Server (Nickerson)
The goal of this exercise is to learn more about SNPs, focusing on inferences from cSNPs using SIFT and PolyPhen.
1. Follow the link on the course website to "ZP3 GeneView SNPs". Under Gene Model you will find a link to the protein sequence. Use this protein sequence and one to two nonsynonymous cSNPs discovered for this gene and run SIFT and PolyPhen.
2. Search for cSNPs in a gene of your own interest and perform the SIFT and PolyPhen analyses. I find it easiest to search using Entrez Gene or the UCSC Genome Browser (turn on SNPs at bottom).
3. Browse Debbie Nickerson's Seattle SNPs genes and look at some of the precomputed SIFT and PolyPhen results.
For all the above analyses indicate if SIFT and PolyPhen give similar or different predictions. If they are different, do you have any hypotheses about the reason for the discrepancy? Look at the alignments for the region around your selected SNP – is the alignment reasonable? Try altering some of the input parameters – do the results change?