Molecular interpretation of genomic changes
from genotype to phenotype
The last time ...
Spoiling the sequence - a pre-exercise game
Check out the codon table.- SST ; make a missense mutation (change codon to code for different amino acid type)
- NBDY ; make a silent mutation (change codon to code for the same amino acid type).
- SPCS1; insert a nucleotide
- PYY ; delete a nucleotide
- IAPP; delete 3 nucleotides (codon)
- INS ; make a stop codon in the middle of the sequence (nonsense mutation
- PRL ; make a "readthrough" mutation
Central dogma - a little more thoroughly
Exercises
In all exercies, the task is to find the position on the genome, explain the impact of mutation, and make a shortish presentation.
You can find (and illustrate) the position on the genom using UCSC Genome Browser.
If the impact of the mutation is protein modification, use PyMol to make the illustration.
Some general hints/advice
when using UCSC GB
- pay attention and chose the right assembly - it is the coordinate system in which the gene address is given
- when looking for a position on the genome, select an interval of +/- 10 nucleotides; for example, if the position of interest is chr11:5,248,233, type in the search window: "chr11:5,248,223-5,248,243"
- mouseover over an exon will give you the exon number in a given splice
when using PyMol
- ‘fetch 1xyz’ to read in the structure 1xyz directly from the PDB (Protein Data Bank)
- ‘select somename, chain A and resi 235’ so that the residue 235 from chain A would appear as a selection on the right-hand side menu
In all exercises:
find the position in the genome browser. What is the consequence of the given mutation? (Use the codon table as appropriate; beware of the direction of translation.) Which mutations in the same place would have no effect? (Give an example)- Exercise 1: Chr4:1,803,657 (on Assembly GRCh37) A→T; PDB: 1ry7
- Exercise 2: Chr6:18,130,918 (on Assembly GRCh37) A→G;
- Exercise 3: Chr17: 41,256,943 (on Assembly GRCh37), del (single nucleotide deletion)
- hint 1 (use the gene name you found on the genome)
- hint 2 (Figure 2, never mind the rest)
- hint 3
- How common are the mutations in this part of the gene? In which cancers is this gene mutated?
- Exercise 4: Chr1:94,480,243 (on Assembly GRCh37) G→A;
- Exercise 5: Chr18:58,038,687 (on Assembly GRCh37), C→A