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Bioinformatics Exercise - Identifying Genes Related to Disease
1. Please record your answers to all questions that follow.
2. Open this link to the NCBI glossary to help you understand words and acronyms you come across as you
proceed. http://www.ncbi.nlm.nih.gov/books/NBK21106/
3. Go to the NCBI home page and under the Resources (on the left,) click on “Genetics and Medicine” and
then scroll down and click on “Genes and Disease”.
4. Choose a disease category that interests you and read the synopsis.
5. Scroll down, choose a disease and read the synopsis. What disease did you choose to investigate?
6. In the pane on the right, click on the link to “Online Mendelian Inheritance of Man” (OMIM). This
database characterizes the disease in many ways.
7. At OMIM, you can click on the table of contents links on the right or you can just scroll down. Click on
several of these links to see a description of the disease, what clinical symptoms are associated with this
disease, how this disease is inherited, etc.
8. Decide which one of the genes you want investigate further. What is its Gene Symbol?
9. Go back to the OMIM disease page. On the right pane, click on “Genome View”, or if it isn’t available,
click on “Map Viewer”.
10. The graphic on the top of the page shows the human chromosomes. The genes associated with this disease
are in red under one or more chromosomes. A description is below the graphic display. On the right in the
“Quick filter” box, check “Gene” if it is available, which will simplify the search results. How many genes
are associated with this disease?
11. Click on the number below one of the chromosomes containing hits. This takes you to a large section of
that chromosome. The gene you selected should be highlighted in pink. (If it isn’t, in the blue pane on the
far left click to zoom in. This will narrow down the region of the chromosome where your gene of interest is
located.) Note the brief description of the gene as well as that of other nearby genes.
12. Click on the gene symbol.
13. Scroll down to the section “Genomic regions, Transcripts and Products.” This is a graphic view of the gene
on the chromosome, showing introns and exons in green. Click on the “Genbank” link on the right and
scroll down to the view the sequence and other info about the gene. Note that you can have NCBI pick
primers (see next step if you want to try it!). Why would you want to pick primers?
14. On the right of the screen, select “pick primers” and scroll down to the bottom of the screen, check the
“open results in a new window” box and click “Get Primers”. Then wait patiently. How many primer pairs
did the program provide?
15. Under “Genomic regions, Transcripts and Products,” in the region below the gene (green), mouse over the
purple icons in the row of “Clinically Associated Variants”. Are there any “probably pathogenic alleles” of
this gene? How many? If so, click on the dbSNP id to take you to the database of single nucleotide
polymorphisms. Copy or record the SNP id (or several SNP ids) for use later in step 17.
16. Scroll down to Gene model and note the missense mutation. What effect does the mutation have on the
amino acid that is coded for by this gene?
17. View the structure of this protein with its mutation:
a. Starting with the SNP id you found in the last step (E.G. rs58524323,) go back to the NCBI
homepage. At the top of the page select “SNP” from the pull-down menu of “All databases”and
enter the SNP id in the search box.
b. Click on the Protein 3D box in the graphic summary.
c. In the resulting table, three amino acids are listed for each SNP: the amino acid in the reference
protein (e.g., NP_000231; protein context), the amino acid change due to the SNP, and the amino
acid in the most sequence-similar structure (structure neighbor). Check the boxes at the right under
"Cn3D" for each SNP of interest. Scroll down and click the "Selected" button.
d. SNPs are shown as colored triangles on the grey bar representing the protein sequence. Matching
structures are listed below. Click on a pink bar representing a structure.
e. Click on the "View structure and alignment in Cn3D" button on the left.