Carver AP Bio 4: Making sense of the first exercise

exercise 1: mouse BRCA1

Unpacking the exercise: "Find out if the mouse BRCA1 gene has non-synonymous SNPs, color them blue, and get external data about a codon-changing SNP."

 

What are synonymous and non-synonymous SNPs?  When a nucleotide differs between two different gene DNA sequences, sometimes the different codons code for the same amino acid.  For example, the amino acid threonome (thr) is encoded by four different RNA codons, each ending in a different nucleotide (see the genetic code in an earlier post).  So the DNA that is transcribed to make the RNA can also differ.  A non-synonymous SNP, on the other hand, DOES result in a difference in the amino acids in the protein.  In other words, synonymous SNPs don't "matter" to organisms, but non-synonymous SNPs might very well matter.  In the exercise, I assume "codon-changing SNP" means non-synonymous, since that's what we're after.

How am I supposed to know what "appears to be the real BRCA1?"

The tutorial chooses a choice I don't have listed: the nearest name ends in "pe.2" rather than "pe.1"  The two are alike in where they begin in the genome (chr11:101350078), but differ in their ending positions.  Also, the "pe.2" is called "breast cancer type 1 susceptibility PROTEIN," whereas I am looking for a gene.  I suspect that the choices have changed since the tutorial was made, but I can't say why one would disappear.  I note from the descriptions in my browser window that most of the list is proteins or subunits or other things I don't recognize as genes.  The first thing in the list, though, simply says "Full=Breast cancer 1;" so I will choose this.

Nope.  I'm not in the same place in the chromosome as the tutorial, the same region isn't visible; so I will manually input the coordinates from the tutorial.  There!

After you go to the Variations and Repeats section at the bottom of the page, and click the "SNPs (128) link, note that this is about Simple Nucleotide Polymorphisms rather than Single Nucleotide Polymorphisms.  Single-nucleotide polymorphisms are single-base differences between individuals of the same or different species that originally resulted from a mutation, while simple nucleotide polymorphisms is a broader category that includes single-nucleotide polymorphisms and also single-base insertions or deletions (which would change the reading frame if in a gene), as well as changes of a few bases length.

The packed SNP display in my browser doesn't look exactly like that in the tutorial, but I can locate the same snip the tutorial selects: it is the only blue one in the 2nd full-length column: rs28273098. 

 At the end of the exercise I wanted to look at the SNP in question.   Near the top of the SNP page you find that the reference base in this position is G, while the observed variant is A.  [If you go back and use the "Get DNA" button on the previous page, you can call up a text window with as much of the sequence around that SNP as you like (use the windows for adding bases "upsteam" and "downstream").  You will find that the reference strand is the one shown, since it shows the SNP as G.]  Another interesting piece of information is the Function: the variant is a missense mutation, which is defined here.  By the way, Wikipedia has very helpful definitions of many terms you may run into here.

If you've gotten this far, you're ready to try the next exercise!  Good luck!