Designing nested primer sets for LM-PCR (dsg 10/9/06)

Retrieve sequence for the region of interest from flybase and paste into a text file.

Go to primer 3 to identify PCR primers.  Paste sequence corresponding to the region approximately 230 base pairs from the farthest region of interest.  For example, if Pol II initiates transcription at +1, analyze the sequence from +1 to +230.

Focus the primer selection on the distal regions of the sequence.  Insert a "<" about 50 nucleotides from the 5' end and a ">" about 50 nucleotides from the 3' end. 

Try identifying a nested set of primers with Tm's of 54oC, 58oC and 62oC (+/-1oC).  If this doesn't work, try Tm's of 58oC, 61oC, 65oC (+/-1oC).  After identifying the first primer, remove part of the 3' end of the sequence to force the search for the next primer towards the 5' end.  Repeat this to identify the third primer.  The nested set of primers should have increasing Tm's and overlap so that each primer blocks the 3' end of the preceding primer from annealing to the DNA.

Next, go to the IDT web site to make certain this set of primers is not prone to forming hetero or homo dimers.   Also check for compatibility with linker primer A', which is GCGGTGATTTAAAAGATCTGAATTC.

Finally, BLAST the primer sequences against the Drosophila genome using flybase.