Changes in genes happen, polymorphisms will be discovered. Consider single base changes. They may be the result of the chemical mutagen EMS, where G:C to A:T transitions predominate. They may be the result of the chemical mutagen ENU, where the spectrum of changes varies with the organism and tissue treated. They may be the result of random, spontaneous mutation - in humans transitions are more common than transversions and transitions from CpG are many times more frequent than transitions from any other dinucleotide. While there are many polymorphisms to be discovered, one makes a priority of discovering and analyzing base changes which are most likely to affect phenotype.
CODDLe [for Choosing codons to Optimize Discovery of Deleterious LEsions] identifies the region(s) of a user-selected gene and of its coding sequence [CDS] where the anticipated point mutations are most likely to result in deleterious effects on the gene's function. CODDLe separately handles 1) the prediction of changes which should truncate the protein and destabilize the RNA - nonsense changes and splice junction changes, and 2) the prediction of missense changes which should alter function of the gene product - those in conserved amino acid blocks in the CDS. Because the region(s) identified will be PCR amplified by the user and that amplicon will be used for polymorphism discovery, the application delivers primer pairs selected by Primer3 [Steve Rozen, Helen J. Skaletsky (1996,1997,1998)Primer3.] After selecting a primer pair, CODDLe returns a window with the selected amplicon and tabulates the effects of all possible polymorphisms which could be detected in that amplicon.
CODDLe will not identify the regions of a gene where polymorphisms are most likely to be discovered. Others have shown that naturally occurring SNPs are found more often in the untranslated regions of a gene.
A reminder to the reader: Nonsense changes change an amino acid encoding codon into a stop codon. Missense changes change the amino acid that is encoded. Silent changes alter the codon, but do not change the amino acid encoded. Transitions change purine to purine and pyrimidine to pyrimidine and are most succintly expressed as G:C <-> A:T changes. All other single nucleotide changes are transversions.
For help filling out the CODDLe web form, or help in interpreting the results, please visit the CODDLe glossary.
Created 14 January 2003, last modified 14 January 2003
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