Analysis of Mutations

Once the exact nucleotide change of a mutation is known through sequencing, online programs can be used to predict the effect on the encoded protein. One such program is called PARSESNP (Project Aligned Related Sequences and Evaluate SNPs) (Taylor and Greene 2003). This program uses the supplied reference DNA and mutation sequence information to locate and determine if the nucleotide change alters the protein sequence. The PARSESNP program also compares the sequence of the gene of interest to already compiled blocks of homology in a database to score a position specific scoring matrix (PSSM) difference (Henikoff and Henikoff 1996). Another useful software program, SIFT (Sorting Intolerant From Tolerant), can be used in concert with PARSESNP. SIFT searches current databases for similar sequences and provides a score based on amino acid conservation that predicts whether or not a change will be tolerated (Ng and Henikoff 2003). If a mutation has a high PSSM and a low SIFT score on the PARSESNP program output, it is likely that an amino acid change at that position is rare and is therefore predicted to have a severe effect on protein function. These predictions can help prioritize mutations for phenotypic analysis, especially when an abundance of mutations are discovered for a single gene target.

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