Detecting Frameshift Between Splice Variants Of A Gene

Question

[Anupam]

Dear all, I have a large number of protein sequences of Homo sapiens. Groups of these are splice variants of different genes. How do I computationally detect frameshift mutations between the splice variants(protein sequences) of a gene? What are the tools that I could use for accomplishing this task ?

Thanks and Regards,

Anupam

Answer 1

[Larry_Parnell]

When comparing alleles of the same gene or protein where one has a frameshift mutation, the alignment of those two sequences will give evidence of the frameshift. You stated you have protein sequences, so align those of the same protein/gene to each other. In some regions of the alignment, the matches will be perfect or nearly so (if there is a SNP changing one amino acid). The frameshift will alter nearly all of the codons downstream of that frameshift and as such the protein alignment will show many mismatches. Thus, the similarity goes from very high to rather low beyond the site of the frameshift.

If the alignment returns to high similarity, there was either a compensating frameshift to put things back in the right reading frame (rather unlikely), or an alternate exon. It is possible that two versions of a protein you are studying share, for example, exons 1, 2, 3, 5, 6, 7, where exon 4a is used by one splice variant and exon 4b is used by another.

CLUSTALW or MUSCLE or TCOFFEE or any other multiple sequence alignment tool will be good if you have more than 2 proteins from a given gene to align. If you need to align just 2 proteins, try the BLAST tool Align.

[Larry_Parnell]

You're welcome. If a response is helpful, it is generally voted up so that other users of BioStar recognize that. This is one of the key aspects of the site that make it stand out.

[Anupam]

Thanks a lot Larry. That was helpful.