Question: How To Interpret The Loss Or Gain Of Stop Codons
gravatar for Ashutosh Pandey
6.4 years ago by
Ashutosh Pandey11k wrote:

Hi All,

I am working on a particular mouse strain. I aligned the reads and called for the variants and then annotated the variants against Ensembl gene models. Now, I have the list of Stop codon lost and Stop codon gained genes.

As we always compare the donor genome to reference genome, a stop codon gained in donor gene is same as stop codon lost in reference gene. How we can know which genome has the functional gene ? It may happen that the stop codon for the translation is at the right position in the donor genome but there was this mutation in reference gene which is making a longer form of the same protein (lets assume it to be non-functional protein).

Is there any way we can say that the mutation is specific to the reference genome or the donor genome ?


codon • 5.0k views
ADD COMMENTlink modified 6.4 years ago by Larry_Parnell16k • written 6.4 years ago by Ashutosh Pandey11k

What does saying the mutation is "specific to" a certain genome actually mean? If you are trying to figure out what the "normal" version is, try comparing it to other "normal" mice.

ADD REPLYlink written 6.4 years ago by Fwip490

Thanks Fwip. The problem is that I dont know if the given protein is functional or not in normal mice. I am talkign about genes that have been less or never been studies to an extent so that we know whether a particular strain codes for functional or non-functional protein.

ADD REPLYlink written 6.4 years ago by Ashutosh Pandey11k
gravatar for Larry_Parnell
6.4 years ago by
Boston, MA USA
Larry_Parnell16k wrote:

To gain insight into which gene is functional, or both, compare the affected genes to rat (especially), human and other mammals in a multiple sequence alignment. If you have a long list of affected genes, you could parse BLASTP output looking to see which query (stop codon gained, stop codon lost) has a better set of numerical values taken from the BLASTP alignment(s) (or HSPs as they are called, to other mammalian entries, say those from RefSeq.

Look for stop codons gained/lost in alternate exons. It could be a situation where an alternate exon can supply a different COOH tail to the protein. And this could be a "normal" situation.

Also keep in mind that protein truncation mutants have their greatest biological impact, generally speaking, when those mutations occur mid-protein, while mutations close to either end (amino or carboxy) have reduced effect. I think this work was first described for S. cerevisiae.

Lastly, I'd use something like Pfam to tell me if the stop codon altered a known protein (functional) domain and SIFT/Polyphen to tell me if the amino acid change is deleterious or tolerated.

ADD COMMENTlink modified 6.4 years ago • written 6.4 years ago by Larry_Parnell16k

Thanks Larry. This is a wonderful explanation.

ADD REPLYlink written 6.4 years ago by Ashutosh Pandey11k
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