how to define nonsense mutation

[Jon_Keats]

You sure about that ".com" ending?

My company filter blocked me saying it was a gambling site. A quick search on Google gave www.hgvs.org as most probable address.

B.

Opps my bad I've updated the link... thanks for the heads up

[BaCh]

This thread shows a common problem of lack of international standards and referencing. Last time I checked hgvs (www.hgvs.com) is a standards group ...

You sure about that ".com" ending?

My company filter blocked me saying it was a gambling site. A quick search on Google gave www.hgvs.org as most probable address.

B.

[Joann]

harmonization

Nomenclature groups should strive for harmonization and cite the earliest published convention assembled by an authoritative group--for use in naming an identical concept/event, that is. Nuances and hierarchical relationships should be explored and articulated as part of gaining consensus. There is nothing like using exactly the right word in annotating sequence data, no?

[laura]

The Sequence Ontology consortium being the people who define ontologies in genomics/bioinformatics are trying to solve this problem by providing a standard ontology and being open to suggestions about additions or changes

Ensembl is certainly adopting the SO consequence ontology so lets hope others follow suit

[Jon_Keats]

Agreed, hopefully there can be a clear winner in the very near future. This thread started with a very junior question that has a definite unequivocal answer, as the definition of a nonsense change is well established and an accepted nomenclature for the type of event. Hopefully a standard can be reached soon, as the number of genome papers and data sharing will only increase and standardized nomenclature will becomes ever so important.

[bioinfosm]

2 standards already then = "No-Stop" and "Stop lost"

I think the key is, enforce a standard locally, but be aware of the synonyms, because bioinformatics standardization is not present yet

[laura]

The Sequence Ontology group are defining a standard ontology for variant consequences

You can browse their resource here

http://www.sequenceontology.org/cgi-bin/miso.cgi

stop lost seems to be their term for this

http://www.sequenceontology.org/miso...erm/SO:0001578

[Jon_Keats]

'Read through' are what they are called then!

We also recently saw quite a few 'loss of stop codon' mutations in exome data.. and was not sure how to interpret/annotate/log them

This thread shows a common problem of lack of international standards and referencing. Last time I checked hgvs (www.hgvs.org) is a standards group that most follow or should follow. What you, your facility, your boss thinks is correct or even others follow is not a standard that deserves an exclamation mark in a public form!!

Thus "No-Stop"

[bioinfosm]

'Read through' are what they are called then!

We also recently saw quite a few 'loss of stop codon' mutations in exome data.. and was not sure how to interpret/annotate/log them

[laura]

The ensembl database is a good place to look for what the different sort of consequences

This documentation lists them

http://www.ensembl.org/info/docs/variation/index.html

For a consequence which is non synonymous it means the base change results in an amino acid change in the protein sequence

[mard]

From several genetics books I have read, nonsense mutations change a codon for an amino acid to a stop codon.

then how to define a mutation change a stop codon to a codon for an amino acid? still nonsense mutation?

Thanks

Just to let you know Ensembl class those mutations as "Stop lost".

[ntremblay]

I would say it is a non-synonymous mutation as it cause a change in the translated amino acid sequence ...!

[yuanzhi]

I just thought of another question. Can we call this readthrough mutation or non-stop extension as nonsynonymous mutation? Or, nonsynonymous mutation includes missense and nonsense?

[yuanzhi]

awesome! Many thanks to both of you.

Happy Holiday~

[Jon_Keats]

Not a nonsense change for sure as that exclusively means the creation of a stop codon.

These changes that eliminate the proper stop codon and allow translation to continue on into the 3'UTR finally have an official nomenclature (http://www.hgvs.org/mutnomen/recs-prot.html) of "NO-STOP" changes. Though others (http://www.sanger.ac.uk/perl/genetic...ummary&id=5333) use "non-stop extension" which seems a bit more descriptive and I've also see them listed as "missense-stopcodon".

This is definately one of two special mutation classes, that being mutations of the initiating methionine and stop codon.