neuron maintenance

[gocentral]

Hi

this is for RefGenome too.

I am looking at CHRNA1 P02708 and PMID 8872460 the phenotype of people with mutations in this gene (patient 3) show neurodegeneration.

I would therefore like to request the following term:

neuron maintenance as a is_a child of neuron development GO:0048666

Definition: The maintenance of neurons after their formation to allow normal functioning.

Thanks

Ruth

Reported by: RLovering

Original Ticket: "geneontology/ontology-requests/5461":https://sourceforge.net/p/geneontology/ontology-requests/5461

[gocentral]

I'll ask David for his opinion, but I'm not sure we should add this term. We don't have any terms so far for maintenance of a cell in a functional state (there are some terms for maintenance of cell populations, e.g. for stem cells), and I think one reason is that if we don't know of something specific about the maintenance (e.g. negative regulation of apoptosis, or active maintenance of a differentiated state), we end up with a term that's awfully vague.

I would also be reluctant to annotate a gene product to a term like "neuron maintenance" on the basis of a neurodegeneration phenotype -- the gene product's connection to the observed phenotype could be very indirect, and although this concern is present with all IMP annotations, it's particularly relevant in cases where the phenotype is broadly defined or a specific mechanism isn't apparent.

m

Original comment by: mah11

[gocentral]

David's comment:

I think it's typical to use the term "negative regulation of neuron apoptosis" for the normal function of genes that prevent neuron degeneration. There is a synonym for this term called 'neuron survival'.

Original comment by: mah11

[gocentral]

Hi Midori and David

I think there are 2 points to be addressed here. Firstly I completely agree that with many IMP codes it is hard to feel confident about the gene product's connection to the observed phenotype, which may well be very indirect. As Karen pointed out at the previous refgenome jamboree the build up of toxic metabolites can lead to development problems, or in this case tissue apoptosis.

In this case CHRNA1 is cholinergic receptor, nicotinic, alpha 1 (muscle). It appears that the defect in this receptor leads to a decrease in signaling to the muscles and this leads to muscle wastage, however the paper I mentioned also describes how the nerves themselves degenerate, possibly due to lack of signaling here too...

The reason I requested neuron maintenance is because muscle maintenance already exists. There is also the term GO:0014889 muscle atrophy.

MGI have made 36 associations using the GO term GO:0046716 muscle maintenance and 1 association to GO:0014889 muscle atrophy. Conversely GO:0010657 muscle cell apoptosis has no associations via MGI. I hadn't noticed muscle atrophy before and actually GO:0014736 negative regulation of muscle atrophy is probably a good term to use for this phenotype rather than muscle maintenance. I now wonder if muscle maintenance should be merged with negative regulation of muscle atrophy. What do you think?

I would be very reluctant to annotate to neuron apoptosis based on a deterioration of neurons. My understanding of apoptosis is that there are very specific characteristic changes which occur during apoptosis and that to annotate to this term would require some of these changes to be observed. Without this evidence the observation is simply cell death or decreased cell survival.

While looking into muscle maintenance I noticed that PMID: 9668092 describes the phenotypic effect of a mutation in the acid alpha-glucosidase gene (A2AFL3), I expect this is a case where it is the build up of toxic metabolites which leads to muscle deterioration. So I wonder if it would be possible for us to look through some of the GO terms and identify those which may be annotated to due to a phenotype like muscle wasting, T cell development which can be inappropriately annotated to enzymes rather than signaling proteins/transcription factors etc and do some sort of QC to try to pick up the occasional errors.

To summarise (sorry for going on) I would now prefer the NTR negative regulation of neuron atrophy rather than neuron maintenance. And suggest merging the 2 muscle terms as described above.

Thanks

Ruth

Original comment by: RLovering

[gocentral]

David and I had a quick chat about this last week.

I agree that apoptosis (or +/- regulation thereof) is too specific for the mutant phenotypes in the paper.

Thanks for pointing out the muscle maintenance term -- it's not too good! The definition is vague and basically just repeats the term name. All of the terms under 'muscle system process' (GO:0003012) have been thoroughly vetted by experts at a content meeting, as were most of the terms under 'muscle development' (GO:0007517), but 'muscle maintenance' was only considered briefly. I'm not entirely sure anything should be merged, though, since muscle maintenance has parentage in the homeostasis branch and the other muscle-related terms do not.

With muscle we don't have exactly the same situation as for neurons: muscle is a tissue, whereas a neuron is an individual cell of a specific type. The processes required for muscle maintenance can be fairly specifically described at cellular and molecular levels. More importantly, muscle atrophy can be a normal consequence of muscle disuse. I don't know of anything comparable for neuron degeneration or atrophy except for apoptosis under some circumstances.

All that said, David did also say that he's willing to add a term for you to use for neurons. I'm inclined to use 'neuron maintenance' and give it 'cellular homeostasis' as a parent. I'll also improve the muscle maintenance definition.

Original comment by: mah11

[gocentral]

• assigned_to: nobody --> gomidori

Original comment by: mah11

[gocentral]

Added neuron maintenance, GO:0070050. It's under cellular homeostasis, and I've asked David whether it should also be related to neuron development.

m

Original comment by: mah11

[gocentral]

• status: open --> open-accepted

Original comment by: mah11

[gocentral]

David and I have agreed not to add a development parent for the new term. David put the reason nicely:

In general, I think maintenance is not related to development because development is a progression over time. Maintenance does not imply any progression, but rather the status quo.

Original comment by: mah11

[gocentral]

• status: open-accepted --> closed-accepted

Original comment by: mah11