Genetics: CA10

[hotblack]

That’s very positive news! Thanks for doing this @Jonathan Edwards
And good probing questions @voner

 

[Jonathan Edwards]

what did you learn that can be shared with us?

That some other people think this is really interesting!

 

[Kitty]

That some other people think this is really interesting!

Which is really good news!

 

[V.R.T.]

I've been wondering- if CA10 is involved in ME/CFS (or pain disorders) could it (or whatever mechnistic process the CA10 gene finding represents) be directly modulated with drugs in order to stop whatever signals are causing PEM/pain etc? Or is it more of a pointer to the general pathology

 

[Jonathan Edwards]

Or is it more of a pointer to the general pathology

I suspect that.

 

[hotblack]

Inspired by some AlphaGenome stuff I’ve been learning more about and am interested in looking at promoters and enhancers for some of these candidate genes.

Enhancers and promoters are gene-regulatory elements. They are stretches of DNA that help in both eukaryotic and prokaryotic transcription. The promoters are known to initiate transcription, and the enhancers increase the level of transcription

Source

If you look at the genecard for CA10 in the genomics section you can see GeneHancer info on these. There’s lots of interesting stuff in there.

For instance pick the top one, a promoter/enhancer with a high score (it has a little star by it to show this too)
Expand the info and see the location of it is chr17:52158438-52159092
You can zoom in to that location on the DecodeME LocusZoom data and see lots of the hits tie in with this area
The Ensembl info has which tissues these are active in too
Looking at details of all of them a number match with the changes on DecodeME

If I’m interpreting this right it says the changes people with ME/CFS are more likely to have are in these promoters and enhancers in those tissues? So affect expression of CA10 in those tissues? Is that right?

Sorry if this is covering known territory, it’s all new to me. Given the location, at the start of the transcription site, it may be obvious to people thst these are promoters?

I wonder if it’s worth digging through all the Genhancer info for all the genes, especially as some enhancers can be a long way away from the transcription site for the gene.

The EPDnew info will look familiar to anyone who has been looking at AlphaGenome outputs too… I have lots more to learn here.

 

[hotblack]

Short version: it looks like given the location of the variations seen in the DeocdeME data it’s more likely that in people with ME/CFS the CA10 protein is being produced in the wrong amounts in certain tissues

 

[jnmaciuch]

@hotblack you might like to explore some of the tracks on UCSC genome browser--it compiles a lot of this information visually so you can do some exploring.

Here I have it centered on the top DecodeME SNP in the region:

https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&lastVirtModeType=default&lastVirtModeExtraState=&virtModeType=default&virtMode=0&nonVirtPosition=&position=chr17%3A52127451%2D52238561&hgsid=3676089975_BEkeA67B2JkKWyS6cMkL3z6tsVek

You can "highlight" a region by dragging a box over a region and clicking "add highlight" on the box that comes up, that way you can keep track of where a SNP overlaps with features on other tracks


These tracks have a lot of promoter/enhancer/regulatory region info you can play around with (click "show" and then "refresh" to add them.


The GENCODE track under "Genes and Gene Predictions" will mark known genes with their exons and introns

If you want to highlight a lot of SNPs at once there are ways you can add a custom track in a BED file format, though it'll take more effort to figure out

Genome Browser FAQ

 

[hotblack]

@hotblack you might like to explore some of the tracks on UCSC genome browser--it compiles a lot of this information visually so you can do some exploring.

Thanks! The highlighting doesn’t seem very touchscreen friendly unfortunately. But the rest seems to work, I’ll have an explore.

 

[jnmaciuch]

Thanks! The highlighting doesn’t seem very touchscreen friendly unfortunately. But the rest seems to work, I’ll have an explore.

If you start zoomed in on a SNP, you can also hit the "highlight" button down here which will highlight everything in your viewer

 

[Jonathan Edwards]

For instance pick the top one, a promoter/enhancer with a high score (it has a little star by it to show this too)
Expand the info and see the location of it is chr17:52158438-52159092
You can zoom in to that location on the DecodeME LocusZoom data and see lots of the hits tie in with this area

This is more or less exactly what my genetics friends at UCL did when they gave me a presentation of why they thought it was worth picking CA10 for a basic biology project.