4 ms·

Reelin is transcribed 4 genes away from acetylcholinesterase. And is a core collagen component. No wonder it's tied to Alzheimer's..

ghotli 2y ago
Is there some place on the internet that shows this "4 genes away" evidence? I'm imagining that there is some tool that those involved in this work are aware of that I am not.
- bglazer 2y ago
  The UCSC genome browser is the best way to find where genes are mapped to in DNA. Here's a link that shows ACHE (acetylcholinesterase) and RELN (reelin) in the same view. https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&lastVirtModeType=default&lastVirtModeExtraState=&virtModeType=default&virtMode=0&nonVirtPosition=&position=chr7%3A99028414%2D104923413&hgsid=2323597120_2eFL8swae08KyWGhG4U9di1713ry https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&lastVirtMod...
  - ghotli 2y ago
    Very cool, thank you!
pc86 2y ago
"Reelin is transcribed 4 genes away from $ENZYME" sounds like it is of the same general category as "Humans share 98% of their DNA with a chimpanzee and 97% of it with a banana" or whatever. Is that me just not understanding it? I would think 4 genes could have huge impact on functionality.
- jldugger 2y ago
  I believe they're using "4 genes away" as a proxy of basepair distance, not similarity. It's all very messy business but it's not unreasonable that transcription promoters for those other genes also promote reelin transcription.
  - XMPPwocky 2y ago
    Is this (genes physically close together, but not contiguous, being affected by the same/related promoters) something commonly seen? I'd love to learn more about it if so!
    - ted_dunning 2y ago
      There is evidence even from the early days of genomics that recombination and thus evolution worked in (approximate) units at a time. This means that when a new mechanism for regulation appeared, it often regulated many pathways coded in idiosyncratic ways. That leads to the observed local commonality of mechanism. The place that I saw this in my own work was in the way that ends of intervening sequence (introns) was coded for excision during expression of proteins. The different ends of different introns behaved differently and introns in different parts of genomes had slightly different dialects. The relationship of similarity and locality in regulators is different from this, but is another case of proximity being a proxy for similarity.
      - XMPPwocky 2y ago
        Thank you, this is very interesting!
    - flobosg 2y ago
      Not entirely what you asked, but check out regulons: https://en.wikipedia.org/wiki/Regulon https://en.wikipedia.org/wiki/Regulon
      - XMPPwocky 2y ago
        Fascinating, thank you!
wizzwizz4 2y ago
Can you make any future predictions of this type? That could speed up research.
bglazer 2y ago
I'm not sure how you're getting the 4 genes away thing, I'm seeing like 20-30 genes and more than 2 megabases of distance in between RLN and ACHE. I'd be surprised if they were even in the same topologically associated domain.

ghotli 2y ago

Is there some place on the internet that shows this "4 genes away" evidence? I'm imagining that there is some tool that those involved in this work are aware of that I am not.

bglazer 2y ago
The UCSC genome browser is the best way to find where genes are mapped to in DNA. Here's a link that shows ACHE (acetylcholinesterase) and RELN (reelin) in the same view. https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&lastVirtModeType=default&lastVirtModeExtraState=&virtModeType=default&virtMode=0&nonVirtPosition=&position=chr7%3A99028414%2D104923413&hgsid=2323597120_2eFL8swae08KyWGhG4U9di1713ry https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&lastVirtMod...
- ghotli 2y ago
  Very cool, thank you!

pc86 2y ago

"Reelin is transcribed 4 genes away from $ENZYME" sounds like it is of the same general category as "Humans share 98% of their DNA with a chimpanzee and 97% of it with a banana" or whatever. Is that me just not understanding it? I would think 4 genes could have huge impact on functionality.

jldugger 2y ago
I believe they're using "4 genes away" as a proxy of basepair distance, not similarity. It's all very messy business but it's not unreasonable that transcription promoters for those other genes also promote reelin transcription.
- XMPPwocky 2y ago
  Is this (genes physically close together, but not contiguous, being affected by the same/related promoters) something commonly seen? I'd love to learn more about it if so!
  - ted_dunning 2y ago
    There is evidence even from the early days of genomics that recombination and thus evolution worked in (approximate) units at a time. This means that when a new mechanism for regulation appeared, it often regulated many pathways coded in idiosyncratic ways. That leads to the observed local commonality of mechanism. The place that I saw this in my own work was in the way that ends of intervening sequence (introns) was coded for excision during expression of proteins. The different ends of different introns behaved differently and introns in different parts of genomes had slightly different dialects. The relationship of similarity and locality in regulators is different from this, but is another case of proximity being a proxy for similarity.
    - XMPPwocky 2y ago
      Thank you, this is very interesting!
  - flobosg 2y ago
    Not entirely what you asked, but check out regulons: https://en.wikipedia.org/wiki/Regulon https://en.wikipedia.org/wiki/Regulon
    - XMPPwocky 2y ago
      Fascinating, thank you!

wizzwizz4 2y ago

Can you make any future predictions of this type? That could speed up research.

bglazer 2y ago

I'm not sure how you're getting the 4 genes away thing, I'm seeing like 20-30 genes and more than 2 megabases of distance in between RLN and ACHE. I'd be surprised if they were even in the same topologically associated domain.