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VDR's transcription of genes
 Moderated by: Dr Trevor Marshall  

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Frans
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 Posted: Wed Jan 2nd, 2008 20:29

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Hi all,

Trevor has posted some interesting genes definitely and probably transcribed by the VDR, eg some genes regarding Down syndrome, all to be found in the supplemental tables 1 and 4 of Wang, et al (http://tinyurl.com/2v28tl)

There are so many genes in there that give me a sense of: 'this can't be', that I thought it might be interesting to give Wang et al's lists a thread of ther own.

To give two examples other than Down syndrome:

- cystic fibrosis transmembrane conductance regulator, ATP-binding cassette (sub-family C, member 7), which is the gene whose mutations lead to Cystic fibrosis

and another one:

- poliovirus receptor

Furthermore I have searched the tables with the word Syndrome, which also turns up genes that boggle the mind.

It would be interesting to see which of the genes in table 4 will be confirmed by Wang in the future.

Just some thoughts,

Frans



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Dr Trevor Marshall
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 Posted: Wed Jan 2nd, 2008 21:06

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MTSS1 -  Metastasis Suppressing protein #1

MTUS1 - Mitochondrial Tumor Suppressor #1

Last edited on Fri May 30th, 2008 18:05 by Dr Trevor Marshall

Frans
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 Posted: Thu Jan 3rd, 2008 22:54

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Trevor,

something is puzzling me. I wanted to assess how influential the VDR is by finding out how many human genes there are in the genome and holding that number against that of the 23000+ transcribed by the VDR to get an idea about its influence.

The problem is that the best estimate I get about the human genome ranges from 120.000 to 30.000 genes. 40.000 is mentioned several times.

Now if that is true, it would mean that the VDR actually transcribes about half of the genome ??  That can't be right, can it ??

I must be missing something here..  to say the least...  

Sincerely, a puzzled Frans  :?



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 Posted: Thu Jan 3rd, 2008 23:06

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Frans,
If you look at the Brahmachary paper (citation 71 in my new Vit D paper) you will find that indeed the Nuclear receptors are key to the transcription of a significant proportion of the genome. That paper looks at some of the other transcription factors, and is a good place for you to start expanding your knowledge, I think :)

http://www.biomedcentral.com/1471-2105/7/S5/S8

You might also review the fulltext of this excellent paper, which explores the multiplicity of different factors involved in gene transcription. The VDR (for example) could well be involved in expressing these cofactors, or their folding agents, even if it is not directly involved in the transcription at a specific promoter sequence: http://tinyurl.com/yurngs
 

Last edited on Fri May 30th, 2008 18:05 by Dr Trevor Marshall

Frans
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 Posted: Fri Jan 25th, 2008 22:28

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Trevor, another basic question :)

Let's say the VDR transcribes 5 copies of a gene for a certain receptor. Would that also lead to 5 of those receptors?

Sincerely, Frans



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 Posted: Sat Jan 26th, 2008 08:09

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Hopefully they will all be the same, Frans.
The RNA are translated by a ribosome into proteins, and then the proteins are folded by self-forces and eznymes (etc)

..Trevor..

Frans
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 Posted: Mon Jun 1st, 2009 12:07

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Trevor,

I have something that might help us expand Wang's table 1.

I searched pubmed for confirmed VDRE's.

The first paper I found was PMID: 18602086

They found the VDR regulates transcription of:

- p-glycoprotein, also called

- ABCB1 or

- ATP-binding cassette sub-family B member 1

This in itself is quite interesting, since yet another name for it is MDR1, Multidrug Resistance 1 Gene.

This might be one reason why chronically ill people react differently to drugs than 'healthy' people do. (BTW is medicines a better word?)

More info on the gene:
- http://tinyurl.com/n9rktx

However, I looked in table 4 and found this gene.
The corresponding VDRE is GGTCCAGGGGGGTCA

Now, if I search table 4 with this VDRE, it results in another 16 VDR-transcribed genes.

I guess my question is if this reasoning is correct ?

Best, Frans

Last edited on Mon Jun 1st, 2009 12:15 by Frans



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Frans
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 Posted: Sat Jun 6th, 2009 15:58

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bump



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Joyful
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 Posted: Sun Jun 7th, 2009 11:52

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Hey Frans. :)

You seem to be the person who finds research on genes to be interesting.

Here's a review of studies on genes "related to" CFS...
   http://www.aboutmecfs.org/Rsrch/PharmaIVMutations.aspx

Maybe there's a gem or two in there.



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Frans
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 Posted: Fri Jun 12th, 2009 20:32

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Hi all,

I have noticed that sleeping is a very big problem for lots of people on the MP.

Sleeping lots of hours, yet not feeling refreshed is something I have read numerous times here.

Again, Wang et al's table 1, gives us something to think about that might explain some of it.

In the past, I have already posted about the role of Histamine in our circadian rythm. The VDR transcribes 3 of the 4 histamine receptors, possibly explaning part of our sleeping problems.

This week I found another gene (transcribed by the VDR) related to sleep.

It is called: delta sleep inducing peptide, immunoreactor;  DSIPI.

As the name of the gene suggests, it induces Delta Sleep, also known as Slow Wave sleep (SWS), which is part of the non-REM sleep cycle.

Two instances of DSIPI are mentioned in Wang´s table 1. DSIPI is depressed with a factor of 2.6 and 2.7, respectively. (Trevor, does this mean the VDR acts via 2 seperate VDRE's ?)

This means that th1-VDR compromised people have much higher levels of DSIPI, leading to more Slow wave sleep (SWS). People who are woken from SWS are more groggy, less cognitively active, etc.

Sound familiar ?

Another thing I read somewhere is that people who have very long SWS tend to SleepWalk or SleepTalk.

Sleeptalking has always been one of the reasons why my friends avoided sleeping in my room during vacations  :D  Now I understand why...

Seems to explain a lot IMO ?

Perhaps West china hospital can measure this in their patients? See if it changes over time while these persons do the MP ?

PS

Joyful wrote:
You seem to be the person who finds research on genes to be interesting.

Well, the genes found to be regulated by the VDR that is :D

The link you gave is very interesting, I might get back to you on that, thanks for that Joyful !


Best to all, Frans



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 Posted: Fri Jun 12th, 2009 22:19

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Two instances of DSIPI are mentioned in Wang´s table 1. DSIPI is depressed with a factor of 2.6 and 2.7, respectively. (Trevor, does this mean the VDR acts via 2 separate VDRE's ?)

It is the same gene, but they had two different targets on their micro-array, as two commercial sources of a marker were available. In this case the results from both manufacturer's 'reagents' correlated.
 

kbanshee
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 Posted: Sat Jul 11th, 2009 09:07

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This is very interesting to me. I have a huge amount of complex issues around sleep. Mostly too much sleep w/o feeling I've slept (even w/ CPAP for Sleep Apnea) & then sleeping again most of the afternoon -- having no control of staying awake. When my brain is a bit more awake, I'll read more of the articles so I can jump in on the conversation w/ more informed back story...
Kriss



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Ron
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 Posted: Wed Jul 22nd, 2009 23:26

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July 21st, 2009:

Mutation causing one type of male infertility found

The mutation lies in one specific protein present in sperm called PLC zeta.
PLC zeta1 appears to be listed in table 4 of Wang et al...

So could this type of male infertility maybe be reversed by the MP?

Ron



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Dr Trevor Marshall
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 Posted: Wed Jul 22nd, 2009 23:47

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Ron,
Table 4 is not VDR-specific. It contains VDRE which are a little unusual, and which may be targeted by other receptors. PXR and CAR are two receptors which may be involved in expressing the genes in Table 4, and there are probably others yet to be discovered. Table 1 is the table which has the confirmed VDR gene expression ratios.
 
Although even then there may be errors, as there may be other receptors which are activated by 1,25-D and not just the VDR. Science is a moving target...
 

Ron
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 Posted: Thu Jul 23rd, 2009 16:24

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Thanks for that clarification!

Nevertheless, if genetic defects are due to the Th1 pathogens in general, wouldn't then restoring the VDR functionality be the key to recovery?

Also, shouldn't such a mutation be seen as a sign of inflammation and a risk of transferring pathogens to the newborn?

Instead, Big M Medicine is ready to force the conception and repair the symptom by "injecting a correct version of the gene for PLC zeta rather than relying on the sperm cell".

:X




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