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Gestalt's Genova, 23andMe & Yasko Methylation genetic results

roxie60

Senior Member
Messages
1,791
Location
Central Illinois, USA
Thanks guys for pursuing this, this result (AA full defect) now makes more sense given my health experience. I was stunned to have VDR Taq AA and VDR BSM CC be both no variant with original run and I have such difficult time getting my vit D levels just to the low end of the range (taking 5000-10000 / day). Now VDR Taq would be red even though still -/- due to A being the risk allele (provided I am understanding this stuff at all).

(no data from 23andMe on VDR Fok - I really wish they would add this one and a few of the other methylation SNPs that are missing but they are making progress since it seems version 3 had added some SNPs)

I reviewed the thread and I now see where you said you had results from Yasko's test, so that I'm sure is why you have NOS results. I really wish there was a way to relate this one to 23andme. Do you by chance or anyone have an rs# for the SNPs that are tested for in Yasko's test?
 

roxie60

Senior Member
Messages
1,791
Location
Central Illinois, USA
I wish they would all just get on the same allele page. Are they trying to make it more confusing? Does getting this information really help in the long run?

So, I am surprised but it appears in the above study people with the risk allele 'A'('T' in Yasko speak) "tend to have a greater tolerance for methylB12. And those with 'tt' (what the blazes allele is this?- my comment) should consider limited methyl donors". Am I getting this right? I'm not sure the VDR study conclusion is right about the TT being able to handle more methyl donors, if 'TT -/-' is 'AA -/- then there is another Yasko reference that states COMT+/+ or VDR -/- should limit methyl donors. Website-_Yasko_Education

also see heartfixer VDR section, discusses VDR -/- & +/+
 

roxie60

Senior Member
Messages
1,791
Location
Central Illinois, USA
I notice kday you have listed the detox SNPs (I think these are also on Dana's spreadsheet). My question to some one is I am still looking to understand how to look at the 23andMe SNPs and determine what is the risk allele for the SNP. For example of the following SNPs how do I know which is the risk allele, how I determine the '+' '-' status? Thx I have completed the Detox SNPs manually but I am basing the result spreadsheet rather than my personal understanding. I would like to understand so I can apply to other SNPs I'm looking at,

FTO 54137862 rs2540776 A or G
AG Me
AG Lilly Mendel
GG Greg Mendel
 
Messages
57
Hi Gestalt New to this site. I have a double snp in the mthfr and a double snp in the cbs. I have been terrified of taking glutamine bc of neuro excitability. According to heartfixer i shld never touch meat or glutamine. I'm catabolic and having trouble keeping weight on. ALSO NOW TESTINB POSITIVE For diabetes type 1.5. Do you know of a dr who could help me understand this. I'm really sick so need help.

Thanks
dfox
 

Symptomatic

Senior Member
Messages
197
My question to some one is I am still looking to understand how to look at the 23andMe SNPs and determine what is the risk allele for the SNP. For example of the following SNPs how do I know which is the risk allele, how I determine the '+' '-' status? Thx I have completed the Detox SNPs manually but I am basing the result spreadsheet rather than my personal understanding. I would like to understand so I can apply to other SNPs I'm looking at

23andMe does not state the risk allele. You end up having to dig through other sites (e.g. SNPedia and/or some of the links off of there) to find that info.
 

Symptomatic

Senior Member
Messages
197
Keep in mind that Yasko's lingo DOES NOT RELATE TO THE DNA BASE....but to the restriction enzyme site (e.g. she is using FF/ff for Fok which starts with "F", BB/bb for Bsm, which starts with "B", TT/tt for Taq, which starts with "T"). DNA does not contain F or B, so her info is not discussing which specific *base* constitutes the risk allele, only someone's status with regards to whether they possess wild-type or the mutation. It is unfortunate that Taq starts with "T" and thus overlaps with the DNA bases A/C/G/T.

"In general the presence of the restriction site is denoted by a lower case letter and the polymorphism that eliminates the site is denoted by an upper case letter."
 

Symptomatic

Senior Member
Messages
197
And I do agree that the ancestral allele is A, and risk allele is G (talking plus-strand; ancestral is T and risk is C on the minus-strand), which is how it was presented in Calico's spreadsheet.
 

Symptomatic

Senior Member
Messages
197
Which does not explain Fresh Veggie's Yasko vs. 23andMe results. Maybe Sushi can chime in? I believe there are known to be discrepancies amongst the tests from various labs.
 

Sushi

Moderation Resource Albuquerque
Messages
19,935
Location
Albuquerque
Which does not explain Fresh Veggie's Yasko vs. 23andMe results. Maybe Sushi can chime in? I believe there are known to be discrepancies amongst the tests from various labs.

OK, this is interesting--just in that now 2 labs seem to be disagreeing with Yasko. I haven't read this whole thread but a couple of patients had both Yasko and RedLabs VDR test and the results from the two labs were different. So maybe Yasko is off the mark? Or am I reading this wrong?

Sushi
 
Messages
57
OK, this is interesting--just in that now 2 labs seem to be disagreeing with Yasko. I haven't read this whole thread but a couple of patients had both Yasko and RedLabs VDR test and the results from the two labs were different. So maybe Yasko is off the mark? Or am I reading this wrong?

Sushi

Ok, a lot of this sounds like greek to me. I will go to the above site to see if "I get it", but every where I read Yasko's was the only accurate one. This is too much!!!!!

Thanks,
Dfox
 
Messages
57
I have spent an incredible amount of time basing so much of my care around the Yasko panel. I have a quote from the heartfixer.com site, and got this:
Glutamate – GABA Imbalance Þ Excitotoxicity
image028.jpg
Glutamate is the main excitatory neurotransmitter in the body. It is essential for learning and short and long-term memory. Glutamate is also the precursor to our primary inhibitory or calming neurotransmitter, GABA. GABA damps the propagation of sounds so that a distinction can be made between the onset of sound and a background noise. Many other physiologic processes require a balance between glutamate and GABA, which is usually easy to achieve as glutamate, glutamine, alpha-ketoglutarate, and GABA can be interconverted via the enzymes depicted above.
Genomic defects, viral illness, and heavy metals will compromise this balance, leading to excess glutamate, insufficient GABA, excitotoxicity, and eventual neuron loss. Viral infection (individuals with Methyl Cycle defects cannot defend well against viral infection) can lead to antibodies against the vitamin B6 dependent enzyme glutamate decarboxylase (GAD), blocking GABA production (this is felt to occur in the pancreas in kids with juvenile onset diabetes). Aluminum poisons this enzyme as well. Excessive alpha-ketoglutarate generated due to the CBS up regulation can be converted into glutamate, but in the presence of lead and aluminum, the glutamate so created cannot be converted into GABA, glutamine, or back to alpha-ketoglutarate. The result is glutamate-GABA imbalance, agitated behavior, and eventually nerve loss.
Low GABA leads to impaired speech, anxiety, aggressive behavior, poor socialization, poor eye contact, nystagmus, and constipation. Glutamate excess does the same and also wastes glutathione and increases levels of TNF-alpha, an inflammatory mediator that can produce heart cell dysfunction and gut inflammation.

The above quote is in reference the CBS snp. This is MY LIFE. Maybe many others here. I have been plagued by viral infections, and now am testing positive for the GAD65 antibodies or called LADA (Latent Autoimmune Diabetes Adult). Surprise, surprise but if you google diabetes type 1.5 (slang) they talk about viruses attacking the beta cells in the pancreas!

Also, on my oats test from Genova, my alpha-ketogluterate was off the charts. Any ideas, ladies or gents?

Any thoughts?

Blessings,
Dfox
 

Symptomatic

Senior Member
Messages
197
freshveggies

Just out of curiousity, what was your 23andMe Bsm result? Since Taq and Bsm are "supposed" to track together, perhaps that will shed some light?

Per dbSNP (http://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?searchType=adhoc_search&type=rs&rs=rs731236):

Ancestral Allele: T

Also:
Gene Model(s)
Function​
mRNA​
Protein​
SNP to mRNA​
Accession​
Position​
Allele change​
Accession​
Position​
Residue change​
cds-synon​
Rev
1216
ATT ⇒ ATC
352
I [Ile] ⇒ I [Ile]​
cds-synon​
Rev
1338
ATT ⇒ ATC
352
I [Ile] ⇒ I [Ile]​
cds-synon​
Rev
1607
ATT ⇒ ATC
402
I [Ile] ⇒ I [Ile]​

Indicating the change from native "T" to mutation "C".
 

Gestalt

Senior Member
Messages
251
Location
Canada
Also, on my oats test from Genova, my alpha-ketogluterate was off the charts. Any ideas, ladies or gents?

Any thoughts?

I wonder where the rational behind a CBS upreg leading to higher alpha-ketoglutarate comes from? CBS upreg according to the yasko diagram increases alpha-ketobutyric. Maybe heartfixer got the 2 confused?

If you have the CBS upreg, I found yucca to be very beneficial to myself in terms of soaking up excess ammonia which was causing me extreme Excitotoxicity.

Heartfixer does not explain the mechanisms behind this statement: "Genomic defects, viral illness, and heavy metals will compromise this balance, leading to excess glutamate"

If there broad issues in the methylation pathway (CBS, MTHFR,DHPR,NOS,OTC) these will all lead to excess ammonia levels which is a potent excitotoxin. This causes microglial activation which in turn causes a drastic increase in glutamate levels and therefore probably akg levels.


Source: "When activated by proinflammatory stimuli, microglia release substantial levels of glutamate, and mounting evidence suggests this contributes to neuronal damage during neuroinflammation."
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1949347/

So therefore, to get rid of ammonia, fix methylation pathways, take yucca, eliminate dietary sources of free-form glutamate (most refined foods, especially wheat or anything with a "flavor" or "spices" additive; click on this for extended list) and that should help control the "excess glutamate" problems.
 
Messages
57
I wonder where the rational behind a CBS upreg leading to higher alpha-ketoglutarate comes from? CBS upreg according to the yasko diagram increases alpha-ketobutyric. Maybe heartfixer got the 2 confused?

If you have the CBS upreg, I found yucca to be very beneficial to myself in terms of soaking up excess ammonia which was causing me extreme Excitotoxicity.

Heartfixer does not explain the mechanisms behind this statement: "Genomic defects, viral illness, and heavy metals will compromise this balance, leading to excess glutamate"

If there broad issues in the methylation pathway (CBS, MTHFR,DHPR,NOS,OTC) these will all lead to excess ammonia levels which is a potent excitotoxin. This causes microglial activation which in turn causes a drastic increase in glutamate levels and therefore probably akg levels.


Source: "When activated by proinflammatory stimuli, microglia release substantial levels of glutamate, and mounting evidence suggests this contributes to neuronal damage during neuroinflammation."
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1949347/

So therefore, to get rid of ammonia, fix methylation pathways, take yucca, eliminate dietary sources of free-form glutamate (most refined foods, especially wheat or anything with a "flavor" or "spices" additive; click on this for extended list) and that should help control the "excess glutamate" problems.

Thanks Gestalt: Wow, a whole new paradigm sift? So, I am doing targeted amino acid therapy right now. As I have really bad brain fog, does this mean the L-glutamine I am taking is neuro toxic? That is what most of the md's are asking patients to take for "gut repair".

Any ideas how I can get a crash course on this (if my brain will let me). I did the Yasko profile. Was it a waste of time?

Thanks,
Dfox
 

Gestalt

Senior Member
Messages
251
Location
Canada
Thanks Gestalt: Wow, a whole new paradigm sift? So, I am doing targeted amino acid therapy right now. As I have really bad brain fog, does this mean the L-glutamine I am taking is neuro toxic? That is what most of the md's are asking patients to take for "gut repair".

Any ideas how I can get a crash course on this (if my brain will let me). I did the Yasko profile. Was it a waste of time?

Glutamine should be perfectly safe to take, I used it myself for gut repair and muscle achiness. It worked wonders and helped me a lot. There is no evidence linking it to elevated glutamate levels. (refer to the beginning of this thread for more info) Your body regulates that very well. Glutamine has many, many other uses.

I think the Yasko profile is very helpful in that it helps you determine issues in the methylation cycle and how to fix it in order to clean up ammonia and glutamate. Personally yucca helped me the most with brain fog.
 

kday

Senior Member
Messages
369
I am one that can't handle glutamine. I get overstimulated with each 3.5 g scoop. It overstimulates me to the point that I can't concentrate on anything. I gave the supplement away.

I am not convinced that it can't have a negative effect on glutamate levels for some.
 
Messages
57
I am one that can't handle glutamine. I get overstimulated with each 3.5 g scoop. It overstimulates me to the point that I can't concentrate on anything. I gave the supplement away.

I am not convinced that it can't have a negative effect on glutamate levels for some.

Hi Kday: I wonder if checking the suphite or sulphate levels would not tell you this? I am fairly new to this site and looking for someone to help interpret my oats tests. Any ideas would be appreciated? Sushi gave me a few leads, but nothing has panned out yet.

Thanks
dfox
 

roxie60

Senior Member
Messages
1,791
Location
Central Illinois, USA
I think I narrowed down one thing I have been reacting to, I have been taking my supplements for some time now with a protein shake called Nature's Plus Spirutein. I had backed of the shake for almost a month. This week I decided to take the shake alone with almond milk and no other supplements. To my surprise within 30 minutes I became fatigued, sleepy, flt sedated, so weak had to lay down. Took 3-4 hours to recover. I was stunned, I was blaming the supplements all this time. The shake has a lot in it including spirulina, l-glutamine. I did a Google search and found a number of people reporting similar have similar symptoms. Anyone here have similar reaction to their protein shake?