Genetic profile results

[berlin1984]

HeatherRaeINHC, welcome to forum.

Genetic variants plus toxins plus nutritional deficiencies plus gut micriobiota imbalances plus poor vagal tone manifest differently in each person.   

Yes. Finding a single root cause is futile. We (each person individually) need to attack on many angles and find a way to be feeling good enough to make orgasm after effects bearable.

(And the crazy goal of "being able to masturbate 5 times per day without symptoms" is not healthy to be achieved. It's not normal)

[Cosmic1982]

Hello,

You all seem very good with your knowledge of DNA, I havnt a clue when it comes to science and this question may seem like a stupid one for you all but if you find a link between DNA and the POIS what actions are necessary? Are you able to turn on and off certain DNA strains?

It is a very good question, Cosmic!

Genomics can help you by giving you personalized information on your SNPs ( small DNA variations) that can lead to some lifestyle adjustments that will help raise your overall well-being.
For example, if you have a SNP with a risk allele ( the "bad" version") causing that a specific enzyme in your body is 60% less active, you can adjust depending on the biological function of this enzyme.  If, for example, the function of this enzyme is to digest a specific type of sugar, you will then avoid eating food containing that specific type of sugar.  You can also take as a supplement the vitamin or other substance that is a co-factor to this enzyme so that you help boost and support his level of activity.  If an alternative pathway is known for the digestion of this specific type of sugar, you can also help this other pathway with supplementing with the cofactors if this other pathway.
It will especially help if you do that for those SNPs for which you have 2 risk alleles on the same gene locus ( we have two copies of all our genes, one copy from each of our 2 parents).  If you happen, on a specific gene locus, to have 2 "bad" versions, risk alleles, then you have a homozygote, +/+ SNP, there, which usually creates more problems than a +/-, half-"bad" version ( one of your parents gave you the usual, "normal" version). 

Genomics is a young science, there is not useful and clear information for all SNPs, and for some, you will not find anything.  But new information is adding each month in the databases. Apart from accumulating good information, another current challenge is to detect the cumulative effect of many different +/- and +/+ SNPs, and find the specific bad effects of a certain specific combination of SNPs

My opinion is that POIS is possibly caused by the cumulative effect of many SNPs.   I also think that all POISers do not all have the exact same kit of risky SNPs, but similar enough to display similar sets of symptoms.  Like I have written already, I think there is more than one type of POIS.  this is reflected in my POIS Types Chart, and their possible relief methods ( see https://poiscenter.com/forums/index.php?topic=2338.msg19448#msg19448 ).  This would explain why some members get relief from a specific elimination diet, some others from of methylation support, and so on.  It depends on their specific SNPs, leading to specific metabolic problems.

If, let's say, it takes 50 to 80 different risky SNPs to cause POIS, maybe that 30 of them are common to most POIS sufferers, and the other SNPs would account for the different types of POIS ( of course, this is a very speculative hypothesis, it will take many, many years to see if this is the case or not). 

Anyway, I suppose that all those complex syndromes that evade detection by simple blood tests or standard exams will benefit from genomics research.

That's a fascinating read, thank you for giving the time to explain the genome and snp. It does make alot of sense, I have managed to reduce my recovery rate down to 3 weeks now by supplementing and changing my diet. I just wish it would completely go.

Thanks again.
Neil

[Trala151655]

There was a post somewhere and in that post someone replied that  has a client that has pois symptoms and is gonna check some metabolic ( i think) pathways  with the help  of some software.Or does anyone know babout someone who doesn t have poid but had or has a client with pois?

[Progecitor]

https://poiscenter.com/forums/index.php?topic=3694.0

[swell]

First of all Prospero, this is an incredible gem thread.  You even have the SNPs for the P450 family enzymes.  Detoxification/metabolic pathways I think is baseline critical to Pois, even immune system and health.  Though I don't see the 'alleles'?  Once we have all the SNPs and allele's, we can actually find out where our problems lay (not easy, though do'able).  I will gather my SNPs and let you know. 

Cosmic:  This is a new science so probably everyone (and specially myself is new, I knew zero about biology 2 yrs back), so you can easily learnt it.  To your question:  I will make it simple (at risk of over-simplification) so its easily understandable
1.  Our body has many cells. Cells have DNA (the "genetic" code of our body). It is kept closely guarded under lock and key. 
2.  When cells are copied, they can develop defects (SNPs are identification markers for them).  These defects can be important or may not be important (Alleles).
3.  When information needs to be sent, Information stored in DNA is used to make RNA (ribo-nucleuc-acid).  The Covid RNA vaccine works at this level and hence there was all that controversy.
3.  RNA is used to Proteins.  The medications/herbs/compounds we take they affect these proteins.  So you see the defects in our genes are guarded under multiple layers of defense.  The various drugs we take affect these proteins.  They manage the "manifestations" but do not touch the master source of information (for good reasons).  Now genes can be edited (to correct the source of the problem), however due to the severity of repercussions of working at that level, the scope of gene therapy is under research.

So back to your question, you can turn on or off genes (i.e. gene expression) as well you can effect the proteins that are produced (much safer approach), however, until you map things out, balance risk to reward calculation, so hence this would require plenty of work.  You only get 1 life and messing with gene is a serious work.  But we can easily (well with plenty of work) map out the defects, and figure out the corresponding molecules that can be beneficial.

if you find a link between DNA and the POIS what actions are necessary? Are you able to turn on and off certain DNA strains?

[Prospero]

I didn't write the letter of the allele in each case but "+" indicates the less common allele and "-" the more common one (so you can find them with the information +/+, +/-, -/-).

[Iwillbeatthis]

@Prospero https://uk.iherb.com/pr/Life-Extension-SOD-Booster-30-Vegetarian-Capsules/102528 - Superoxide Dismutase breaks down superoxide so it's a useful supplement when we are SOD2 ++.

http://www.heartfixer.com/AMRI-Nutrigenomics.htm this website has invaluable info for anyone who wants to learn about the methyl cycle genes and how to fix them.

Supplementing with high sulfur compounds like taurine might make you feel good in the short run but in the long run if you have any kind of CBS mutation then you will be causing yourself a whole host of problems.

"CBS (Cystathionine Beta-Synthase) is discussed on pages 48-53 of Dr. Yasko’s book, Genetic Bypass..  You are +/+ (all of your CBS enzymes are abnormal) or +/- (half of your CBS enzymes are abnormal) for one of the two CBS gain-of-function up regulations and you may also be +/+ or +/- for one of the BHMT reduced-function down regulations (which act like CBS up regulations).  Homocysteine (and its Methyl Cycle precursors) is thus being “pulled and pushed” down the trans-sulfuration pathway, in this process generating excessive sulfur break down products (sulfite and sulfate, which stimulate the stress/cortisol “fight or flight” response), glutamate (which leads to glutaminergic excitotoxicity), hydrogen sulfide (which produces brain fog), and too much ammonia (which depletes BH4, leading to insufficient dopamine and serotonin production).

This deficiency in BH4 predisposes eNOS (endothelial nitric oxide synthase) to convert arginine in to free radicals (superoxide and peroxynitrite) as opposed to nitric oxide (atheroprotective vasodilator), predisposing you to hypertension and cardiovascular and inflammatory disease states.  Those of you with reduced function alleles for the antioxidant enzymes SOD (superoxide dismutase), CAT (catalase), GPX (glutathione peroxidase), and PON1 (paraoxonase) may be challenged dealing with this superoxide free radical burden. "

[Quantum]

Hi everyone,

I have finally received my Whole Genome Sequencing  (WGS) results a few days ago.  It is a lot of information, and I have to take the time to analyze all this, which will take months.  However, I already have found some significant SNPs ( Single Nucleotides Permutations) that are explaining parts of my POIS.

I will share more in the coming months, but for now, I can share the more significant finding I have done so far:   I have 2 SNPs in the CACNA1S gene that are linked in ClinVar ( a database of SNPs) to a channelopathy called Hypokalemic Periodic Paralysis ( HypoKPP), Type 1.  I already suspected that I had a form of HypoKPP.  However, my two SNPs,rs3850625 (Arg1539Cys) and rs12742169 (Leu458His), are not the more usual ones in HypoKPP, so even in this rare disease, I am a less frequent sub-type.

For me, I do not have downright "paralysis", but lethargy, fatigue, and muscle weakness, linked to abnormal potassium levels. A particularity of my presentation is that it takes days to recover.   The more frequent presentation is that the person is totally paralyzed for some muscles or even the whole body, for 20 minutes to a few hours.   But like POIS, this rare disease has many different presentations, almost unique in each patient.
(P.S. : in my case, both of my CACNA1S SNPs are heterozygote, meaning I have 1 defective version and one usual version on each.  However, most HypoKPP mutations are autosomal dominant ( see https://pubmed.ncbi.nlm.nih.gov/34290819/ ) , meaning that only one defective gene in the pair is enough to have symptoms, although usually less severe. That would explain why I do not have full paralysis, but weakness and extreme fatigue ( I am able to move, but it's a lot more demanding than usual, felt like extreme fatigue )
A current trigger for the attack of PP is exercise or excitement followed by a rest period.  It fits both sexual activity and sport, my two main triggers.  It also explains the delay... my symptoms set in after some rest, not instantly.

I already knew that potassium was good for my POIS, and as you may know, it is part of my pre-pack.  I also take potassium after sport - I have found some years ago that it was helping me recover faster.  However, I was unsure about what type of Periodic Paralysis I have before seeing it in my genetic results.

Be aware that there is a sister channelopathy, with similar symptoms, that is called Hyperkalemic Periodic Paralysis, so taking potassium, in this case, will worsen the symptoms.  So, unless you have your genome results or have a clear diagnosis with a neurologist, potassium is not to be tried, because potassium at high doses can trigger fatal arrhythmia ( a heart problem) !

Hopefully, HypoKPP Type 1, my type, does not come with myotonia ( muscles stiffness, cramps, spasms).  Another gene is related to this type

I have other SNPs that are significant and may contribute to my POIS, like 3 SNPs contributing to low vitamin B12, and another to ammonia elimination being reduced.   Many problems in my genes...but that, I already knew.

If you have a POIS similar to mine, that is, with no cognitive symptoms ( no brain fog, no memory problems, no reduced cognitive abilities during POIS), and have POIS-like symptoms after sport/exercise, and other frequent triggers for other people having PP ( but no me) like cold, eating food with high carb/sugars content, hign salt/sodium intake, and stress, you may take a look at the different types of Periodic Paralysis and see a specialist, or have your genome sequenced, and see if this is relevant for you


So, I think having your whole genome sequencing done can be a very good idea if you are motivated to learn how to dig into it and find some needles in the haystack.  There are great tools now to do it, and sometimes later I will write on the current methods I use to search in my WGS, if anyone is interested.   Also, cost are getting lower and lower.  I got my whole genome sequencing ( yes, whole genome, not only 1% of it like with 23andme or myHeritage ) for $299, and paid for a lifetime subscription to their reports database, a total of $499 I think.  So far, worth it a lot.  I had it done with Nebula Genomics ( good service, but expect 20 to 24 weeks before getting back your results, not the 8 weeks advertised).  Also, I have uploaded my results to sequencing.com for free, and they provide a lot of free tools to search and explore your genome, and some very useful tools at very low cost, like the Genome Explorer Plus, helping you figure out with less work which of your numerous SNPs could be more interesting to analyze.  However, with any method you choose, be prepared to do a lot of work and searching, or else, pay a genetic counselor to do it for you.

For more information on HypoKPP and other forms of Periodic Paralysis, see https://periodicparalysis.org/what-is-periodic-paralysis-2/  and https://rarediseases.info.nih.gov/diseases/6729/hypokalemic-periodic-paralysis

[Prospero]

Interesting news, Quantum.
Do you have a double mutation for the SNPs you mentioned? As for me, I'm heterozygous for rs2297902 in the CACNA1S gene, which is one of the SNPs mentioned for HypoKPP, but I doubt it has an effect alone.
As you told us too, your condition regarding potassium is probably quite specific among Poisers. In any case, nice to see that you're digging in your genetic data!

[Quantum]

Interesting news, Quantum.
Do you have a double mutation for the SNPs you mentioned? As for me, I'm heterozygous for rs2297902 in the CACNA1S gene, which is one of the SNPs mentioned for HypoKPP, but I doubt it has an effect alone.
As you told us too, your condition regarding potassium is probably quite specific among Poisers. In any case, nice to see that you're digging in your genetic data!

Hi Prospero,
Thanks for your very relevant question, because severity is usually greater in homozygous SNPs, that is, variants where both paretnal genes are the defective version.

In my case, both of my CACNA1S SNPs are heterozygote, meaning I have 1 defective version and one usual version on each.  However, most HypoKPP mutations are autosomal dominant ( see https://pubmed.ncbi.nlm.nih.gov/34290819/ ) , meaning that only one defective gene in the pair is enough to have symptoms, although usually less severe.
That would explain why I do not have full paralysis, but weakness and extreme fatigue ( I am able to move, but it's a lot more demanding than usual, felt like extreme fatigue )

Also, I have 7 SNPs in my KCNJ18 gene, another gene associated with a form of HypoKPP, called thyrotoxic PP, and about 3 of them are homozygous, but they are not reported yet in ClinVar, so I do not know yet what to think of my very badly affected KCNJ18 gene, and what could be its effects.  Further development of SNPs databases will bring me more light on this one. ( For those wondering, each gene is composed of hundreds of pairs of DNA bases, and some specific mutations in some specific positions only are known yet to be associated with medical conditions... for many positions with an alternative version ( SNP), there is no data yet about the possible consequences.  Those 7 SNPs I have in this KCNJ18 gene are not reported yet in databases, so it is not known yet what effect they have, but it is already known that other SNPs in that same gene are associated with a condition, Thyrotoxic PP, so there is some potential problem here. Data will be added with time, as more people will have their genome sequencing done... then, by comparing genes of affected persons with larger populations not affected, you find specific mutations for this condition... that is how databases like ClinVar are developed)

To complicate matters more, I also have another very badly mutated gene with many SNPs, associated with another channelopathy affecting sodium, some I may have a compounding effect here, too soon to tell.  However, loss of sodium leads to higher aldosterone secretion, in order to retain sodium, but at the cost of losing potassium in the urine... which is bad if you have another condition that already causes low potassium, like HypoKalemic PP... so I have to sort out this channelopathic puzzle, in the coming months.  I will do what it takes, including finding a channelopathy specialist to consult if needed.

[Iwillbeatthis]

Be sure to check your mutations on promethease or somewhere else where it gives the population frequency for each mutation, if you haven't already. As I have found you can have some homozygous mutations which are very common and completely normal to have. Gene reports like MTHFR support can show you have a ton of homozygous mutations that look bad but when I search them on promethease some of them have a 70% frequency in the general population.

[Quantum]

Be sure to check your mutations on promethease or somewhere else where it gives the population frequency for each mutation, if you haven't already. As I have found you can have some homozygous mutations which are very common and completely normal to have. Gene reports like MTHFR support can show you have a ton of homozygous mutations that look bad but when I search them on promethease some of them have a 70% frequency in the general population.

Good point, IWBT, the frequency is of major interest in determining if our personal conditions are caused by a less frequent variant.
The tools I have access to on the website of the company that sequenced my genome ( Nebula Genomics) give me the frequency, along with much more information.  For others who do not have these data frequencies, they are freely accessible on free websites, like the genomAD browser, at https://gnomad.broadinstitute.org/ 

[begonePOIS]

Is there any effort ongoing to organize a compilation of genetic profiles (SNP-array, whole ex/gen-ome seq, etc.)? If there are sufficient number of profiles (along with some demographics information), it should be possible to analyze the data together using a case-control design in order to detect potential genetic loci involved in POIS. I'm currently doing my PhD in genetics and would be willing to spend some time on this if the data can be put together.

Edit: By genetic profiles, what I want is the raw genotype calls of all the SNPs tested, not just a summary.

[demografx]

begonePOIS, welcome to the forum and….
Great Name!

[berlin1984]

Yes please. If you have any fancy tools from your university to find commonalities I'd happily donate my 23andme SNP txt file.

[Quantum]

Is there any effort ongoing to organize a compilation of genetic profiles (SNP-array, whole ex/gen-ome seq, etc.)? If there are sufficient number of profiles (along with some demographics information), it should be possible to analyze the data together using a case-control design in order to detect potential genetic loci involved in POIS. I'm currently doing my PhD in genetics and would be willing to spend some time on this if the data can be put together.

Edit: By genetic profiles, what I want is the raw genotype calls of all the SNPs tested, not just a summary.

Interesting project, begonePOIS.   I do not think we know exactly how many members here have their genetic profile done.  I, for one, just received my results this month.  I can easily transfer an SNP VCF file or another type of file. 

How many profiles would you need, as a minimum, for this project to be feasible?

[Muon]

Is there any effort ongoing to organize a compilation of genetic profiles (SNP-array, whole ex/gen-ome seq, etc.)? If there are sufficient number of profiles (along with some demographics information), it should be possible to analyze the data together using a case-control design in order to detect potential genetic loci involved in POIS. I'm currently doing my PhD in genetics and would be willing to spend some time on this if the data can be put together.

Edit: By genetic profiles, what I want is the raw genotype calls of all the SNPs tested, not just a summary.

1) How do I know you are not a random data farmer from the internet?
2) My knowledge is severly limited about this subject. What test needs to be done, where can one do such thing?
3) Someone could list labs across the world offering these tests.

[Quantum]

Is there any effort ongoing to organize a compilation of genetic profiles (SNP-array, whole ex/gen-ome seq, etc.)? If there are sufficient number of profiles (along with some demographics information), it should be possible to analyze the data together using a case-control design in order to detect potential genetic loci involved in POIS. I'm currently doing my PhD in genetics and would be willing to spend some time on this if the data can be put together.

Edit: By genetic profiles, what I want is the raw genotype calls of all the SNPs tested, not just a summary.

1) How do I know you are not a random data farmer from the internet?
2) My knowledge is severely limited about this subject. What test needs to be done, where can one do such thing?
3) Someone could list labs across the world offering these tests.

No short answer to explain what genomics is and what it is useful for, so below are some key points to consider.

Since the cost of having your own genome sequenced is going down rapidly, more and more companies, on the web, offer the service.  Typically, you are sent a little box with a swab and instruction to take a sample in your mouth ( inner cheek), that will hopefully contain enough of your own, personal cells, and send that back to the lab.  After a delay, if the sample was ok, and the lab was not too backlogged, you will receive online your genomic data, which you can usually download in different file formats ( it took me about 5 months to get my results... Covid backlogging...)

The use of all this is to compare your own DNA sequence, in your own genes and in all of your DNA, to what is considered the reference human genome in its latest version.  Because, for any locus in any gene, you can have what is called a SNP ( Single Nucleotide Permutation) .  Those are like small mutations on one pair of nucleotides in your DNA ( you do not have the most current one).  Some SNPs have no consequence, some others happen to be on a critical coding section of your DNA, so, for example, the little change can lead to one amino acid being changed in the protein, and, if this protein is an enzyme, it can be non-functional, or be like 60% active compared to the "normal" reference, enzyme.

Many kind of sequencing is available, but currently, since the prices are down big time, the best bargain is to go for a Whole Genome Sequencing (WGS), where you will have 100% of your DNA mapped.  The most popular tests from a few years ago, like 23andMe, and Ancestry,com, typically map about only 1% of your DNA.  It includes most of what is known right now about genomics.  But since the price for a WGS is now the same as a partial sequencing, the near future is WGS, in my opinion, because you will not need to re-do another sequencing in the future for sections you did not have mapped the first time.

I had my WGS done this year.  I have chosen a deep, 30X, mapping.  This means that, on average, for every base pair, you have around 30 samplings done.  I say in average, because for some positions, when quality was not optimal for the testing results, you may get only 12 samples to determine your real base pairs at that specific locus ( those techniques are still rather new).  You have WGS at 10X for 99$, but I feel that 10X mapping will sometimes fall short on a specific locus, so you will not be sure what is your real data at that position. You cannot rely on only 2 or 3 samples on a specific position to determine your own data there, better have a couple of dozens at least, because there are still some discrepancies in the results.  But if you have 26 results on 28 for a locus that says G-A as the pair of nucleotides you have there, you know it is really G-A, and that you are homozygote there ( two identical alleles from both parents). 

There is now 100X WGS available, but too expensive for my taste ( around $1000), and not obvious that it is clearly a plus-value over the 30X.  My 30X was at $299 with Nebula Genomics.  But there are many other companies now offering WGS, and still more offering partial genome sequencing.  For WGS, you have Nebula Genomics, sequencing.com ( $399 for WGS 30X, currently), Invitae, Dante Labs, Veritas Genetics, and so on. Do some research, and compare plans.  Apart from the quality of the sequencing, look for the file formats you will be able to download your data in.  The usefulness of that is that you can then upload your data to other sites offering you both free or paid apps to analyze your data ( However, take a look at the privacy policy of a site before uploading your data there)

Once you have your data, you can use databases to compare your genome with the reference genome, and also to look for which SNPs you have that are already know to probably cause you a problem.  But the analysis is something you have to get used to, it is not simple, and too complex for me to explain it all here.  However, you can just pay to have your data run into a program that will give you a report of what has been found in your genome, considering the current knowledge on genomics.

Special analysis can be done with a specific population having a specific problem, and run the program against a database of "normal" subjects, to see what SNPs the affected subject may have in common that the general population does not have.  This may lead to finding some genetic causes to some specific health problems.  This is what is offered for POIS by begonePOIS.

Genomics is a science on its own, so when you are interested, take the time to learn about it.  The most valuable outcome is that you can find tips and supplements, and a diet that is really adapted to your own genome. One well-studied example is for the gene MTHFR, coding for an enzyme that is important in the methylation pathway - if you have certain known SNPs there, you can adapt your lifestyle, diet, and supplements, and be more healthy.

[berlin1984]

There is a lot of genetics discussion also from here ongoing: https://poiscenter.com/forums/index.php?topic=2373.msg19924#msg19924

[demografx]

…What I find very interesting…that a lot of people in the forum are engineer/science/nerd type of guys…

Could be a coincidence that people like us are more likely to visit this kind of forum, but could also be a genetic clue for something.

I was a large-database statistical-modeling entrepreneur with an advertising business clientele. For many years.

Nerdy!