the 'big 3' FMO3 variants : a cheap way to test

There are 3 common variants for FMO3, that perhaps most 'FMO3 smell people' carry. The easiest and cheapest way to find out is to do the 23andme.com test, or an ancestry test that lets you download the raw data.

FMO3 is a 532 amino acid sequence, and 23andme only test about 50 of the 532, but it does test the 3 main variants at codons 158, 257, 308.
It would be interesting to see if most of carry 2 or more of these.

Estimates of carriers of the 3 main variants :
E158K : 40% people ?
E308G : 20% ?
V257M : 10% ?

DIY STUDY
We should be aiming to flood PUBMED with papers about TMAU, SysBO/Hali etc.
PUBMED is where researchers look to see whats going on.

But for now, as beggars, we can try a DIY STUDY.

Question 
Do you carry E158K, V257M and/or E308G ?

Feel free to put your result in the COMMENT SECTION.
Anon if you want ?
e.g.
E158K : AG
V257M : AA
E308G : AG

HOW CAN I TEST FOR THIS ?
A cheap and easy way to test for the 3 most common FMO3 variants is :

1. Find and buy an ancestry test that lets you download the RAW DATA ...
or buy 23andme.com test.

2. Look for these 3 variants :

rs2266782

variant known as E158K

normal : GG

variant : A

rs1736557

variant known as V257M

normal : GG

variant : A

rs2266780

variant known as E308G

normal : AA

variant : G

FMO3 PROTEIN is a 532 amino acid sequence, but there are 3 most common variants. E158K V257M E308G . Many people carry these faults (Whites carry maximum for the 3 : 45%, 25% 10% ...  estimate from memory). No-one is bothered much to find out if they are 'pathogenic' or not, but it would be interesting to see if those who identify with metabolic malodor tend to carry them in a mix.

My own current view :
I suspect most cases of 'metabolic/systemic body odor' are due to weakness in the FMO3 enzyme, but there may be other enzyme disorders too.

COMMENT SECTION
Feel free to put your result in the comment section. Anon if you want.

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By sysbodyodor

fecal body odor, fmo3, genetics, important, systemic body odor, TMAU research

8 comments

2nd licensed Gene Therapy drug approved

The 2nd GENE THERAPY drug to be approved by the EU authorities has hit the market in Europe.
The first gene therapy drug, Glybera, was approved by the EU in 2014.
The new drug, Strimvelis, is for 'bubble boy disorder'.
Gene Therapy will likely be a cure for genetic systemic malodor disorders.

Gene Therapy is of interest to those with metabolic genetic malodor disorders because gene therapies will likely be 'cures' for genetic disorders. So if someone has a sub-par FMO3 enzyme that causes systemic body odor and/or halitosis, gene therapy could be considered the 'holy grail' cure.

Gene therapy has been suggested for about 30 years but a main obstacle was that it often involves viruses and these could cause a severe/fatal immune reaction. Also there may be some resistance from big pharmas as a one-treatment cure may mean loss of revenue. And investment costs and cost of treatment were seen as too costly (Glybera cost around $1.2 million per treatment.

But finally the obstacles seem to be clearing, and the technology has caught up.

FMO3 protein
Oxidizes/reduces many sulfides and  amine (and phosphates)
Gene produces a 532 amino acid code (and a stop at 533)

How would gene therapy be relevant to metabolic/systemic body odor/halitosis ?
My view is that most causes of systemic B.O/halitosis are probably to do with a sub-par FMO3 enzyme issue. In these cases gene therapy should make the FMO3 enzyme work normally. Gene therapy has taken 30 years to get to this stage but over the next 10 years could quickly become cures for genetic disorders.

How do Gene Therapies work ?
My impression is that they are usually manufactured viruses that are put in the target gene to make the gene work correctly. It will probably be to do with what type of fault you have in the gene. For FMO3, Most people have 'missense' faults, where an incorrect amino acid has been put in the 532 amino acid sequence. So this would probably require a 'missense' drug. Another severe type is a 'nonsense' fault, where the 532 long FMO3 code is told incorrectly to stop early on (a false stop). One drug, Ataluren, is being targeted to ignore this 'false stop' so in the case of FMO3 the 532 code will ignore the false stop. But 'nonsense' mutations are much rarer than missense and I presume a nonsense targetting drug would not help with a missense mutation.

Links to story on Strimvelis drug approval :
BBC news site
News18.com

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By sysbodyodor

fecal body odor, gene therapy, genetics, metabolic malodor, research

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Exome/Genome Consumer Test list

To me, it's getting to the point where it's possibly economically and future-proofing best to Exome or Genome test rather than test for single genes (partly or fully) or groups of genes. And Direct to Consumer (no need for Dr, health professional and their fees etc)

So here is my list ...

Aims :
Exome or Genome testing
Direct to consumer
Note : For health-related testing the advice seems to be to go for 30x coverage at least

my List : Exome / Genome Consumer Test companies

COMPANY	EXOME / GENOME	COMMENT
Full Genomes link	Exome 33x $775 Genome 30x	Other links : ISOGG Facebook
Veritas Genetics link	Genome 30x  £999	Other links :

update : 19 May 16

Exome is about 1.5% of the Genome.
But Exome is the CODING PART, whereas rest of Genome is junk / promoter region etc.
But you can have faults in the junk part which can affect the gene coding.

Main reasons for choosing Exome or Genome
Exome is the coding part, and probably cheaper to do
Genome includes everything, and perhaps in future more will be known and you will already have your full data.

FMO3 :
Readers will be aware I currently suspect FMO3 enzyme as the main suspect for most cases of Systemic Body Odor. FMO3 coding part would be included in both Exome and Genome testing.

FMO3 gene code : 532 amino acid sequence (532 codons from 1596 (532x3) Nucleotides) plus stop codon at codon 533.

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By sysbodyodor

fmo3, FMO3 DNA saliva test, genetics, systemic body odor, systemic malodor syndrome, tmau test

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Video on FMO3 gene

Recent video on youtube.
A general overview of the genetics of FMO3 enzyme.
I think by a member of the public.
Below is an embed of the video.
If the original is deleted this copy will auto-delete.


My comments :
The person has done a good job. I agree with the terminology they use. I think it probably best to discuss FMO3 mutations/variants in that terminology (e.g. E158K, E308G etc)
FMO3 enzyme is a 532 amino acid coding sequence
Think of it as a train track or ladder. You need both sides to make up the amino acid.
Each 'rung' is called a codon
So FMO3 gene has 532 codons (coding sequence)

I agree with what is said in the video, but I would go further and say some' carriers' are probably 'transient sympotmatics' too. In fact I think most probably fit this category.

What I am saying is, at the moment the consensus is that there are sufferers and carriers. I'm saying that some carriers will in fact be sufferers, and the genetic spectrum will go from 'severe' to 'mild' much further than experts currently suggest. This would drag maybe more into the 'danger zone' at times.

For example, e158k and e308g are very common variants, thought to be harmless. I reckon perhaps in tandem with other variants, or in homozygous form (e.g. e158k / e158k), the person may at times fall into the 'danger zone'.  Also many will be 'compound heterozygotes'.

Link : my list of FMO3 532 coding sequence

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By sysbodyodor

fmo3, genetics, video, videos, youtube

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My list of the FMO3 'normal' codon sequence

FMO3 is an enzyme. It is a protein made up of a 532 DNA coding sequence then ended with a 'stop' codon. My naive impression is that the 'wild type' DNA code for a protein is the 'perfect' coding for the protein. I am not sure if anyone ever has the ideal 'wild type' code (as it may be the case that most/all humans carry faults that usually have no effect). However it gives someone a code to compare their own coding sequence with. If your code differs from the wild type, you then have to wonder if your 'faults' will cause problems in practice. DNA testers will have a list of 'faults' they think can cause problems, and also sometimes the faults might be little faults that added together might cause problems (cumulative).

So for reference purposes, the 10 photos in this post show the 532 DNA coding sequence to build a FMO3 protein that will then act as an enzyme.
 

 

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links :
Pubmed list of documented FMO3 'SNPs'
FMO3 coding sequence on Pubmed website

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By sysbodyodor

fmo3, FMO3 reference, genetics, systemic body odor, systemic malodor syndrome

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Genetics : different shades of gray

People tend to think of a genetic problem as being 'black and white'; that either you have a genetic fault or you don't, or you carry a fault or you don't. In fact it is usually more complex than that, and more about a % game in terms of function. So someone can have 20% function and someone else have 80% function, but both are deficient in some way.

With FMO3 enzyme, there is no agreed level of normal %, but the current consensus seems to be around over 90% function, though mentioned has also been over 95% or even over 97%.

Severe and mild genetic faults

People with severe FMO3 deficiency will have a very low % function. Say under 50% and probably even lower. This would be people with, say, 2 nonsense mutations. Types of genetic faults that cause such low levels of function are known as 'pathogenic mutations'. 

There is a 'milder' type of fault which are known as variants. Often these are regarded as not a problem until a study finds that they are. FMO3 is made up of a 532 amino acid sequence. Often variants are when the wrong amino acid is inserted in the sequence. Typically these cases will be regarded as 'genetically mild' but in practice this can mean you smell terrible but perhaps only intermittently. 

2 common variants are at codons 158 and 308 which are thought to be present in about 10% of the population. Currently it is thought that only if you receive these bad copies from the same parent (homozygous) are you likely to have a mild deficiency. However, as data grows, perhaps it will turn out that if you get a copy from each parent (heterozygous) then you can be 'at risk' of transient smells too. Only time will tell.   

So it's important not to think of genetic FMO3 deficiency as either 'on or off', but rather it is a % game and you really want to be above 95% (probably higher in my opinion) all the time 

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By sysbodyodor

fmo3, genetics

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