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 

By sysbodyodor

fmo3, genetics

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