Only one copy of a gene that turns choline to acetylcholine - is increasing dose of choline in diet pointless?

[moonkitty79]

I appreciate it's a randomly specific question but my knowledge of genetics is rusty and my memory says we have two copies of each gene as there's two halves of a chromosome. My son has a deletion at 2q12.3-13 which means that he only has one copy of SLC5A7. This facilitates the transfer of choline to acetylcholine which is a neurotransmitter. He has some behavioural problems and I think this is a big factor, I would assume that he is only running on half capacity for this transfer. My question is whether if I gave him choline supplements would he have more stable acetylcholine production or would the fact that he only has one copy mean that it's working as best it can and throwing more choline at it would just result in it being wasted. I would assume therefore that unless I can miraculously get hold of an acetylcholine supplement, there is unlikely to be a positive effect on his brain health. Is my reasoning correct or am I missing something because of my rusty knowledge?

[CharonY]

Unfortunately the translation from genetic information to phenotype is not quite as simple and I would like to start off that I am only speculating here, as I have no expertise knowledge on this specific subject.

 

But in principle it depends a lot on the type of deletion and how the system is regulated. For example, a single copy does not have to result in reduced biochemical activity as it could be compensated by higher expression.

What does happen in cases where a copy is silenced or truncated (depends also a lot on where the deletion is) is that regulation could be disrupted. Thus the phenotype could be much more complex than a reduction in cholin transport efficiency, for example. And even if that was the case it does not necessarily mean that nutrient supplement could remedy it as the whole regulation of choline metabolism/conversion/signaling is quite complex.

I would ask a specialist in the medical field whether there are things to improve brain health as the simple reasoning is not likely accurate enough to provide good intervention strategies.

[moonkitty79]

Ok, thank you very much for replying, that's interesting. His deletion is quite large, and SLC5a7 sits comfortably within the deletion (from 2:108403223 to 2:110457727) so I would assume that he just has one whole copy of the gene on the good side of Chromosome 2, and nothing at all on the bad part, but you raise a good point in that I can't simply assume that he runs on half capacity. It's likely to be far more complex as far as phenotype goes. He's diagnosed as autistic with a chromosome deletion but I feel that so little is understood about the deletion that perhaps autism is too simple as an explanation for his behaviour patterns. When I discovered that SLC5a7 is directly involved with a neurotransmitter I was keen to find out more about whether that could explain his phenotype more. There's other genes in that section so it's very complicated and because it's such a rare deletion, with no child specifically matching that size and location of deletion, the specialists basically told me they didn't have any advice or information to give me, there's no specific syndrome, no research and so they said stick to autism support! I wasn't entirely happy with that so requested the cytogenics report and started looking at the genes in the deleted section. SLC5a7 seems like the most likely contributor but as you can see, my knowledge is limited to the first semester of university before I changed to a Business Management course. How ironic that I'd actually need that knowledge in the future! I do appreciate your help, thank you again.