1) I often share relevant personal experience - did so in a post this morning. When my SNPs are relevant I will discuss those too.
I didn't bother in this discussion because I was simply trying to make a general point about a particular SNP and what it does or doesn't do. I didn't think my own experience or genetic status made any difference to that discussion and didn't want to overcomplicate the post.
Since you think it important, I am happy to reveal that I have several CBS+/- SNPs (including C699T), several +/-BHMT SNPs, none of which amount to anything, plus one BHMT +/+ which does have a small effect. I have normal homocysteine and ammonia levels and don't have problems with thiol -containing foods.
2) I have never claimed to have total knowledge/authority. Where I have researched SNPs, usually because I have them, I am always happy to share what I have discovered.
With the CBS SNPs under discussion, I didn't bother to give references yet again because they have in fact been discussed over and over again on PR. Many people do know about them but I agree, I shouldn't presume that everyone reading this thread does.
So here are a few basic references to CBS summarising what is known about it's SNPs, most particularly defining which are the pathogenic ones. There are links to the original papers.
http://www.omim.org/entry/613381?search=cbs&highlight=cbs
http://www.ncbi.nlm.nih.gov/clinvar?term=613381[MIM]
http://www.ncbi.nlm.nih.gov/clinvar/variation/92426/
The first two summarise all SNPs and their clinical effect, the third is just for C699T.
The latter shows several interesting things - the SNP was last evaluated relatively recently (Dec 2014), its status as a benign variant is unchanged and it is a synonymous codon change - ie the nucleotide change has no effect on the amino acid sequence of the gene product.
In other words, the enzyme produced by the variant gene is identical to the one produced by the ancestral or wildtype gene.
This tells you immediately that the SNP doesn't amount to much.
There are situations where a nucleotide change without protein change could make a difference - for example, the nucleotide change could destabilise the mRNA and this in turn could lead to less of the enzyme being produced. This doesn't apply to a single nucleotide change however, but rather to the effect of a number of SNPs in concert. This has never been found for CBS as far as I am aware and in any case, less enzyme would lead to less activity, not the upregulation that is claimed for this SNP.
Alternatively, the SNP could be in linkage disequilibrium with something else and it is the something else that is having the effect. I do recall reading that this is thought to be behind the small upregulation that has sometimes been observed for this SNP. I can't lay my hand on that paper at the moment but
here is a summary of the variable effects that have been observed for the SNP in a methionine loading test and the reasons the SNP does not have negative effects. It has links that you can follow if you want to read the original studies.
And what of Yasko's claim about a 10 x upregulation?
Here is an old thread (from April 2013) in which this was discussed on PR. One member tracked down the reference which Yasko said the claim was based on, plus other studies by the same authors, and reported
here and
here.
Basically, Yasko completely misinterpreted the paper. The scientists had created a truncated mutant (in yeast) to study aspects of enzyme activity - it had no relationship to the SNPs Yasko was interested in.
3) If you have a problem with OMIM or ClinVar then I'm sorry, but the difficulty lies with you, not the reference. Yes the summary is just someone's analysis but it is a quick way of gathering together information and you can read the originals if you want to. If you don't trust the report of dbkita, who once made many helpful posts on PR on many aspects of biochemistry, then I suggest again that the problem lies with you. In any case, you can read the originals yourself - they are referenced in the thread.
4) I've never thought I needed to present my credentials in order to make posts. Nor have I demanded it of anyone else. But since you claim it is important, and more to the point, claim that I don't have any credentials, I'd better lay them out.
I have a PhD in biochemistry and spent almost 30 years working in medical research in various university medical schools. For the last couple of years of my working life, before I retired due to ill health, a few colleagues and I set up a company to commercialise our research and conduct clinical trials in humans, using the protein that we discovered.
I have run my own research lab, written and received research grants from national and international granting bodies, had many scientific papers published in reputable journals, presented my research to national and international scientific meetings and have supervised PhD students.
While my greatest expertise is in protein biochemistry, because our lab was trying to understand the function of a new protein, I became familiar with a wide range of biological systems. I also became very familiar with recombinant DNA technology which I used to produce large amounts of the protein I had originally purified so laboriously from biological sources. In doing so I worked closely with geneticists and molecular biologists and gained a good working understanding of these disciplines.
So I am well able to understand a wide variety of scientific subject matter.
I think I can add some information or experience that might be helpful to someone else. Sometimes it is to correct misinformation. In this respect, Yasko's many erroneous claims and dubious theories would be a common source of such posts.
These and related claims have completely distorted the SNPs discussion. People have come to believe that they have serious mutations which are the source of their health problems. While it is true that some SNPs have very serious consequences, these are relatively rare and they are not the ones that Yasko has fixated on.
This latter group often do nothing at all, or have relatively small effects. Some combinations may indeed make a contribution to health problems but it is a contribution, not the main event and I think it is important that people understand their SNPs in a proper context
I am certainly guilty of pointing out the errors behind Yasko's claims but I wonder why this is considered to be a problem.
I am perfectly happy to agree to disagree with you but I do not accept your attribution of improper motives to myself and others
