No, the Cheat Sheet has some uses of it, and some of the protocols have some use of it, but I will not be producing a generic “how to use whole genome sequencing” resource as that is to vast and unwieldy of a topic to make anything that generic that is also useful.
I had a whole genome sequence because of a suspected inherited condition in my family, which I turned out not to have. I used sequencing.com because their price was competitive and they seemed quite good on privacy. They try to funnel you into a subscription so that you can be alerted when new discoveries are made that are relevant to your genome, but I wasn't interested.
There are industry standard genetic file formats, the most immediately useful of which is VCF. A human whole genome sequence VCF file from sequencing.com is 1.8GB; it's a text file, and you can browse it using a file reader designed specifically for large text files, for example this one: https://web.archive.org/web/20140908181354fw_/http://swiftgear.com/ltfviewer/features.html, so when you read in the literature about some genetic variant that you think you might have, it's quite nice to be able to look it up in your genome. You can use bioinformatics tools such as plink to convert VCF into the more compact 23andMe format, which is quite useful for uploading to various websites that will generate reports on health conditions, such as promethease.com, codegen.eu and even Chris's MTHFR analysis tool on this website, although that one wouldn't take my file because it was too large! The VCF file gradually becomes outdated, because it describes your genome relative to a specific human reference genome, and from time to time new versions of that reference genome are published, for example to correct mistakes. So it's good to future-proof your genome by keeping the BAM format file which is around 84GB and contains the raw sequencing data, which can in principle be used to build a new VCF using any reference genome that may be adopted in the future.
There are many reference websites where you can look up genetic variants, and they are maintained collectively rather like Wikipedia; one site that the general public tends to use is https://snpedia.com.
Regarding benefits of WGS, I would say they are probably not massive for most people. Most people would get more value from a decent blood test. So much of the interpretation of these genomes is on the lines of "this variant makes you X% more susceptible to cardiovascular disease but the effect can be overridden by lifestyle choices" while somewhere else in your genome you're likely to have other variants that make you Y% LESS susceptible to cardiovascular disease. Certain rare genetic disorders aside, most of the information you get from a WGS is surprisingly vague and contradictory, and a lot of the associations with disease are found in regions that don't even code for proteins, regions which are likely involved in making different cell types act differently, in ways we don't yet understand. Sequencing certainly didn't decrypt the whole of medicine in the way that people perhaps hoped it would 25-30 years ago. It's hard enough to predict what somebody even looks like from their genome; the reports I've seen like that on my own genome are hilariously wrong: wrong eye colour, wrong hair colour, apparently my genes say I'm almost certainly bald. The big healthcare charities do a lot of misdirected and fruitless genetic research, because their pharma industry donors want to develop complex patentable gene-based treatments. At some point, AI may tell us a lot more about the genome, at which point a WGS could be more interesting.
I can assure you this is definitely not the case, except maybe as a very minor contributor, because MTHFR polymorphisms are very common compared to EDS.
See my MTHFR protocol for what to do about MTHFR. Whatever is not fixed by that — or more likely by a very small amount of riboflavin alone — is definitely not caused by MTHFR.
That's very true! I only ruled out the condition (an amyloidosis that's actually pretty common) as being mediated through a particular (very rare) genetic variant.
Hi Chris- Can you give some more information about the Whole Genome Sequencing you recommend? Do you have a link or any video discussing the benefits?
No, the Cheat Sheet has some uses of it, and some of the protocols have some use of it, but I will not be producing a generic “how to use whole genome sequencing” resource as that is to vast and unwieldy of a topic to make anything that generic that is also useful.
I had a whole genome sequence because of a suspected inherited condition in my family, which I turned out not to have. I used sequencing.com because their price was competitive and they seemed quite good on privacy. They try to funnel you into a subscription so that you can be alerted when new discoveries are made that are relevant to your genome, but I wasn't interested.
There are industry standard genetic file formats, the most immediately useful of which is VCF. A human whole genome sequence VCF file from sequencing.com is 1.8GB; it's a text file, and you can browse it using a file reader designed specifically for large text files, for example this one: https://web.archive.org/web/20140908181354fw_/http://swiftgear.com/ltfviewer/features.html, so when you read in the literature about some genetic variant that you think you might have, it's quite nice to be able to look it up in your genome. You can use bioinformatics tools such as plink to convert VCF into the more compact 23andMe format, which is quite useful for uploading to various websites that will generate reports on health conditions, such as promethease.com, codegen.eu and even Chris's MTHFR analysis tool on this website, although that one wouldn't take my file because it was too large! The VCF file gradually becomes outdated, because it describes your genome relative to a specific human reference genome, and from time to time new versions of that reference genome are published, for example to correct mistakes. So it's good to future-proof your genome by keeping the BAM format file which is around 84GB and contains the raw sequencing data, which can in principle be used to build a new VCF using any reference genome that may be adopted in the future.
There are many reference websites where you can look up genetic variants, and they are maintained collectively rather like Wikipedia; one site that the general public tends to use is https://snpedia.com.
Regarding benefits of WGS, I would say they are probably not massive for most people. Most people would get more value from a decent blood test. So much of the interpretation of these genomes is on the lines of "this variant makes you X% more susceptible to cardiovascular disease but the effect can be overridden by lifestyle choices" while somewhere else in your genome you're likely to have other variants that make you Y% LESS susceptible to cardiovascular disease. Certain rare genetic disorders aside, most of the information you get from a WGS is surprisingly vague and contradictory, and a lot of the associations with disease are found in regions that don't even code for proteins, regions which are likely involved in making different cell types act differently, in ways we don't yet understand. Sequencing certainly didn't decrypt the whole of medicine in the way that people perhaps hoped it would 25-30 years ago. It's hard enough to predict what somebody even looks like from their genome; the reports I've seen like that on my own genome are hilariously wrong: wrong eye colour, wrong hair colour, apparently my genes say I'm almost certainly bald. The big healthcare charities do a lot of misdirected and fruitless genetic research, because their pharma industry donors want to develop complex patentable gene-based treatments. At some point, AI may tell us a lot more about the genome, at which point a WGS could be more interesting.
You cannot rule out a condition with WGS.
https://news.tulane.edu/pr/could-vitamin-deficiency-cause-%E2%80%98double-jointedness%E2%80%99-and-troubling-connective-tissue-disorder
Most likely ehlers danos is caused by MTHFR. Can we infer that people with MTHFR have some level of problem with collagen? If so, what should we do?
I just discovered that I have MTHFR and my knees have been dislocating since I was six.
I can assure you this is definitely not the case, except maybe as a very minor contributor, because MTHFR polymorphisms are very common compared to EDS.
See my MTHFR protocol for what to do about MTHFR. Whatever is not fixed by that — or more likely by a very small amount of riboflavin alone — is definitely not caused by MTHFR.
That's very true! I only ruled out the condition (an amyloidosis that's actually pretty common) as being mediated through a particular (very rare) genetic variant.
Right, and and you didn’t rule out that you had a different rare variant, perhaps one not even documented yet, in the same gene.