How to sequence your genome at home
blog.booleanbiotech.com
blog.booleanbiotech.com
However if detected early, the treatment is dead simple. Regular phlebotomies to keep iron in line. One trip to the blood bank every few months means that the disease has literally zero impact on health or quality of life. Without genenome sequencing, I likely would have lost 10-20 years of life, and even more in terms of quality adjusted years. And this isn't some freak corner case. As many as 1 in 200 Northern Europeans have the genetic condition.
Ancestry/23andme-type medical results are (in my opinion) almost entirely a nice write-up and display of public databases of research on SNPs, e.g. https://www.ncbi.nlm.nih.gov/snp/docs/entrez_help/, https://www.snpedia.com/
You could (for example) submit the data you get to Promethease which will do the processing for you. Promethease is now owned by MyHeritage, so I'm not sure how their terms are looking - I'd be a little cautious about using that.
we don't have even the slightest idea of where it could go right now. look 30 years ago and DNA wasn't a thing that people were worried about and now it's catching sloppy criminals. the technology opens up new, unexpected opportunities
Far far better idea to just pay someone to do short read resequencing. Long read sequencing is great for assembling genomes and finding structural variants.
Nanopore looks cheap in the first instance, but it's just not designed for this job. HiFi sequencing gives the best of both worlds - accuracy of short reads and decent length.
https://www.pacb.com/smrt-science/smrt-sequencing/hifi-reads...
Not accessible to the home user though.
I'd probably approach it by ordering primers for my regions of interest, doing PCR to amplify them, then running it through the flongle in a single shot.
Of course anything this DIY would be useless for diagnosis or research - you want Sanger sequencing for accurate transcription of each gene, and whole-genome sequencing for identifying candidate mutations - but it's enough motivation to try such a fun little project. Also I can potentially play along at home with the results of the HEDGE study, which is trying to find the cause of hEDS.
The "human sample" bit might be tricky. Doing this today I would check out https://www.scienceexchange.com/
Oh and obviously if you're in the Bay Area go to BioCurious (https://biocurious.org/) or Counter Culture Labs (https://www.counterculturelabs.org/) for all your DIY bio dreams
Doesn't cooking/frying destroy the DNA?
I have my dna from 23andme what markers should I be looking for? How does it affect you personally, what is disabling about it for you?
Do you have a french background?
There is also an increased anxiety with high functioning autistic behavior. It causes insomnia and noise intolerance. It seems to reduce the sex hormones. There also seems to be a link to higher IQ.
I have a distant West German background on the affected side.
I do also have high IQ, ASD, horrid anxiety and insomnia, and I wonder if the sex hormone thing is what made me trans.
It sucks.
As for how I'm disabled: I have to use a rollator full-time now, and I've just been prescribed a neck brace, despite doing PT religiously for most of a year. I'm just too loose.. my knees give out, I sprain ankles all the time, my neck is too wobbly to hold my head up etc. I also have neurological issues that make me really clumsy, and dysautonomia that leaves me fatigued and woozy. Brain fog is the worst of it, since my mind is my livelihood.
No French background, Scots-Irish. Weirdly I don't know anyone else in the family with it, but I'm extremely hypermobile so it may have been a new mutation.
My theory, and this isn't standard, is that for hEDS the hormones drive the collagen deposition. Other EDS have a more direct link for mutation in collagen. I subscribe to the metabolic trap theory of CFS (see Dr Ron Davis) work, in my view this trap could upset the hormones which affects collagen.
In the past month I've been taking collagen peptides and other joint supplements and have noticed my fingernails have become substantially harder. I think the common refrain in the hEDS community that those don't help is wrong.
Trans men report a substantial improvement with TRT. There is an actual trial going on now treating women with testosterone.
There is anecdotal evidence that healing peptides and hGH is very effective. Especially for neck instability, or in my case degenerative disk disease. My gray market supply should arrive in a few days. I didn't want to wait for modern medicine to catch up. The pipeline for hEDS treatments is pretty sparse.
Long Covid seems to have a ton of similarities to heads so hopefully treatments will cross over.
on the subject of sketchy gray-market meds, have you heard of BPC-157? I know an hEDSer who seemed to really bounce back after using it, but I can't quite work up the nerve to inject myself with internet peptides.
What do you read to stay informed about this stuff?
Even if someone seeks a hEDS diagnosis they are given a false negative 85% of the time. The vast majority don’t know to even seek it. It’s surprisingly prevalent, but also a spectrum. Many will present as just anxiety and burnout.
I read preprint research on ResearchGate and the NIH website - including mouse studies, as well as research done in Eastern Europe. I chat to friends who work in computational biology and longevity. I read a ton of comments across Facebook, Reddit, YouTube, and Twitter looking for anecdotal data. Bodybuilders and athletes are another good source of anecdotal information.
I used to be an applied researcher in machine learning; so I’m used to finding mistakes in others work. There is a lot of false confidence in medicine due to p-hacking and selection biases. I worked with behavioral data so I’m also used to cleaning anecdotal data and making it useful.
I got lucky; I was told young that weightlifting will help straighten my back and keep my shoulders from subluxating so I’ve worked out most of my life. Also why I knew more PT wasn’t going to help. At my high school gifted program I was warned that people at my level pretty much always burn out young; so I’ve always kept that in mind and readily slow down when burning out. It has been hell but it could easily have been worse.
I think the weightlifting helps a ton with the testosterone and hGH and maybe other hormones. So does sunlight, it’s more than just vitamin D. But I can’t maintain the intensity and invariably get injured and relapse. This has been a cycle for me for many years.
There is also the mitochondrial repair approaches which I’ve yet to experiment with.
I think it could easily be 5-10-15 years for a proper cure. It’s a very neglected field.
I think transitioning hormonally accelerated it.. estrogen and progesterone loosen ligaments, and I lost my muscle mass from T.
To get a comparable genome using the method suggested in the blog post will be much much expensive, in part because you have to buy all the equipment. But also because it’s Nanopore sequencing which has a much higher baseline error rate.
It is much cheaper, easier, and more accurate to use a service like Nebula Genomics. 300 dollars for an exome is an incredible deal. When looking for deleterious mutations, it is actually really important to have a highly accurate methodology, otherwise you may find errors you think are true deleterious mutations.
Is the 30x coverage sufficient for finding all deleterious mutations? Or is the 100x option needed?
Depending on the circumstances, clinical use of genomes requires 100x-500x coverage. Depending on your purposes, you may accept less sequencing depth/coverage. If I was just a hobbyist wanting some idea about my genome, 30x would be sufficient for me.
His symptoms greatly subside when he takes Niacin (1000mg/2x/day) along with magnesium l-threonate (2x/day).
Was wondering if there was an issue with B vitamin metabolism.
Was going to run the data through Promethease, but wasn't sure if the additional fidelity would help my search for a possible diagnosis.
Variant callers are a family of algorithms that look at the DNA in your sample and determine the SNPs. When thinking about coverage, quality scores assigned to sequence reads, and other pieces of information that may affect the variant caller, I would think about these inputs through their effect on detecting/classifying a variant. In other words, through metrics like accuracy, false positive rate, or false negative rate. State of the art variant callers are a little more complicated now, but simpler variant calling pipelines filter out variants that are of insufficient quality or read depth. This will primarily improve the false positive rate. If you are okay with casting a wide net in your search for a diagnosis and acknowledge that you may be seeing more false positives, then it's okay to go with a lower coverage assay.
As other commenters have pointed out, 30x coverage is widely accepted for germline sequencing. This is in contrast to somatic sequencing, which is more often done in the clinic for conditions like cancer where we expect much more variation among the DNA in the sample. Since that is not a concern in this case, you are probably fine to go for lower coverage options.
Edit: spelling