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I might actually try this! I have a disabling genetic disorder (hypermobile Ehlers-Danlos syndrome) for which the genes responsible haven't yet been identified,

I might actually try this! I have a disabling genetic disorder (hypermobile Ehlers-Danlos syndrome) for which the genes responsible haven't yet been identified, but there are a few dozen genes of interest. Since the diagnosis is clinical, my geneticist didn't order testing for me, so I've stayed curious. 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.

forgotpwagain 5y ago
Have you looked into Nebula Genomics? They will do 30X coverage WGS for $299, and will give you the underlying data so you can analyze it on your own (in addition to their analyses). Link: https://nebula.org/whole-genome-sequencing-dna-test/ https://nebula.org/whole-genome-sequencing-dna-test/
- sterlind 5y ago
  This looks quite amazing. I'd seen services like this, but not at this price point, and not without prescription.
tito 5y ago
As a middle ground between DIY and leaving it unknown you could also hire a contract lab to do this with you. As an experiment in this, I found a contract lab, ordered PCR primers, and sent in McDonalds burgers and McFish samples to do species identification. (Result: $300 all in, nothing too exciting, Bovine and iirc Alaskan Cod). The "human sample" bit might be tricky. Doing this today I would check out https://www.scienceexchange.com/ https://www.scienceexchange.com/ Oh and obviously if you're in the Bay Area go to BioCurious (https://biocurious.org/ https://biocurious.org/) or Counter Culture Labs (https://www.counterculturelabs.org/ https://www.counterculturelabs.org/) for all your DIY bio dreams
- deleted 5y ago
  [deleted]
- amelius 5y ago
  > and sent in McDonalds burgers and McFish samples Doesn't cooking/frying destroy the DNA?
  - whoisburbansky 5y ago
    From [1], it seems like cooking doesn't completely destroy DNA, but does make it so you get smaller segments post-PCR. Maybe species identification is okay with small segments? 1. https://pubmed.ncbi.nlm.nih.gov/18791146/ https://pubmed.ncbi.nlm.nih.gov/18791146/
ipaddr 5y ago
As someone who recently found out my birth mothers side is filled with Ehlers-Danlos syndrome relatives this interests me. 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?
- abz10 5y ago
  Not OP; but have hEDS. CFS with brain fog is the most disabling part. Chronic back pain is the second. Post exertion malease means if I accidentally overexert myself I can be stuck in bed for days recovering. Bad posture due to loose ligaments. 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.
  - sterlind 5y ago
    Yup! The chronic fatigue and brain fog are definitely the worst for me. My mobility is pretty limited now, and I'm getting much worse at being able to type, but brain fog could end my career. 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.
- sterlind 5y ago
  For markers, I don't recall off the top of my head, but I'd go with one of the connective tissue disorder gene baskets, and add other genes that are metabolically connected to those. The collagen genes COL3A1, etc. and TNXB definitely. 23andme is not likely to tell you much since it's just the 50k "greatest hits" of the human genome. 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.
abz10 5y ago
I have this as well - I only found out a month ago after decades of searching and dozens of doctors, hundreds of tests, across 4 countries, all telling me there is nothing wrong. It should have been super obvious in retrospect. The vast majority of people who have hEDS will never know it. I highly recommend everyone check themselves for it. It could easily be 1% of the population. I only found out when my sister recently came down with CFS/ME in much the same way I did so I searched for genetic causes of CFS/ME. It can affect your whole life in a way you don’t even know isn’t normal, because everyone around you is telling you it is normal.
- sterlind 5y ago
  A lot of people seem to do well until their 20s and then come abruptly crashing down. That was the case for me. As a kid I had pain and could do all the crazy party tricks, but was more or less abled. Now at 30 I've fully dislocated my shoulder taking my jacket off, and need a walker. I think transitioning hormonally accelerated it.. estrogen and progesterone loosen ligaments, and I lost my muscle mass from T.
new299 5y ago
NGS (Illumina style) is high enough quality to identify mutations. You can get a whole human genome for as little as 150 Euros (Dante labs has an offer at this price in 2020). Much cheaper per genome than suggested in the post, and you just send in the sample. 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.

forgotpwagain 5y ago

Have you looked into Nebula Genomics? They will do 30X coverage WGS for $299, and will give you the underlying data so you can analyze it on your own (in addition to their analyses). Link: https://nebula.org/whole-genome-sequencing-dna-test/ https://nebula.org/whole-genome-sequencing-dna-test/

sterlind 5y ago
This looks quite amazing. I'd seen services like this, but not at this price point, and not without prescription.

tito 5y ago

As a middle ground between DIY and leaving it unknown you could also hire a contract lab to do this with you. As an experiment in this, I found a contract lab, ordered PCR primers, and sent in McDonalds burgers and McFish samples to do species identification. (Result: $300 all in, nothing too exciting, Bovine and iirc Alaskan Cod). The "human sample" bit might be tricky. Doing this today I would check out https://www.scienceexchange.com/ https://www.scienceexchange.com/ Oh and obviously if you're in the Bay Area go to BioCurious (https://biocurious.org/ https://biocurious.org/) or Counter Culture Labs (https://www.counterculturelabs.org/ https://www.counterculturelabs.org/) for all your DIY bio dreams

deleted 5y ago
[deleted]
amelius 5y ago
> and sent in McDonalds burgers and McFish samples Doesn't cooking/frying destroy the DNA?
- whoisburbansky 5y ago
  From [1], it seems like cooking doesn't completely destroy DNA, but does make it so you get smaller segments post-PCR. Maybe species identification is okay with small segments? 1. https://pubmed.ncbi.nlm.nih.gov/18791146/ https://pubmed.ncbi.nlm.nih.gov/18791146/

ipaddr 5y ago

As someone who recently found out my birth mothers side is filled with Ehlers-Danlos syndrome relatives this interests me. 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?

abz10 5y ago
Not OP; but have hEDS. CFS with brain fog is the most disabling part. Chronic back pain is the second. Post exertion malease means if I accidentally overexert myself I can be stuck in bed for days recovering. Bad posture due to loose ligaments. 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.
- sterlind 5y ago
  Yup! The chronic fatigue and brain fog are definitely the worst for me. My mobility is pretty limited now, and I'm getting much worse at being able to type, but brain fog could end my career. 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.
sterlind 5y ago
For markers, I don't recall off the top of my head, but I'd go with one of the connective tissue disorder gene baskets, and add other genes that are metabolically connected to those. The collagen genes COL3A1, etc. and TNXB definitely. 23andme is not likely to tell you much since it's just the 50k "greatest hits" of the human genome. 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.

abz10 5y ago

I have this as well - I only found out a month ago after decades of searching and dozens of doctors, hundreds of tests, across 4 countries, all telling me there is nothing wrong. It should have been super obvious in retrospect. The vast majority of people who have hEDS will never know it. I highly recommend everyone check themselves for it. It could easily be 1% of the population. I only found out when my sister recently came down with CFS/ME in much the same way I did so I searched for genetic causes of CFS/ME. It can affect your whole life in a way you don’t even know isn’t normal, because everyone around you is telling you it is normal.

sterlind 5y ago
A lot of people seem to do well until their 20s and then come abruptly crashing down. That was the case for me. As a kid I had pain and could do all the crazy party tricks, but was more or less abled. Now at 30 I've fully dislocated my shoulder taking my jacket off, and need a walker. I think transitioning hormonally accelerated it.. estrogen and progesterone loosen ligaments, and I lost my muscle mass from T.

new299 5y ago

NGS (Illumina style) is high enough quality to identify mutations. You can get a whole human genome for as little as 150 Euros (Dante labs has an offer at this price in 2020). Much cheaper per genome than suggested in the post, and you just send in the sample. 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.