[HN Gopher] How to sequence your genome at home
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How to sequence your genome at home
Author : sprague
Score : 120 points
Date : 2021-06-07 14:03 UTC (8 hours ago)
(HTM) web link (blog.booleanbiotech.com)
(TXT) w3m dump (blog.booleanbiotech.com)
| sterlind wrote:
| 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 wrote:
| 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/
| abz10 wrote:
| 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.
| tito wrote:
| 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/
|
| 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
| amelius wrote:
| > and sent in McDonalds burgers and McFish samples
|
| Doesn't cooking/frying destroy the DNA?
| whoisburbansky wrote:
| 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/
| [deleted]
| ipaddr wrote:
| 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 wrote:
| 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.
| new299 wrote:
| 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.
| colordrops wrote:
| I've been wary about submitting my DNA to a company so this is
| very intriguing. Is there enough data and/or a community and open
| software to support things like ancestry and disease profiles
| locally?
| caymanjim wrote:
| I've been curious about what my DNA says, and went so far as to
| buy a 23andme kit years ago. I never sent it in, because I
| don't like the idea of some company retaining that kind of
| deeply personal data about me. It's useless to resist, though;
| my sister and some cousins submitted theirs, and that's enough
| to destroy any real sense of anonymity I might have. I don't
| have any particular concern; it's just one of the myriad ways
| that privacy no longer exists.
| weaksauce wrote:
| > I don't have any particular concern
|
| 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
| adenadel wrote:
| I get your point, but your timeline is pretty far off. The
| first human gene therapy happened in 1990 so DNA has been a
| thing for awhile.
| Retric wrote:
| The first use of DNA in a criminal case only goes back to
| 1987. As such 30 years ago people generally weren't
| really aware of generic testing or any of it's
| implications.
| weaksauce wrote:
| I am talking about DNA wrt crimes... it was first
| proposed as possible in 85 and in the early 90s used for
| it. I'd say my timeline was fairly ok for an off the cuff
| recollection of events.
| teachingassist wrote:
| It's tricky to organise, but in theory, yes, you can interpret
| your own results.
|
| 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.
| riedel wrote:
| Would be rather interesting to create sth like bloom filters
| from ones DNA to find relatives. In contrast to phone numbers
| the DNA space here might really be big enough for private
| "contact" discovery to work ...
| beaugunderson wrote:
| 23andMe does this already; I've found relatives from some
| distant parts of the family this way!
| gremloni wrote:
| I don't know if it's relevant anymore but I ran my SNP data
| through promethase years ago. It has a ridiculous amount of
| information.
| amelius wrote:
| Good question. I'm always afraid most of the useful medical
| data will be kept secret by these giant corporations, but let's
| hope this is not already the case.
| jltsiren wrote:
| There is plenty of open software and data in genomics. The hard
| part is knowing what to do, using the software correctly, and
| interpreting the results. Bioinformatics is still mostly
| research-level work, so you'll need years of experience and
| lots of trial and error to get anything done.
| andai wrote:
| I'd wager for most people, DNA still isn't a thing they're
| worried about.
| searine wrote:
| Most of bioinformatics/computational biology is open source and
| so are most of the data sets. The companies that do this
| definitely have a 'special sauce' for ancestry, but most all of
| the disease annotations are public (see dbSNP).
|
| As for the paranoia about DNA companies, you are an anonymous
| drop in the ocean of sequenced DNA. There are laws against
| using it to inform insurance coverage. Sequencing yourself at
| one these companies and opting in for use in research is
| actually really important to collecting the sample sizes
| necessary to discover new causative variants for disease.
| searine wrote:
| Oxford nanopore isn't that great for resequencing a human genome.
| Human DNA is too big and the minIon or flongle is too small and
| error prone. MinIons are best used for long reads for niche
| experiments like assembly or for field work, in my experience.
|
| 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.
| aantix wrote:
| Nebula offers "Deep Whole Genome Sequencing - We decode 100% of
| your DNA at 30x"
|
| Is the 30x coverage sufficient for finding all deleterious
| mutations? Or is the 100x option needed?
| aabaker99 wrote:
| Coverage isn't directly relevant to whether a mutation is
| deleterious or not. Coverage is about getting accurate reads
| in the face of short-read sequencing. Modern sequencing will
| chop up DNA into 200-nucleotide-long fragments and then align
| those fragments against the reference genome. Because of the
| variation between individuals, sequencing errors, and the
| fact that there are only 4 nucleotides, one sequencing read
| may not be enough to unambiguously determine which DNA is
| present at what position in the genome. Coverage at a
| particular genomic coordinate or locus is the number of reads
| which have been aligned to that position.
|
| 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.
| aantix wrote:
| My son has been diagnosed with oppositional defiance
| disorder.
|
| 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.
| adenadel wrote:
| 30X is considered standard for germline whole genome
| sequencing and higher coverage is typically used for
| detecting somatic variation. That being said, all detection
| is statistical and there are regions of the genome that are
| inherently hard to sequence.
| miley_cyrus wrote:
| Sequencing a genome is the easy part -- the difficulty is making
| sense of all of the data in a clinical/medical sense. I got my
| DNA sequenced/analyzed by https://www.nagenomics.com and found
| some interesting things that matched personal/family medical
| history.
| jrhawley wrote:
| This is definitely true. Even looking at risk SNP databases for
| a particular disease is fraught with caveats. You really need
| someone with experience in the field, like a medical
| geneticist, to interpret the data you get. 23andMe and Ancestry
| can at least provide that for people, but I don't necessarily
| like giving up that data to a company to hold for me. But
| that's cool you were able to find some known markers of your
| personal medical history
| dcolkitt wrote:
| For anyone wondering if there's any real benefit to having your
| genome sequence, here's my anecdote. Thanks to Promethease, I
| found out at a young age that I had hereditary hemochromatosis.
| This condition basically results in the slow over-accumulation of
| iron over a period of decades. The symptoms are so non-specific
| that without genetic testing, it's very rarely diagnosed until
| major damage has been done.
|
| 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.
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