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The human genome is, at long last, complete
- pdm55 5y agoIt was enlightening to learn that to further increase the diversity and functioning of proteins, sugar groups are added (glycosylation) to our proteins at specific organelles within the human cell (think, Golgi apparatus, endoplasmic reticulum). Historically, proteins were studied first as they were more readily purified, then in the 1990s, decoding our genome took precedence in research funding. What is the next key funding target?
- xbar 5y agoIs it free?
- smoldesu 5y agoI think most people ship with a copy from birth.
- bqmjjx0kac 5y agoCan't wait for v2 to ship. Maybe it will have drivers for the latent psychic hardware.
- smegger001 5y agoI would settle for a plugin api and a descent man file
- mmmrtl 5y agohttps://github.com/marbl/CHM13/commit/85644b74e188aa2124943bbb26e113d1cb873840 https://github.com/marbl/CHM13/commit/85644b74e188aa2124943b... v2, now with a Y chromosome
- paskozdilar 5y agoYeah, but it's in compiled form. Average person does not possess tools or skills to read the code and see what it does or modify it's behavior. We need to stop using proprietary genomes. Free genomes, free society.
- brimble 5y agoI'm pretty sure there a bunch of very popular, high-traffic sites with tons of content that demonstrates the build process.
- dotancohen 5y agoThis guy's interested in reading the make file. Those sites just show people running make.
- brimble 5y agoThere are sites to cater to those who prefer reading about the build process, too. Uh, so I hear.
- ece 5y agohttps://www.ncbi.nlm.nih.gov/assembly/GCA_009914755.4#/def https://www.ncbi.nlm.nih.gov/assembly/GCA_009914755.4#/def
- wonderwonder 5y ago2013 Supreme court case Molecular Pathology v. Myriad Genetics, Inc says yes. Although I would guess the right to read the results of the study are not necessarily free.
- awenger 5y agoThe data from the project is released to the public domain (CC0). The research article is also free to access. See https://github.com/marbl/CHM13 https://github.com/marbl/CHM13 and https://www.science.org/doi/10.1126/science.abj6987 https://www.science.org/doi/10.1126/science.abj6987.
- jghn 5y agoNow on to the more important challenge. Making our understanding of the human genome more diverse and less specific to certain geographic areas. This is already having an impact in studies, drug development, etc based on genomics. Investing in organizations such as H3Africa will be important.
- jahewson 5y agoI don’t think it’s “more important”, without a reference genome it’s impossible to take the next step and the Human Genome Project successfully took us from 0 to 1. Going from 1 to n is much easier. The Human Pangenome Project is working on this and should have 350 diverse genomes sequenced within the next couple of years. Note that this has nothing to do with collecting variations in individual genes - that’s easy and widely available. But about collecting variations in the actual content and structure of the genome. e.g. Some populations have a bunch of extra DNA that most other humans lack, amazing.
- asdff 5y agoOne of the issues is in terms of sample size. African populations are the most genetically diverse, so you would need a much larger sample to draw the same power you get from a less diverse population of say icelanders (1), who are even less genetically diverse than western europeans. Another favorite population for geneticists for similar reasons is a group of mormons from utah. 1. https://en.wikipedia.org/wiki/DeCODE_genetics https://en.wikipedia.org/wiki/DeCODE_genetics
- jghn 5y agoYes. Which is better or worse depends on the use case. The bias in available samples causes bias in things like medical treatments.
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- cato_the_elder 5y agoI feel I've read the same headline quite a few times over the years. Here's one from last year: https://www.theatlantic.com/science/archive/2021/06/the-human-genome-is-finally-complete/619172/ https://www.theatlantic.com/science/archive/2021/06/the-huma...
- dogline 5y agoYes, and I've had a hard time parsing what's different this time than last time. Anybody?
- ma2t 5y agoThe Atlantic article is based on a preprint of one of the papers now formally published in Science. They both describe the same T2T-CHM13 assembly.
- ece 5y agoThere are telomeres and centromeres on the ends and middle of chromosomes that have really long repeating sequences, which until recently were hard to sequence. This sequenced those long sequences, from a fertilized egg that apparently didn't have any female DNA. Next steps are sequencing more individuals. If this sequencing tech gets cheap enough, individualized medicine could take a big leap forward. I hope that's a good summary. https://www.washingtonpost.com/science/2022/03/31/human-genome-complete/ https://www.washingtonpost.com/science/2022/03/31/human-geno...
- ma2t 5y agoHas no male DNA (no Y chromosome), and is completely homozygous which simplified the assembly. https://web.expasy.org/cellosaurus/CVCL_VU12 https://web.expasy.org/cellosaurus/CVCL_VU12
- ece 5y agoThe cell was female, but due to a quirk, the DNA was all male? Or I'm not understanding what the WaPo article said. The genome does have a Y chromosome: https://www.ncbi.nlm.nih.gov/assembly/GCA_009914755.4#/def https://www.ncbi.nlm.nih.gov/assembly/GCA_009914755.4#/def
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- lordnacho 5y agoMaybe someone can explain what exactly it means. Are all the variants of every allele now mapped? Of course everyone might have a slightly different variant, so what does it mean? What does complete mean?
- busyant 5y agoFrom the Science article: "However, limitations of BAC cloning led to an underrepresentation of repetitive sequences, and the opportunistic assembly of BACs derived from multiple individuals resulted in a mosaic of haplotypes. As a result, several GRC assembly gaps are unsolvable because of incompatible structural polymorphisms on their flanks, and many other repetitive and polymorphic regions were left unfinished or incorrectly assembled (5)." Looks like there were "gaps" in the sequence due to technical limitations associated with the original sequencing methods and the authors have filled in those gaps. I haven't read the full paper, though.
- robwwilliams 5y agoYes.
- dekhn 5y agoNo, not all variants of every allele are now mapped. You would have to sequence a significant fraction of the human population, and imho the very idea of mapping all the variants of alleles doesn't quite square with what would be the most useful way to understand human genotype to phenotype variation.
- robwwilliams 5y agoAin’t gonna happen. Every human has unique de novo germline mutations (estimated to be in the range of 100 to 200). In addition every cell (other than RBCs) will have a small number of its own unique somatic mutations. And then there is radiation!
- 323 5y agoImagine a sequence in the DNA like this: TAAAAAAAAAAAACAAAAAAAAAAG. The way sequencing worked is the DNA is split into small parts and then they are aligned back together. But if we split the sequence above we might get these pieces: AAAAAA AAAAAA AAACAA AAAAAG TAAAAA. You know the first and last letter of each piece overlaps, but due to the high repetition count of A there is no way to figure out what the proper order is. With new techniques you generate much longer pieces, so there is much less confusion.
- carbocation 5y agoWe'll get another batch of "the human genome is complete" articles when we start publishing graph genomes.
- robwwilliams 5y agoToo cynical. Pangenomics is a different kettle if fish entirely. It attempts to provide a full view if all types of the more common and rare germline variants in a family, population, species, genus… And can be applied to cancers too.
- carbocation 5y agoAs a human geneticist, I'm not being cynical: I look forward to taking advantage of graph genomes. I'm just making a prediction about what people will say.
- inciampati 5y agoI think those will be saying "we have just begun the sequencing of the human pangenome". The problem is endless. Life on earth is huge.
- robwwilliams 5y agoOne does not “sequence” a pangenome. Pangenomes are single graphical assemblies of many diverse genomes—ideally T2T genomes. Pangenome assemblies will improve accurate health care. Pangenomes allow us to discard the kludge of a “reference” genome.
- gerdusvz 5y agonow at long last we can be... better
- yoyopa 5y agowhen can i grow a second a set of arms?
- akira2501 5y agoThat's just the Homeobox[1] genes. They're actually incredibly simple given their complex function. [1]: https://en.wikipedia.org/wiki/Homeobox https://en.wikipedia.org/wiki/Homeobox
- ineedasername 5y agoIf you're in the US you have the Constitutional right to bear's arms. I'd choose grisly bear, or maybe panda.
- astrange 5y agoBut no right to bear claws, so you have to find your own bakery.
- tyjen 5y agoEh, it's referring to base pair variations. The title is on the sensationalistic side when you consider how most lay people will interpret it. The cool stuff people imagine about in response to the title won't happen until researchers finish figuring out regulatory regions in the DNA; and, how DNA interacts with itself and environment, both spatially and temporally. Regulatory regions are promoters, enhancers, silencers, and insulators, and impact gene expression and regulation.
- ak217 5y ago> it's referring to base pair variations No. > The title is on the sensationalistic side when you consider how most lay people will interpret it. The title refers to a large scientific collaboration that has succeeded in utilizing single-molecule sequencing technology that only matured in the last 3-5 years to sequence regions of the human genome that were previously unmapped, bringing the completeness of the mapping to 100%. That doesn't seem sensationalistic.
- colordrops 5y agoThe human genome, or a human genome?
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- marcosdumay 5y agoA single one. But completely mapped.
- amelius 5y agoMan/woman?
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- Jailbird 5y agoAlmost certainly.
- mmmrtl 5y agoand yet neither "A complete hydatidiform mole (CHM)"
- tomjakubowski 5y agoThe answer is complicated. The molar pregnancy which CHM13 was made from had two copies of one man's X chromosome and, separately, the project sequenced another man's Y chromosome. https://www.science.org/content/article/most-complete-human-genome-yet-reveals-previously-indecipherable-dna https://www.science.org/content/article/most-complete-human-... The genome’s Y chromosome came from Peshkin, and the rest of the DNA sequenced by the Telomere-to-Telomere (T2T) Consortium comes from a so-called molar pregnancy, a uterine growth that results on rare occasions when a sperm enters an egg that has no chromosomes. The fertilized cell can copy the sperm’s 23 chromosomes, creating two identical sets, and begin to replicate. The question remains open of whether the owner of CHM13’s genome could be identified using public DNA sequences in genealogy databases. Phillippy thinks not because CHM13’s genome only represents one-half of that person’s DNA. Even if it were possible, NHGRI officials argue it would be unethical to reveal him for any reason, including to get consent. Because CHM13 has an X chromosome but no Y, the T2T Consortium added Peshkin’s DNA
- syngrog66 5y agoif the planet shuts down today and we all melt into a hydro-carbon haze, then, this will be why. project complete
- vaylian 5y ago> CHM13 lacks a Y chromosome, and homozygous Y-bearing CHMs are nonviable, so a different sample type will be required to complete this last remaining chromosome. (from the paper itself) It is a respectable achievement. But the Y chromosome is too important to be left out in order to call this the complete human genome.
- tonto 5y agoy-chromosome was added since the preprint was made https://twitter.com/aphillippy/status/1509594880623796226 https://twitter.com/aphillippy/status/1509594880623796226 and was made from the hg002 cell sample (which is heavily analyzed by the genome in a bottle project https://www.nist.gov/programs-projects/genome-bottle https://www.nist.gov/programs-projects/genome-bottle)
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- robwwilliams 5y agoLoL: Chr Y is famously junk DNA —to come back to the head of this amusing thread.
- sterlind 5y agowithout the SRY gene you probably wouldn't be named Rob.
- mint2 5y agoI’m bothered by the description of the history of “junk” dna. Going by this article dna, researchers labeled it junk just because they couldn’t analyze it well and prioritized the easier 92% and thus didn’t understand it. Calling it junk just seems like trying to compensate for not understanding it like “I don’t understand it but that’s fine because it’s junk anyway” And the scientist quote seems so wrong. if missing almost 10% of something when that ~10% is not like the other 90% then it seems like a very bad assumption to assume that it doesn’t show a lot of important features. The quote: “ You would think that, with 92 percent of the genome completed long ago, another eight percent wouldn’t contribute much“
- swayvil 5y agoIt's a common trope. Anything that cannot be intellectually digested is labeled "junk", ignored and, eventually, becomes invisible. You would be astonished at how much of reality falls into that category.
- robwwilliams 5y agoWrong. It is not called junk DNA out of ignorance but because we know much of it is ancient viral insertion. There is no way to cleanse the genome effectively.
- sterlind 5y agothere must be some genome-cleaning processes active, surely. otherwise wouldn't the size of all genomes slowly ratchet up in every species, until organisms just can't cope anymore and everything goes extinct? also, do you consider introns to be junk DNA? those didn't evolve from viral insertion (probably?) so though they might end up hosting "junk", presumably they're not all "junk."
- asdff 5y agoThere is a balance to genome size in terms of selection. If you have a smaller genome, mutations are more likely to have an effect, which means faster evolution (good if you are a pathogen for example). There are smaller energy requirements with replicating a smaller genome, and fewer atoms needed from the environment with shorter DNA. There is probably some optimal physical size to the nucleus, which gets larger as there is more DNA inside. Deletions can occur during cell division. A deletion bias is observed over a duplication bias: https://en.wikipedia.org/wiki/Bacterial_genome#Deletional_bias https://en.wikipedia.org/wiki/Bacterial_genome#Deletional_bi...
- csours 5y agoExcellent, now we can watch it change!
- WallyFunk 5y ago> The Human Genome Project essentially handed us the keys to euchromatin, the majority of the human genome, which is rich in genes, loosely packaged, and busy making RNA > Jarvis and Formenti hope that their contribution will not only help tie a bow on the Human Genome Project, but also inform research into diseases linked to the heterochromatic genome—chief among them cancer So the TL;DR or ELI5 version of this is this completion can help fight cancer. Had to wade through this article to get as to why we would want a complete sequencing. Any other non-obvious things we can do after this? Like perhaps life extension or other diseases we can cure?
- jahewson 5y agoCancerous cells can have a rapidly changing genome, with the heterochromatin “glue” between genes playing an important role in this, including altering how much those genes get expressed. This work has sequenced the “glue” so we know what’s supposed to be there and can better understand what’s different about cancerous cells beyond the usual gene mutations.
- mmmrtl 5y agoLiterally any genetic disease (or shortcomings like aging) could have missing facets hidden in these newly-complete regions of the genome. It's kind of the same reason you would want a complete anything, it's not ideal to go hunting for knowledge while blinded to a nonrandom 8% of the territory.
- ncmncm 5y ago"Cancer" is the gimme-funding word. It is quite doubtful that this work will enable much better cancer treatment than what we already had. But it's science. Nobody knows what might come out, which is really the point.
- robwwilliams 5y agoIt is infrastructure! What can you do with a road or a bridge?
- bendbro 5y agoIt is unfortunate we are still misdirecting funds to fruitless endeavors like genetics. As we know, genetics has little influence on your individual biology or behavior, as race is a social construct and each human shares 99.9% of their DNA with each other. Further, hegemonic tools of assigning assumed traits to people, like gender and IQ, are also social constructs, so any connection they have to genetics is moot. If we are truly interested in having a diverse, equitable understanding of people, we should instead invest in efforts that actually seek to understand them as people: therapy, rehabilitation, and decolonization work. https://www.discovermagazine.com/planet-earth/race-is-real-but-its-not-genetic https://www.discovermagazine.com/planet-earth/race-is-real-b... https://en.m.wikipedia.org/wiki/Race_and_genetics#Race_and_human_genetic_variation https://en.m.wikipedia.org/wiki/Race_and_genetics#Race_and_h... https://www.independent.co.uk/news/science/iq-tests-are-fundamentally-flawed-and-using-them-alone-to-measure-intelligence-is-a-fallacy-study-finds-8425911.html https://www.independent.co.uk/news/science/iq-tests-are-fund...
- ineedasername 5y agoIf you do a few basic searches on the applications of this knowledge then you will see that the vast majority of research & benefits that have built off of it have nothing to do with anything you mentioned here. Information about the benefits of genomic research are trivially easy to find. To get you started in general, checkout [1] below. For one of the most prominent examples-- the way it fundamentally transformed cancer research, checkout [2]. [1] https://www.google.com/search?q=genomic+research+applications https://www.google.com/search?q=genomic+research+application... [2] https://www.icr.ac.uk/news-features/latest-features/how-the-human-genome-project-shook-the-world-of-cancer-research https://www.icr.ac.uk/news-features/latest-features/how-the-...
- astrange 5y ago> As we know, genetics has little influence on your individual biology or behavior, as race is a social construct and each human shares 99.9% of their DNA with each other. The first part of your sentence doesn't follow from the second despite the second part being true. (well… the "99.9%" part is pop science bullshit.) Genomes do run in families, that being the whole point of them. And they certainly do have health effects whether they're shared with everyone or unique to you.
- ThinBold 5y agoAfter ten years of "we are getting to the last mile" and "we are finally completing", it just feels like bio people cannot give up this good reason when justifying their funding so we have to re-complete human genome every other year.
- robwwilliams 5y agoNot so. This work is real progress brought about by significant technical innovations over the last 5 years. I name three: 1. Two cool long-read sequencing technologies (PacbBio HiFi and Oxford Nanopore) 2. Hydatiform moles carrying human chromosomes for easier sequencing 3. Excellent code for assembly through complex regions of the human genome (e.g., code for assembling pangenomes by Garrison and Li).
- pabs3 5y agoHow long would it take to sequence the genome of an individual human instead of an immortal human cell line?
- mylons 5y agohow much do you want to spend? you could do it in a couple days if you use a few sequencers. how long would it take to assemble? how much do you want to spend, etc. how useful is it? not very at the moment. most analysis is still around specific variants that are understood. most function is not understood.
- robwwilliams 5y agoThe DNA prep and sequencing would take about two weeks if you worked hard using both HiFi and the latest ONP systems. Cost would be under $25,000 for great depth (about 20X for both platforms=overkill). The hard part is the de novo assembly. At least a few weeks in cottage industry mode. A few days if in full factory mode.
- mylons 5y agoI think we're on the same page. It's a matter of $$ for speed in the sequencing and analysis phases. However, the big problem that Isaac Asimov posed and is still relevant, is the understanding of the results. Having your entire genome sequence is achievable now, but understanding it isn't. As far as I know 23andMe and other services only look for a subset of well understood variants and that's it.
- astrange 5y agoNebula has a 23andMe-like service with 100x WGS and provides traits that are actually polygenic and not just SNPs, so have some hope of being causal and not random associations… but it's still practically useless for all kinds of obvious statistical bias reasons. For instance it says I'm "99th percentile genetic predisposition" for melanoma - yes, thanks, I know I'm Scottish - and left-handedness, which I'm not.
- robwwilliams 5y agoNot quite: Centromeres are still a messy tangle of repeats sequence. Give it a few more years.
- stolsvik 5y ago“Junk DNA”, i.e. “non-coding DNA”, are the code segments of the DNA, while the “coding DNA” (“non-junk”) are the data segments. As a programmer, I find the code segments the most interesting.
- pmarreck 5y agoWhere can I download it? (I still have a copy of the originally-announced one from like 20 years ago, somewhere...)