Hacker News Board Hacker News, browsed like a classic message board
Live data from Hacker News

No human genome has ever been completely sequenced

statnews.com

Post reply on HN
Print view View original

21–30 of 96 posts

Re: No human genome has ever been completely sequenced

#21

Post by khedoros1 »

slavik81 wrote: post #13
hprotagonist wrote: post #2

what do you mean, "the" human genome?

The was flag killed. I vouched for this because I had the same question. What does it mean to have sequenced the human genome? If different individuals have a different genome, what is the human genome?

From Wikipedia: "The "genome" of any given individual is unique; mapping the "human genome" involved sequencing a small number of individuals and then assembling these together to get a complete sequence for each chromosome. Therefore, the finished human genome is thus a mosaic, not representing any one individual."

Members of a species share most of their genetic material with each other, but there are known areas of high variability between individuals. So to build a specific individual's sequence, it seems like they take the baseline "human genome" data, and overlay the areas that are known to change.

Re: No human genome has ever been completely sequenced

#22

Post by cycrutchfield »

iskander wrote: post #3

It's strange that this article ends as an advertisement for PacBio sequencing (which can ~50k-60k base reads) but makes no mention of Oxford Nanopore (which has gotten megabase reads and keeps improving). Single molecule nanopore sequencing is on track to sequence across the centromeres of human chromosomes in the next few years.

How many sequencers has Oxford Nanopore sold? It seems like it has perennially been a “in the next few years” technology.

Re: No human genome has ever been completely sequenced

#24

Post by toufka »

grabcocque wrote: post #9

One of the things the HGP revealed is that we have way fewer genes than anyone expected. Given that the amount of data encoded in genes appears to be far too small to account for the sophistication and variability in humans, it strongly implied that large areas of DNA that were previously considered marker/filler DNA were of great epigenetic importance.

There are also a lot more steps between 'genomic dna' -> 'protein' than was previously appreciated or thought to be of importance. There are a lot of ways to regulate and produce new protiens and variation that is not itself a genomic change.

Alternative splicing, readthrough regulaton, multiple kinds of ribosomes, post-translational regulation, etc. all produce significant variation outside of the dna itself.

Re: No human genome has ever been completely sequenced

#25

Post by coldtea »

phyzome wrote: post #14
coldtea wrote: post #4

In other words they don't know what they're doing and they're making it up as they go along -- "yeah, that part there is probably unused", "oh, wait, it's important after all".

As the article says, we know there's important stuff in those repetitive regions, it's just really hard to read.

Well: "“A lot of people in the 1980s and 1990s [when the Human Genome Project was getting started] thought of these regions as nonfunctional,” said Karen Miga, a molecular biologist at the University of California, Santa Cruz. “But that’s no longer the case.” "

And: "“I’m between agnostic and a little skeptical that these bits will be important for disease, but maybe I’m saying that because we can’t read them,” Lander said.".

Re: No human genome has ever been completely sequenced

#26

Post by sctb »

xj9 wrote: post #10
coldtea wrote: post #4

In other words they don't know what they're doing and they're making it up as they go along -- "yeah, that part there is probably unused", "oh, wait, it's important after all".

yes, that's kind of the idea of doing research. you know, to learn things that we don't know yet. or did you think science was a book of unambiguous answers that only the godly scientist may read?

Please leave the name-calling out of comments, like the guidelines ask.

https://news.ycombinator.com/newsguidelines.html

Re: No human genome has ever been completely sequenced

#27

Post by nether »

shpx wrote: post #12
jessriedel wrote: post #6

As usual, the journalist spends many paragraphs painting a picture of human conflict before actually getting on to the interesting claim. > The reason for these gaps is that DNA sequencing machines don’t read genomes like humans read books, from the first word to the last. Instead, they first randomly chop up copies of the 23 pairs of chromosomes, which total some 3 billion “letters,” so the machines aren’t overwhelm…

https://youtu.be/fCd6B5HRaZ8 is the best visualization of how the most popular type of DNA sequencer works (that I've found). Imagine you have a string of length 3 billion made by randomly choosing from 4 characters. Like this dna = ''.join(random.choices('atgc', weights=[30.9, 29.4, 19.9, 19.8], k=3_234_830_000)) you get to randomly sample 1 billion[3, page 7] overlapping substrings of length 200[3, page 7] with .1%…

Side note: your comment is one of the few times I've seen the code tag used for actual code on HN, rather than quotations or just indentation.

Re: No human genome has ever been completely sequenced

#28

Post by [deleted] »

cycrutchfield wrote: post #22
iskander wrote: post #3

It's strange that this article ends as an advertisement for PacBio sequencing (which can ~50k-60k base reads) but makes no mention of Oxford Nanopore (which has gotten megabase reads and keeps improving). Single molecule nanopore sequencing is on track to sequence across the centromeres of human chromosomes in the next few years.

How many sequencers has Oxford Nanopore sold? It seems like it has perennially been a “in the next few years” technology.

[deleted]

Re: No human genome has ever been completely sequenced

#29

Post by throwanem »

chrisamiller wrote: post #15
slavik81 wrote: post #13

Earlier quoted context omitted.

The was flag killed. I vouched for this because I had the same question. What does it mean to have sequenced the human genome? If different individuals have a different genome, what is the human genome?

You're right, and the next frontier in genome assembly and mapping algorithms is using graph-based genomes, where differences between individuals or populations can represented as different paths through a sequence graph. (There are lots of better explanations with pretty pictures out there with a little searching)

That's more of a representation problem, isn't it? I'm not seeing where it would require any new development to produce such a graph - just a lot of CPU time to assemble one from a collection of FASTA files, or whatever linear representation. (And a lot of wall-clock time, to convince people to use it...)

Re: No human genome has ever been completely sequenced

#30

Post by coolnow »

cycrutchfield wrote: post #22
iskander wrote: post #3

It's strange that this article ends as an advertisement for PacBio sequencing (which can ~50k-60k base reads) but makes no mention of Oxford Nanopore (which has gotten megabase reads and keeps improving). Single molecule nanopore sequencing is on track to sequence across the centromeres of human chromosomes in the next few years.

How many sequencers has Oxford Nanopore sold? It seems like it has perennially been a “in the next few years” technology.

I'm not sure how many they've actually sold but i do know that they have a loan/test program where you can pay a relatively small amount (around $2000 or less) to get set up with a MinION kit. The main recurring cost is the flow cell. I'm currently trying to figure out how to join together short multiplexed samples (150bp - 200bp) and get it sequenced on the MinION. Current short-read sequencers from Illumina or ThermoFisher cost orders of magnitude more than Oxford Nanopore's offering. Hopefully someone else is trying to use the platform for short reads.
Post reply on HN