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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 d

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?

chrisamiller 9y ago
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)
- throwanem 9y ago
  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...)
  - chrisamiller 9y ago
    Right - It's not so much algorithmic development as development of the toolchains that will enable such representations to be actually useful for downstream analyses.
grzm 9y ago
The article acknowledges this, though perhaps obliquely: > “As a matter of truth in advertising, the ‘finished’ sequence isn’t finished,” said Eric Lander, who led the lab at the Whitehead Institute that deciphered more of the genome for the government-funded Human Genome Project than any other. “I always say ‘finished’ is a term of art.” The phrasing of your parent is arguably dismissive and does little to further substantive discussion. Can one meaningfully discuss "the human genome"? As you point out, each human (with the exception of identical twins) has a unique genome. I think it's reasonable and useful to be able to say "the human genome" as opposed to "the chimpanzee genome" or "the drosophila genome". If one would rather insist on using the indefinite article, i.e., "a human genome", one can present it without resorting to a rhetorical question replete with scare quotes.
nonbel 9y ago
Not only do different individuals have different genomes, each cell from the same person will have different genomes. It is more like an "average" human genome, one that no actual cell has ever contained.
- deleted 9y ago
  [deleted]
- viewtransform 9y ago
  "each cell from the same person will have different genomes" Did you mean each cell will have different gene expression ? I thought all the cells have the same nucleotide sequences barring maybe occasional mutations (like in cancer)
  - nonbel 9y ago
    Mutation rates are high enough that we should expect at least a few every division. There are supposedly n~6e9 base pairs[1] and mutation rate is said to be p~1e-8 per bp per division[2]. Assuming each mutation is independent, etc, etc we get a back of the napkin via the binomial distribution with mean = n*p ~ 60 mutations per division. [1] https://en.wikipedia.org/wiki/Human_genome https://en.wikipedia.org/wiki/Human_genome [2] https://en.wikipedia.org/wiki/Mutation_rate https://en.wikipedia.org/wiki/Mutation_rate
    - chrisamiller 9y ago
      Most estimates I'm familiar with are substantially lower than that - between 0.1 and 3 errors per cell division.
      - nonbel 9y ago
        Thanks, actually the wikipedia link was "per generation" and they assume ~ 100 divisions/mitoses per human generation. So it should be 1e-10 mutations/bp/division. However, that is for germline, somatic mutation rates are apparently 10-100x more more common: https://www.nature.com/articles/ncomms15183 https://www.nature.com/articles/ncomms15183 These rates no doubt vary by cell type, environment, etc. I was actually thinking something like 1e-6 to 1e-10 mutations/bp/division.
khedoros1 9y ago
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.

chrisamiller 9y ago

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)

throwanem 9y ago
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...)
- chrisamiller 9y ago
  Right - It's not so much algorithmic development as development of the toolchains that will enable such representations to be actually useful for downstream analyses.

grzm 9y ago

The article acknowledges this, though perhaps obliquely: > “As a matter of truth in advertising, the ‘finished’ sequence isn’t finished,” said Eric Lander, who led the lab at the Whitehead Institute that deciphered more of the genome for the government-funded Human Genome Project than any other. “I always say ‘finished’ is a term of art.” The phrasing of your parent is arguably dismissive and does little to further substantive discussion. Can one meaningfully discuss "the human genome"? As you point out, each human (with the exception of identical twins) has a unique genome. I think it's reasonable and useful to be able to say "the human genome" as opposed to "the chimpanzee genome" or "the drosophila genome". If one would rather insist on using the indefinite article, i.e., "a human genome", one can present it without resorting to a rhetorical question replete with scare quotes.

nonbel 9y ago

Not only do different individuals have different genomes, each cell from the same person will have different genomes. It is more like an "average" human genome, one that no actual cell has ever contained.

deleted 9y ago
[deleted]
viewtransform 9y ago
"each cell from the same person will have different genomes" Did you mean each cell will have different gene expression ? I thought all the cells have the same nucleotide sequences barring maybe occasional mutations (like in cancer)
- nonbel 9y ago
  Mutation rates are high enough that we should expect at least a few every division. There are supposedly n~6e9 base pairs[1] and mutation rate is said to be p~1e-8 per bp per division[2]. Assuming each mutation is independent, etc, etc we get a back of the napkin via the binomial distribution with mean = n*p ~ 60 mutations per division. [1] https://en.wikipedia.org/wiki/Human_genome https://en.wikipedia.org/wiki/Human_genome [2] https://en.wikipedia.org/wiki/Mutation_rate https://en.wikipedia.org/wiki/Mutation_rate
  - chrisamiller 9y ago
    Most estimates I'm familiar with are substantially lower than that - between 0.1 and 3 errors per cell division.
    - nonbel 9y ago
      Thanks, actually the wikipedia link was "per generation" and they assume ~ 100 divisions/mitoses per human generation. So it should be 1e-10 mutations/bp/division. However, that is for germline, somatic mutation rates are apparently 10-100x more more common: https://www.nature.com/articles/ncomms15183 https://www.nature.com/articles/ncomms15183 These rates no doubt vary by cell type, environment, etc. I was actually thinking something like 1e-6 to 1e-10 mutations/bp/division.

khedoros1 9y ago

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.