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Just to pile on to the existing comments... if you're getting the raw FASTQ files, you will have telomeric and centromeric DNA sequences. You just won't necessa

Just to pile on to the existing comments... if you're getting the raw FASTQ files, you will have telomeric and centromeric DNA sequences. You just won't necessarily be able to accurately align the data. Sequencing those regions is easy... you just can't assemble the data into larger contiguous regions because of the lack of variation. And given the consistency of those regions, you will have 99(.999)% of all of the information you would need to make a copy of your DNA. There are some regions that are difficult to sequence, but the major problem isn't getting the raw sequence, but the alignment process.

henearkr 4y ago
Then that's an annoying ambiguity in the word sequencing. If sequencing is the technique, then it's true that you can sequence anywhere in the DNA, but the technique will not always be able to give you the actual DNA sequence, in particular for centromeres or telomeres. If sequencing meant "find out the DNA sequence", which is what people are actually buying, then it is just false that you can "sequence" anywhere in the chromosomes.
- mbreese 4y ago
  No, it does give you the sequence… what it doesn’t give you is the context. The WGS data we’re talking about here only give you two 150bp fragments. You know these fragments are 100-300bp away from each other, but that’s it. There are other techniques for getting more of the context, but that’s not the WGS we are talking about here. It’s like copying pages from a book, but without page numbers. And some pages might be copied more than once. Or not at all (Poisson statistics FTW!). You can get fragments of stories, and can probably get the gist of the plot. But this might not give you an exact copy of the full book, in the right order. To keep going with the analogy — what you’re asking for (telomeres and centromeres) would be the equivalent of placing every “this page left intentionally blank” page in the right place. Even though, they are all quite similar. You will be able to “copy” (sequence) each of these pages, but putting them in the right order is still difficult.
  - henearkr 4y ago
    You sum up exactly the problem: the WSG technique does not give the whole global sequence of bases, from telomere to telomere through all of the centromere and for each chromosome branch. This is what I would like to see as an affordable product: get the whole sequence, so that ultimately one could theoretically re-synthesize their own chromosomes in the future. And get it now that we are still young and there is not too much damage in the DNA, information to be stored for later. One point in what you wrote: the blank pages (introns) can be really important (like for gene expression regulation, through chromatine folding, or promoters of transcription), we just can't be sure, and that's why it is paramount (when thinking of chromosomes synthesis applications) to have it all. About the specifics of our discussion: Again, ambiguity! Because we're saying the same thing. When I say it does not give the sequence, I mean the whole sequence (not only local subsequences), which means including the context. (Although the notion of context is actually meaningful only if we are talking about local subsequences, as the global sequence is the context (or includes the context, if we reduce "context" to mean the reference global sequence against which the subseqs are aligned)). Of course with your meaning you are right.
    - yellowcake0 4y ago
      This really is putting the cart before the horse though, we will have whole genome assembly technology long before we understand functional genomics well enough to do the type of restorative genetic engineering that you propose.
      - henearkr 4y ago
        Well you're right but the idea of getting all of the DNA information is precisely to be sure to not rely on what we think we know, so that if in the future we discover that previously thought useless parts are meaningful we would already have them in store (gathered long before the DNA gets damaged by age). Once we have everything, we can apply additional knowledge to this data as soon as it is discovered and without needing to do more sequencing.
    - mbreese 4y ago

henearkr 4y ago

Then that's an annoying ambiguity in the word sequencing. If sequencing is the technique, then it's true that you can sequence anywhere in the DNA, but the technique will not always be able to give you the actual DNA sequence, in particular for centromeres or telomeres. If sequencing meant "find out the DNA sequence", which is what people are actually buying, then it is just false that you can "sequence" anywhere in the chromosomes.

mbreese 4y ago
No, it does give you the sequence… what it doesn’t give you is the context. The WGS data we’re talking about here only give you two 150bp fragments. You know these fragments are 100-300bp away from each other, but that’s it. There are other techniques for getting more of the context, but that’s not the WGS we are talking about here. It’s like copying pages from a book, but without page numbers. And some pages might be copied more than once. Or not at all (Poisson statistics FTW!). You can get fragments of stories, and can probably get the gist of the plot. But this might not give you an exact copy of the full book, in the right order. To keep going with the analogy — what you’re asking for (telomeres and centromeres) would be the equivalent of placing every “this page left intentionally blank” page in the right place. Even though, they are all quite similar. You will be able to “copy” (sequence) each of these pages, but putting them in the right order is still difficult.
- henearkr 4y ago
  You sum up exactly the problem: the WSG technique does not give the whole global sequence of bases, from telomere to telomere through all of the centromere and for each chromosome branch. This is what I would like to see as an affordable product: get the whole sequence, so that ultimately one could theoretically re-synthesize their own chromosomes in the future. And get it now that we are still young and there is not too much damage in the DNA, information to be stored for later. One point in what you wrote: the blank pages (introns) can be really important (like for gene expression regulation, through chromatine folding, or promoters of transcription), we just can't be sure, and that's why it is paramount (when thinking of chromosomes synthesis applications) to have it all. About the specifics of our discussion: Again, ambiguity! Because we're saying the same thing. When I say it does not give the sequence, I mean the whole sequence (not only local subsequences), which means including the context. (Although the notion of context is actually meaningful only if we are talking about local subsequences, as the global sequence is the context (or includes the context, if we reduce "context" to mean the reference global sequence against which the subseqs are aligned)). Of course with your meaning you are right.
  - yellowcake0 4y ago
    This really is putting the cart before the horse though, we will have whole genome assembly technology long before we understand functional genomics well enough to do the type of restorative genetic engineering that you propose.
    - henearkr 4y ago
      Well you're right but the idea of getting all of the DNA information is precisely to be sure to not rely on what we think we know, so that if in the future we discover that previously thought useless parts are meaningful we would already have them in store (gathered long before the DNA gets damaged by age). Once we have everything, we can apply additional knowledge to this data as soon as it is discovered and without needing to do more sequencing.
  - mbreese 4y ago