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Important note: whole genome does not mean whole DNA. Their claim to sequence 100% of the genome could not be true if it was 100% DNA, as some locations like n

Important note: whole genome does not mean whole DNA. Their claim to sequence 100% of the genome could not be true if it was 100% DNA, as some locations like near the centromere or the telomeres are notoriousy difficult to sequence (and just impossible with the technique of alignment that they use). It's not that bad, you can already know a lot of interesting things with a whole genome, but it won't be enough information to e.g. synthesize a copy of your DNA or be able to repair all of your adult cell's genetic damages (supposing this kind of tech exists in some future). There are also more and more research on how the introns (DNA not in some gene) participate in the regulation of genes and are involved in many diseases. I'd like to see some real (and affordable) 100% DNA sequencing in a near future! Edited: s/exon/intron/

aroch 4y ago
I have no skin in this particular game (Though I work in the sequencing industry), but... I don't think anyone is fooled/trying to trick anyone when they say "whole genome sequencing" or that they sequence 100% of the genome. That is the term of art for non-targeted/unenriched sequencing of DNA (nb: it may be RNA/ribosome depleted, so fine it's technically enriched but not in a meaningful way). Also exons are genic region, are you thinking introns (arguably genic or at least adjacent), or promoters/enhancers and chromatin state?
- henearkr 4y ago
  Thanks, I've fixed the mistake s/exon/intron/.
brofallon 4y ago
Just to clarify, exons are the portions of genes that code for protein sequence (they are expressed). Introns span the distance between exons and may contain regulatory or splicing information. Areas between genes are referred to as intergenic, and also may contain regulatory sequences that affect how genes are expressed. Part of the issue with centromeric or telomeric sequence is that not only is it hard to sequence (being super repetitive), little is known about what a sequence variant in such an area might mean. It's kind of a chicken-and-egg issue: it doesn't get much attention because no one knows how to interpret variants there, and since no one knows how to interpret variants there it doesn't get much attention
mbreese 4y ago
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

aroch 4y ago

I have no skin in this particular game (Though I work in the sequencing industry), but... I don't think anyone is fooled/trying to trick anyone when they say "whole genome sequencing" or that they sequence 100% of the genome. That is the term of art for non-targeted/unenriched sequencing of DNA (nb: it may be RNA/ribosome depleted, so fine it's technically enriched but not in a meaningful way). Also exons are genic region, are you thinking introns (arguably genic or at least adjacent), or promoters/enhancers and chromatin state?

henearkr 4y ago
Thanks, I've fixed the mistake s/exon/intron/.

brofallon 4y ago

Just to clarify, exons are the portions of genes that code for protein sequence (they are expressed). Introns span the distance between exons and may contain regulatory or splicing information. Areas between genes are referred to as intergenic, and also may contain regulatory sequences that affect how genes are expressed. Part of the issue with centromeric or telomeric sequence is that not only is it hard to sequence (being super repetitive), little is known about what a sequence variant in such an area might mean. It's kind of a chicken-and-egg issue: it doesn't get much attention because no one knows how to interpret variants there, and since no one knows how to interpret variants there it doesn't get much attention

mbreese 4y ago

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