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It's infuriating to read about DNA fingerprinting being used such critical cases when DNA sequencing could be used to far more accurately and robustly compare s

by new299 10y ago

It's infuriating to read about DNA fingerprinting being used such critical cases when DNA sequencing could be used to far more accurately and robustly compare sample and targets identities. Fingerprinting uses common relatively large changes in the genome as proxy for an individuals identity. It uses these locations because that's what you could do in the 1980s easily. It's possible to screw up both the experiments and interpenetration relatively easily. Technology has moved on, you can now sequence a complete genome for around 1000USD. Comparing complete genomes would unambiguously assign identity. You'd effectively just be doing a string comparison over two very long, unique, strings. The only reason we still use fingerprinting is that forensics is highly conservative. I'd guess it'll take at least another 10 years for them to move to sequencing (if not longer). It is however infuriating.

viraptor 10y ago
> Comparing complete genomes would unambiguously assign identity. Would we ever get full genomes from any sample though? As far as I remember, most sequencing doesn't happen on full strings. Instead, many pieces are first unwound, then split into pieces, then sequenced one after another and the whole genome is reconstructed from overlaps. So that's still assuming you have enough samples that you can reconstruct the whole string. And that you can tell the samples apart if you have a mixture like in the first case from the article.
- bhickey 10y ago
  It looks like the lower bound for commercial whole genome sequencing is about 250 nanograms. To put this in perspective, you can get 4000 nanograms of DNA from a 2 microlitre blood draw. Your mental model of sequencing needs an update. :) Prior to sequencing, DNA is amplified via PCR. This dramatically increases the amount of DNA you have (2^30, iirc.)
  - new299 10y ago
    Yes, I've seen single cell preps too. So it basically just depends on your sample prep and what's practical (and what you can put into production). However you do it, as you say there's a bunch of amplification that happens prior to sequencing (currently).
  - dekhn 10y ago
    PCR also amplifies the noise, and in a nonlinear way, especially with very small samples.
  - viraptor 10y ago
    You're talking about a clean blood draw though. I don't know how well it compares to dried cells you left somewhere for hours which are possibly mixed with many other people's cells. Do you have information about that?
pbhjpbhj 10y ago
Whatabout identical twins, chimaera, ... Also, in practice you'd be doing partial string matches presumably.
- new299 10y ago
  Yes, there would be rare edge cases. But they should be rare and well characterized. Unlike the current situation. Practically how the comparison is done depends on the informatics (yes it's unlikely to be implemented as a X~million symbol string match, more likely as comparing lists of called SNPs against a reference).
- new299 10y ago
  One other point about twins. Twins while genetically similar, are not identical [1]. I'd guess that the differences are still significant enough to be able to assign identity through whole genome sequencing. [1] http://www.scientificamerican.com/article/identical-twins-genes-are-not-identical/ http://www.scientificamerican.com/article/identical-twins-ge...
  - pbhjpbhj 10y ago
    Your citations says: >"Geneticist Carl Bruder of the University of Alabama at Birmingham, and his colleagues closely compared the genomes of 19 sets of adult identical twins. In some cases, one twin's DNA differed from the other's at various points on their genomes. At these sites of genetic divergence, one bore a different number of copies of the same gene, a genetic state called copy number variants." // So, it's "in some cases" monozygotic twins differ by having copy number variants [TIL! thanks]. So, not all cases (according to this citation) and so the point still stands that "Comparing complete genomes would unambiguously assign identity" appears to be false (albeit at a very low false match rate). Interestingly the article says that copy number variants appear to arise as a subject ages. Doesn't this mean that different cells in the body will have different multiples of particular genes; so a mismatch wouldn't necessarily mean that the DNA wasn't from the same twin?

by new299 10y ago

viraptor 10y ago

> Comparing complete genomes would unambiguously assign identity. Would we ever get full genomes from any sample though? As far as I remember, most sequencing doesn't happen on full strings. Instead, many pieces are first unwound, then split into pieces, then sequenced one after another and the whole genome is reconstructed from overlaps. So that's still assuming you have enough samples that you can reconstruct the whole string. And that you can tell the samples apart if you have a mixture like in the first case from the article.

bhickey 10y ago
It looks like the lower bound for commercial whole genome sequencing is about 250 nanograms. To put this in perspective, you can get 4000 nanograms of DNA from a 2 microlitre blood draw. Your mental model of sequencing needs an update. :) Prior to sequencing, DNA is amplified via PCR. This dramatically increases the amount of DNA you have (2^30, iirc.)
- new299 10y ago
  Yes, I've seen single cell preps too. So it basically just depends on your sample prep and what's practical (and what you can put into production). However you do it, as you say there's a bunch of amplification that happens prior to sequencing (currently).
- dekhn 10y ago
  PCR also amplifies the noise, and in a nonlinear way, especially with very small samples.
- viraptor 10y ago
  You're talking about a clean blood draw though. I don't know how well it compares to dried cells you left somewhere for hours which are possibly mixed with many other people's cells. Do you have information about that?

pbhjpbhj 10y ago

Whatabout identical twins, chimaera, ... Also, in practice you'd be doing partial string matches presumably.

new299 10y ago
Yes, there would be rare edge cases. But they should be rare and well characterized. Unlike the current situation. Practically how the comparison is done depends on the informatics (yes it's unlikely to be implemented as a X~million symbol string match, more likely as comparing lists of called SNPs against a reference).
new299 10y ago
One other point about twins. Twins while genetically similar, are not identical [1]. I'd guess that the differences are still significant enough to be able to assign identity through whole genome sequencing. [1] http://www.scientificamerican.com/article/identical-twins-genes-are-not-identical/ http://www.scientificamerican.com/article/identical-twins-ge...
- pbhjpbhj 10y ago
  Your citations says: >"Geneticist Carl Bruder of the University of Alabama at Birmingham, and his colleagues closely compared the genomes of 19 sets of adult identical twins. In some cases, one twin's DNA differed from the other's at various points on their genomes. At these sites of genetic divergence, one bore a different number of copies of the same gene, a genetic state called copy number variants." // So, it's "in some cases" monozygotic twins differ by having copy number variants [TIL! thanks]. So, not all cases (according to this citation) and so the point still stands that "Comparing complete genomes would unambiguously assign identity" appears to be false (albeit at a very low false match rate). Interestingly the article says that copy number variants appear to arise as a subject ages. Doesn't this mean that different cells in the body will have different multiples of particular genes; so a mismatch wouldn't necessarily mean that the DNA wasn't from the same twin?