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Biotech Science

DNA Differences Observed Between Blood and Organs 85

Posted by kdawson from the same-old-same-old dept.
Scrameustache writes "Researcher working on a rare type of aortic abnormality found that the DNA from diseased tissue did not match the DNA from the blood of the same patients So far it's unclear whether these differences in the blood and aortic tissue are the consequence of RNA editing, which changes the messenger RNA but not the gene, or DNA editing, which involves differences in the gene itself. Based on the evidence so far, the researchers believe the differences resulted from developmental rather than somatic DNA alterations. 'Traditionally when we have looked for genetic risk factors for, say, heart disease, we have assumed that the blood will tell us what's happening in the tissue,' lead author Bruce Gottlieb said in a statement. 'It now seems this is simply not the case.'"
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DNA Differences Observed Between Blood and Organs More

DNA Differences Observed Between Blood and Organs

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  • Chimera (Score:4, Interesting)

    by John Hasler ( 414242 ) on Sunday July 19, 2009 @05:00PM (#28750115) Homepage
    Perhaps some of those patients were chimeras [wikipedia.org].

    • Re: (Score:1, Insightful)

      by Anonymous Coward
      Don't be ridiculous. Obviously the devil wanted to trick the scientists to think that blood and organs could have slightly different DNA. Or maybe god just made it that way so that the scientists could have something to discover! Yeah, yeah that's the ticket.
    • Maybe. But then again, mutations happen in our body all the time. Sometimes they are detrimental to the cell's functioning, in which case the cell either repairs it or kills itself. Sometimes they are neoplastic, in which case the cell develops into a tumour cell and either thrives or is killed by the immune system. Sometimes the mutations don't matter much (i.e. the mutant protein functions like the original one), in which case we may see a situation where there exists different versions of genes within on

    • Re: Mosaic (Score:4, Interesting)

      by nbauman ( 624611 ) on Sunday July 19, 2009 @08:10PM (#28751369) Homepage Journal
      Actually TFA did raise the possibility of chimeras. My thought was that it could be a mosaic http://en.wikipedia.org/wiki/Mosaic_(genetics) [wikipedia.org]

      People sometimes get mosaicism after stem cell transplants or organ transplants.

      I saw an interesting example of mosaicism in a medical journal. An infant was born with half male genitals, half female genitals. The most obvious explanation was that he/she was born of two embryos, one male, the other female, that combined at an early stage (but not too early) and formed a mosaic individual, with patches of male and female cells. Mosaicism actually is pretty common in biology. Sometimes you get patches of skin that vary between 2 colors. The later the embryo recombines, the bigger the patches are.

      But this raises the possibility that the DNA of the cells in one developmental branch -- the arteries, or the aorta -- goes through some epigenetic doubling, on a routine basis, because it happened in several samples, even healthy tissue. I wonder if it happens in mice.

      My understanding of the article was that they sequenced DNA -- both strands -- not the RNA. But for reasons I don't understand, Schweitzer said it might be the consequences of RNA editing, to the messenger RNA.

      Actually they got into chimerizaton at the end of TFA:

      In an e-mail message to GenomeWeb Daily News, Navigenics Co-founder and Chief Science Officer Dietrich Stephan said the team's work is interesting and deserves further investigation.

      "Differences between the germ-line genome and somatic cells is well established in cancer. It is also well described that chimeras can result from early DNA changes in early embryonic development that propagate to form regional differences in the genome across the body," Stephan noted.

      • My understanding of the article was that they sequenced DNA -- both strands -- not the RNA. But for reasons I don't understand, Schweitzer said it might be the consequences of RNA editing, to the messenger RNA.

        From the paper published in the journal Human Genetics [doi.org] (subscription required), the authors sequenced the mRNA from aortic tissue and genomic DNA from the blood of individuals. To sequence mRNA, researchers must first extract the mRNA from cells and convert the mRNA into a DNA sequence (called complementary DNA or cDNA) using the enzyme Reverse Transcriptase. The reason why we do this is because DNA is much more stable than RNA (our bodies contain many enzymes that rapidly degrade RNA. These enzymes ar

        • Re: (Score:2)

          by RDW ( 41497 )

          'Because the authors of the study looked only at the mRNA from the aortic tissue, they cannot exclude the possibility that the mutations in the mRNA arose from RNA editing, and not somatic mutation. It seems like it would have been fairly simple to sequence the genomic DNA from the aortic tissue, and I'm curious as to why the authors did not perform these analyses'

          Indeed. It's pretty hard to know what, if anything, to conclude from this paper as it's not making a like-for-like comparison. It seems quite pos

      • I saw an interesting example of mosaicism in a medical journal. An infant was born with half male genitals, half female genitals. The most obvious explanation was that he/she was born of two embryos, one male, the other female, that combined at an early stage (but not too early) and formed a mosaic individual, with patches of male and female cells. Mosaicism actually is pretty common in biology. Sometimes you get patches of skin that vary between 2 colors. The later the embryo recombines, the bigger the patches are.

        That has nothing to do with recombining of the embryo (don't know about the story You mention, there it can be an explanation, I am talking about the 2 color story, e.g. a cow or a dog, and mosaicism in general), the different patches exist because of mutations in one embryo. These mutated cells will divide just as the not mutated ones. And the sooner these mutations occur, the bigger the patches will be. And You don't need a stem cell or organ transplant to get mosaicism, You get it in the woomb.

    • Re: (Score:2)

      by smchris ( 464899 )

      My first thought too. The question is whether they sequenced _only_ for the BAK anomaly or whether they looked for other differences -- like whether the diseased tissue was from the patient's mother and not thriving in the patient's body.

  • complexity (Score:2, Funny)

    by martas ( 1439879 )
    is there an end to the human body's complexity? first they tell us dna has all the answers, then they tell us its dna + environment, then they find out its genes + weird stuff everyone thought was garbage and didn't have any functions, now this? WILL IT EVER END?

    • Re: (Score:3, Informative)

      by Darkness404 ( 1287218 )
      In short, no. However, I do think there will be a point where we can know enough to figure out all the known illnesses, however there will always be new ones.

    • Re: (Score:1)

      by Pandare ( 975485 )
      Yeah, probably. My guess is nukes or monoculture domination.
    • >is there an end to the human body's complexity?

      uuhmm... death? I recently, (the past +2yrs), tried to review and fathom the whole 'What is Life?' issue. I came up all but dumb but did come away with a new way to look at the issues. First developmental biology provides a compartment in terms of the initial programme. I found evo-devo (evolutionary biology) to be a big boon in terms of grasping the how of the what, so to speak. R. Raff's book 'The Shape of Life' is a good starting point. 'Fins into Li

      • Re: (Score:3, Funny)

        by nbauman ( 624611 )

        I came away envisioning our genetic programme as a Bach Fugue that develops various voices from an initial set of themes.

        More like John Cage.

    • Re: (Score:2, Interesting)

      by jeffliott ( 1558799 )

      Unfortunately, yes, if there is nothing magical about the chemistry that occurs in our bodies. This is unfortunate because at some point, we will stop being interesting to look at. However, the idea of a disease free world is probably well worth it, and we shouldn't be discouraged to keep trying to figure this stuff out simply because it is getting harder.

      • Re: (Score:1)

        by martas ( 1439879 )
        although understanding and fixing are two very different things. even if i know exactly what's in a broken piece of glass doesn't mean i can put it back together.

        • Oh and preventing! Don't tell me about preventing!

          Try to find one single doctor who will without asking tell you how to prevent what you got, and what the external (!) source is! I dare you!

          Because I can't find one.

      • Re: (Score:2, Insightful)

        by E++99 ( 880734 )

        Just because there is "nothing magic" doesn't imply that we will ever understand it all.

    • it's complex for sure but also *understandable*. The same mechanisms are responsible for our development as a species as before just now we understand more about the system than we did previously.

      • Good luck with that "understanding". There are plenty of "emergent" properties of complex systems, not predictable from the simpler rules used to create the physical basis of it, but which emerge as the system grows in size, duration, or complexity.
  • what happened to the days of pre-history and we didnt need this, we just ate grass if we didnt feel good

    • Re: (Score:3, Insightful)

      by fuzzyfuzzyfungus ( 1223518 )
      We died, a lot, mostly early.

    • Re: (Score:2, Interesting)

      by designlabz ( 1430383 )
      Well, i guess, medicine is what happened. In the "good old days" if you were seriously messed up on birth, you would simply die. But now days, doctors can patch you up, so you give birth to more messed up humasn, that will then breed with healthy humans, and eventually create a race where no one is really healthy. That is called backward evolution and is nicely described in Idiocracy ( http://www.imdb.com/title/tt0387808/ [imdb.com] ). Some people would call it inhuman or sick, but in my humble opinion medicine shoul

      • Re:good old days (Score:4, Insightful)

        by Anonymous Coward on Sunday July 19, 2009 @06:15PM (#28750675)

        Not all mutations are "all good" or "all bad". Granted, many are instantly fatal others cancerous, and some serve no known purpose. But to propose that we should limit the genetic diversity to include only genes that we currently think are "good" is foolhardy. Our species - or it's descendants - are best served by having a large base of mutations in the inventory. This way, when nature throws us a curveball, we may have an existing population of humans with the genetics to survive. For example, there are supposedly some tribes in the Amazon who have a mild form of Cystic Fibrosis, which prevents them from sweating their salt out. It seems like a bad idea, until you consider they are living in an extreme environment where sweating is a poor method of cooling due to the high dew point, and it would kill most "healthy" people who lived there. Malaria resistance is improved by being a heterozygous carrier for sickle cell anemia. Et cetera.

        As for your link, I see your IMDB and raise you an XKCD (http://xkcd.com/603/).

        • Re: (Score:1, Flamebait)

          by znerk ( 1162519 )

          As for your link, I see your IMDB and raise you an XKCD (http://xkcd.com/603/).

          And as for your link [xkcd.com], I see you failed. Don't worry too much about it, though... basic HTML escapes many people.

      • Re: (Score:1)

        by maxume ( 22995 )

        Don't worry, the 6.5 billion relatively healthy people are still breeding a hell of a lot faster than the 500 million people that are made out of goo.

        Basically, if you actually see the prevalence of certain genes increasing, start to worry. Until then, don't worry about it. If you are really worried about it, screen your partner.

      • Re: (Score:1, Insightful)

        by Anonymous Coward

        Please don't say "backwards evolution". I know what you mean, and you know what you mean, but it confuses a lot of people who don't fully understand evolution into thinking that evolution has a direction, while we know that it does not.

      • Not to put too find a point on it, but you are an idiot.

        Evolution does not have a direction.

        Let me repeat that, in all caps:

        EVOLUTION DOES NOT HAVE A DIRECTION.

        There's no such thing as 'backward' evolution, or 'forward' evolution, or 'sideways' evolution. Evolution is the adaptation of species. That's it, that's all. Evolution is a process of change, evolution does not have 'progress'. Evolution isn't something you can 'give up on'.

        As you say, 'just look at complexity of our bodies'. You cannot predict how

        • Re: (Score:3, Insightful)

          by znerk ( 1162519 )

          Not to put too fine a point on it, but you are an idiot.

          Fixed that for you. Do yourself a favor - when trying to show how someone else is intellectually inferior, try not to make yourself out to be an idiot with the first line.

        • Well, if You weren't so hasty to call me an idiot and maybe gave your brain a second to process what I was saying, you would see that that was my point also. I never said that we should decide who should survive. I just said that ALL MUTATIONS ARE RANDOM and some will be beneficial while others are just mistakes. So, let me put that in simple words: say one day you are making coffee and, by mistake you add vanilla flavored sugar to it. You might like it, and repeat it often cos that would add some value t
  • ... could something like this be overlooked over the past several decades? Wouldn't anybody think to check the DNA across the board, or are we just getting lazy?

  • Seems like a blindingly obvious discovery, DNA alterations to the blood producing cells don't always immediately and inevitably result in diagnosed Leukemia?

  • I'm curious and not a Biologist- (Score:4, Interesting)

    by mckinnsb ( 984522 ) on Sunday July 19, 2009 @05:45PM (#28750451)
    ... but would this discovery have any potential legal ramifications on DNA testing, potentially casting doubt on its validity? Their testing method has to be accurate, or else they could not observe the differences in DNA between blood and organ cells - but are the differences enough to cause one person's DNA to be mistaken for another, or are they small enough to not risk a false positive? I'm not a lawyer or a biologist, but thats the first thing that popped into my head.

    • Re:I'm curious and not a Biologist- (Score:4, Interesting)

      by turtledawn ( 149719 ) on Sunday July 19, 2009 @06:02PM (#28750603)

      Typically one would compare DNA collected via the same method as the original specimen- thus if you were testing for DNA in a skin flake, you would get a skin sample, while for semen, you'd get a semen sample, etc. It shouldn't make a difference in a well-run criminal case (and I'm not going to touch whether or not DNA-reliant cases are well run).

  • What about the rest of the body? (Score:3, Insightful)

    by Tubal-Cain ( 1289912 ) on Sunday July 19, 2009 @05:49PM (#28750481) Journal

    DNA from diseased tissue did not match the DNA from the blood

    And which (if either) matched DNA from the rest of the body?

  • title misleading (again) (Score:5, Informative)

    by dltaylor ( 7510 ) on Sunday July 19, 2009 @06:01PM (#28750597)

    The researchers did NOT say, definitively, that the patients DNA varied between blood and aorta.

    What they said was that the SEQUENCING showed a difference. The sequencer used cannot distinguish between messenger RNA and DNA differences.

    While it is possible that micro-environment, such as being blood vs. being aorta could result in changes to DNA, it is far more likely to result in tweaks to messenger RNA.

    Since they found the same SNPs in aortic tissue from the organ bank, it could just be a common adaptation for that tissue.

    • Re: (Score:1, Informative)

      by Anonymous Coward

      I'm sorry, but you're wrong. Sequencers can and do distinguish between mRNA and DNA, because you have to use reverse transcription to sequence RNA at all. Without using the RT step, you're still only going to amplify gene (from TFA: BAK1), because you're still using a Taq DNA polymerase, not a reverse transcriptase, which would be necessary to amplify from RNA. As far as a "common adaptation for the tissue", you're speculating about tissue adapting over the course of an organism's life which - although inte

      • Re: (Score:1)

        by E++99 ( 880734 )

        I don't think it's a matter of tissues "adapting", but of specializing. As I understand it, there are DNA edits that take place at every step of leucocyte specialization. I'm not at all surprised that it would happen with other cells as well.

      • Re:title misleading (again) (Score:4, Informative)

        by rnaiguy ( 1304181 ) on Sunday July 19, 2009 @10:51PM (#28752321)
        While you are technically correct, you missed the point entirely.

        If you read TFA (not the news piece, the actual one), then you will see that they sequenced cDNA, which means that they have the RNA sequence, but NOT the DNA sequence, and therefore cannot tell whether the changes occurred at the DNA or RNA level (such changes occurring at the RNA is old news). The GP did not quite express this clearly, but is correct in spirit.

        What I cannot fathom, is why they did not simply sequence the DNA of their gene of interest (really just the area around the mutation(s)) for a few patients. This would be really straightforward (can be done in a week), and i woud have thought any reasonable peer reviewer would request it. Overall, there is not enough evidence to support the hype in the news piece, as far as I'm concerned, which explains why it's not published in a high-end journal.

        • Re: (Score:1)

          by SUB7IME ( 604466 )

          This is really the correct response. As an aside, your username is rather apropos for this discussion.

  • House episode? (Score:1, Interesting)

    by Anonymous Coward
    Wasn't there a House M.D. episode covering something just like this where the organs and the blood DNA didn't match?
    • In that episode, the patient was a chimera, which is caused when two early embryos fuse to produce one individual (this is also used as a lab technique in mice to produce gene knock-outs). In other words, different body areas, pretty much at random, will have different DNA. To my knowledge, it's unclear how often this actually occurs in normal humans.

  • It's cDNA, _c_DNA! (Score:1, Informative)

    by Anonymous Coward

    The summary made no sense until I RTFA and found out that they sequenced cDNA, not genomic DNA. The "c" is important, people. It's like the "m" in "vim" or the "ba" in "bash" - if you omit it it's not too far wrong, but in certain contexts it makes a world of difference.

    cDNA is a lab-made copy of RNA. That's what the RNA editing versus DNA editing confusion is about. Genomic DNA gets copied to RNA, and then it's further processed. The researchers isolated that processed RNA, and made a cDNA copy of it. This

  • I am not a doctor nor did I completely follow the article, but I assume the cell lifetimes differ between blood and organ tissues. Given this, would we not expect some some sort of micro-evolution going on in frequently-reproducing cell types?

    • Re: (Score:3, Interesting)

      by Tacvek ( 948259 )

      I do know that a form of micro-evolution is how the body produces antibodies. The antibody producing cells attempt to produce mutations in the antibody gene. Some form of regulatory system promotes the cells that produce the antibodies that best bind to the pathogen, and destroys others. Eventually antibodies that bind really well to the pathogen will result.

      I'm sure that is is simplified explanation, but that is roughly what I was taught in biochemistry.

      But I don't think mutations otherwise occur at high e

  • Original article (Score:2, Informative)

    by mattb112885 ( 1122739 )
    For those who are interested, the original article is published in Human Mutation journal, and can be found here: DOI [doi.org] It requires access to the journal to read beyond the abstract.

  • Wasn't there a Russian claim that the serial killer, Chikatilo (sp?) had different sperm DNA than his blood or saliva,
    thus causing a delay in his eventual capture?

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