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DNA Differences Observed Between Blood and Organs
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.'"
Perhaps some of those patients were chimeras .
Warning: this article may contain humor, sarcasm, parody, and perhaps even irony. Read at your own risk.
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?
weinersmith
what happened to the days of pre-history and we didnt need this, we just ate grass if we didnt feel good
Someday we'll hit the human carrying capacity. And the band will just play on.
... 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.
DNA from diseased tissue did not match the DNA from the blood
And which (if either) matched DNA from the rest of the body?
Checking DNA "across the board" would be effectively impossible up until very recently. Even now, DNA sequencing is a horrendously laborious procedure (in spite of what CSI would have you believe). You'll note that even in this study they didn't sequence any DNA; they just looked at the expressed mRNA.
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.
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.
You'll note that even in this study they didn't sequence any DNA; they just looked at the expressed mRNA.
I couldn't quite figure that out from TFA. It sounded like they sequenced the DNA and cDNA, but then they talk about mRNA.
http://www.genomeweb.com/sequencing/snps-non-cancerous-tissue-may-differ-those-blood-study-finds http://74.125.93.132/search?q=cache:0S55-4qOoysJ:www.genomeweb.com/sequencing/snps-non-cancerous-tissue-may-differ-those-blood-study-finds+SNPs+in+Non-Cancerous+Tissue+May+Differ+From+Those+In+Blood,+Study+Finds&cd=2&hl=en&ct=clnk&gl=us Sneaky cache to avoid login
On the other hand, when the team sequenced BAK1 cDNA from healthy aortic tissue obtained from a Quebec transplant service, they found the same three SNPs as in the aortic tissue from the AAA cases. The researchers verified their findings by sequencing both strands of DNA and repeating the sequencing several times.
So far, Schweitzer said it's unclear whether these BAK1 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.
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?
For those who are interested, the original article is published in Human Mutation journal, and can be found here: DOI It requires access to the journal to read beyond the abstract.