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DNA Differences Observed Between Blood and Organs

kdawson posted more than 5 years ago | from the same-old-same-old dept.

Biotech 85

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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I'm Dr Wilke (-1, Troll)

Anonymous Coward | more than 5 years ago | (#28750067)

As you can tell from my name I have a large "wilke" that needs "treatment". I'm sure you slashdot nerds know what to do.

Re:I'm Dr Wilke (-1, Troll)

Anonymous Coward | more than 5 years ago | (#28750235)

Unless that has something to do with Lunix, Dragons & Dungeons, living in your parent's basement or goatse [goatse.fr] , they will have no idea what you are talking about.

Chimera (3, Interesting)

John Hasler (414242) | more than 5 years ago | (#28750115)

Perhaps some of those patients were chimeras [wikipedia.org] .

Re:Chimera (1, Insightful)

Anonymous Coward | more than 5 years ago | (#28750143)

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.

Re:Chimera (0)

Anonymous Coward | more than 5 years ago | (#28750459)

God gave you a purpose in life:

Trolling Slashdot. Having accomplished the mission, prepare to be raptured away.

Re:Chimera (1)

Tubal-Cain (1289912) | more than 5 years ago | (#28752251)

Reminds me of a Despair, Inc. [despair.com] poster.

Re:Chimera (1)

oneirophrenos (1500619) | more than 5 years ago | (#28750277)

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 one individual.

not Chimeras (0)

Anonymous Coward | more than 5 years ago | (#28750321)

This is common to all human.
For e.g. a male homo sapiens sapiens the reproductive organs contain octopus DNA.

Re:not Chimeras (1)

shentino (1139071) | more than 5 years ago | (#28750809)

[citation needed]

Re:not Chimeras (1)

eltaco (1311561) | more than 5 years ago | (#28750841)

I do believe this to only apply to japanese males in hentais.

Re:Chimera (0, Offtopic)

XPeter (1429763) | more than 5 years ago | (#28750373)

What the hell are you talking about? I was just playing Warcraft and clearly a chimera is a two-headed dragon.

Re:Chimera (4, Informative)

broken_chaos (1188549) | more than 5 years ago | (#28751027)

http://en.wikipedia.org/wiki/Chimera_(genetics) [wikipedia.org]

The name comes from the mythical chimera, but is actually an organism (humans can possibly have this) with two or more distinct types of DNA in it's body. For example, if a human had one set of DNA in their kidneys and a different set in their liver.

Re:Chimera (1)

bsDaemon (87307) | more than 5 years ago | (#28752019)

Do transplant recipients count? Is Steve Jobs no more mythic than before? Inquiring minds and all that....

Re:Chimera (0)

Anonymous Coward | more than 5 years ago | (#28752045)

TLC sometimes airs a good special on this...it's called "I Am My Own Twin" or something like that...

Re:Chimera (0)

Anonymous Coward | more than 5 years ago | (#28750547)

Looks like you gotta pay to gawk at the real article so all we're getting is filtered news distorts.
Differing DNA (including SNPs) between healthy and disease tissue is not new. Cancer always has this.
There may be some disease that's not cancer but lethal that exhibits somatic mutation.

REgardless, was the observation repeated in using alternative technologies? (i.e. taqman vs. affy vs. sanger vs. shortread vs. whatever)? They could be sequencing a look alike pseudo gene. by accident.

31 samples? yikes. not big. what's the p-value?

frikin article says it could be RNA editing; in which case the source DNA is the same. (That's same code; different pre-processor for you "c' geeks).

They could also be messing up their DNA copying. (consistency indicates not, though).

dunno, man. "Journal of Human Mutation". Never heard of it.

Re:Chimera (0)

Anonymous Coward | more than 5 years ago | (#28751073)

I certainly know i fall under this category.

Shit sucks man. Fuck autoimmune.

Re: Mosaic (3, Interesting)

nbauman (624611) | more than 5 years ago | (#28751369)

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.

Re: Mosaic (1)

structural_biologist (1122693) | more than 5 years ago | (#28753235)

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 are secreted from our skin, so if you literaly touch an RNA sample it begins to degrade. I know because I work with RNA and it is a pain). Furthermore, sequencing procedures are optimized for sequencing DNA strands, not RNA strands. So, when the article refers to sequencing cDNA, it really means sequencing mRNA (indirectly).

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 (perhaps they knew that other groups had made similar findings and wanted to rush the paper out before others could publish?).

Re: Mosaic (1)

RDW (41497) | more than 5 years ago | (#28754987)

'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 possible that they're simply looking at RNA editing, and it isn't even possible to say whether this was tissue specific, because they didn't look at cDNA in the blood samples. Also, although the SNPs (sequence variants) turned up in cDNA from aneurysms, they were also present in cDNA from healthy aortic tissue, so there's no evidence that they are involved in any disease process.

Re: Mosaic (1)

Laughing Pigeon (1166013) | more than 5 years ago | (#28754137)

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:Chimera (1)

smchris (464899) | more than 5 years ago | (#28751489)

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 (2, Funny)

martas (1439879) | more than 5 years ago | (#28750155)

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:complexity (2, Informative)

Darkness404 (1287218) | more than 5 years ago | (#28750325)

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:complexity (1)

Pandare (975485) | more than 5 years ago | (#28750423)

Yeah, probably. My guess is nukes or monoculture domination.

Re:complexity (1)

mindbrane (1548037) | more than 5 years ago | (#28750425)

>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 Limbs' edited by B. Hall when read in conjunction with Raff's book is really superb. For all my efforts I came away envisioning our genetic programme as a Bach Fugue that develops various voices from an initial set of themes. E.O. Wilson said we evolved to reproduce, not to be happy. As, perhaps, neotenic apes, once our initial programme runs we begin to run down and that's where things seem to get really complex and go wrong.

Re:complexity (2, Funny)

nbauman (624611) | more than 5 years ago | (#28751387)

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:complexity (2, Interesting)

jeffliott (1558799) | more than 5 years ago | (#28750427)

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:complexity (1)

martas (1439879) | more than 5 years ago | (#28750589)

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.

Re:complexity (1)

Hurricane78 (562437) | more than 5 years ago | (#28762157)

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:complexity (2, Insightful)

E++99 (880734) | more than 5 years ago | (#28751127)

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

Re:complexity (1)

wizardforce (1005805) | more than 5 years ago | (#28750467)

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.

Re:complexity (1)

Antique Geekmeister (740220) | more than 5 years ago | (#28752995)

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.

good old days (2, Funny)

Dayofswords (1548243) | more than 5 years ago | (#28750275)

what happened to the days of pre-history and we didnt need this, we just ate grass if we didnt feel good

Re:good old days (2, Insightful)

fuzzyfuzzyfungus (1223518) | more than 5 years ago | (#28750441)

We died, a lot, mostly early.

Re:good old days (0, Troll)

ColdWetDog (752185) | more than 5 years ago | (#28750473)

I'm pretty sure we still die. So, what have we done? With all that work and money, we could just be watching television.

Re:good old days (0)

Anonymous Coward | more than 5 years ago | (#28750993)

Stopped dieing early?

Re:good old days (0, Redundant)

maxume (22995) | more than 5 years ago | (#28751011)

Most of us are.

Re:good old days (3, Informative)

shentino (1139071) | more than 5 years ago | (#28750839)

Don't you know that being born in the early half of the century is the number one cause of death these days?

Re:good old days (1)

oblivionboy (181090) | more than 5 years ago | (#28756607)

Aubrey de Gray would agree with you.

http://www.mfoundation.org/ [mfoundation.org]

Re:good old days (0)

Anonymous Coward | more than 5 years ago | (#28756777)

Didn't realize there was a large number of deaths in 1-9 year olds.

Re:good old days (1)

Attila Dimedici (1036002) | more than 5 years ago | (#28760283)

There aren't, but how many children under 9 years old died this year who weren't born in this century? See, the OP was right.

Re:good old days (1)

shentino (1139071) | more than 5 years ago | (#28760511)

GP fail ftw!

Re:good old days (2, Interesting)

designlabz (1430383) | more than 5 years ago | (#28750517)

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 should be limited to fixing injuries and curing viruses and infections, rather than helping non-adapted survive. Life is a game of numbers. Not everyone is meant to win. Just look at complexity of our bodies... there is so many things that can and often do go wrong. Call it God or Evolution... each and every one of us is an experiment... and not all experiments lead to a great discovery... in fact, most of them fail. But, in a world governed by emotions, empathy and cash no one ever cares about real progress. Bottom line: When we started cheating in a game of life, we gave up on evolution. That was the moment we stopped being a specie and started being... a goo?

Re:good old days (4, Insightful)

Anonymous Coward | more than 5 years ago | (#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:good old days (0, Flamebait)

znerk (1162519) | more than 5 years ago | (#28752219)

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:good old days (1)

maxume (22995) | more than 5 years ago | (#28751029)

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:good old days (1, Insightful)

Anonymous Coward | more than 5 years ago | (#28751085)

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.

I'm sorry but Idiocracy is for idiots (-1, Troll)

Anonymous Coward | more than 5 years ago | (#28751101)

Some people would call it inhuman or sick, but in my humble opinion medicine should be limited to fixing injuries and curing viruses and infections, rather than helping non-adapted survive.

I call that idiotic. You don't have any idea of how natural selection works, do you? The basic concept isn't that physically the best survive. It is that those most fitted to the society survive and can continue.

In historic times it meant that if someone had a genetic problem that made him physically weak, his line would likely die off sooner or later. In modern days, other things are just as important or significantly more important for our society so that is no longer the case. It doesn't mean that natural selection wouldn't work, the criteria has just became more suitable.

These days a large variety of people gain advantage in mating (and even enjoying life themselves, not just passing their genes). Very intelligent (thus often successfull, wealthy, etc.), the creative (good artists and the like), those who can enjoy their life to the fullest (those who party a lot and so on), those who can keep their bodies in good shape, those who... Well, the list would go on and on but you get the point.

The physical fitness and the cunningness required to hunt are no longer the major factors but it doesn't mean that the new things couldn't take our society forwards to the better direction.

You know, by your logic, Stephen Hawking shouldn't have received the extensive medical care that he has, because he is just non-adapted to survive. Medicine shouldn't be used to help the likes of him, right?

Based on someone's genes, it is pretty difficult to assume who has poor genes but will - if the problems are treated - become a politician who manages to change the whole society to a better direction. The reason why people with genetic flaws can pass them forward now is not some sort of "backwards evolution", it is because our society has advanced to the degree that they matter less than the other things. That we have ability to fix or ignore the problems caused by them. It is a good thing! And if it will ever become a problem, this thing will fix itself.

I find it very scary that the people who have watched idiocracy and think that this "backward evolution" really has a point also think that they are some sort of intellectual elite of the society for understanding this...

I could just link you to the obvious XKCD comic about idiocracy [xkcd.com] but I think that this [xkcd.com] more recent comic is much more fitting about those people.

Re:I'm sorry but Idiocracy is for idiots (1)

leppi (207894) | more than 5 years ago | (#28756543)

Why is this rated a troll?? Are the producers of Idiocracy mods now? The post was well thought out and reasoned. quite the opposite of "troll"-like.

Re:I'm sorry but Idiocracy is for idiots (1)

T Murphy (1054674) | more than 5 years ago | (#28799351)

Posts like this make me wish the troll mod took two votes to stick (although it only uses up the first mod point). I've had jokes modded troll due to people missing the sarcasm, but seeing insightful comments buried by someone with their own agenda is just wrong. I spend too many mod points undoing bad troll mods. At least /. could limit mods to one -1 for every 5 points they give out.

Yeah, this is offtopic, but if any mod sees this please mod up the "troll" first.

Re:good old days (1)

MrMista_B (891430) | more than 5 years ago | (#28751949)

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 every single gene will increace the odds of species survival in every single circumstance. Genetic diversity of a species is a strength, and by saving those people you want killed or left to die, we strengthen the genetic diversity of the species, and thus its survival strength.

What you want to do, just letting die those who cannot save themselves, would lessen genetic diversity, and weaken the species.

Not to mention, that what you are advocating is more commonly called 'eugenics', and is inherently morally evil, in the truest sense of the word 'evil'.

You want to let people die because you don't think they help this mystical 'forward evolution' you believe in? Then please, volunteer to be the first to die. I'm sure the millions of people who are alive today because people like you weren't in positions to kill them or let them die would be grateful.

Re:good old days (2, Insightful)

znerk (1162519) | more than 5 years ago | (#28752241)

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.

Re:good old days (0)

Anonymous Coward | more than 5 years ago | (#28752423)

It was just a typo. D and E are typed with the same finger, and the statement was still readily interpretable, even by you.

On the other hand, the point that he was demolishing was, at best, intellectually shallow; at worst, willfully misanthropic.

Re:good old days (0)

Anonymous Coward | more than 5 years ago | (#28755123)

You are a moron.
Evolution does not have a direction in the same sense that an object can travel east or west. But evolution allows a species to better fill a particular environmental niche or expand into an environmental niche. If a mutation doesn't allow for an improved chance of passing the resulting genes on to the next generation it is a failed mutation. The problem the poster was pointing out was that by not letting evolution cull the bad mutations we are weakening our species as a whole. Yes you can call this eugenics if you wish and it probably is to a degree but it isn't being practiced by humans but by nature. I do not believe he is suggesting someone should have the power to choose who survives and who doesn't but rather letting nature decide, you know the way it was done for thousands of years before humans believed sicknesses and malformations were caused by sins against god/gods/spirits/the local witchdoctor.
You are also right that evolution isn't something that you can escape but you can change the evolutionary pressures on a species changing how the species evolves. Ask any biologists who has played with any organism that has a very short reproductive speed. (I've done it with E.coli.) Right now the only evolutionary pressure I can see on the human race is that of who breeds the most which usually is the ones who can't figure out birth control, doesn't have access to birth control or are very religious and not allowed to use birth control.
As for lessening the genetic diversity, you are completely wrong. By letting those who can't survive die, you have freed up resources for those who can survive and thrive and produce more children each with a chance to have a mutation that could help the human race. Look at any species that is not managed by humans and you can see this. Hell the legend (because I don't have any actual proof) of the Eskimos leaving their young and very old out in the cold during bad winters also testifies to this.
Personally, I agree with the poster and would be more then willing to be judged by those standards, for good or bad. What about you?

RE: Evolution does not have a direction (1)

designlabz (1430383) | more than 5 years ago | (#28758853)

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 to your cup of coffee. But, if instead of vanilla it was a salt you added, or even something toxic, you damn sure wouldn't continue to make it, cos that would make your coffee worst. What i was saying was that we shouldn't make people drink salty coffee just because someone made it by mistake.

How... (1)

digitally404 (990191) | more than 5 years ago | (#28750295)

... 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?

Re:How... (2, Informative)

xZgf6xHx2uhoAj9D (1160707) | more than 5 years ago | (#28750519)

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.

Re:How... (3, Informative)

nbauman (624611) | more than 5 years ago | (#28751491)

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 [genomeweb.com] 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 [74.125.93.132] 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.

Re:How... (1)

SUB7IME (604466) | more than 5 years ago | (#28752431)

cDNA comes from mRNA.

Re:How... (1)

budgenator (254554) | more than 5 years ago | (#28750923)

In the past we've made some assumptions that would make our problem set workable but knew some of them would be later shown to be wrong; for example to sequence the human genome we took thousands of cells, extract the DNA and sequenced it. Where the data was noisy we assumed it was experimental error rather than genomic differences yet we knew the assumption was unsupported. Right now we are extracting DNA form hundreds of cells such as cancerous and non-cancerous and sequencing them and seeing differences between the two because our techniques and equipment is a lot better and faster. One day we may be able to sequence individual cells and see genomic differences at a finer level. It's not lazyness, it's the limitations of our techniques and equipmemt.

future leukemia patient? (1)

vlm (69642) | more than 5 years ago | (#28750305)

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

in what country's was it recearched? (0)

Anonymous Coward | more than 5 years ago | (#28750331)

in what country's? there might be an external factor at play, besides cancer and chimeric cells. in mice there was an increase of foreign dna present in rats eating modified foods, this is for meat and vegetable products. also why the EU/china banned genetically modified foods.

I'm curious and not a Biologist- (3, Interesting)

mckinnsb (984522) | more than 5 years ago | (#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- (3, Interesting)

turtledawn (149719) | more than 5 years ago | (#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).

Re:I'm curious and not a Biologist- (0)

Anonymous Coward | more than 5 years ago | (#28864587)

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.

This isn't true.

For instance, a large number of Forensic DNA cases involve sexual assaults where a male leaves behind semen in a female's body cavity. A DNA profile is developed from this semen which is then later matched to the male through a known DNA sample typically taken in the form of a buccal swab.

The same is true for any case where a suspect would leave behind their own blood at a crime scene (e.g. a property crime where they busted through a window and cut themselves). The DNA profile developed from this blood would later be matched to them via a known DNA sample taken in the form of a buccal swab.

I've never heard of any case where a suspected rapist is forced to provide a semen sample for comparison purposes, nope.

What about the rest of the body? (2, Insightful)

Tubal-Cain (1289912) | more than 5 years ago | (#28750481)

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

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

Re:What about the rest of the body? (1)

vandelais (164490) | more than 5 years ago | (#28751389)

Jonas Venture Jr

This sounds like a job for... (1)

Aphonia (1315785) | more than 5 years ago | (#28750565)

Dr. House!

title misleading (again) (4, Informative)

dltaylor (7510) | more than 5 years ago | (#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:title misleading (again) (1, Informative)

Anonymous Coward | more than 5 years ago | (#28751047)

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 interesting - seems unlikely because the cells that divide are not the same as the cells that are subject to "selection" due to the division of myoblasts into myocytes (muscle cells). It is also unclear what that selection would be.

Re:title misleading (again) (1)

E++99 (880734) | more than 5 years ago | (#28751141)

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) (0)

Anonymous Coward | more than 5 years ago | (#28751501)

The recombination that occurs in immune cells (B and T) is vastly different from the observed differences in the article, which were SNPs. They are not comparable, and there exists no known mechanism for the controlled generation of SNPs; maybe the research will illuminate one.

Re:title misleading (again) (0)

Anonymous Coward | more than 5 years ago | (#28752235)

I'm going to have to agree with the above Anonymous Coward. I'm currently working in a lab were we do this fairly regularly on mouse tissues. Just to add to what he/she said, the article states that the researchers were looking at the cDNA of the BAK1 gene. To do this, you essentially grind up your sample in a special reagent (we use a reagent called TRIzol) which separates DNA and RNA into different phases. You can then take the RNA phase and perform reverse transcription (as mentioned by my fellow coward) to get the cDNA, and this is what you would use to do your sequencing. So I suppose I would agree that the sequencer itself cannot distinguish, however you as a researcher would know what you've started with (DNA or RNA) to do your sequencing.

Interesting article though. I will be curious to see what, if any, ramifications this might have for future blood tests for various diseases.

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

rnaiguy (1304181) | more than 5 years ago | (#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:title misleading (again) (1)

SUB7IME (604466) | more than 5 years ago | (#28752445)

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

House episode? (1, Interesting)

Anonymous Coward | more than 5 years ago | (#28751049)

Wasn't there a House M.D. episode covering something just like this where the organs and the blood DNA didn't match?

Re:House episode? (1)

rnaiguy (1304181) | more than 5 years ago | (#28752043)

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.

Re:House episode? (0)

Anonymous Coward | more than 5 years ago | (#28752923)

it's unclear how often this actually occurs in normal humans.
About once every 3-4 seasons.

It's cDNA, _c_DNA! (1, Informative)

Anonymous Coward | more than 5 years ago | (#28751293)

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 is NOT the conventional way DNA gets sequenced. 99% of the time if you talk about sequencing someone's genes, you're talking about sequencing the genomic DNA directly, without the intermediate RNA step.

Small Scale Evolution? (2, Interesting)

NoMoreFood (783406) | more than 5 years ago | (#28751751)

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:Small Scale Evolution? (2, Interesting)

Tacvek (948259) | more than 5 years ago | (#28752255)

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 enough a rate in other cases for micro-evolution to occur.

Original article (2, Informative)

mattb112885 (1122739) | more than 5 years ago | (#28751869)

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.

lame (1)

Sam36 (1065410) | more than 5 years ago | (#28752347)

dna is stupid

mo3 0p (-1, Flamebait)

Anonymous Coward | more than 5 years ago | (#28752939)

the numbers. T4e [goat.cx]

DNA mismatch on Russion serial killer (1)

mhaskell (658865) | more than 5 years ago | (#28761243)

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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