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Sorry, but the length guide is *not* sufficient.

While it's more specific than sequence homology predicts, it's less specific than the laser focus it's portrayed as having.

I understand the need to portray it as being as close to perfect as possible to preserve funding (and the research *should* be funded!), right now, the best method we have of ensuring that off-target mutations do not occur is via post-sequencing.

See these papers regarding "Dammit, I missed!":

New Sequencing Methods Reveal Off-Target Effects of CRISPR/Cas9
https://www.genomeweb.com/sequ...

Unbiased detection of off-target cleavage by CRISPR-Cas9 and TALENs using integrase-defective lentiviral vectors
http://www.nature.com/nbt/jour...

Analysis of off-target effects of CRISPR/Cas-derived RNA-guided endonucleases and nickases
http://www.ncbi.nlm.nih.gov/pm...

CRISPR-Cas9 Specificity: Taming Off-target Mutagenesis
http://www.genecopoeia.com/res...

Digenome-seq: genome-wide profiling of CRISPR-Cas9 off-target effects in human cells
http://www.nature.com/nmeth/jo...

Quantifying on- and off-target genome editing
http://www.cell.com/trends/bio...

CRISPR/Cas9 Guide
https://www.addgene.org/CRISPR...
Salient quote: "The randomness of NHEJ-mediated DSB repair has important practical implications, because a population of cells expressing Cas9 and a gRNA will result in a diverse array of mutations (for more information, jump to Plan Your Experiment). In most cases, NHEJ gives rise to small InDels in the target DNA which result in in-frame amino acid deletions, insertions, or frameshift mutations leading to premature stop codons within the open reading frame (ORF) of the targeted gene. Ideally, the end result is a loss-of-function mutation within the targeted gene; however, the “strength” of the knock-out phenotype for a given mutant cell is ultimately determined by the amount of residual gene function."

P.S.: And you know as well as I do that the 'P' in "CRISPR" stands for "Palindromic".

they still can't patent discoveries. Now, synthetic DNA yes, you can patent that. But then you didn't discover that, you made it. Although the problem with that is at what point did you 'discover' it or just make something naturally occurring...

Due to a new technique called "CRISPR-Cas9", there's been a whole lot of rapid development on the gene-identification front, and likely to be an explosion of new ones in coming months/years.

It's definitely being used here: Linky.

Likely lots of half/false leads will also come out of all this too, but thanks to all this, we're getting a lot further into exploring the whole nature/nurture beyond simple debating points, and I think it's all amazing and interesting.

Ryan Fenton

This was last friday.

So what kept you from posting a story about this article yourself on Friday or Saturday?

This was last friday.

AC because of professional involvement.

No, continuous monitoring will not be the next big thing. The next big thing will be personalized medicine, in which a thorough analysis provides an insightful and predictive diagnosis, rather than broad sweeping categorization. There are probably 20-50 major categories of Type-2 diabetes, diagnosable via "integrated personalized 'omics" (their term), specifically metabolomics, so correctly identifying those categories will provide much more effective treatments.

Without getting into all the details, the field of metabolomics has existed to some degree for the last 30 years, and it is only within the last year that a company (Agilent) has made official forward progress towards certification of a metabolomics analytical tool as a medical device. They now have the first two steps in place: certified manufacturing facility and Class I Medical Device. Combine information like that, with publications like this one, and project like this personalized medicine in Luxembourg), and you can see that we're right on the cusp of being able to tell exactly how you're sick, and coming up with very targeted approaches to address illness.

There's a chance this might actually substantially reduce medical costs, in addition to provide orders of magnitude more information. The problem with current medical tests is that they're based on technology decades old: they're also highly specific in terms of design, and require a lot of sensitive reagents (coupled antibody-based assay). That makes them tough to design, produce, and store. In comparison many of these 'omics procedures are generic: we can extract with one protocol and use the extracted material to assay for 5000 compounds in one test. Cost of extraction in $5-10 in materials, maybe $30 in time, and $100-300 in instrument time. Economy of scale could reduce that, but even as it is currently I believe that's substantially cheaper than a thorough blood panel, and it gives much more useful data.

They did reprogram the worms. No doubt people have done DIY genetics with these worms before too. It's not as easy as genetic splicing with yeast or ecoli, but enthusiasts could definitely make their own transgenic worms in their garage. If you buy or make your own PCR machine, that's probably the biggest barrier right there.

'Of course, that may just be the plateau before it falls off the next cliff.'

The next cliff is already emerging through the mist, e.g.:

http://www.genomeweb.com/sequencing/life-tech-outlines-single-molecule-sequencing-long-pieces-dna

http://www.wired.com/wiredscience/2011/01/guest-post-introduction-to-nanopore-sequencing/

It's not clear which 'single-molecule' technology will eventually win out, but it will almost certainly have the word 'nano' in it somewhere.

Yeap, old news.

http://www.genomeweb.com/peer-review-broken
http://www.slate.com/id/2116244/

All it takes is one bad reviewer that doesn't know what he's talking about, or only skimmed over the paper, to get a paper rejected.

Direct insertion of DNA sequences from other species is different to breeding and selection.

End of story.

Beginning of story, actually.

Viruses are not precisely reliable. They'll frequently inject genetic material into a cell but then the reproductive phase will fail. This can cause cancer, various metabolic faults in the cell including immediate cell death, or frequently nothing at all because the genetic material will usually remain inert. Usually it's nothing to worry about because it's just one cell.

But what if the cell is a reproductive cell that turns into a zygote, forming an embryo? What'll happen is that the viral DNA will get replicated into every cell in the embryo --- including the embryo's own germ cells. This means the change will breed true. Viral DNA has now part of the animal's bloodline. It's rare, but it happens --- and the viral genetic material may not stay inert; it's frequently coopted and used. Apparently it's fairly well proven that the genetic sequence that protects babies from the immune systems of their mothers was stolen in this way from a retrovirus like HIV.

But this also works in reverse. A virus can attack a cell, reproduce, and accidentally scoop up host DNA. Now the animal's genetic material has entered the viral bloodline (as it were).

Add the two together, and what do you get? A mechanism for directly inserting DNA sequences from one species to a totally unrelated species. And it's all completely natural.

It's called horizontal gene transfer.

That's just animals. Plants are even worse --- they're extremely lax about cellular security, and will happily swap genetic material with organisms nearby. If you look on the verges of fields planted with a pesticide-resistant crop, you can frequently find unrelated weeds that have become pesticide resistant themselves; they've snapped up the useful genetic sequences from the crops nearby. I don't know if they've found the mechanism for this yet --- anyone know?

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.

Microsoft has started buying up biotech software companies (most recently Rosetta Biosoftware). There almost has to be some link, but all of Rosetta's software runs on Linux, with only a handful of clients on Windows, and no direct usage of VxWorks - although I'd be surprised if the actual hardware doing the data collection was running a server OS rather than an embedded OS.

Speculation on a possible connection?

If I send those to a slashdot-style forum, my boss will laugh. They'll count something less than a one-line quote in a small town newspaper.

This is true. Even though I supported the public library of science initiative (reported earlier on slashdot, and also here , I'm about to submit an article to TIBS. An article on GenomeWeb just won't cut it.

However, that is not going to be the case forever. As data mining techniques become more available and sophisticated, that is to say, when real data mining (as opposed to just text matching) becomes a major way in which academics access content, articles in "free" journals are going to be *more* visible to your colleagues, and as important discoveries are coordinated using such techniques, citations will rise, and those journals will rise in prestige. This is going to aggravate what is allready a real schism within the academic community, of int. property versus the pursuit of truth. I think it's going to be a struggle - for the very soul of academia which is really under threat here - but I think we're going to win, because cutting out the middle-man makes for a more efficient way of sharing information, because history isn't over and materialism isn't really the driving force behind human creativity, and because people who love science for it's own sake are better at it.

An earlier poster said that the current system drives the smartest people out of academia and into industry. I couldn't disagree more - I don't think people in (the biotech) industry are very smart at all. They're kind of pathetic, mostly. I'll agree that there are a lot of frankly stupid "scientists" doing terrible work at supposedly public universities on the private dollar, and that the people who jump ship into industry are often a bit smarter than they are; but the smartest, most devoted people are still in the public sector.

More coverage.

Genomeweb article
http://www.genomeweb.com/articles/view-article.asp ?Article=2001119102156

CNET News.com
http://news.cnet.com/news/0-1003-200-4534657.html

Yahoo
http://news.search.com/click?sl,news.43.232.940.0. 4.compaq+sandia+celera.0,http%3A%2F%2Fc%2Emoreover %2Ecom%2Fclick%2Fhere%2Epl%3Fk14425460

ABCNews.com
http://abcnews.go.com/sections/scitech/DailyNews/g enome_compaq010119.html