Friday, August 8, 2008

The DNA Network

The DNA Network

The updated dope on the mismapped mutation in the dopamine D2 receptor [Discovering Biology in a Digital World]

Posted: 08 Aug 2008 05:35 PM CDT

A few weeks ago, I wrote about a paper in Science(1) that I read on a connection between a mutation in the dopamine D2 receptor and the genetics of learning.

Only, it turned out that when I looked at the gene map...

Read the rest of this post... | Read the comments on this post...

New Yorker on Superbugs [The Tree of Life]

Posted: 08 Aug 2008 05:26 PM CDT

Still catching up after being out sick with an antibiotic resistant infection. But I had to post on this one. The New Yorker has new piece by Jerome Groopman on, well, antibiotic resistant bacteria. See Medical Dispatch: Superbugs: Reporting & Essays: The New Yorker

Thanks to Saul J for pointing this out.

I particularly like the ending
No one, Moellering said, has developed a way to disarm bacteria sufficiently to allow the human body to naturally and consistently defend against them. I asked him what we should do to combat these new superbugs. "Nobody has the answer right now," he said. "The fact of the matter is that we have found all the easy targets" for drug development. He went on, "So the only other thing we can do is continue to work on antibiotic stewardship." Meanwhile, new resistant bacteria, Moellering asserted, aren't going to go away. "We can temper things, we might be able to slow the rate of emergence of resistance, but it's unlikely that we will ever be able to conquer it."

Think Gene User Survey [Think Gene]

Posted: 08 Aug 2008 05:08 PM CDT

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Werd (LHC rap) [Bayblab]

Posted: 08 Aug 2008 03:44 PM CDT

WTF is transmission ratio distortion [Bayblab]

Posted: 08 Aug 2008 03:02 PM CDT

So I had a mission this afternoon to figure out what the hell this "t-complex" was. I tried reading some papers about it, and quite frankly I couldn't get past the intro. The other strange thing is that there seems to be little to no paper on the subject that date from after the 80's. So I finally broke down and started reading reviews and what I found is an interesting and seemingly forgotten story. Apparently this was all the rage 70 years ago, and one of the biggest mysteries of mouse genetics.

It all started with mice that were captured in the wild and bred with "T mutant" lab mice which had short tails (the t in t-complex stands for tail). Somehow when you bred them together you got mice with no tail. There was some kind of "modifier" in one of the mice which was exacerbating the phenotype. People tried to map this supposed modifier, but the linkage was all messed up, and the heredity wasn't Mendelian.

Well this modifier wasn't in fact a gene it was a large region of chromosome 17. This region could either be wildtype (+) or be severely remodeled and called t-haplotype (t). The remodeling involved several rearrangements including multiple inversions which basically prevented the region from ever recombining with a normal (+) carrying chromosome 17. On top of that the region contains multiple mutant genes which are in a really strong linkage disequilibrium (IE you either get a bunch of mutants or the wt, no mixing at meiosis).

Males carrying two t-haplotypes are infertile, and so you would expect this anomaly to be quickly swept under the evolutionary rug. However there was a strange case of selfish gene interfering with the process. The het males (+/t) transmit the t to all the offsprings, and completely ignore poor Mendel and display a male transmission ratio distortion (TRD). How can this be? Obviously those genes where interfering with either meiosis or reproduction, and making sure they were passed on preferentially. Well it turns out that in that region there are a number of genes which affect sperm flagellar development.

It wasn't that the embryos getting the + allelle from the +/t father were dying, it wasn't that the +/t males were only producing t sperm, it was much more insidious. Somehow the t sperm is a better swimmer and the t-complex genes conspire to cripple the + sperm. How is that possible you may ask. Well through a quirk of sperm development: the syncithium. while the spermatocytes are maturing they share cytoplasm via bridges, so proteins and RNAs are free to flow between + spermatocytes and t spermatocytes. This way some problems of the mutants can be overcome by shared wt protein. This explain how the t survives but not how the + get crippled. Turns out that among the mutant genes being passed along together in the t-haplotype is a gain of function mutant which rescues the other mutants and is only expressed late in spermiogenesis, after the bridges between sperm have been burned. So the t spermatocyte share the poison to all connected sperm when the syncithium is present, but they save the antidote for later.

So this is how you get an entire selfish region to behave as a unit and be passed along preferentially despite being recessive lethal. Neat huh.

ChIP-ing Away at Analysis [FinchTalk]

Posted: 08 Aug 2008 02:22 PM CDT

ChiP-Seq is becoming a popular way to study the interactions between proteins and DNA. This new technology is made possible by the Next Gen sequencing techniques and sophisticated tools for data...

Medical Records, Insurance and Prediction: GINA Will Not Keep this Fox Out of the Henhouse [PredictER Blog]

Posted: 08 Aug 2008 11:09 AM CDT

In a recent Washington Post article (4 August 2008), "Prescription Data Used to Access Consumers", Ellen Nakashima writes about the availability of medical records for data mining. Insurance companies have begun to use databases of prescription records to assess the risks of insuring individuals or when deciding to pay for a treatment. For example, a report could show that an "individual has been on the highest does of the cholesterol-reducing drug Zocor for 18 months" and an insurance company could determine that the patient has "a very high, near-intractable cholesterol problem … and could avoid a costly blood test". The article also points out that these records are more honest than many applicants for insurance and could reduce the cost of insurance while facilitating faster decision making. While HIPAA stipulates that patient consent must be acquired before these records can be accessed, "HIPAA does not give the Department of Health and Human Services the ability to directly investigate or hold accountable … pharmacy benefit managers". Nakashima reports that the increasing availability of electronic records will result in a market in which data mining organizations compete to sell the most complete and cheapest sources of patient data to insurers. Joy Pritts, of the Georgetown University Health Policy Institute observes that "Most people don't even know these organizations exist . . . ." Privacy consultant, Bob Gellman notes that "consumers will likely continue to have no real meaningful choices if they want insurance". Richard Dick, a database designer, suggests better privacy tools for consumers which would allow patients to be more specific when consenting to release medical information, "Otherwise … you have the fox in charge of the henhouse".

I want to know what incentives motivate patients to consent to release this information in the first place. I'm guessing that insurance coverage may depend upon consent; if so, is this real "consent"? – J.O.

John Hawks on Why Scientists Should Blog [adaptivecomplexity's column]

Posted: 08 Aug 2008 10:30 AM CDT

Science blogger and University of Wisconsin scientist John Hawks recently demonstrated that it really is possible to blog and get tenure.

Continuing this discussion, he now explains why scientists should take the time to blog. It will help you make an impact on the culture at large:

You might give media interviews, public lectures, or write more accessible treatments of your research or your field. You might even blog. By serving the public and your own colleagues, you raise the game. Science depends on criticism, on many eyes examining hypotheses and finding observations that test them. Science bootstraps itself, it can only advance when people near the top of the mountain send a hand down to lift others up. That means teaching your methods to others, and helping a broader public understand why the mountain is worth climbing.

Read More...

Around the Blogs [Bitesize Bio]

Posted: 08 Aug 2008 05:48 AM CDT

We’ve reached the end of another week here on Bitesize Bio, so let’s close with the usual survey of what’s happening Around the Blogs. I’m not linking to too many posts (just five), and am instead trying to pick quality over quantity.

I hope you find them interesting.

Support Animal Research, Save Lives - Sandra discusses the injustices perpetrated at the hands of “animal rights’” terrorists, and links to a bunch of other great blogs discussing the same thing.

Motivating Students (and Motivating Women) to Pursue Science Careers - Commentary from PZ on an article in the Chronicle of Higher Education regarding how our culture keeps students out of science.

How to Blog, Get Tenure, and Prosper: A very useful engine - The latest installment in John Hawks’ series on blogging and tenure, including some great reasons for blogging.

PCR: Learning the Cheats - Less is More - Some very practical thoughts on planning your PCR stoichiometries.

New Understanding of Biology - Alex discusses a Nature article by Paul Nurse espousing the virtues of systems biology. I still think that, at least as Nurse put it, it’s a bunch of holistic nonsense. Alex takes it a bit more seriously, and argues more persuasively for it though, so go check it out.

The vicarious BioBarCamper [business|bytes|genes|molecules]

Posted: 07 Aug 2008 10:45 PM CDT

I am not at BioBarCamp. Couldn’t make it for various reasons, so I missed out on meeting a whole bunch of cool folks. Luckily we do live in the world of new media and instant community. While, I haven’t been able to follow every discussion, between Twitter, Cameron’s Mogulus feed and Friendfeed, I was almost there.

Lots of people who should take a bow, but none more so that Attila Csordás. I owe you one my friend. Given the success of this event and SciBarCamp, there are now four events on the science geek calendar that are going to be firmly circled in my calendar for next year, the others being the Scienceblogging Conference, now renamed ScienceOnline (a good change) and Scifoo. I hope to make at least three of them.

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New DNA based assay rapidly identifies E. coli [Think Gene]

Posted: 07 Aug 2008 09:44 PM CDT

My first paper just got published in this month’s issue of the Journal of Clinical Microbiology. We, primarily researchers at Children’s Hospital of Pittsburgh, developed an assay using a technique called Loop Mediated Isothermal Amplification (LAMP) to identify E. coli in a sample, ranging from blood to urine, without the need to first extract the DNA or to use a PCR machine. Rather, a sample can be added directly to a reaction mixture and heated on a heating block for 30-60 minutes. The sample will change color and fluoresce under UV light, allowing a positive result to be quickly and easily identified. We hope that this technique can be used in out patient clinics and clinics in developing countries to identify E. coli infections such as a UTI (urinary tract infection).

Further research is currently being conducted to develop these rapid tests for other infectious agents and bring them into clinical use.

Hill et al. Loop-Mediated Isothermal Amplification Assay for Rapid Detection of Common Strains of Escherichia coli. Journal of Clinical Microbiology. 46 (8): 2800. (2008)

More Neanderthal DNA Sequenced [adaptivecomplexity's column]

Posted: 07 Aug 2008 09:25 PM CDT

A paper in Cell is reporting the sequence of a Neanderthal mitochondrial DNA genome. Mitochondrial DNA, which you inherit only from your mother, has long been among the most useful DNA regions for tracing your ancestry. In the Neanderthal mitochondrial genome, researchers found, not surprisingly, that the sequence differences are well beyond the range of what we see within human populations, meaning that Neanderthals clearly were a distinct biological sub-species.

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1 comment:

dark_one said...

My name is Todd Thomas and i would like to show you my personal experience with Zocor.

I am 55 years old. Have been on Zocor for 4 years now. Zocor did lower my cholesterol. I also have RA and did not know which caused pain stopped Zocor, pain improved dramatically, but weakness remains. Dr says permanent damage. Now I my cholesterol is high.

I have experienced some of these side effects -
Leg pain and weakness

I hope this information will be useful to others,
Todd Thomas

Zocor Prescription Medication