The DNA Network |
| The right to get yourself genotyped [business|bytes|genes|molecules] Posted: 17 Jun 2008 08:09 PM CDT
If we really want to build a participatory healthcare system, then we need to let consumers gain some control of their own information. I am the first to admit that taking decision making away from physicians has a lot of risks. After all they are trained to make risk/benefit decisions, but spending some money to get yourself genotyped is something I’d like to be able to do on my own terms. What the data are used for is my decision. If there is a mandate saying that doctors need to be given access to such information, then it’s one thing, but you are not taking the tests to make immediate medical decisions. In fact, I’ve hoped that the software and material available on these sites will make more people aware of human genetics and how things work or don’t. The personal genome project uses informed consent, but it’s a project that requires public sharing of data and that was a choice that needed to be made cause of the cost (free) and public sharing requirements. 23andme, etc are running a business and it’s their right to do so and our right to avail of the service as long as we know what we’re signing up for. That the business has long term medical potential due to the treasure trove of data that can be used in the drug development process is the icing on the cake. I do not get mad often, but actions like these make me so. If you don’t like what the service offers, or think there is an issue with the information offered, why don’t you educate people about the issues and let them make an informed choice. I do not get mad often, but actions like these make me so. If you don’t like what the service offers, or think there is an issue with the information offered, why don’t you educate people about the issues and let them make an informed choice. One doesn’t need Jedi powers to feel lobbyists at work in this whole mess. Image via Wikipedia Technorati Tags: 23andme, Genetic Testing, Personal Rights  |
| ASM Bloggers Breakfast and Lost Notes [The Tree of Life] Posted: 17 Jun 2008 06:14 PM CDT Oops. I wrote some additional notes to post for the ASM Meeting but seem to have deleted or misplaced the file. One of the things I wanted to write about was how glad I was to have dropped by Moselio (aka Elio) Schaecter's breakfast discussion of blogging and microbiology. Fortunately Moselio has posted about this on his wonderful "Small Things Considered" Blog. I note it was also good to finally meet Tara Smith, who also has a great blog "Aetiology" and to meet/remeet some of the others. I was also inspired by some of the people there to start rebuilding my "OpenWetWare" lab page. Though I arrived late, the breakfast for me was the most inspiring thing about the whole meeting ... |
| Posted: 17 Jun 2008 05:11 PM CDT In its simplest sense, we imagine that learning occurs through a series of positive and negative rewards. Some actions lead to pleasure, others to pain, and it seems reasonable to expect that people will repeat the actions with pleasurable results and avoid those that ended in pain. Yet, we all know people who aren't deterred by the idea of punishment. We all know people who never seem to learn.
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| The inherent problem of scientific theories [Think Gene] Posted: 17 Jun 2008 04:50 PM CDT The inherent problem of scientific theories is that there exists an infinite equally valid explanations. Why? Because unlike in mathematics, we never have perfect information in science. First, some background on Bayes’ theorem. Bayes’ theorem is used to judge how likely an event caused an observation, like how likely a test result means cancer. Yet, Bayes Theorem produces probabilities, not axioms. There is always a chance that our belief is wrong.
Statement of Bayes’ theorem. This says: the probability of A given B is the product of the probability of B given A and the ratio of the probability of A to the probability of B. In science, Bayes theorem determines if observations support a theory. However, an infinite number of theories can explain the observations. We can eliminate theories by testing, and we can judge how likely a theory explains observations, but we can never certain. For example, in physics, many theories successfully explain observations, like String Theory and the Standard Model. Yet an infinite number of other theories exist that explain all our observations, even though we haven’t thought of them yet. OK, so our world understanding improves as we verify models, like if the Large Hadron Collider finds the Higgs… right? Theoretically, no. An infinite number of theories that are just as “probable” as the others still exist to be tested. All that was done was eliminate some of the theories. Subtracting anything from infinity is still infinity. An infinite number of theories exist because we can never have perfect information about everything, both practically (we can’t be everywhere and observe everything) and theoretically. For example, the Heisenburg Uncertainty Principle states that the more one knows about a particle’s momentum, the less one may know about its position and vice versa. Even if one was momentarily omniscient, it’s theoretically impossible to know the prior state of every particle in the universe. A simpler example: say my entire life, every swan I see is white. With reasonable confidence, I can assume that all swans are white. However, somewhere in the universe, there may be a black swan, disproving my theory. So then I could reasonably adjust my theory to say almost all swans are white. However, suppose I live in a region predominantly occupied by white swans, but really, black swans are the predominant type of bird. Or maybe black swans simply avoid me and my colleagues. How would I know? In essence, while science finds theories that explain the observations that we see, we have no way of proving if it is the one correct theory. It’s probably wrong —all refuted theories in the past have been. We can never know the truth, and we can never have the real model of anything we don’t define ourselves. The best we can do is agree to use a model that works for humanity’s tiny set of observations. For further reading on this topic: WHAT IS WRONG WITH BAYES NETS? Nancy Cartwright. 2001. Causation: One Word, Many Things. Nancy Cartwright. 2004. |
| Scientists discover DNA knot keeps viral genes tightly corked inside shell [Think Gene] Posted: 17 Jun 2008 04:03 PM CDT A novel twist of DNA may keep viral genes tightly wound within a capsule, waiting for ejection into a host, a high-resolution analysis of its structure has revealed.
By assembling more than 12,000 microscopic views of frozen viral particles from different angles, UCSD chemists Jinghua Tang, Norman Olson and Timothy Baker, a professor of chemistry and biological sciences, have determined the structure of a bacteriophage called phi29 with a resolution finer than 8 Angstroms (one Angstrom equals a tenth of a nanometer). Their project was part of a long-term collaboration with molecular virologist Dwight Anderson and his colleagues at the University of Minnesota. Although the structures of spherical viruses with a high degree of symmetry have been resolved using similar methods, many more images were required to accomplish the same task for the head-and-tail shape of phi29. The UCSD scientists said their images of phi29 are twice as fine as those created in previous efforts to visualize viruses with a similar shape. A comparison between images of the virus with and without its DNA cargo revealed that the DNA twists tightly into a donut shape, or toroid, in the neck of the virus between its head and tail. “This highly distorted DNA structure is unlike anything previously seen or even predicted in a virus,” said Timothy Baker who headed the research team. “It’s an improbably tight turn for DNA, which is generally considered inflexible over very small distances.” During assembly of the virus, a molecular motor in the neck winds the DNA strand into a tight coil within the head. “It’s under tremendous pressure — about 20 times that of champagne in a bottle,” said Tang, the lead author of the paper. The knot-like shape of the toroid, along with interlocking bumps in the protein envelope, may keep the DNA wedged into the capsid until the virus docks onto the host cell. “It’s poised in this tube waiting to go through the bacterial wall,” Baker said. “All of the components work together to create an infection machine.” Source: University of California - San Diego Josh says: Biology continues to amaze us. It makes sense for the DNA to be tightly packed and under a lot of pressure, thereby ensuring it is effectively delivered to the host upon infection. I’m sure there was a strong selection in favor of the viral particles that did this the best. |
| DNA Biobanks: The Five Minutes Between Nashville and Dundee [PredictER Blog] Posted: 17 Jun 2008 03:21 PM CDT Here at PredictER we're very interested in the attitudes of healthcare professionals regarding DNA biobanking. In fact, we recently collaborated in a study of attitudes at a local children's hospital. Thus, I was excited to read the results of similar survey research from Vanderbilt University School of Medicine. David A. Leiman, Nancy M. Lorenzi and some other bioinformatics folk in Nashville appear to have been working on this topic for a few years now - beginning with focus groups in 2000 and including a recent international, comparative survey. In "US and Scottish Health Professionals' Attitudes toward DNA Biobanking" [J Am Med Inform Assoc. 2008 May-Jun;15(3):357-62. Epub 2008 Feb 28. | PMID: 18308988], the authors compare the attitudes of healthcare professionals in Nashville with the attitudes of those in Dundee, Scotland. While they expected that the difference between a mostly private (U.S.) and a more socialized (U.K.) healthcare system would impact attitudes, they discovered that the attitudes were not that far apart. Presumably, the authors thought that U.S. health professionals would worry that genetic information might be misused by insurance companies in the private healthcare system and, thus, would be less likely to support biobanking. As it turns out the attitudes of the two survey groups were very similar. Of the fifteen questions in common, significant differences in attitude were found on only three questions. The Dundee professionals were slightly less supportive of creating a DNA biobank and (most importantly) were less comfortable with the idea that they might be asked to consent patients for DNA samples. In the discussion of the results the authors speculate that time constraints in Scotland might be at the root of this slight difference in professionals' attitudes about "consenting" patients into participating in the biobank: While many U.S. practices are expected to see patients 12-15 minutes, Scottish doctors are expected to perform the same visit in 7-10 minutes. The additional burden of consenting, or even explaining a biobank project, may be an overwhelming challenge to integrate into the existing workflow. Those "extra" five minutes of time in which to meet a patient's needs in the U.S., therefore, might account for the greater support ("Strongly Agree" versus "Agree") for DNA biobanking. The authors also mention the difficult nature of obtaining consent for this research – without a complicated: "Traditional consent procedures require researchers to contact participants each time a new investigation is undertaken with the same existing information". Let's hope that the validity of the patient's consent isn't sacrificed to better accommodate the busy schedules of the healthcare professionals. - J.O. |
| From Twitter to Wikis in Plain English: A series of videos [ScienceRoll] Posted: 17 Jun 2008 03:08 PM CDT Social Media:
Twitter:
Podcasting:
Wikis:
RSS:
Blogs:
Bookmarking:
Google Docs:
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| Posted: 17 Jun 2008 02:54 PM CDT There are few afflictions that affect as many people and are as severe as left-handedness. However I recently heard of another that is almost as bad, and affirms my genetic superiority. Indeed I am not tune deaf (TD). A recent Science Friday program talks to Dr. Allen Braun who investigates tune deafness. Tune deaf essentially means that you can't really distinguish when notes are played off key. Take the Distorted Tunes Test to see if you are tune deaf (beware Quicktime!). If you failed that test I find it hard to believe that you could ever really appreciate music, but a couple of callers into the science friday program say that despite TD they do enjoy music. Fortunately this affects only 2% of the general population so it is not as prevalent a problem as left-handedness. Unfortunately it is highly heritable. More interestingly, from ScienceNOW (link added): As expected, these subjects did not have the typical MMN response to poorly played tunes, the team reports today in PLoS One. But to their surprise, the researchers did detect the P300 response to the incorrect notes. Braun believes these results show that the brain can detect the differences even though tune-deaf people aren't aware. Thus these subjects possibly have a deficiency in transfer between conscience and unconscience knowledge of incorrect tones. The authors of the paper propose: In light of this, TD may provide a novel opportunity to study conscious perception. Unlike lesion-based disorders such as blindsight it should be possible to study the process in a brain that is structurally intact, and in a patient population that is far larger. In addition, TD is a highly heritable condition, and investigations currently underway may identify the genetic variants that underlie this condition. The tune deaf population may thus constitute a group in which the problem of consciousness might be approached at the cellular and molecular level using the tools of genetic research. |
| Medicine 2.0: The show goes on [ScienceRoll] Posted: 17 Jun 2008 02:53 PM CDT
Medicine 2.0 is a blog carnival dedicated to e-health and the impact of web 2.0 on medicine and healthcare. This is the 26th edition and the 5th time I host it myself. These days you can review abstracts for the Medicine 2.0 Congress which we, some medical bloggers, plan to attend this September in Toronto. Take a look at the review page and cast your vote. Until then, let me share some interesting articles and blogposts with you. Pubmed in focus: Laika’s Medlib Blog had two great posts about the past, present and future of Pubmed, the search engine of health science data (part I and part II). Euan Adie at Nature Network presented Pubmed FaceOff, a new mashup:
Gadgets: Joshua Schwimmer at The Efficient MD says our next stethoscope should be electronic and he tells us why. Deepak Singh at bbgm talks about medicine and the iPhone. The Medgadget Team shared some 21st Century Flashcards with us on, of course, iPhone.
Healthcare: Scott Shreeve at Crossover Healthcare had some comments about consumerism in healthcare.
Jay Parkinson gave a revolutionary presentation at HIMSS. Don’t forget to take a deeper look at this fantastic presentation: Web 2.0 Tools Web 2.0 and Beyond:
Social networks, wikis and more: The Clinical Cases and Images blog is curious whether there is a feed for job search for physicians. David Rothman shared CoPub, a text-minig tool, with us. Walter Jessen at Highlight Health told us seven ways to connect with the Highlight HEALTH Network. Uri Ginzburg at Medical 2.0 reported a web world for junior scientists. Alan J Cann at Science of the Invisible listed the reasons for the lack of adoption of social networks for postgraduate laboratory scientists. Bunny Ellerin at Pharma 2.0 says physicians continue to get social. YS at Prem4MD found free resources for MRIs Xrays CTs. And me at Scienceroll presented Second Life Fitness:
If you want to be up-to-date in this field of medicine, check the next edition of Medicine 2.0 out at Highlight Health 2.0. Or follow me on Twitter or follow the life scientists on Friendfeed. Submit your articles through the official form and drop me an e-mail if you plan to host an edition in July.         |
| Posted: 17 Jun 2008 11:50 AM CDT  Above is a map of regional use of generic terms for soft drinks in the US (curiously, 'soft drink' doesn't make the cut). I find the use of 'coke' as a generic term kind of interesting. It's sort of like kleenex, except if you ask for a kleenex nobody is going to complain if you get a Scott tissue instead of a Kimberly-Clark. "I'll have a coke please" "What kind?" "7-up" To see what classifies as 'other', or for Canadian statistics, go here (Massachusetts calls it 'tonic') [h/t: Gene Expression] |
| I told you he was a Trojan horse [Synthesis] Posted: 17 Jun 2008 11:32 AM CDT Way back when he was running for Governor of my fine state, I told everyone I could that Bobby Jindal was a Trojan horse for the religious right. I predicted that he was going to get right on the legislation they wanted. I thought he was going to go after stem cell research instead of evolution first, but I didn’t know what was going to happen with iPS cells in the meantime. Now look: Louisiana has a “protect the teaching of creationism” bill and he’s being considered as a VP candidate for McCain. Quid pro quo, no? .gif) This post is about creationism, GOP, jindal, louisiana, PoliticsRelated posts |
| Seven Ways to Connect with the Highlight HEALTH Network [Highlight HEALTH] Posted: 17 Jun 2008 10:59 AM CDT
Maybe you’ve a recent visitor … maybe you’ve been reading much longer. Whichever the case, there’s a number of ways to access content on the Highlight HEALTH Network. From RSS feeds to e-mail alerts to social networks, there’s bound to be a resource that works best for you. I'd also love to get your feedback in the comments below to help keep improving the Highlight HEALTH Network. Here’s seven ways to connect with the Highlight HEALTH NetworkRSS feedUse an RSS feed reader? Subscribe to the full text Highlight HEALTH Network RSS feed using your favorite RSS feed reader. E-mail alertsReceive e-mail alerts of new articles and links on the Highlight HEALTH Network. Are you a member of Facebook? Check out the Highlight HEALTH Network Facebook page. Become a fan and join in the conversation! Are you a Twitter user? Follow Highlight HEALTH Network posts on Twitter. Social BookmarkingAt the bottom of every article on Highlight HEALTH and Highlight HEALTH 2.0 there’s a “Bookmark and Share” link. By clicking on it, you can bookmark the post to one of many sites, including del.icio.us, Google Bookmarks, StumbleUpon and Newsvine. These sites make it easy to save or share an interesting article. Apple Dashboard widgetUse a Mac? The Highlight HEALTH Network RSS Dashboard Widget provides one-click access to the latest posts on the Highlight HEALTH Network. The widget is designed for use on the Apple Dashboard. Version 2.0 of the Highlight HEALTH Network RSS Dashboard widget includes content from Highlight HEALTH 2.0. The Highlight HEALTH Network RSS Dashboard widget is now listed on Apple.com. You can download the widget here.
OfflineWant to read content offline? Beneath the tags of every article on Highlight HEALTH and Highlight HEALTH 2.0, there is a “Print Post” link, which displays a printable version of the story, including all hyperlinks. Don’t have time to read online? Print it out and take it with you. Additionally, the Highlight HEALTH Network now offers a new and completely free professional resource. Browse a free selection of biotechnology and pharmaceutical magazines, white papers, downloads and podcasts. Topics include genetics, bioinformatics and genomics. No credit cards, coupons or promo codes required! ParticipateYou can participate in the Highlight HEALTH Network community by leaving your thoughts or questions in the comment section below every article on Highlight HEALTH and Highlight HEALTH 2.0. I try to reply to all comments. You can also e-mail me or use the contact form. Interested in guest posting? I’m always looking for people with an interest in Web 2.0 and Health/Medicine to contribute articles for Highlight HEALTH 2.0 and the hundreds of daily readers. Please e-mail me if you’re interested. Get connectedDon’t miss out on any of the great content on the Highlight HEALTH Network. Choose the resource(s) that work best for you and get connected today! .gif) Thank you for subscribing by RSS or email. I work hard to make the articles on Highlight HEALTH engaging and I truly appreciate your interest and readership!This article was published on Highlight HEALTH. Related articles |
| The Pope Has Delayed My National Institutes of Health Progress Report [adaptivecomplexity's column] Posted: 17 Jun 2008 10:53 AM CDT How is it that a statement by the Vatican has delayed my annual report to the National Institutes of Health? Not being Catholic, I generally don't pay much attention to Papal announcements, but maybe I need to start listening. Apparently back in March, the Vatican suggested that "genetic manipulations which alter DNA" are mortal sins. Since just about everything I do in the lab involved genetic manipulations which alter DNA (in fact the only organisms in our lab which aren't genetically engineered are the people who work there), I can add one more item to my long list of reasons for why I'm headed to eternal condemnation. But before I get to Hell, I need to submit my annual NIH Fellowship update. I have a fellowship from the National Institutes of Health, which pays my not-so-large salary. In return for the money, I tell the NIH what I've been doing every year. That's fair enough - the NIH should expect something for their money. Everything that I have done this year, however, has involved some sort of genetic engineering - which apparently upsets the Pope. This is unfortunate, because if we eliminated all genetic engineering, essentially all biomedical research would grind to a halt. Genetic engineering, in some restricted applications, has its risks, but the vast majority of genetic engineering that goes on every day in thousands of labs all over the world is essential to our efforts to understand both basic biology and the impact of genes on our health. |
| Adaptation to hypoxia via ACE polymorphism [Yann Klimentidis' Weblog] Posted: 17 Jun 2008 10:52 AM CDT Sherpas have a different allele frequency of the ACE I/D polymorphism than non-Sherpas. Adaptation to high altitude in Sherpas: association with the insertion/deletion polymorphism in the Angiotensin-converting enzyme gene. Droma Y, Hanaoka M, Basnyat B, Arjyal A, Neupane P, Pandit A, Sharma D, Ito M, Miwa N, Katsuyama Y, Ota M, Kubo K. Wilderness Environ Med. 2008 Spring;19(1):22-9. OBJECTIVE: Sherpas are well-known for their physical strength at high altitudes. They adapt to high altitude so well that little acute or chronic mountain sickness has been documented in them. The possible genetic basis for this adaptation is, however, unclear. The objective of this study was to elucidate the genetic background underlying this characteristic among Sherpas with respect to the angiotension-converting enzyme (ACE) gene. METHODS: We enrolled 105 Sherpa volunteers in Namche Bazaar (3440 meters) and 111 non-Sherpa Nepalese volunteers in Kathmandu Valley (1330 meters) in Nepal. Information about high-altitude exposure and physiological phenotypes was obtained via fieldwork investigation. The genotype of the insertion/deletion (I/D) polymorphism in the ACE gene was identified by polymerase chain reaction. Serum ACE activity was also measured. RESULTS: The distribution of the I dominant genotype (II & ID) and the I allelic frequency were significantly more prevalent in Sherpas (II & ID: 94.3%, I allele: 73.3%) than in non-Sherpas (II & ID: 85.6%, P = .035; I allele: 64.0%, P = .036). Moreover, despite residing at high altitude, the circulating ACE levels of Sherpas were statistically similar to those of non-Sherpas at low altitudes (Sherpas: 14.5 +/- 0.4 IU/L/37 degrees C; non-Sherpas: 14.7 +/- 0.4 IU/L/37 degrees C; P = .755). CONCLUSIONS: These findings suggest that the overrepresented I allele of the ACE gene in Sherpas might be one of the fundamental genetic factors responsible for maintaining physiological low-altitude ACE activity at high altitude, which may have an advantageous physiological role in adapting to a high-altitude environment. |
| CA calls for halt on genetic tests [Mary Meets Dolly] Posted: 17 Jun 2008 09:51 AM CDT Genetic testing is an amazing thing. It can provide such valuable information while at the same time confusing the heck out of everyone including your doctor. The question isn't just whether or not a genetic test is accurate, but whether or not the test has any clinical relevance. In other words, so your test says you have a certain mutation, is there sufficient evidence to show that that mutation may have a impact on your health? If the test is brand spankin new, offered by some internet start-up, I wouldn't trust it. If you want to order genetic testing online for yourself, go for it. Knowledge is power, just be aware that you are going to have to do some serious digging to make sure you know what your test results really mean. California authorities have recently ordered 13 companies to halt genetic testing to CA residents until said companies can prove they are in compliance with California state law. From the San Jose Mercury News:
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| Attn, California & NY: DNA is Data [Epidemix] Posted: 17 Jun 2008 08:34 AM CDT About the news that California health regulators have sent cease-and-desist letters to a baker’s dozen genetic testing firms, forbidding them from selling tests without a doctor’s order: I have two observations. First, I know that the direct-to-consumer personal genomics twosome, 23andMe and Navigenics, have been diligent in working with the FDA to make sure that their tests line up with current testing regulations and efficacy rules. So on some level, this may be a turf battle between state health departments (NY state has sent a previous notice) and the Feds. Second, this to me reflects as much a cultural disagreement as a legal or regulatory one. That is, there is the assumption in the states’ letters that, because genetic information has medical implications, the dissemination of this information must fall under their jurisdiction. But there are, in fact, all sorts of areas in life that have medical implications that we don’t consider the province of government - a pregnancy test, most obviously. We neither want nor assume that doctor’s should have a gatekeeper role in establishing whether we are or are not pregnant, nor do we look to the state to protect us from that information. Pregnancy is a part of life, and it has all sorts of implications and ramifications. So too with DNA. To my mind, genetic information is a new sort of personal information that the state and even the physician community are terribly slow and old-fashioned in reckoning with. Even those with knowledge in genetics, such as the Gene Sherpa blogger, assume a paternalistic tone: “I am just shocked and awed that some in the public think that they can do this on their own without professional help. Do you build your own home? What about fight your own court cases? Some do their own taxes…but only when it isn’t complicated. Trust me, this IS COMPLICATED!” Now, I agree with Steve Murphy about a lot of things, but I totally diverge from him on this. Having been tested by both 23andMe and Navigenics, I can say that, yes, it’s complicated. But frankly I don’t need a doctor, and I don’t want a doctor, to facilitate my understanding of what my DNA means. Yes, there are some medical implications, but these are hardly live-or-die moments. What’s more, when I have shared my results with physicians, they’re largely greeted with a shrug. I don’t want to “trust” a doctor, no matter how skilled or well trained, I want the access to my genetic data just as I want to know, without government approval or physician filtering, all sorts of information about myself. The assumption that there must be a layer of “professional help” is exactly what the new age of medicine bodes - the automation of expertise, the liberation of knowledge, and the democraticization of the tools to interpret and put to use fundamental information about who we are as people. Not as patients, but as individuals. This is not a dark art, province of the select few, as many physicians would have it. This is data. This is who I am. Frankly, it’s insulting and a curtailment of my rights to put a gatekeeper between me and my DNA. This is *my* data, not a doctor’s. Please, send in your regulators when a doctor needs to cut me open, or even draw my blood. Regulation should protect me from bodily harm and injury, not from information that’s mine to begin with. |
| Tree of Life hitting the big screen ... [The Tree of Life] Posted: 17 Jun 2008 07:42 AM CDT The "Tree of Life" is really hitting the big time. I just found, in a google search, that there is a movie coming out in 2009 called, "Tree of Life (2009)." The plot summary is as follows: In a mystical world of folklore, several individuals embrace in a race to find the Tree of Life, said to give immortality, fertility, and other supernatural powersAnd if that does not excite you, well, maybe this will. The cast includes Brad Pitt, Sean Penn and a few other big shots. Stay tuned here for more updates, or check out the wikipedia page for the movie here. Also see: Brad Pitt and The Tree of Life, Brad Pitt Scales Tree of Life, Malick's Tree of Life caught on camera, Brad Pitt looks young in Tree of Life movie |
| Height and hypertension genes in Nature Genetics [Genetic Future] Posted: 17 Jun 2008 03:44 AM CDT The advance online edition of Nature Genetics is stuffed with juicy complex human genetics goodness. Firstly, there are three massive genome-wide scans for genes involved in regulating human height, each of which analysed more than ten thousand individuals. As I've mentioned before, height appears to be one of those traits (like bipolar disease) that thumbs its nose at genome-wide association studies (GWAS). That's evidently clear from these studies, each of which - despite their unprecedented size (one of them scanned more than 25,000 individuals!) - managed to capture variants explaining less than 5% of variation in height. I note that a few previously identified height genes, like HMGA2 and GDF5, pop up in more than one of the three studies, while a new gene (ZBTB38) appears as the top candidate in all three of the studies. However, there doesn't seem to be a huge amount of overlap in the lower-ranked genes (although I need to read the articles more carefully to be sure). ScienceDaily puts a positive spin on the story ("Scientists are beginning to develop a clearer picture of what makes some people stand head and shoulders above the rest"), but the real story is this: despite the massive scale of these studies, they're still only capturing less than 5% of the total variance in a trait that is almost entirely (~80%) genetic. This is a powerful demonstration of the inability of current GWAS technology to access the genetic variants responsible for the vast majority of heritable variation in at least some complex traits, for reasons I've discussed recently. Researchers interested in the genetics of common diseases are no doubt experiencing a sinking feeling as they read these studies, since there's every reason to expect that what holds true for height will also apply in at least some of these conditions. If so, the number of patients required to characterise even a trivial proportion of the total genetic risk using GWAS will be astronomical. However, there is a light at the end of the tunnel: large-scale sequencing, once it drops in price, will provide researchers with access to the rare variants and structural variation currently missed by chip-based GWAS technologies, and should help to capture a substantial proportion of the missing variation. This leads into another Nature Genetics article, which used an interesting candidate gene resequencing strategy to detect variants linked with variation in blood pressure. Readers persistent enough to slog through yesterday's post on the genetics of bipolar disease might recall that hypertension is another disease in which the GWAS approach has yielded little success; in the comments to that post, G from Popgen ramblings notes that admixture mapping (an approach to gene identification using populations with mixed ancestry) has also failed to produce consistent signals, despite a profound difference in hypertension risk between populations. The Nature Genetics study took a different approach, sequencing the full coding regions of three genes associated with rare, serious hypertension conditions in previous family studies in more than 3,000 individuals from the Framingham Heart Study cohort. They found a scattering of rare variants - all present in a single copy in any given individual - with either inferred or biochemically verified effects on protein function. When the individuals carrying these rare mutations were analysed as a group they showed significantly lower blood pressure than non-carriers. This combination of targeted resequencing and functional analysis is a difficult road, but it's one that researchers will have to follow increasingly often as they attempt to characterise the rare variants that likely comprise a significant fraction of common disease risk. I'll have more to say about this in future posts.  Subscribe to Genetic Future. |
| Everyone is digging for gold, but I want to sell them shovels [Mailund on the Internet] Posted: 17 Jun 2008 01:11 AM CDT Years back, when I was studying computer science, I took a course on virtual machine design by Lars Bak. At the time he had just returned to Denmark but was still working at SUN and he managed to get a VP from SUN to give one of his lectures for him (I forget who it was, as I said it was many years ago). That particular lecture wasn’t about building object oriented virtual machines but about building successful software companies. (No snide remarks about someone from SUN talking about that, please). This was during the .com bubble or just while it was bursting, and the advice he gave was: “when everyone is digging for gold, you get rich by selling shovels”. If you build the basic infrastructure that everyone needs, it might not be as glamorous and if you are selling commodity products you won’t get rich over night, but if you are selling something that everyone needs, you won’t loose your market over night. Personal genomics and medicine shovels, anyone?I’m telling this story because I just read this post at Genetics Future. It concerns genetic testing and how it will soon change with complete re-sequencing which will be cost-effective Real Soon Now(tm). The post ends:
The personal genomics and genetic testing field is another gold rush (although one where small garage companies aren’t quite in on the game yet). Right now there’s plenty of testing labs, but with resequencing we’ll probably only get a few large companies, at least until the price for resequencing drops significantly. I don’t want to compete here. I’m sure I’ll lose. I would absolutely love to be selling shovels to the gold diggers! What will all these companies need? Of course they will need IT infrastructure to manage their data and statistical methods to correlated genotypes with phenotypes. The question is, of course, whether it will be possible to sell bioinformatics to such companies, or whether they will want to build all their informatics in house. Some, they want to, of course, as that will give them a competitive advantage, but surely there will be some commodity software they will want to buy somewhere else. They won’t build their own OS or database system, but probably their own specialised statistical models. Somewhere in between, there is money to be made, if I can only figure out how… |
| 4 (Well, 5) Facebook Applications for Biologists [Bitesize Bio] Posted: 17 Jun 2008 12:14 AM CDT If you love spending time on Facebook, but want to keep on working while “Facebooking” (or whatever the correct verb is) don’t fear. Here are 4 (5) biology-related Facebook applications, most of which you can claim to be working while using. F@H Protein Researcher Folding@Home (F@H) is a distributed computing project where individuals allow their free CPU time to create a world-wide super-computer that is used for the study of protein folding. The Protein Researcher Facebook application tracks user statistics for the F&H and includes team pages/walls, a profile box with your individual statistics, and ranked standings. SciBook - Science Social Network SciBook is a Life science social network for scientists. It’s a way for scientists to add the publications they are reading or have successfully published to their profile and discover others on Facebook interested in the same papers. Latest PHD Comics This application puts PHD comics on your profile. It updates automatically, so you don’t have to keep checking the website for new comics Pubface. This application allows you to search pubmed directly from Facebook. It also has a tell-a-friend feature, where you can forward interesting papers onto your friends, and a library feature that allows you to store up to 300 articles. I’m not really sure why you’d want to search Pubmed from a social networking site but who am I to judge? Another application - PubMed Search - does a similar job. Photo: pshab |
| TED talks: Medicine [Mailund on the Internet] Posted: 17 Jun 2008 12:00 AM CDT Cool talks related to medicine… Table of contents for TED Talks |
| Posted: 16 Jun 2008 11:10 PM CDT La Jolla Institute for Allergy & Immunology (LIAI) scientists have discovered one for the textbooks. Their finding, reported Friday in the scientific journal Immunity, illuminates a new, previously unknown mechanism in how the body fights a virus. The finding runs counter to traditional scientific understanding of this process and will provide scientists a more effective method for developing vaccines. “Our research grew from the question, “why do you get good antibody responses to some parts of (virus) pathogens and poor responses to other parts?” said LIAI scientist Shane Crotty, Ph.D., the lead researcher on the paper, “Selective CD4 T cell help for antibody responses to a large viral pathogen: deterministic linkage of specificities.” Alessandro Sette, Ph.D., a renowned vaccine expert and director of the LIAI Center for Infectious Disease, also was a key contributor on the study. Dr. Crotty said the team studied the smallpox vaccine, considered the “gold standard” of vaccines, and found some startling answers. “We expected one thing based on textbook knowledge and that didn’t happen at all,” he said. It was known previously that getting a good antibody response requires two different cells of the immune system — B cells and CD4 T cells, both soldiers in the immune system’s defensive army. Antibody responses are important because they help the body fight off viruses and they also are key to vaccine development. Surprisingly, however, Dr. Crotty said the researchers found that B cells and CD4 T cells recognize the same piece of the virus. “Previously, it was thought that the CD4 T cell could react to any part of the virus, but now we realize it must be specific to the same part as the B cell,” he explained. “When you have a hundred different parts, this knowledge makes a big difference. It narrows down the search for the right antigens tremendously.” Scientists use knowledge of which antigens (virus pieces) trigger an antibody attack to develop vaccines. Vaccines work by exposing the individual to a milder form of a particular virus, so that the body makes antibodies to fight off the virus. Consequently, if the individual is later exposed to the actual virus, the body already has an army of antibodies built up that can fight off this stronger viral attack before it can overtake the body and cause sickness. With the knowledge gained from the LIAI study, scientists will now be able to more easily figure out the most important viral pieces to focus on in developing a vaccine. “The fact that it requires two components to fight the (virus) pathogen is important to understand,” Dr. Crotty said. “So now when we find out which viral pieces are producing a strong response from the B cells, we can cross check that against the viral pieces eliciting a good response from the CD4 T cells. The point at which these virus pieces cross – in other words where the same piece is eliciting a response from both the B cells and CD4 T cells – then we know we have found our best candidate for creating a vaccine.” Source: La Jolla Institute for Allergy and Immunology Josh says: It’s too bad this probably won’t help that much with developing an HIV vaccine, since the virus mutates so quickly. Though, there have been reported cases of humans developing antibodies specific to the part of the virus that binds to the CD4 receptors, which can’t mutate. |
| Share science at FriendFeed [My Biotech Life] Posted: 16 Jun 2008 09:52 PM CDT I’ve been using FriendFeed for a while now and it was initially just another spot to share my content flow. Recently, the folks at FriendFeed made it possible to create rooms where users could now congregate and drop in links. I think this was a very smart move because it allowed some organization within the enormous flow of content that even a small group of friends generates. Given these conditions, a small group of life science buddies set up a room called The Life Scientists and it grew quickly to a jam packed 100+ “full” room. What I find really cool about all this is not just the ability to follow what colleagues and friends are doing online but the comments that they provide. A great example can be seen in the image that follows: FriendFeed has been growing quite rapidly and by keeping things simple it’s been useful for sharing web content and also maintaining light conversation around specific topics. Let’s hope it keeps that way! Read more about FriendFeed here and here or catch the latest FriendFeed “Best of” here. Post from: My Biotech Life |
| Test of bacteria toxin delivery system could pave way for new antibiotic drugs [Think Gene] Posted: 16 Jun 2008 09:41 PM CDT Researchers at the Hebrew University of Jerusalem have achieved a breakthrough in monitoring the toxin-delivery system of highly pathogenic bacteria – an accomplishment that could help pave the way for new drugs that will be capable of neutralizing those germs. Most bacteria are harmless and do not cause infections. Some, however, are pathogenic and are equipped with special accessories that are used to deliver toxins (also termed “effectors”) into the cells of the infected person. Numerous bacteria that cause disease, ranging from food poisoning to life threatening infection, employ a syringe-like nano-organelle (a specialized part of a cell having a specific function) that is used to inject toxic effectors into attacked host cells. This process is termed a type III secretion system (TTSS). Among these pathogens are Salmonella; the cause of typhoid fever, Yersinia; and enteropathogenic (intestinal) E. coli, which is responsible for the death of up to one million infants per year, mostly in developing countries. The bacterial syringe employed by these bacteria is an excellent potential target for drugs (not yet available) to combat these diseases. In order to develop such drugs, however, a better understanding of the syringe functions is needed, requiring development of better methods for measuring the syringe activity. The Hebrew University researchers – Ilan Rosenshine, the Etta Rosensohn Professor of Bacteriology at the Hebrew University Faculty of Medicine, and his associates — Erez Mills, Kobi Baruch, Xavier Charpentier and Simi Kobi — have designed a new, real-time test that allows monitoring the syringe activity. Using this test, they have discovered new properties of this system, which might be used to develop drugs that will inhibit the syringe activity and thereby prevent disease and infection by these dangerous pathogens Their achievement was described in a recent article in the journal Cell Host & Microbe. Source: The Hebrew University of Jerusalem Josh says: This certainly would have a LOT of applications. |
| Immune molecule that plays a powerful role in avoiding organ rejection identified [Think Gene] Posted: 16 Jun 2008 09:28 PM CDT When a mouse’s immune system is deciding whether to reject a skin graft, one powerful member of a molecular family designed to provoke such a response can effectively reduce the visibility of the mouse’s own cells and help the graft survive, researchers say. “This is a molecule with huge potential to regulate immune response,” Dr. Anatolij Horuzsko, reproductive immunologist at the Medical College of Georgia Center for Molecular Chaperone/Radiobiology and Cancer Virology, says of HLA-G dimer. Dimer appears to be the most powerful among several known forms of HLA-G at inhibiting the immune response, researchers have found. Fetuses use this natural mechanism to hide from the mother’s immune system and it’s at work in some transplant patients as well. Now that the scientists know which HLA-G is best at down-regulating the immune response and how it works, they believe the molecule’s action can be augmented in people with organ transplants and autoimmune disease and turned down to help fight a tumor. Measuring endogenous levels of HLA-G dimer may also help physicians identify which transplant patients require little, if any, immune suppression. Research published online in Proceedings of the National Academy of Sciences details that when HLA-G dimer binds with its inhibitory receptor, ILT4, it triggers a signaling pathway in which immune molecules IL-6 and STAT3 play a major role. “Biologically this is an interaction that requires several important suppressive molecules,” says Dr. Horuzsko, the study’s corresponding author and a faculty member in the MCG Schools of Medicine and Graduate Studies. They looked at the resulting strong signaling in culture, then measured its impact on skin graft survival in mice and found it prolonged survival. Now Dr. Horuzsko is working with Dr. Laura Mulloy, chief of the Section of Nephrology, Hypertension and Transplantation Medicine in the MCG School of Medicine, to see if this dimer form is at work in kidney transplant patients who avoid rejection. HLA-G dimer’s target is another MHC molecule, which is essentially an individual’s unique tissue signature; HLA-G itself is a type of MHC. In fact, HLA - human leukocyte antigen - matching is done for organ and bone marrow transplants to try minimize the recipient’s reaction to the new organ. Transplant patients also take drugs that broadly dampen the immune response but can leave them more vulnerable to infections and disease. Dr. Horuzsko notes that HLA-G can work through other cells, not just MHC molecules, and that not every HLA-G form is good at down-regulating MHC. He plans to look at HLA-G dimer levels in tumor patients as well. “Tumors already down- regulate MHC molecules,” he says, referencing how tumors turn down their tissue expression so they can fly below the radar of the immune system. “We need to see what form of HLA-G cancers - including leukemia, lymphoma, melanoma and breast cancer - use and see their level of expression.” He notes that HLA-G isn’t the only mechanism cancers use to escape the immune response but that being able to control a tumor’s use of this molecule could offer a new way to target tumors for natural destruction. A recent grant from the National Multiple Sclerosis Society is enabling studies of whether down-regulating MHC expression in multiple sclerosis patients can slow or arrest the immune system’s attack of the nerve’s protective covering. “The expression of the MHC molecule for some reason goes up - an infection might trigger the recognition of your own tissue - and the immune system attacks,” says Dr. Horuzsko. “We can generate a mouse with MS-like disease and target the HLA-G inhibitory receptor to see if it effectively down-regulates the disease.” He’ll look to see which, if any, of the HLA-G forms are most powerful in this autoimmune scenario. Source: Medical College of Georgia Josh says: I’ve always found immunology fascinating, and at one point was considering going into the field. This press release is a little on the technical side, as I’m not familiar with many of the molecules other than MHC (Major Histocompatibility Complex), which basically allows an organism to recognize itself from that which is foreign. |
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