The DNA Network |
| The shadow of Digg [business|bytes|genes|molecules] Posted: 02 Jun 2008 07:25 PM CDT Everyone wants to emulate Digg. I use Digg somewhat loosely here. Essentially, whether you’re in the tech world, or the science world, or some other, many services have tried to emulate the success of Digg, the poster child for bringing the impact of crowds (I refuse to use “wisdom” and “Digg” in the same sentence, this one excluded) to news. The latest effort in the life sciences, news.thinkgene.com space is actually not too bad, at least at first glance. The site is brought to you by the folks at Think Gene and allows you to vote on stories (not sure there is a down vote). As usual, I have not done sufficient stress testing with the site, but it’s simple enough to get started. For starters, news.thinkgene.com automatically pulls in posts from the DNA Network into the recent tab, so at the very minimum, it’s allowing users to vote DNA Network stories up or down (although they need to do a better job with attribution instead of the generic “feeds.feedburner.com”. You can also submit your own favorite stories, and there are the obligatory site widgets etc. So what’s missing? Well, community. Right now, the ranking really doesn’t mean anything because the number of votes is somewhat limited and the discussion is somewhat small. The reason FriendFeed is so attractive is that we have an active community there and getting a discussion going is easier than any other place I’ve been. new.thinkgene.com is a decent enough site, but to succeed, they definitely need to get a core set of active users, who submit content and participate, because without that, the other 99%, i.e. the consumers won’t come, and this is a challenge every such effort has. Give it a shot and let me know what you think. Like, dislike, don’t care Technorati Tags: news.thinkgene.com, social networking, wisdom of crowds  |
| Country of Jokes: death of a democracy [the skeptical alchemist] Posted: 02 Jun 2008 06:05 PM CDT I have to interrupt my usually calm blogging on science and other topics to bring you this news: a democracy is dying. While I wish the best to the newest republic in the world, I have to announce that, in the heart of Europe, one of the youngest democracies, celebrating its anniversary today, is as close to death as it has ever been since its inception. In these days, in Italy, we are seeing things that have not occurred probably since the times of Mussolini. You must think I am exaggerating - Italians are passionate people who tend to complain a lot and exaggerate things, right? Think again. I am not asking you to believe me, either. I am asking you to watch this with your own eyes. And you do not need to understand the language at all, to see what I am talking about. You might have heard about the Italian garbage emergency. No? Too engrossed in the American campaign, uh? OK, no problem, I will give you a blitzkrieg-style introduction to what is going on. Not so long ago, Berlusconi came to power for the third time. Immediately, he tried to pass a law (fortunately he did not succeed) to protect his televisions, one of which is illegally taking over frequencies that should belong to another broadcaster. At this time, the garbage scandal, exploded under the now defunct Prodi government, reached such gravity that immediate action was required to address the issue. So he moved to try and solve a crisis avoiding all the most reasonable solutions, and continuing on the road taken by his predecessors: instead of implementing a recycling program immediately, he gave one man (the "commissary") power to handle the whole issue, and promised to open more dumps, as well as have the police and the army defend these sites in case people opposed this move. People surely opposed it, as they always have. One of the sites will be an old cave in Chiaiano, a Naples neighbourhood. A place where there are hospitals, about 250,000 inhabitants, and where a solar power plant was supposed to be built. They happen to have old caves made of porous materials, materials which will not be able to protect underground waters used for drinking and agriculture. So the people of Chiaiano decided to protest. They did this peacefully. Some pushing here and there, but the protest was peaceful. You do not believe me? In the videos below the fold, look at the raised hands, at the police charging unarmed men and women, throwing tear gas at them, and even beating up journalists. In this area, more and more towns are starting to adopt recycling. Reusing and reducing are the only ways out of this crisis, a crisis created by governments (national, regional and provincial) as well as businesses (Impregilo, among these, deserves a special note) which have profited from the misery of a region infested by criminality, and blessed with the most fertile lands in the country...and some of the highest tumor loads, because of all the illegal (and legal) garbage dumping. Look at how our democracy is dying, with the armed forces are taking over the streets, citizens being ignored AND punished for speaking up, and all decency and rationality being thrown out of the window. In the meantime, our media are becoming more and more censored, so that now you are forced to find information on the internet. In the current climate of desperation, people are unable to find jobs (the unemployment rate is sky-high, inflation at 3.6%, and 40% of degree holders unable to find a job two years after graduating), xenophobia and environmental degrade are raging, and I expect that the attacks to our young democracy will become worse and worse in the months to come. The silent dictatorship of the powerful, the criminal and the corrupt is growing stronger, and this birthday feels like a morning bell for the so-called Second Republic. Watch the videos below the fold. The actual charge - here it comes. Some of the protesters are shouting "murderers" at the police (they expect the dump will bring increased cancer incidence to the town. They are not wrong). [If you cannot see the video, you can watch it here.] Here, Euronews reports on the clashes in Chiaiano. [If you cannot see this video, watch it here.] Here, a national news broadcast reports on, and condemns, the beating of a reporter in Chiaiano. [If you cannot see the video, watch it here.] A slideshow of the protest..and the beating. [If you cannot see this video, you can watch it here.] Check out the related videos for more. View blog reactions |
| Historic Events [The Gene Sherpa: Personalized Medicine and You] Posted: 02 Jun 2008 05:44 PM CDT First I would like to congratulate the World Science Festival for putting together a wonderful program. My friend Misha shared his thoughts today. A long time ago I was asked to help with this.... [[ This is a content summary only. Visit my website for full links, other content, and more! ]] |
| A genetic marker for nearsightedness? Update on vitamins and AMD [Think Gene] Posted: 02 Jun 2008 04:16 PM CDT The June 2008 issue of Ophthalmology, the journal of the American Academy of Ophthalmology, includes a groundbreaking study on genetic factors and nearsightedness, a cautionary tale on age-related macular degeneration (AMD) patients' vitamin use, and good news for people who have had an acute attack of optic neuritis. Strong Evidence for a Genetic Marker for Nearsightedness Research by Gu Zhu, M.D., and colleagues supports the theory that the refractive errors known as nearsightedness and farsightedness are primarily inherited. The group also identified the probable location—on the long arm of chromosome 5—of genes that help determine axial length, a key factor in these refractive errors. Axial length is a specific measurement from the front to back of the eye; this distance is longer than normal when a person is nearsighted and shorter than normal in a farsighted person. Dr. Zhu's study focused on nearsightedness, or myopia, building on previous research on genetic aspects and environmental factors. Myopia compromises the eye's ability to focus on and see objects clearly at a distance. Especially when myopia is severe, it is expensive to treat and costly to patients' quality of life. The disorder is on the rise in the United States and globally and research efforts have intensified accordingly. Dr. Zhu's team recruited 893 individuals from the Tasmania Twin Eye Study and Brisbane Adolescent Twin Study (BATS), Australia, and obtained axial length measurements. They analyzed the proportional impacts of genetic and environmental factors on axial length in this sample of identical and fraternal twins, and found that genetic factors explained approximately 80 percent of the axial length values, after adjusting for age and sex. This study breaks new ground in linking axial length to the heritability of refractive error. Research team member David Mackey, M.D., said that new measurement techniques will likely make collection of axial length data routine in future research on myopia and other refractive error. By performing a genome scan on a subset of 318 individuals, the researchers found "strong evidence" for the role of chromosome 5 (specifically the 5q region) in the inheritance of axial length. Dr. Zhu's team has launched a genomic analysis of a larger study group to confirm and refine this finding. Other studies have suggested that environmental factors such as regular periods of outdoor play during childhood—rather than having children concentrate only on reading and other "near work"—might help reduce the development of nearsightedness, at least in those who are genetically susceptible. Identifying strong genetic markers could further this and other preventive efforts. Vitamins Help Prevent Vision Loss from AMD—If Used Correctly A study of individuals with age-related macular degeneration (AMD), based at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, found that nearly 40 percent of those likely to benefit from specific vitamin/mineral supplements were either not taking the supplements or not using the recommended dosage. The study also showed that some patients used high-dose supplements even in the absence of evidence that these would be effective for their levels of AMD or other eye conditions. The ophthalmic researchers, led by Susan B. Bressler, M.D., concluded that AMD patients appear to lack a clear understanding of supplement use in AMD treatment, and that "improved patient education may be vital to maximize the potential" of this therapy. The public health impact could be substantial: in the United States if the appropriate patients used the correct supplements, about 300,000 people could potentially avoid advanced AMD within a five year period. At least eight million Americans are at risk for advanced AMD which can destroy the central vision needed to recognize faces, read, drive and enjoy daily life. In 2001 the Age-Related Eye Disease Study (AREDS) reported findings on its clinical trial that identified a specific formula of antioxidants (vitamin C, vitamin E and beta-carotene) and zinc that reduced the probability of progression to advanced AMD by 25 percent— either the "wet" or central geographic atrophy forms—among individuals at risk. Those who have AMD and smoke may need to use a formula that omits beta-carotene since high doses of this micronutrient have been associated with increased rates of lung cancer and mortality. Though effective treatment for advanced AMD is available, it can be expensive and is limited to the "wet" form. Also, since such treatment may not restore vision already lost to the illness, it remains important to use all effective approaches to preventing AMD progression. The Wilmer Institute-based study surveyed 332 individuals who identified themselves as having AMD; the median participant age was 79 years. Of these, 228 were considered candidates for benefit from the AREDS formula, but only 140 patients (61 percent) in this group were using the correct formula as recommended. Nearly 50 percent of the candidates-for-benefit did not correctly answer questions on the relevance of vitamin/mineral supplements to their eye condition and how their vision might benefit. But patients who indicated that they partially or fully understood the rationale for supplements were about twice as likely to be using the AREDS formula correctly. Optic Neuritis Patients Recover Good Vision What are the long term vision consequences when a person has an acute attack of optic neuritis, a sudden-onset eye disease of the nerves that carry visual signals to the brain” Are the consequences different if the person is treated with corticosteroids, or if the patient's attack is complicated by having multiple sclerosis (MS)” The Optic Neuritis Study Group recently conducted a 15-year follow-up study of 454 patients who had acute optic neuritis–a disorder that is often the first sign of MS—in one eye and who participated in the Optic Neuritis Treatment Trial (ONTT), a 1988 – 1991 randomized clinical trial. Optic neuritis causes symptoms such as blurred vision, blind spots, dimmed colors and sometimes eye pain. The researchers concluded that ophthalmologists (Eye MDs) can advise acute optic neuritis patients that the "long-term outlook for their vision is favorable," even if they currently have or develop MS. Of the original ONTT study cohort, 294 patients completed the follow-up exam in 2006. Seventy-two percent of patients had 20/20 vision or better in the affected eye and 66 percent had 20/20 or better vision in both eyes. Mild decreases in vision (20/25 to 20/40) were attributed to lens changes in nine patients, which would be expected in an age group with an average age of 48, the life-stage when the eye's lens becomes less flexible and many people need reading glasses. Long-term vision quality was similar among patients who were treated with high-dose intravenous corticosteroids and patients who were not, although the initial recovery period was shorter for treated patients. Even though their vision was found to be normal about 60 percent of the time, the patients with MS were more likely to report somewhat reduced quality-of-life, including: difficulty with daily tasks like parking a car and using a computer, and problems such as double vision and trouble focusing on moving objects. Source: American Academy of Ophthalmology Gu Zhu, MD, PhD, Alex W. Hewitt, MBBS, Jonathan B. Ruddle, FRANZCO, Lisa S. Kearns, BOrthOphSci(Hons), GradDipGenCoun, Shayne A. Brown, DipAppSc, MAppSc, Jane R. MacKinnon, FRCOphth, Christine Y. Chen, MBBS, Christopher J. Hammond, MD, Jamie E. Craig, DPhil, FRANZCO, Grant W. Montgomery, PhD, Nicholas G. Martin, PhD, David A. Mackey, MD, FRANZCO. Genetic Dissection of Myopia: Evidence for Linkage of Ocular Axial Length to Chromosome 5q. Ophthalmology. June 1, 2008; 115 (6). Michael L. Klein, MD, Frederick L. Ferris III, MD, Jane Armstrong, Thomas S. Hwang, MD, Emily Y. Chew, MD, Susan B. Bressler, MD, Suresh R. Chandra, MD, AREDS Research Group. Retinal Precursors and the Development of Geographic Atrophy in Age-Related Macular Degeneration. Ophthalmology. June 1, 2008; 115 (6). Optic Neuritis Study Group. Visual Function 15 Years after Optic Neuritis: A Final Follow-up Report from the Optic Neuritis Treatment Trial. Ophthalmology. June 1, 2008; 115 (6). Josh says: The papers aren’t available yet, but the first study involving the gene for nearsightedness is the most interesting to me. I think most of us assume that there had to be some genetic link to myopia, since it seems to run in families. Perhaps this is something that can be targeted early in life to prevent children from needing glasses as they get older. |
| Researchers identify proteins making up mechanosensitive ion channels [Think Gene] Posted: 02 Jun 2008 04:05 PM CDT Researchers at Washington University in St. Louis are the first to identify two proteins responsible for mechanosensitive ion channel activities in plant roots. Scientists have long known that plant cells respond to physical forces. Until now, however, the proteins controlling the ion channel response remained a mystery. As the name suggests, mechanosensitive channels are paths through the cell membrane that respond to mechanical forces such as gravity, pressure, or touch. Under certain forces, a channel opens, allowing the flow of ions, such as calcium and potassium ions, into and out of the cell. Different forces might close the channel, stopping the flow. This cross-membrane ion flow has been measured electrophysically, using a technique called the patch-clamp method. But the molecular nature of the channels themselves was not known. Now, knowing the proteins involved makes it possible to discover what the channels do for the whole plant. “People have been characterizing mechanosensitive channels in plants for 20 years,” said Elizabeth Haswell, Ph.D., assistant professor of biology at Washington University in St. Louis and lead investigator of this project, “This is the first time anybody has been able to show which proteins underlie these activities.”
Plants do it, bacteria do it
The two proteins governing ion channels in Arabidopsis root are MSL9 and MSL10, according to the study published in the May 20 issue of Current Biology. MSL stands for MscS-Like proteins because of their similarity to a family of bacterial channels known as MscS (mechanosensitive channels of small conductance). Even though bacteria and plants are not closely related in terms of evolution, this study shows that bacterial and plant cells are probably using the same types of proteins to respond to mechanical forces. To establish that the channels were in fact mechanosensitive, Haswell’s French colleagues used the patch-clamp method to measure the movement of ions across the membrane of Arabidopsis root cells as the pressure inside the cell increased. These experiments demonstrated that increasing cellular pressure also increased the ion flow across the membrane. Likewise, as the pressure inside the cell went down, the ion flow decreased. To determine whether MSL9 and MSL10 were responsible for this ion flow, Haswell created a mutant line of Arabidopsis without either type of protein. When the root cells of the plants lacking MSL9 and MSL10 were tested, the researchers saw very little change in ion flow across the membrane as the pressure inside the cell increased. In other words, without these two proteins, very little channel activity was seen. And the little channel activity they did measure was shown to be caused by different proteins.
Two to tango
Having shown that MSL9 and MSL10 were responsible for the ion channel activity, Haswell and colleagues set out to determine if both were required for the response or if only one did most of the work. Therefore, they tested plants that lacked only one of each protein and were surprised to discover that cells with only MSL9 showed one type of activity and cells with only MSL10 showed a different type of activity. And, importantly, cells with both proteins showed a third type, suggesting that both MSL9 and MSL10 are required to produce the mechanosensitive channel activity seen in wild-type Arabidopsis root. Haswell and colleagues propose that the channel is composed of subunits of both proteins MSL9 and MSL10 and that this combined structure results in the unique mechanosensitive ion channel behavior observed in the wild-type plants and not in any of the mutant lines. Despite identifying proteins that govern this ion channel response in Arabidopsis root, mysteries remain. To determine how the mutant plants might be defective and reveal the purpose of the channels, Haswell’s group grew the plants that lacked these channels under challenging conditions, including high salt, root barriers, and dehydration. “We tried hundreds of experiments, but we never saw a difference between the mutant and wild-type,” said Haswell, “but that’s definitely one of the next big steps – to find out what the channels really do and why they’re important.” Source: Washington University in St. Louis Josh says: I wouldn’t be surprised if humans also have similar ion channels, perhaps related to our sense of touch, though I’m not familiar with this field. We’ll know a lot more about how they function once someone solves the x-ray crystalography structure of them. |
| Brian Greene on Getting Kids Excited About Science [adaptivecomplexity's column] Posted: 02 Jun 2008 02:52 PM CDT Physicist and author Brian Green had an interesting opinion piece in yesterday's NY Times, arguing that we need to care about more than just science literacy - we have to promote excitement about science: |
| Medicine 2.0 carnival at Discovering Biology in a Digital World [ScienceRoll] Posted: 02 Jun 2008 02:26 PM CDT The 25th edition is up at the Discovering Biology in a Digital World! Check out all the posts and news about the world of medicine 2.0 and health 2.0. Thank you, Sandra Porter, for hosting Medicine 2.0! Medicine 2.0 is a blog carnival about the impact of web 2.0 on medicine and healthcare.  Medicine 2.0 editions so far:
The next edition is due to be published on the 15th of June 2008 at Scienceroll. Submit your blog article to the next edition of medicine 2.0 using our carnival submission form. And read about this interesting and emerging field here.         |
| Posted: 02 Jun 2008 02:17 PM CDT If you haven't yet heard, a Colorado man has held a press conference to reveal footage of an alien caught on tape in 2003.  From the looks of it, the video is a typical grainy, inconclusive Bigfoot-style shot that will convince believers and fail to impress skeptics. (And haven't the little green men heard of the Prime Directive?) But what if it was convincing? It would probably alter NASA's space program. Groups would try to figure out a way to kill it, or weaponize it. Biologists would have a field day. If suddenly presented with solid, convincing evidence of extra-terrestrial life, how do you think life on Earth would change (if at all)? What about your personal worldview? |
| All’s fair at the Fair [genomeboy.com] Posted: 02 Jun 2008 02:07 PM CDT
(l to r) Brian Greene, some photobomber, Paul Nurse, Nikolas Rose, Jim Evans, Francis Collins The World Science Festival was as delightful as advertised. The street fair was overflowing with stuff to do, especially for kids. Next year I hope to bring mine. Bravo to Brian Greene! I don’t know how my fellow panelists or the audience felt, but I thought our session, “Your Biological Biography,” was both fun and engaging, largely due to the masterful moderating job of Sir Paul Nurse, who is the antithesis of the stereotypical egocentric Nobel laureate/major university president. He is quick-witted, modest to a fault, and a brilliant conversationalist, someone you could chat with for hours on just about any subject. Drs. Rose, Evans and Collins responded in kind with thoughtful and nuanced discussion of personal genomics and all of the surrounding medical, legal, ethical and social issues. My only regret is that Dr. Latanya Sweeney was not able to make it and share her insights on genomic privacy. I talked about getting my SNP data from George and from Navigenics, the limitations of it, SNPedia, my family history, my own curiosity, and how I’m probably not a terribly zealous early adopter after all. At the end I tried to make two points. One is that genome scientists themselves are succeeding in killing genetic determinism where bioethicists and philosophers have failed. That is, by finding that traits like type 2 diabetes and height are influenced by some ridiculous number of genes and the environment, genomicists are putting to rest the notion that single genes typically exert powerful, inexorable effects that determine who we are. Yeah, that happens in some cases, but complex traits are still complex, which makes accurate genetic predictions harder to achieve and genetic discrimination even harder to justify. The other thing I tried to get across is that simply trashing personal genomics companies is not terribly helpful. Whatever their shortcomings (and they have plenty), these companies are here to stay in some way, shape or form. The more productive things to do, in my opinion, are to find out why people want this information, what their expectations are for it, how it should and shouldn’t be regulated, and how personal genomics, in all of its guises, can be assimilated by both the health care community and the public in useful ways. |
| Progress in the Hunt for Autism Genes [adaptivecomplexity's column] Posted: 02 Jun 2008 02:05 PM CDT Much of the coverage of autism in the media focuses on the arguments of advocates, scientists, and government officials over the relationship between vaccines and autism. But out of the spotlight, a bigger story is brewing: the hunt for autism genes, a technically difficult hunt which is pressing forward using all of the tools modern genetics has to offer. If you are like me, news stories about autism have left you with only a vague impression of the current scientific state of understanding, the impression that researchers strongly deny any link between autism and vaccines, but have little else to say about what the real cause of autism might be. If that is your impression, you'll perhaps be surprised to learn that roughly 20% of autism cases in the US are linked to known genetic changes, a minor fraction of autism cases to be sure, but much higher than I would have guessed. That autism has a genetic basis is a well-established finding, and while this by no means rules out environmental factors, genetics is at the core of the recent progress scientists have made in understanding autism. The genetics of autism, however, is not simple - no surprise, since autism involves our most complex organ, the brain, in one of its most complex functions, social interaction. Untangling the genetic and environmental factors that underlie autism will be tough, but in the process we will learn more about how many different genes work together in a child to control the developing brain. |
| Science is so much more than its technical details [Tomorrow's Table] Posted: 02 Jun 2008 12:57 PM CDT Please read this lovely opinion piece by Brian Greene (physicist and co-founder of the world science festival) in yesterday's New York Times A few tidbits: "Science is a way of life. Science is a perspective. Science is the process that takes us from confusion to understanding in a manner that's precise, predictive and reliable — a transformation, for those lucky enough to experience it, that is empowering and emotional. To be able to think through and grasp explanations — for everything from why the sky is blue to how life formed on earth — not because they are declared dogma but rather because they reveal patterns confirmed by experiment and observation, is one of the most precious of human experiences. Science is the greatest of all adventure stories, one that's been unfolding for thousands of years as we have sought to understand ourselves and our surroundings. Science needs to be taught to the young and communicated to the mature in a manner that captures this drama. We must embark on a cultural shift that places science in its rightful place alongside music, art and literature as an indispensable part of what makes life worth living. It's the birthright of every child, it's a necessity for every adult, to look out on the world... and see that the wonder of the cosmos transcends everything that divides us. " The accompanying picture shows a kayaker about to launch into the universe. I found the image intriguing, especially because I was in a car stuffed with kayaking gear. My husband, children and I were on the way to Shirttail canyon on the North Fork of the American River. Within minutes of being on the water Cliff (age 8) said softly and intently "I love this" and Audrey (age 7) was yelling "Yippee!", with both hands on the paddle raised over her head. They marveled at the height of the canyon, the clearness of the water, the apricot colored sticky monkey flowers, and the frogs they caught at the put-in. They learned to climb high side if we hit a rock, to not stand up in the water if they fall out of the boat, that the sticky monkey flowers are related to the empress tree in our backyard, that the Kellog's oak do not grow at lower or higher elevations, that the water is of simple composition and that their bodies are made mostly of water. They marveled at that too. At the end of the day, they were completely satisfied and so were Raoul and I. Today, my mind is less cluttered with technical details, and I am grateful, once again, to be a scientist. |
| Posted: 02 Jun 2008 11:45 AM CDT Nakamura E, Kozaki K, Tsuda H, Suzuki E, Pimkhaokham A, Yamamoto G, Irie T, Tachikawa T, Amagasa T, Inazawa J, Imoto I Array-based comparative genomic hybridization (array-CGH) has good potential for the high-throughput identification of genetic aberrations in cell genomes. In the course of a program to screen a panel of 21 oral squamous-cell carcinoma (OSCC) cell lines for genome-wide copy-number aberrations by array-CGH using our in-house bacterial artificial chromosome arrays, we identified a frequent homozygous deletion at 4q35 loci with approximately 1 Mb in extent. Among the seven genes located within this region, the expression of the melatonin receptor 1 A (MTNR1A) messenger RNA (mRNA) was not detected or decreased in 35 out of the 39 (89%) OSCC cell lines, but was detected in immortalized normal oral epithelial cell line, and was restored in gene-silenced OSCC cells without its homozygous loss after treatment with 5-aza-2′-deoxycytidine. The hypermethylation of the CpG (cytosine and guanine separated by phosphate) island in the promoter region of MTNR1A was inversely correlated with its expression in OSCC lines without a homozygous deletion. Methylation of this CpG island was also observed in primary OSCC tissues. In an immunohistochemical analysis of 50 primary OSCC tumors, the absence of immunoreactive MTNR1A was significantly associated with tumor size and a shorter overall survival in patients with OSCC tumors, and seems to be an independent prognosticator in a multivariate analysis. Exogenous restoration of MTNR1A expression inhibited the growth of OSCC cells lacking its expression. Together with the known tumor-suppressive function of melatonin and MTNR1A in various tumors, our results indicate MTNR1A to be the most likely target for epigenetic silencing at 4q35 and to play a pivotal role during oral carcinogenesis. |
| Posted: 02 Jun 2008 11:45 AM CDT Kim JC, Cho YK, Roh SA, Yu CS, Gong G, Jang SJ, Kim SY, Kim YS Clinicopathologic features of sporadic colorectal adenocarcinomas were compared using integrated data from 244 patients subjected to curative resection. Individual steps in the tumorigenesis pathway, that is, adenomatosis polyposis coli (APC), Wnt-activated, base excision repair mutations, mismatch repair defects, RAF-mediated, transforming growth factor (TGF)-beta-suppressed, bone morphogenic protein (BMP)-suppressed, and p53 alterations, were examined in terms of genetic and epigenetic changes, as well as protein expression. Genetic and molecular alterations of right colon cancers were distinct from those of left colon and rectal cancers. Rectal cancers showed the attenuated phenotype of left colon cancers. Tumors most frequently displayed either TGF-beta- or BMP-suppressed alterations (81.2%), followed by RAF-mediated alterations (78.6%), and mismatch repair defects (38.4%), constituting a total of 24 integrated pathways. Tumors lacking APC mutations or carrying the RAF alteration (V600E) were frequently associated with lymphovascular invasion and lymph node metastasis (P < 0.05). Poorly differentiated or mucinous adenocarcinomas were generally associated with high level microsatellite instability, Axin2 suppression, TGF-beta1 or BMPR1A suppression, loss of heterozygosity of D18S46 or D18S474, and absence of base excision repair mutations (P < 0.0001-0.05). Early tumor recurrence was significantly correlated with lack of APC mutations (P = 0.036). Moreover, tumors that concurrently displayed APC/Wnt-activated, TGF-beta/BMP-suppressed, and p53 alterations were significantly predisposed to early recurrence (P = 0.026). Our data clearly indicate that particular steps or pathways of colorectal tumorigenesis are closely associated with characteristic clinicopathologic features that, in turn, determine biological behavior, such as tumor growth, invasion, and recurrence. |
| Hepatitis B virus-cell interactions and pathogenesis. [Epigenetics News] Posted: 02 Jun 2008 11:45 AM CDT Nguyen DH, Ludgate L, Hu J Like all viruses, hepatitis B virus (HBV) replication and pathogenesis depends on the critical interplay between viral and host factors. In this review, we will focus on the recent progress in understanding the virus-host interactions at the level of the infected cell. These interactions include the requirement of cellular chaperones for the initiation of HBV reverse transcription, the role of the HBV X protein (HBx) in modifying viral and cellular transcription and signaling, the formation of the HBV episomal DNA and its epigenetic regulation in viral persistence, and the cellular factors involved in viral entry, nucleocapsid maturation, and virion secretion. |
| Chromatin organization and virus gene expression. [Epigenetics News] Posted: 02 Jun 2008 11:45 AM CDT Lieberman PM Many viruses introduce DNA into the host-cell nucleus, where they must either embrace or confront chromatin factors as a support or obstacle to completion of their life cycle. Compared to the eukaryotic cell, viruses have compact and rapidly evolving genomes. Despite their smaller size, viruses have complex life cycles that involve dynamic changes in DNA structure. Nuclear entry, transcription, replication, genome stabilization, and virion packaging involve complex changes in chromosome organization and structure. Chromatin dynamics and epigenetic modifications play major roles in viral and host chromosome biology. In some cases, viruses may use novel or viral-specific epigenetic modifying activities, which may reflect variant pathways that distinguish their behavior from the bulk of the cellular chromosome. This review examines several recent discoveries that highlight the role of chromatin dynamics in the life cycle of DNA viruses. |
| Oogenesis: Prospects and challenges for the future. [Epigenetics News] Posted: 02 Jun 2008 11:45 AM CDT Rodrigues P, Limback D, McGinnis LK, Plancha CE, Albertini DF Oogenesis serves a singular role in the reproductive success of plants and animals. Of their remarkable differentiation pathway what stands out is the ability of oocytes to transform from a single cell into the totipotent lineages that seed the early embryo. As our understanding that commonalities between diverse organisms at the genetic, cellular and molecular levels are conserved to achieve successful reproduction, the notion that embryogenesis presupposes oogenesis has entered the day-to-day parlance of regenerative medicine and stem cell biology. With emphasis on the mammalian oocyte, this review will cover (1) current concepts regarding the birth, survival and growth of oocytes that depends on complex patterns of cell communication between germ line and soma, (2) the notion of “maternal inheritance” from a genetic and epigenetic perspective, and (3) the relative value of model systems with reference to current clinical and biotechnology applications. |
| Posted: 02 Jun 2008 11:45 AM CDT Hall LL, Byron M, Butler J, Becker KA, Nelson A, Amit M, Itskovitz-Eldor J, Stein J, Stein G, Ware C, Lawrence JB The clinical and research value of human embryonic stem cells (hESC) depends upon maintaining their epigenetically nave, fully undifferentiated state. Inactivation of one X chromosome in each cell of mammalian female embryos is a paradigm for one of the earliest steps in cell specialization through formation of facultative heterochromatin. Mouse ES cells are derived from the inner cell mass (ICM) of blastocyst stage embryos prior to X-inactivation, and cultured murine ES cells initiate this process only upon differentiation. Less is known about human X-inactivation during early development. To identify a human ES cell model for X-inactivation and study differences in the epigenetic state of hESC lines, we investigated X-inactivation in all growth competent, karyotypically normal, NIH approved, female hESC lines and several sublines. In the vast majority of undifferentiated cultures of nine lines examined, essentially all cells exhibit hallmarks of X-inactivation. However, subcultures of any hESC line can vary in X-inactivation status, comprising distinct sublines. Importantly, we identified rare sublines that have not yet inactivated Xi and retain competence to undergo X-inactivation upon differentiation. Other sublines exhibit defects in counting or maintenance of XIST expression on Xi. The few hESC sublines identified that have not yet inactivated Xi may reflect the earlier epigenetic state of the human ICM and represent the most promising source of NIH hESC for study of human X-inactivation. The many epigenetic anomalies seen indicate that maintenance of fully unspecialized cells, which have not formed Xi facultative heterochromatin, is a delicate epigenetic balance difficult to maintain in culture. |
| Fear and Loathing in Boston for the ASM Meeting [The Tree of Life] Posted: 02 Jun 2008 10:40 AM CDT  OK Here is my confession. I hate, I mean hate, big meetings. If a conference has more than 200 people I start to feel icky. And now this AM I head off to Boston for the gigantic ASM "General Meeting". I am in part dreading the whole thing. Anytime one needs to use an online planner to schedule which talks one might want to go to, it is not really my kind of meeting. But, I was invited to give the "Division R" lecture. Division R is the "Systematics and Evolutionary Microbiology" section of ASM and this year they are having a session on "Linking evolution of protein families to genome annotation efforts." This is right up my alley as it was for genome annotation that I first started working on phylogenomic methods (and for which I coined the phrase "phylogenomics") (e.g., see my 1998 paper in Genome Research for more detail on this and see my 1995 paper on SNF2 proteins in NAR where I first discussed using evolutionary trees to predict gene function). And since the meeting is in Boston (where I was born), I agreed to go. Add I am sure I will see some great things there. But travel and I do not agree well right now and I am I guess dreading the whole thing. If you want to learn more about phylogenomics go to the division R session (Kimmen Sjolander, Patricvia Babbitt, and Margrethe Serres are also talking). And I will try to blog from the meeting but we shall see ... |
| Is it heritable? A new series on twin studies. [DNA and You] Posted: 02 Jun 2008 10:14 AM CDT Twin studies are one of the foundations of modern human genetics. Researchers take advantage of a basic biological fact (that identical or monozygotic twins share essentially 100% of their genomes while fraternal or dizygotic twins share 50%) to study to what degree certain traits (disease risk, etc.) are heritable (i.e., how much of the disease risk is conferred by the genes versus the environment or just random events). Twin studies offer a very interesting window into human genetics and can often be extremely thought-provoking. Here at DNA and You, I will periodically point out an interesting twin study as food for thought. For example, it is commonly assumed that any familial effect on political party choice is environmental in nature, but these authors set out to look into this in further detail. Basically the results suggest that although there is a modest effect of genetics on political party choice, this is probably conferred through intermediate genetic influences on attitudes about key political debates and other things like church attendance and social class. |
| Posted: 02 Jun 2008 09:57 AM CDT Gastric (Stomach) cancer is one of the most common cancer types world-wide. As the fourth most common cancer worldwide and the second most common cause of cancer death, it is an important public health problem, particularly in Asia where is is quite common. There are two major subtypes of gastric cancer that can be recognized under the microscope: "intestinal" and "diffuse." The intestinal type seems to be associated with Helicobacter pylori infection and is particularly common in some high risk geographic regions, including Asia. In contrast, the diffuse type seems unrelated to the presence of H. pylori and has a much more uniform geographical distribution. We've known for a long time that there is an hereditary component to risk for at least some diffuse gastric cancer cases. A major breakthrough came when mutations in the CDH1 gene were found to be responsible for a familial form of diffuse gastric cancer: "Hereditary Diffuse Gastric Cancer." The CDH1 gene provides the coding information necessary for our bodies to make a protein called "E-cadherin," which is important in the molecular connections between adjacent cells in the stomach, the breast, and also other areas of the body. Loss of E-cadherin function - associated with mutations in the CDH1 gene - is seen in diffuse type cancers of the stomach and also a specific type of breast cancer: invasive lobular breast cancer. Individuals inheriting a familial mutation in CDH1 have an approximately 75% lifetime risk for developing diffuse gastric carcinoma and women with an inherited CDH1 mutation have about a 40% lifetime risk for developing lobular breast cancer. Nevertheless, inherited Hereditary Diffuse Gastric Carcinoma with mutations in CDH1 is pretty rare. With this in mind, some research groups have been looking for other genes that might be involved in risk for diffuse gastric carcinoma, particularly the non-familial type (i.e., diffuse gastric carcinoma in an individual without a family history of this type of cancer). Recently, a Japanese research group, "The Study Group of Millennium Genome Project for Cancer," reported in Nature Genetics (abstract available here) the results of a new study demonstrating the involvement of the PSCA gene in risk for diffuse type gastric cancer. The authors focused the study design on "sporadic" (i.e., non-familial or occurring in someone without a family history of the disease) diffuse gastric cancer. In other words, they figured that an individual's genes might influence risk for this cancer type even in the absence of a family history of the disease. A genome-wide association study (GWAS) performed initially in 188 people with sporadic gastric cancer and 752 controls revealed an association of a single nucleotide polymorphism (rs2976392) in the gene PSCA (aka prostate stem cell antigen) with diffuse gastric cancer. Re-sequencing of the PSCA region in the affected individuals revealed a number of SNPs that could potentially be responsible; however, it appears that a non-synonymous SNP (i.e., one that changes an amino acid in the PSCA protein), rs2294008, is most likely responsible for conferring disease risk. As it can change the first amino acid from methionine (which must be the first amino acid when proteins are produced) to threonine, it appears likely to affect both the efficiency of PSCA protein production and also the length of the resultant protein. Interestingly, the authors did include some cases of intestinal type stomach cancer in the analysis and showed that the effect of genetic variation in PSCA was much stronger on risk for diffuse gastric cancer than for the intestinal type. Finally, in addition to replicating their results on a second set of samples in Japan, they also showed an association of PSCA SNPs with diffuse gastric cancer in Korean individuals. So, what are the clinical implications? As the allele-specific odds ratios are less than 2, these SNPs are unlikely to have a major impact on clinical practice in the near term. They do teach us something interesting about gastric cancer causation and also - importantly - may identify a novel drug target or pathway in this disease. Interestingly, the risk variants exist as "major alleles" in the Japanese population. This means that most people carry them. Thus, it might explain some of the increased frequency of diffuse gastric cancer in this population. Additionally, as the authors did not have information about Helicobacter pylori infection for most study patients, is is unclear whether the PSCA SNPs directly affect disease risk or might instead influence an individual's susceptibility to H. pylori infection, which is itself a risk factor for gastric cancer development. Perhaps further studies will be able to clarify this point. Genes of Interest Key References Brooks-Wilson AR et al. Germline E-cadherin mutations in hereditary diffuse gastric cancer: assessment of 42 new families and review of genetic screening criteria. Journal of Medical Genetics 41: 508-17, 2004. Guilford P et al. E-cadherin germline mutations in familial gastric cancer. Nature 392: 402-5, 1998. Kaurah P, Huntsman DG. (Updated 31 August 2006). Hereditary diffuse gastric cancer. In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Available at http://www.genetests.org. Pharoah PD et al. Incidence of gastric cancer and breast cancer in CDH1 (E-cadherin) mutation carriers from hereditary diffuse gastric cancer families. Gastroenterology 121: 1348-53, 2001. The Study Group of Millenium Genome Project for Cancer. Genetic variation in PSCA is associated with susceptibility to diffuse-type gastric cancer. Nature Genetics; published online 18 May 2008; doi:10.1038/ng.152.
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| Fantastic Animation of DNA, RNA and Protein [The Daily Transcript] Posted: 02 Jun 2008 07:44 AM CDT I must say that the animators omitted many details, such as the RNA polymerase's c-terminal repeats, splicing, the assembly of an RNP, the workings of the nuclear pore complex, and the assembly of a translation initiation complex ... but WOW! We need more of these videos! Read the comments on this post... |
| Sunshine Monomer and the X-ray Sidestep [Sciencebase Science Blog] Posted: 02 Jun 2008 07:00 AM CDT
Also in the June 1 issue - Sunshine monomer - Australian researchers have built a model of the skin pigment that protects us from harmful ultraviolet rays, that could help explain how the pigment can absorb and dissipate the energy of 99.9% of solar UV. Meanwhile crystallographers in the USA may have found a way to side-step one of the most frustrating steps in obtaining a molecular structure using X-ray diffraction, the crystallisation process itself. Instead, they’re using lasers to align molecules in the gas phase so that they can get Bragg-like diffraction pattern with pulses of high-energy synchrotron X-rays. The work could open up protein science in an entirely unprecedented way allowing proteins that cannot be crystallised to be studied with atom-by-atom detail. More on that, here. A post from David Bradley Science Writer Sunshine Monomer and the X-ray Sidestep |
| Birth of the Cell Doctrine [Bitesize Bio] Posted: 02 Jun 2008 05:09 AM CDT
That’s generally why I liked The Birth of the Cell so much when I read it. Dissatisfied by the standard accounts of the origin of the cell doctrine, Henry Harris read the original writings of the relevant early cytologists from the first visualization of animalcules to the identification of the cell nucleus and binary fission. Although very dense reading, the result is a book that describes the slow, awkward development of a science and the rivalries of the scholars involved.
Purkyn? also made significant and early correlations between plant and animal tissues, before those of Schwann (who largely avoided citing Purkyn?). As a consequence, it is the 1837-38 work of Schleiden, Schwann, and the mentor Johannes Müller, presented in widely circulated monographs, that are remembered. Similarly, the work of Robert Remak, also an outsider in German society, was largely stolen by Rudolf Virchow, who was a better lecturer than scientist. Virchow himself conceded that he could was not the discoverer of the ideas which he was putting forward, but he did gladly take credit as the propagator of those ideas, for which he gained fame. From Page 135:
Harris gleaned all of these observations from reading the journal articles, monographs, and textbooks of the period, to see what the scientists actually thought at the time, and how those minds changed over time. |
| Brain scanning vs personal genomics [Genetic Future] Posted: 02 Jun 2008 02:40 AM CDT  Personal genomics companies like 23andMe, deCODEme and Navigenics have taken substantial media flak recently over their limited ability to make useful disease risk predictions based on genome scan data.There's certainly some truth to that accusation, but all three of these companies have been generally good at conveying this uncertainty to their customers. In particular, I've been amazed by the tendency of deCODEme to play down the usefulness of their tests in terms of disease prediction. I've previously mentioned deCODE's Kari Stephansson's admission at Cold Spring Harbor Laboratory that deCODEme is "marketing these tests without any claim that they will impact on people's lives"; a couple of weeks ago I attended a seminar on personal genomics in Cambridge, UK, where deCODEme's Agnar Helgason volunteered that "what we can offer at the moment is pretty meagre". Navigenics and 23andMe tend to avoid such frank admissions, but their predictions are still very carefully phrased in statistical terms. In any case, the accuracy of predictions based on personal genomics starts to look much more impressive when it's compared to some of the other 'science-based' prediction industries out there. A recent article in Wired has a fairly scathing review of one such field: the use of functional brain scans to predict risks of mental illness, personality traits, dishonesty, political views and consumer behaviour. Given the $3,300 price tag for one of the services on offer (from a company that is "dedicated to optimizing the brain-life connection in our patients and people worldwide", according to their website), this is a pretty expensive piece of foolishness. No doubt some patients benefit from the service, but it's likely that they would have gained just as much from a visit to a good counsellor without the fancy brain scans, at a small fraction of the cost. Long-term readers will know that I don't recommend current genome scans - my suggestion is that potential customers save their money for a few years, by which time large-scale sequencing will be affordable, and we will know much more about disease-associated genetic variants - but if I had to pick a fancy technology to waste my money on I'd go with a genome scan over a brain scan any day.  Subscribe to Genetic Future. |
| Interview Series III - Terry Barton [The Genetic Genealogist] Posted: 02 Jun 2008 02:00 AM CDT “Terry is co-founder of WorldFamilies.net, President of the Barton Historical Society (BHS) and Co-Leader of the 193 member Barton DNA Project. He is the "Line Leader" for the Thomas (1,2,3) Barton family of Stafford Co VA and for the David Barton married Ruth Oldham family. He has made a number of presentations about using DNA in Genealogy, the Barton DNA project and his great-grandparent’s “Barton House” and has written many articles for the BHS Newsletters and website.” In the following interview, I ask Terry about his introduction to genetic genealogy, the origin of the World Families Network, and his thoughts on the future of genetic genealogy. The Genetic Genealogist: How long have you been actively involved in genetic genealogy, and how did you become interested in the field? Terry Barton: I got involved in genetic genealogy in 2001 as assistant admin for the Barton Surname Project - when it was formed. We worked with BYU’s Center for Molecular Genealogy - which eventually became Relative Genetics. Our first two rounds of testing were in “batches”, with 52 men in the first batch and 42 in the second. I became the lead admin with batch 2 and have led the project since then. I was already actively researching my ancestry by traditional means and was President of the Barton Historical Society, leading that group into becoming the sponsoring organization for the Barton DNA Project. TGG: Have you undergone genetic genealogy testing? Were you surprised with the results? Did the results help you break through any of your brick walls or solve a family mystery? TB: I am personally tested on 116 yDNA markers, the available SNPs and the Full mtDNA Genetic Sequence. I have tested my son to the same 116 markers (we match perfectly) However, my Dad and I each started a mutation (his is at DYS388, while mine is at DYS452) So, I am 41/43 when compared to my Uncle. I use this example to explain how you can’t count mutations to determine how closely related you are to someone. I was pleased to identify the probable ancestral home of my Bartons as Lancashire and the probable home of my mother’s Hodges family as Kent. My Bartons appear to be the Celts and my mother’s Hodges to be the Frisians (both conclusions are still tentative) I have also learned that most southern American Bartons are my genetic kin and that a number of the southern American Hodges are my genetic kin. I have dna tests for another half dozen of my ancestral lines and mtDNA FGS tests on my Dad and Wife. There are too many success stories across this range of testing to share here. TGG: You are one of the co-founders of the World Families Network. How did the site come about, and what are its goals? TB: My partner, Dr. Richard Barton (also co-admin of the Barton Project) is my genetic kin - we found each other through the project. Our most recent common ancestor was born no later than c1620s - we have no paper trail connection. (Rich is a 43/43 match to my Uncle) We used Rich’s website leadership to help us address our early project weakness of low internet visibility and started thinking in early 2004 about how we could share our learning with other surname projects who needed information and/or website help. Over the course of 2004, we evolved into much of what you see today, providing an array of helpful information and supporting many surname projects in a variety of ways. Our goal is to provide an array of useful services to the Genetic Genealogy community - and to have fun doing it. TGG: What other genetic genealogy-related projects are you involved with? TB: I am lead or support admin for over 50 of my ancestral surname dna projects. In many cases, I have evolved to being only the technical advisor or support, while I (or our staff) provide leadership for many more of the projects than I wish (which means I haven’t found the right cousin to get involved). I love the connections I’ve made and am constantly amazed at how many folks will go out of their way to help me - or to share info with me. I also co-lead the Va-1600s geographical projects and the mt-T1 haplogroup project and am one of four admins on the T_FGS research project. I am webmaster and founding board member of the Journal of Genetic Genealogy, serve on the Board of the Cobb County Genealogical Society and a member of ISOGG. I continue as President of the Barton Historical Society and am a founding member of the Hodges-Hodge Society, which came out of the Surname dna project it now sponsors. I speak regularly on genetic genealogy. I probably missed something. TGG: What do you think the future holds for genetic genealogy?
TB: When I started in 2001, 12 markers was a lot! By the time Barton (finally) got our first batch of results in 2002, we received info on 23 markers - which was incredible. I used to think 100 markers and 100 members would bring all of the answers (neither did). When I look to the future and try to imagine - I really can’t identify specifics - other than to anticipate that we’ll know so much more than now. I realize that we are building the foundation for that future and hope that those who follow appreciate what we have done (as they laugh at the primitive info and understanding that we had “way back in 2008″. ) My personal quest is to develop enough learning through dna to replace the lost paper trails. I don’t know if that will be possible - but I intend to keep trying. TGG: Thank you, Terry, for this terrific interview! Other posts in the TGG Interview Series:
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| Potential treatments from cryptic genes [Think Gene] Posted: 01 Jun 2008 11:47 PM CDT Big pharma gave up on soil bacteria as a source of antibiotics too soon, according to research published in the June issue of Microbiology. Scientists have been mining microbial genomes for new natural products that may have applications in the treatment of MRSA and cancer and have made some exciting discoveries. “Over the last eight years we have been looking for new natural products in the DNA sequence of the antibiotic-producing bacterium Streptomyces coelicolor,” said Professor Gregory Challis from the University of Warwick. “In the last 15 years it became accepted that no new natural products remained to be discovered from these bacteria. Our work shows this widely-held view to be incorrect.” In 1928 Alexander Fleming discovered penicillin, which was subsequently developed into a medicine by Florey and Chain in the 1940s. The antibiotic was hailed as a ‘miracle cure’ and a golden age of drug discovery followed. However, frequent rediscovery of known natural products and technical challenges forced pharmaceutical companies to retreat and stop looking for new molecules. Currently the complete genetic sequences of more than 580 microbes are known. It is possible to identify pathways that produce new compounds by looking at the DNA sequences and many gene clusters likely to encode natural products have been analysed. ‘Genome mining’ has become a dynamic and rapidly advancing field. Professor Challis and his colleagues have discovered the products of two cryptic gene clusters. One of the clusters was found to produce several compounds that inhibit the proliferation of certain bacteria. Three of these compounds were new ones, named isogermicidin A, B and C. “This discovery was quite unexpected,” said Professor Challis. “Our research provides important new methodology for the discovery of new natural products with applications in medicine, such as combating MRSA infections.” The other product they discovered is called coelichelin. Iron is essential for the growth of nearly all micro-organisms. Although it is the fourth most abundant element in the Earth’s crust it often exists in a ferric form, which microbes are unable to use. “The gene cluster that directs production of coelicehlin was not known to be involved in the production of any known products,” said Professor Challis. “Our research suggests that coelichelin helps S. coelicolor take up iron.” Many researchers have followed Professor Challis and his colleagues into the exciting field of genome mining. “In the near future, compounds with useful biological activities will be patented and progressed into clinical or agricultural trials, depending on their applications” said Professor Challis. Source: Society for General Microbiology G. L. Challis. Mining microbial genomes for new natural products and biosynthetic pathways. Microbiology; 154: 1555-1569 (not available at time of publication. Link goes to “Future Table of Contents”) Josh says: I’m not surprised at all that they found new potential antibiotics in soil bacteria. They are known for producing antibiotics, and it only makes sense that different species will produce different antibiotics. If they didn’t, they would become ineffective, like we’re seeing now with MRSA. Since I can’t read the paper, I’m don’t know if they known the mode of action of these antibiotics, but my impression from the press release is that it prevents the bacteria from uptaking iron. Andrew says: Soil bacteria genome mining is also interesting for potential insertional gene therapies to metabolize waste substances which accumulate in the body and contribute to aging. I’m excited to learn about those genes as they’re discovered. |
| Genetic mutations in human brain linked to walking on all 4s [Think Gene] Posted: 01 Jun 2008 10:32 PM CDT What are the genes implicated in upright walking of humans? The discovery of four families in which some members only walk on all fours (quadrupedality) may help us understand how humans, unlike other primates, are able to walk for long periods on only two legs, a scientist will tell the annual conference of the European Society of Human Genetics tomorrow (Monday 2 June). The quadrupedal families in Turkey previously attracted attention in 2005, when they were discovered. Now the Turkish team reports that they have found the first gene implicated in quadrupedal locomotion in these families. Professor Tayfun Ozcelik, of Bilkent University, Ankara, Turkey, and colleagues, studied four unrelated families where some members were affected by the rare quadrupedic condition, Unertan syndrome, which is also associated with imperfect articulation of speech, mental retardation, and defects in the cerebellum, a part of the brain involved in motor control. They found that the affected individuals in two families had mutations in the gene responsible for the expression of very low density lipoprotein receptor (VLDLR), a protein which is known to be critical to the proper functioning of the cerebellum during development. Although the families lived in isolated villages 200-300 km apart and reported no ancestral relationships, the scientists expected to find a single genetic mutation implicated in the condition. They were surprised to find that this was not the case. “We carried out genome-wide screening on these families”, said Professor Ozcelik, “and found regions of DNA that were shared by all those family members who walk on all fours. However, we were surprised to find that genes on three different chromosomes are responsible for the condition in four different families. “In families A and D there were mutations in VLDLR on chromosome 9, and in family B the phenotype maps to chromosome 17 to a region that contains at least 157 genes, and we are still looking for the precise mutation. Neither region appears to be implicated for family C.” In all cases, the affected individuals were the offspring of consanguineous marriages, which suggests that if they had married outside the family they would not have had the condition. All of them had significant developmental delay in infancy. “Whereas normal infants make the transition to walking on two legs in a relatively short period”, said Professor Ozcelik, “these individuals continued to move on their palms and feet and never walked upright. Although they can stand from a sitting position and maintain this upright position with flexed hips and knees, they virtually never initiate bipedal walking on their own.” It has been suggested in the past that lack of access to medical care exacerbated the effects of an under-developed cerebellum, and that this led to quadrupedality. “Although it may be true that family B lacked proper medical care, families A and D had consistent access to good medical attention, and both families sought a correction of quadrupedality in their affected children”, said Professor Ozcelik. “Indeed, an unaffected member of family A is a physician, who has been actively involved in the medical interventions. In addition, the parents in family A also discouraged their affected children from walking on all fours, to no avail. We think that social factors are unlikely to be involved in the development of quadrupedal locomotion.” Mutations causing VLDLR deficiency are also found in Hutterites, a group of Anabaptists who live in colonies of North America. There, however, most of the affected individuals cannot walk at all. The neurological characteristics of the affected members of the Turkish families and the Hutterites seem similar, with the most striking difference being that the Turkish individuals are able to walk on all fours, said the scientists. They hypothesize that the Hutterites may be more profoundly affected due to the deficiency in VLDLR and a neighbouring gene, and therefore lack the motor skills even for quadrupedal locomotion. Along with brain enlargement, speech, and the ability to make tools, upright walking has long been regarded as one of the key traits that have led to modern humans. Professor Ozcelik’s team have opened a window on how mutations in VLDLR affect brain development and influence gait in humans. “It will be interesting to see if the VLDLR gene is involved in other types of cerebellar ataxias. In addition, we hope to identify the defective genes associated with quadrupedal locomotion in families B and C”, he says. Source: European Society of Human Genetics Josh says: While not really practical immediately, it’s an interesting study. I think the title and content are a bit misleading, as there are mutations that disrupt neurological development and a side effect of some of these is quadrupedality. It would almost seem to me that perhaps the brain reverts to a more “primitive” setup and just defaulted to quadrupedality. Andrew says: I think that this is misleading, too, so I changed the title a bit. (original title was “genetic mutation linked to walking on all 4s,” which implied some “missing link” gene. The mutations are various flaws in a lipoprotein receptor which impairs cerebellum development, not all the complex skeletal, muscular, and neurological mutations (and more) plausibly necessary to produce a viable quadruped human. The link-bait here is the “mutation of the missing link,” and that’s an irritating and fundamental misunderstanding about how evolution works that doesn’t need to be perpetuated here. But what I do think is significant is that this suggests that an advanced cerebellum evolved first, and then the relevant skeletal-muscular changes gradually accumulated to make modern bipedal humans from an already somewhat transitory bipedal/quadrupedal evolutionary state (like primates). Mutations which favor bipedality at the expense of quadrupedality are only an evolutionary advantage once the brain can process the locomotion, something that an advanced cerebellum apparently can do. But, an advanced cerebellum is probably a net advantage (or at least, not a disadvantage) before bipedality. This supports contemporary evolutionary theory. |
| Posted: 01 Jun 2008 08:19 PM CDT In part I, I wrote about my first semester of teaching on-line and talked about our challenges with technology. Blackboard had a database corruption event during finals week and I had all kinds of struggles with the Windows version of Microsoft Excel. Mike wrote and asked if I thought students should be working more with non-Microsoft software and what I thought the challenges would be in doing so. I can answer with a totally unqualified "it depends." |
| Ken and the Senate [The Gene Sherpa: Personalized Medicine and You] Posted: 01 Jun 2008 08:04 PM CDT "GINA is a laudable gain, but it is only half of the regulatory reform needed. We need to turn to genetic testing itself, which, surprisingly, has escaped comprehensive federal oversight. One of the... [[ This is a content summary only. Visit my website for full links, other content, and more! ]] |
A simpler, gentler eye test based on Raman spectroscopy could spot ocular infection and other problems without irritating patients, although they may be required to yawn during the procedure. Whichever way you look at them, whether through the emotional blur of crying or as lachrymal secretions ripe for analysis, tears are complex. Now, researchers in the UK, have taken a close look at this aqueous solution of proteins, metabolites, electrolytes and lipids using Raman spectroscopy and obtained results that would make any ocular enthusiast cry with joy. Read more about this today in a sneak preview of 
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