A startup called Genome Liberty is developing a consumer genetics test to gauge an individuals ability to metabolize prescription drugs.

A personal genetics startup thinks that there is one set of DNA variants that everyone should know: the ones that help determine how you respond to drugs.

Genome Liberty, a New Jersey-based startup, wants to provide a $99 test that will tell customers, based on their genetics, if they should take a nonstandard dose of a drug because their body will break it down faster or slower than most people. In some cases the test might suggest a particular drug someone should take or avoid. The idea is to give you a card to keep in your wallet, or an iPhone app, which says which medications you shouldnt take, says cofounder Jeffrey Rosenfeld, a genome scientist at Rutgers University.

The company would offer these tests directly to consumers, who could then relay any relevant information to their doctors, Rosenfeld says.

Genome Liberty isnt the first company to offer such tests. The consumer genetics company 23andMe also offers some drug response tests in its genome scan, which also includes tests for things like eye color and the genetic risk for developing serious diseases. Rosenfeld says Genome Liberty wanted a more focused test. The idea is to provide information that is usable, that you can act on, he says.

Consumers who get the Genome Liberty drug response test would send a sample of saliva to the companys lab. The company scans the genome for DNA variations in 11 liver enzyme genes, which are a subset of the dozens of genes encoding enzymes for drug metabolism. Enzymes in the liver process drugs and can either deactivate or activate drugs, depending on the compound. Different people carry different versions or amounts of many of these enzymes, which can affect how they respond to drugs. Some patients may process a drug more quickly, more slowly, or perhaps not at all.

Genome Liberty says that variants in those 11 enzymes can affect the activity of nearly 80 drugs in the body. The test will tell people which medications they should take and which they should avoid based on markers in their DNA, says Rosenfeld.

The company is using a crowdfunding site to raise money to develop its test, which is available for pre-order. The recent U.S. Supreme Court decision that limited the patent claims that companies can make on genes (see U.S. Supreme Court Says Natural Human Genes May Not Be Patented) helped spur Genome Liberty to launch. We were worried about whether we could start this company or not, says Rosenfeld. Until that decision, he says, most genes were covered by a patent.

It is still not clear whether genetic tests sold directly to consumers will come under regulatory scrutiny. In 2010, the FDA warned 23andMe and other consumer genetics companies that their services amount to medical devices and thus need regulatory approval. But since then, the U.S. government has not come up with clear rules for these companies. Nevertheless, 23andMe applied for regulatory approval for portions of its test last year (see Personal Genetics Company Seeks Regulatory Approval).

Another question is whether doctors will make use of information from a consumer genetics test. Physicians dont always trust the results of direct-to-consumer tests and may not have clear medical guidelines for how to use it (see Why We Have a Right to Consumer Genetics). But the connections between the liver enzyme variants and drug response are well-supported, says Rosenfeld. If a doctor doesnt want to accept these results, he says, then find a different doctor.

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Consumer Genetic Test Can Predict Your Drug Response

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Aug. 13, 2013 A study investigating the function of the recently discovered enhancer RNA molecules may open new avenues for gene therapy. According to the study researchers, altering the production and function of these molecules could affect the expression of genes and, in consequence, possibly also the progression of various diseases.

Published in Molecular Cell on 8 August, the study was carried out in collaboration between the University of California, San Diego and the University of Eastern Finland.

Besides promoters located in the beginning of genes, gene expression is also regulated by enhancers which may be located as far as thousands of base pairs away from the gene they regulate. Enhancers have been shown to be responsible for cell-specific gene regulation. Previously, it was thought that the number of enhancer sequences in a differentiated cell is static; however, recent findings are starting to disprove the idea. In 2010, it was discovered that non-coding RNA molecules were being produced from the enhancer regions. The first observations relating to the biological function of these enhancer RNAs, or eRNAs, were published earlier this year. However, no study to date has addressed the question of whether enhancer transcription is of functional importance.

In the study researchers used genome-wide approaches to demonstrate that inflammation response causes the emergence of novel enhancers in primary macrophage cells. For the first time ever, the study used this formation of novel enhancer regions to describe the selection of enhancers and the progression of the activation from transcription factor binding to histone acetylation and eRNA transcription, finally leading to the mono- and dimethylation of histone H3 lysine 4 (H3K4me1/2). The H3K4me1 and H3K4me2 histone modifications are the very markers generally used to identify the location of enhancer regions on DNA. This type of histone methylation enables the function of these regions as enhancer sequences, i.e. as marks that can be identified by specific proteins which boost gene transcription.

The study showed that the direction and extent of eRNA transcription and H3K4me1/2 regions show strong correlation and that the inhibition of eRNA transcription with polymerase inhibitors inhibited histone methylation and thus also the emergence of novel enhancer sequences. Furthermore, the study showed that histone methyltransferases Mll1, Mll2/4 and Mll3 play a key role in de novo H3K4 methylation.

The results show that enhancer transcription causes long-term epigenetic changes in cells. Furthermore, besides offering valuable insight into the function of this novel RNA type, the researchers also believe that the findings will open new avenues for novel treatments in which cell-specific enhancer sequences can be targeted to alter gene expression. In June, this same group of researchers published a study in Nature, reporting for the first time reduction in target gene expression using eRNA knockdown in experimental animals.

Postdoctoral Researcher Minna U. Kaikkonen at A.I. Virtanen Institute for Molecular Sciences at the University of Eastern Finland was one of the two lead authors of the current study, carried out under Professor Christopher Glass. Dr Kaikkonen completed her post doc study in Professor Glass' research group at the University of California, San Diego in 2009-2012. Besides Dr Kaikkonen, the UEF contributors to the earlier study from June also include Postdoctoral Researcher Hanna P. Lesch.

The main funders of the study are Fondation Leducq, Sigrid Juslius Foundation, the Academy of Finland, ASLA Fulbright, the Finnish Foundation for Cardiovascular Research, the Finnish Cultural Foundation (North Savo Regional Fund), Orion-Farmos Research Foundation and the US National Institutes of Health grants DK091183, CA17390, and DK063491.

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In 1980, though, he opened up the journal Science and suddenly understood how doctors might someday cure Lesch-Nyhan, along with thousands of other genetic disorders that had once seemed incurable. Two Stanford biologists, Richard Mulligan and Paul Berg, had figured out a way to transplant genes into cells, effectively rewriting their DNA. The phrase gene therapy had been floating around medical circles for decades, but Wilson realized that its time had come. As soon as he finished his degrees, he and his wife moved to Boston so he could learn about gene transplantation from Mulligan, now at MIT. After nearly three years under Mulligans tutelage, he headed back to Michigan to set up his own lab.

The first disease that Wilson targeted was called familial hypercholesterolemia, in which the patient lacks the gene that produces receptors for grabbing bad cholesterol, or LDL, from the blood, which the liver normally filters out. Vessels become so badly clogged that many sufferers have heart attacks in their forties and fifties, and sometimes even before age 30.

Wilson figured out how to make a vector to attack the conditiona virus with a working version of the gene loaded on it. He first tested it on a type of rabbit genetically prone to high levels of LDL, and the gene therapy lowered those levels considerably. For a human trial in 1992, he and his colleagues chose a 28-year-old woman from Canada. Surgeons removed part of her liver, and then Wilson and his colleagues infected its cells with the virus, which delivered a working version of the defective gene. Finally, Wilson and his colleagues injected those cells back into the womans liver, where they took hold and grew. The womans LDL levels dropped by 23 percent.

The result, published in 1994, was a milestone in the young field. GENE EXPERIMENT TO REVERSE INHERITED DISEASE IS WORKING, The New York Times reported, noting that Wilsons paper was the first to report any therapeutic benefits of human gene therapy. Thanks to this study and others, the FDA gave the green light to more clinical trials every year, jumping from zero in 1989 to 91 in 1999. Universities set up gene therapy programs to stake a claim in the new field.

One of those was the Institute for Human Gene Therapy at the University of Pennsylvania. At age 38, Wilson became the institutes head, overseeing a staff that soon grew to more than 200. They launched new clinical trials, including a sequel to Wilsons study on familial hypercholesterolemia and on another genetic disorder in the liver: OTCD. Wilson now wanted to take the surgery out of gene therapy, so he and his colleagues searched the scientific literature for a virus that could seek out liver cells in the body.

They settled on a virus known as an adenovirus. Adenoviruses are best known for causing the common cold, but other scientists had found that they were very good at delivering genes into cells. Everything seemed to be moving forward nicelyuntil Jesse Gelsinger checked into Childrens Hospital of Philadelphia.

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Manila, Philippines -- Hospitals and health facilities offering stem cell therapy have until August 31 to apply for accreditation from the Department of Health (DoH).

DoH Secretary Enrique T. Ona said a number of hospitals in Metro Manila have already applied for accreditation to perform this "innovative" treatment that has not yet been accepted as standard mode of care in the country since it needs further tests and several more layers of research.

In the first mid-year convention of the Philippine Society for Stem Cell Medicine at the Manila Hotel yesterday, Ona reiterated that stem cell therapy is "the future of medicine."

"Stem cell therapy is not a cure-all medical treatment. Patients have yet to be presented first with standard of treatment, and in many cases, stem cell treatments have to be done in conjunction with other standard modalities of treatment," he said.

The Bureau of Health Facilities and Services (BHFS) of the DoH is accepting the applications for accreditation while a bio-ethics committee and a hospital-based review board will go over the applications and decide on their approval.

Five big hospitals in Metro Manila have already applied for accreditation, said Nick Lutero, chief of the BHFS.

Lutero said initial checks have revealed that these hospitals possess the required equipment needed for the treatment but they would still have to check on requirements set by the Food and Drug Administration (FDA) in relation to the practice.

Lutero said institutions that are offering stem cell treatments can still perform the procedures pending the approval of applications. However, once formal accreditations are already given, unaccredited institutions should cease offering stem cell therapy.

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DOH sets deadline for stem cell therapy accreditation

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Public release date: 12-Aug-2013 [ | E-mail | Share ]

Contact: Elizabeth Allen allenea@uthscsa.edu 210-450-2020 University of Texas Health Science Center at San Antonio

SAN ANTONIO -- Adding to the picture of what prompts breast cancers to form, researchers from the Cancer Therapy & Research Center (CTRC) at The University of Texas Health Science Center San Antonio today announced that "distant estrogen response elements" (DEREs) can act independently of oncogenes to spur tumor development.

DEREs appear to be depots or hubs that remotely and simultaneously control multiple target genes in response to estrogen stimulation, said Pei-Yin Hsu, Ph.D., lead author of the paper in Cancer Cell. As such, they are prime targets for the study of novel therapies for breast cancer and could also be useful in diagnosis.

Copy numbers

Where DEREs are multiplied or present in abnormal numbers, this contributes to tumor development, especially in estrogen receptor-positive breast cancers, said study senior author Tim Hui-Ming Huang, Ph.D., deputy director of the CTRC.

Decreasing the number of DERE copies could have therapeutic potential to treat women with this aggressive form of cancer, Dr. Huang said.

DEREs at 2 sites

The researchers analyzed two DERE clusters on human chromosomes 17 and 23. They found that the DEREs induce pro-growth factors and inhibit growth-suppressing genes. "It is worthwhile to note that DERE-DERE interactions, instead of DERE interactions with genes, may also contribute to tumor development," Dr. Hsu said.

The team found a correlation between a subset of DERE-regulated genes and tamoxifen resistance. Tamoxifen is a widely prescribed hormone therapy for breast cancer. It may be possible to evaluate how a woman will respond to tamoxifen by measuring DERE activity, Dr. Hsu said.

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Javascript is currently disabled in your web browser. For full site functionality, it is necessary to enable Javascript. In order to enable it, please see these instructions. 12 hours ago Rice University researchers adapted a computer algorithm to find the parts of two distantly related adeno-associated viruses that could be recombined into new and useful viruses for gene therapy. They intend to determine the rules by which custom viruses can easily be designed for therapies. Credit: Benjamin Adler/Rice University

Rice University researchers are making strides toward a set of rules to custom-design Lego-like viral capsid proteins for gene therapy.

A new paper by Rice scientists Junghae Suh and Jonathan Silberg and their students details their use of computational and bioengineering methods to combine pieces of very different adeno-associated viruses (AAVs) to create new, benign viruses that can deliver DNA payloads to specific cells.

The research appears this month in the American Chemical Society journal ACS Synthetic Biology.

AAVs are found in nature and commonly infect humans but cause no disease. That makes them good candidates to serve as carriers that target cells and deliver genes to treat diseases.

The team, which included graduate student and lead author Michelle Ho and undergraduates Benjamin Adler and Michael Torre, wants to define rules to design a variety of viruses that deliver therapeutic genes. They used computer models to find likely AAV candidates for recombination and then tested the model predictions by engineering 17 unique virus capsid proteins and evaluating their ability to fold and assemble into capsid-encased viruses.

Gene therapy shows promise in the treatment of not only genetic disorders but also cancer and cardiovascular diseases, said Suh, an assistant professor of bioengineering at Rice's BioScience Research Collaborative.

"But you need a mechanism to get the correct gene into the human body and to the target cells," she said. "To do that, people use gene vectors, and viruses encompass the largest category of vectors. They've naturally evolved to deliver genes into the body. Our goal is to reprogram them to target specific organs or tissues.

"The big challenge is to go about this in a rational manner," she said. "People have done a lot of work to solve the structure of viruses. We know what they look like. The question is: How can we use that information to guide the design of our viral vectors?"

The team's answer starts with the "SCHEMA" algorithm they adapted to predict how parts of very large viruses can recombine by homing in on the viral protein sequences that work well together.

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Writing rules for gene-therapy vectors: Researchers compute, then combine benign viruses to fight disease

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Aug. 12, 2013 More than 50 million people worldwide have epilepsy, with a third of these being children. The most common forms of epilepsy in children occur without any apparent trigger and only affect certain regions of the brain. This condition is known as idiopathic focal epilepsy (IFE). The hallmark of IFE is the origin of the fit being in what is termed the rolandic region of the brain. Now, thanks to the considerable input of MedUni Vienna researchers, two pan-European research networks have successfully identified the first disease gene for IFE.

The gene concerned is known as GRIN2A. Changes to this gene cause one of the key ion channels in the brain to malfunction, affecting the electrical excitation of nerve cells. This explains the increased number of electrical discharges in the brain and therefore the manifestation of epileptic fits. The results of the study, which were obtained through the two research networks EuroEPINOMICS and IonNeurOnet, have now been published in the journal Nature Genetics.

The research project came into being from collaboration between numerous groups of researchers in Europe who shared a common goal: to understand the genetic causes of this type of childhood epilepsy. "What was crucial for our breakthrough was the close cooperation of doctors carrying out clinical research with theoretical researchers," explains Fritz Zimprich from the University Department of Neurology at the MedUni Vienna, who coordinated the researchers involved in the project from Vienna, Graz and Innsbruck. "A third of the patients investigated with state-of-the-art genetic methods come from Austria.

All in all, genetic material from 400 patients with IFE was analysed. In 7.5 per cent of sufferers, the scientists found changes in the GRIN2A gene. In "rolandic epilepsy," which accounts for 15 per cent of cases of childhood epilepsy and therefore makes it the most common form of the condition, these mutations disrupt the function of the NMDA receptor, one of the brain's key ion channels. The flow of ions in this type of channel influences and determines the nerve cells' electrical excitation.

It is however still not yet fully understood how the mutation in the gene on the NMDA receptor leads to epilepsy. Says Zimprich: "We only see the condition as a result of the mutations; we haven't yet fully discovered the mechanisms behind it." The next target is to understand these mechanisms. This is also an essential step in the development of more effective and more tolerable anticonvulsant medications.

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Disease gene discovered for frequent epilepsy in childhood

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SOURCE: Cystinosis Research Foundation

IRVINE, CA--(Marketwired - Aug 12, 2013) - Six grants totaling $1,295,377 were issued to cystinosis researchers investigating better treatments and a cure for the disease by the Cystinosis Research Foundation in its first round of proposals in 2013. Included is funding for additional research on stem cell and gene therapy, which holds the greatest promise to cure the rare, deadly metabolic and genetic disease.Cystinosis afflicts about 500 children and young adults in the United States and 2,000 worldwide.

"A cure is within sight.These new studies will accelerate the research process and will provide the critical data we need to realize our goal of finding a cure for cystinosis.CRF funded research has led to new research discoveries and treatments for cystinosis and as an unexpected, positive result, helped other more prevalent diseases such as Parkinson's and Huntington's disease.We believe that there will be an autologous stem cell trial for patients with cystinosis within three to four years.We are committed to continue to fund research until we find the cure," said Nancy Stack, CRF Trustee and President.

The CRF's spring grants were awarded to research programs at hospitals and universities in the United States and Canada.In the last 11 years the CRF has raised more than $22 million and has funded 108 studies and fellowships in 11 countries. The CRF is the only funding source for bench and clinical investigations of cystinosis worldwide.

"CRF is guided by a Scientific Review Board, a world renowned group of cystinosis experts and scientists who evaluate every research application we receive.Their expertise and leadership ensures that CRF funds only the most promising research studies. These new research projects are important in the sequence of solving the mysteries of this disease," Stack said.The scientific panel is headed by Dr. Corinne Antignac, a Paris researcher who first identified the CTNS gene in 1998.

Dr. Stphanie Cherqui, assistant professor Department of Pediatrics, University of California, San Diego, was on Dr. Antignac's team that discovered the cystinosis gene. She is a member of the Scientific Review Board and chairs the CRF Cystinosis Gene Therapy Consortium.Dr. Cherqui's work, in 2009 reversed the disease and halted tissue damage in mice.

Cystinosis is a metabolic disease that slowly destroys every organ in the body, including the liver, kidneys, eyes, muscles, thyroid and brain. There is a medicine, cysteamine that prolongs the children's lives, but there is no cure.

CRF's mission to find a better treatment for cystinosis was realized with the discovery of delayed-release cysteamine by researchers at UC San Diego. In 2008, Raptor Pharmaceuticals bought the worldwide license for the CRF-funded research and completed the necessary clinical trials to bring the drug to market and after years of waiting, Raptor received FDA approval on April 30, 2013.The drug will be sold under the name Procysbi.In addition, cysteamine and its delayed-release formula is being used in clinical trials for Huntington's disease and NASH, a progressive liver disease.

The CRF also has launched the Cure Cystinosis International Registry (CCIR), whose purpose is to consolidate information about cystinosis patients into a single data repository which will help advance research and clinical trials leading to future treatments and cures.

Stack and her husband, Geoffrey, a managing director of the SARESREGIS Group, an Irvine real estate company, have a daughter, Natalie, 22, with cystinosis.

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Cystinosis Research Foundation Awards $1.29 Million in Grants to Find a Cure for Deadly Genetic Disease

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Public release date: 12-Aug-2013 [ | E-mail | Share ]

Contact: Rachel Steinhardt rsteinhardt@licr.org 212-450-1582 Ludwig Institute for Cancer Research

August 12, 2013, New York, NY Loss of a gene required for stem cells in the brain to turn into neurons may underlie the most severe forms of neuroblastoma, a deadly childhood cancer of the nervous system, according to a Ludwig Cancer Research study. Published in Developmental Cell today, the findings also provide clues about how to improve the treatment of this often-incurable tumor.

Neuroblastoma can appear in nervous tissue in the abdomen, chest and spine, among other regions of the body, and can spawn body-wracking metastasis. The most severe tumors respond poorly to treatment, and the disease accounts for 15 percent of cancer deaths in children.

Johan Holmberg, PhD, at the Ludwig Institute for Cancer Research Stockholm took a close look at the role of the CHD5 tumor suppressor during normal nervous system development. Previous studies had shown that the gene CHD5 is often inactivated in the most severe forms of neuroblastoma, but little was known about its function in healthy tissue or how it operates. The study, which was conducted in close collaboration with colleagues at Trinity College, Dublin, Ireland, addressed these two key issues.

The researchers found that CHD5 is required for the cellular transition from a stem cell to a mature neuron. In one experiment, the researchers knocked down the CHD5 gene by injecting a small RNA into the brains of fetal mice while in the womb.

"The result was a complete absence of neurons," says Ludwig researcher Holmberg who is based at the Karolinska Institutet. "Instead of becoming neurons, the cells with CHD5 knocked down stayed in a limbo-like state between an actively-dividing stem cell and a mature nerve cell. It was a very robust effect," added Holmberg.

The researchers also dissected how CHD5 operates, showing that it sticks to certain modifications of histone proteins. These modifications help control how genes are turned on and off. In the absence of CHD5, key stem cell genes are not turned off, and genes required for neuronal maturation are not turned on. The findings highlight how the failure of a cell to properly mature into its terminal state can underlie cancer, a relatively understudied area of research.

"It is necessary for cells in the healthy nervous tissue to be able to go from stem cells to neurons," explains Holmberg. "If you lose this capacity, these cells become locked in an immature state, which might yield quite dangerous tumor cells, especially in combination with additional cancer-promoting cellular events."

The research could also lead to new ways to treat neuroblastoma, perhaps using currently approved drugs. One component of neuroblastoma treatment is retinoic acid, a drug that can drive neuronal maturation. Holmberg and his colleagues found that knocking down the expression of CHD5 in more benign neuroblastoma cells blocked their capacity to mature in response to retinoic acid treatment. "These cells were completely insensitive to treatment, no matter how much we gave them, mirroring the same unresponsiveness to retinoic acid in the more malignant CHD5-negative neuroblastoma cells," says Holmberg.

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Public release date: 12-Aug-2013 [ | E-mail | Share ]

Contact: Vicki Cohn vcohn@liebertpub.com 914-740-2100 Mary Ann Liebert, Inc./Genetic Engineering News

New Rochelle, NY -- Body mass index (BMI) or a change in BMI is often the sole measure used to evaluate whether an intervention intended to combat childhood obesity is effective. But a new study clearly shows that an intervention can have beneficial effects on other health outcomes, such as cardiovascular fitness, regardless of its effect on BMI. Focusing on a single factor like the degree of BMI change is restrictive and can overlook other important outcomes, according to an article published in Childhood Obesity, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. The article is available free on the Childhood Obesity website at http://www.liebertpub.com/chi.

Maria Kolotourou and a team of authors involved in the Mind, Exercise, Nutrition...Do It! (MEND) trial from University of London, University College London, and Mytime MEND gathered data from a group of obese children before they participated in the MEND childhood obesity intervention and again at 6- and 12-month follow-up intervals. The researchers measured BMI, degree of change in BMI, waist circumference, cardiovascular fitness, physical activity, sedentary behaviors, and self-esteem.

In the article "Is BMI Alone a Sufficient Outcome to Evaluate Interventions for Child Obesity?" the authors report improvements, in several of the parameters measured, independent of whether a child's BMI decreased, increased, or remained the same.

"Good interventions aimed at helping overweight children lose weight should be equally directed at helping them to find health. This article suggests that health benefits may be seen independent of weight change, per se, and we are thus better served by evaluation strategies that encompass an array of relevant and important measures," says David L. Katz, MD, MPH, Editor-in-Chief of Childhood Obesity and Director of Yale University's Prevention Research Center.

###

About the Journal

Childhood Obesity is a bimonthly journal, published in print and online, and the journal of record for all aspects of communication on the broad spectrum of issues and strategies related to weight management and obesity prevention in children and adolescents. The Journal includes peer-reviewed articles documenting cutting-edge research and clinical studies, opinion pieces and roundtable discussions, profiles of successful programs and interventions, and updates on task force recommendations, global initiatives, and policy platforms. It reports on news and developments in science and medicine, features programs and initiatives developed in the public and private sector, and includes a Literature Watch. Tables of content and a sample issue may be viewed on the Childhood Obesity website at http://www.liebertpub.com/chi.

About the Publisher

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Child obesity interventions -- is change in BMI a good measure of success?

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Robert Preidt HealthDay News Posted: Sunday, August 11, 2013, 2:00 PM

SUNDAY, Aug. 11 (HealthDay News) -- Five major mental disorders share common inherited genetic variations, a new study finds.

The overlap is highest between schizophrenia and bipolar disorder (15 percent), moderate between bipolar disorder and depression and between attention-deficit/hyperactivity disorder (ADHD) and depression (about 10 percent), and lowest between schizophrenia and autism (3 percent).

Overall, common genetic variations accounted for 17 percent to 28 percent of risk for the five mental disorders, according to the study published in the Aug. 11 issue of the journal Nature Genetics, which the researchers say is the largest genome-wide study of its kind.

The project involved more than 300 scientists at 80 research centers in 20 countries and was supported by the U.S. National Institute of Mental Health (NIMH).

The investigators analyzed the genomes of several thousand people with the five mental disorders and people without the disorders.

"Since our study only looked at common gene variants, the total genetic overlap between the disorders is likely higher," study co-leader Naomi Wray, of the University of Queensland in Australia, said in an NIMH news release. "Shared variants with smaller effects, rare variants, mutations, duplications, deletions, and gene-environment interactions also contribute to these illnesses."

The genetic overlap between schizophrenia and depression could prove important in terms of research and diagnosing patients, according to the study authors. They expected to see more overlap between ADHD and autism, but said the moderate overlap between schizophrenia and autism is consistent with emerging evidence.

"Such evidence quantifying shared genetic risk factors among traditional psychiatric diagnoses will help us move toward classification that will be more faithful to nature," said Bruce Cuthbert, director of the NIMH's adult translational research and treatment development division. Cuthbert is also the coordinator of an NIMH project that is working to develop a mental disorders classification system for research based more on underlying causes.

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Genetic overlap seen in five mental disorders

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Public release date: 11-Aug-2013 [ | E-mail | Share ]

Contact: Bobbi Nodell bnodell@uw.edu 206-543-8309 University of Washington

Some patients with a rare type of epilepsy called epilepsy aphasia have something else in common. They have mutations in the same gene. Epilepsy aphasia disorders are characterized by seizures and speech abnormalities.

University of Washington researchers headed a recent study on genetic association. Their report, "GRIN2A mutations cause epilepsy-aphasia spectrum disorders," is published in the Aug. 11 issue of Nature Genetics.

The scientists sequenced genes in 519 patients with severe seizure disorders. Within the group, 44 patients had epilepsy aphasia and four of those -- or 10 percent -- and their affected family members had mutations in the GRIN2A gene.

"For a long time, people have debated whether this type of epilepsy had a genetic component, mostly because so few families have the disorder. To find a genetic cause is really interesting," said Gemma Carvill, senior fellow at the UW Department of Pediatrics, Division of Genetic Medicine, and the lead author of the study.

Carvill said to find 10 percent of patients with a genetic mutation for a particular epilepsy disorder "is quite sizable."

"In the families we looked at, multiple individuals were affected with epilepsy aphasia and all had a mutation in GRIN2A," she said.

Heather C. Mefford, assistant professor of pediatrics, said clinical testing for this gene could be done for individuals with epilepsy aphasia disorders who are wondering if they will pass on epilepsy to a child. In families with a mutation in GRIN2A, the risk of passing on a genetic mutation carrying the disorder is 50 percent.

Mefford said two other studies report similar findings.

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Progress made in linking some forms of epilepsy to genetics

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Public release date: 12-Aug-2013 [ | E-mail | Share ]

Contact: Jennifer Sereno jsereno@morgridgeinstitute.org 608-770-8084 University of Wisconsin-Madison

MADISON, Wis. Using human pluripotent stem cells and DNA-cutting protein from meningitis bacteria, researchers from the Morgridge Institute for Research and Northwestern University have created an efficient way to target and repair defective genes.

Writing today (Monday, Aug. 12, 2013) in the Proceedings of the National Academy of Sciences, the team reports that the novel technique is much simpler than previous methods and establishes the groundwork for major advances in regenerative medicine, drug screening and biomedical research.

Zhonggang Hou of the Morgridge Institute's regenerative biology team and Yan Zhang of Northwestern University served as first authors on the study; Dr. James Thomson, director of regenerative biology at the Morgridge Institute, and Erik Sontheimer, professor of molecular biosciences at Northwestern University, served as principal investigators.

"With this system, there is the potential to repair any genetic defect, including those responsible for some forms of breast cancer, Parkinson's and other diseases," Hou said. "The fact that it can be applied to human pluripotent stem cells opens the door for meaningful therapeutic applications."

Zhang said the Northwestern University team focused on Neisseria meningitidis bacteria because it is a good source of the Cas9 protein needed for precisely cleaving damaged sections of DNA.

"We are able to guide this protein with different types of small RNA molecules, allowing us to carefully remove, replace or correct problem genes," Zhang said. "This represents a step forward from other recent technologies built upon proteins such as zinc finger nucleases and TALENs."

These previous gene correction methods required engineered proteins to help with the cutting. Hou said scientists can synthesize RNA for the new process in as little as one to three days compared with the weeks or months needed to engineer suitable proteins.

Thomson, who also serves as the James Kress Professor of Embryonic Stem Cell Biology at the University of WisconsinMadison, a John D. MacArthur professor at UWMadison's School of Medicine and Public Health and a professor in the department of molecular, cellular and developmental biology at the University of California, Santa Barbara, says the discovery holds many practical applications.

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New gene repair technique promises advances in regenerative medicine

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#39;Genetics of Sand #39; May Shed Light on Evolution
An evolutionary ecologist is using "grains of sand" mdash; the fossils of microscopic aquatic creatures mdash; to understand more about the process of evolution. Source:...

By: LabEquipment

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'Genetics of Sand' May Shed Light on Evolution - Video

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Mini Belted Galloway Bull...Awesome Genetics
This bull produces great calves.

By: Charles Jacobson

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Mini Belted Galloway Bull...Awesome Genetics - Video

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Beef + Lamb New Zealand is proposing to merge three of its genetic databases into a single $8.8 million tool.

The proposal will mean amalgamating Ovita, Sheep Improvement Ltd (SIL) and the Central Progeny Test (CPT) into a new entity called Beef + Lamb Genetics.

The levy-funded farmer organisation has been working on this project for 15 months, the general manager of Beef + Lamb's farm programme, Richard Wakelin, said.

It will need farmer approval, to be sought in a vote at the organisation's annual meeting in November.

Beef + Lamb hoped to have it up and running by January, Wakelin said.

Beef + Lamb would put up $2.89m and an additional $1.5m would come from industry investors, Wakelin said.

Beef + Lamb has also applied to the Ministry of Business, Innovation and Employment for funding of $4.4m.

"It will be an $8.8m per annum investment for five years," Wakelin said.

Northern North Island director James Parsons said Beef + Lamb spent about $400,000 a year on SIL and the CPT.

About 80 per cent of rams sold by ram breeders are entered into the SIL database, which determines estimated breeding values and other data farmers see in sale catalogues when they buy a ram.

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Aug. 12, 2013 Rice University researchers are making strides toward a set of rules to custom-design Lego-like viral capsid proteins for gene therapy.

A new paper by Rice scientists Junghae Suh and Jonathan Silberg and their students details their use of computational and bioengineering methods to combine pieces of very different adeno-associated viruses (AAVs) to create new, benign viruses that can deliver DNA payloads to specific cells.

The research appears this month in the American Chemical Society journal ACS Synthetic Biology.

AAVs are found in nature and commonly infect humans but cause no disease. That makes them good candidates to serve as carriers that target cells and deliver genes to treat diseases.

The team, which included graduate student and lead author Michelle Ho and undergraduates Benjamin Adler and Michael Torre, wants to define rules to design a variety of viruses that deliver therapeutic genes. They used computer models to find likely AAV candidates for recombination and then tested the model predictions by engineering 17 unique virus capsid proteins and evaluating their ability to fold and assemble into capsid-encased viruses.

Gene therapy shows promise in the treatment of not only genetic disorders but also cancer and cardiovascular diseases, said Suh, an assistant professor of bioengineering at Rice's BioScience Research Collaborative.

"But you need a mechanism to get the correct gene into the human body and to the target cells," she said. "To do that, people use gene vectors, and viruses encompass the largest category of vectors. They've naturally evolved to deliver genes into the body. Our goal is to reprogram them to target specific organs or tissues.

"The big challenge is to go about this in a rational manner," she said. "People have done a lot of work to solve the structure of viruses. We know what they look like. The question is: How can we use that information to guide the design of our viral vectors?"

The team's answer starts with the "SCHEMA" algorithm they adapted to predict how parts of very large viruses can recombine by homing in on the viral protein sequences that work well together.

Silberg, an associate professor of biochemistry and cell biology, said approaches to virus design can lean either toward brute force -- "Let's make 1,000 of them and maybe we'll get lucky" -- or purely computational, where a biophysicist will try to predict the role of small changes to the virus capsid.

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IRVINE, CA--(Marketwired - Aug 12, 2013) - MRI Interventions, Inc. (OTCQB: MRIC) today announced treatment of the first patient in a Phase I clinical trial utilizing uniQure B.V.'s glial cell line-derived neurotrophic factor (GDNF) for treatment of Parkinson's disease. This gene therapy holds promise in the battle against the degenerative and debilitating disorder, which affects 1.5 million people in the United States.MRI Interventions' ClearPoint Neuro Intervention System is being used in the clinical trial to enable direct infusion of the gene therapy into an area of the brain affected by Parkinson's disease.

Dr. Krystof Bankiewicz, MD, PhD at University of California, San Francisco (UCSF), and Dr. John D. Heiss, MD at the National Institute for Neurological Disorders and Stroke, part of the National Institutes of Health (NIH), are leading the trial.uniQure B.V., a leader in human gene therapy, is providing the GDNF gene. uniQure made headlines last November by receiving regulatory approval in Europe of a first-in-class gene therapy to treat orphan diseases.

The hypothesis of the Parkinson's disease trial is that GDNF's neuro-regenerative and protective properties may protect and strengthen brain cells that produce dopamine, a chemical that affects brain function.In Parkinson's disease, dopamine production is reduced in an area of the brain responsible for movement, which leads to the debilitating symptoms experienced by many patients with the disease. The affected area is a tiny spot located deep within the brain, and the ClearPoint System provides the visualization and precision necessary to deliver a desired amount of the gene therapy directly to this very small target without disrupting other critical neurological structures in the process.

"The success of gene therapy in patients requires accuracy in delivery," said Dr. Krys Bankiewicz of UCSF."The ClearPoint System enables this precision, with the safe and accurate infusion of our gene therapy product into a miniscule target in the brain while we observe the procedure and confirm results in real time."

"We are very pleased with our first patient procedure," Dr. Heiss stated. "The ClearPoint System worked exceptionally well, enabling us to achieve precision targeting into the putamen and to observe administration of the therapeutic agent as it occurred."

The ClearPoint navigation platform is the only technology to enable minimally-invasive neurosurgery under continuous MRI guidance, offering surgeons a direct view of the inside of a patient's brain during a procedure.

"We are delighted to be working with UC San Francisco, the National Institutes of Health and uniQure, to help advance a novel treatment for Parkinson's disease," said Kimble Jenkins, CEO of MRI Interventions.

"At uniQure we are convinced that success for gene therapyrequires the most advanced andreliabledelivery technologies," said uniQure CEO Jrn Aldag. "Together with our collaborators at UCSF, the NIH and MRI Interventions, we are paving the way to further advances in the treatment of Parkinson's Disease."

The study, sponsored by the NIH, is a Phase I open-label dose escalation safety study that will include 24 patients over 4 cohorts.The first patient was dosed on May 20 and there have been no safety issues.

About MRI Interventions, Inc.Founded in 1998, MRI Interventions is creating innovative platforms for performing the next generation of minimally invasive surgical procedures in the brain and heart.Utilizing a hospital's existing MRI suite, the company's FDA-cleared and CE-marked ClearPoint system is designed to enable a range of minimally invasive procedures in the brain.MRI Interventions has a co-development and co-distribution agreement with Brainlab, a leader in software-driven medical technology, relating to the ClearPoint system.In partnership with Siemens Healthcare, MRI Interventions is developing the ClearTrace system to enable MRI-guided catheter ablations to treat cardiac arrhythmias, including atrial fibrillation. Building on the imaging power of MRI, the company's interventional platforms strive to improve patient care while reducing procedure costs and times. MRI Interventions is also working with Boston Scientific Corporation to incorporate its MRI-safety technologies into Boston Scientific's implantable leads for cardiac and neurological applications.For more information, please visit http://www.mriinterventions.com.

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What is an Example of Personalized Medicine? Edward Abrahams, Ph.D.
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THE genetic causes of some of the most devastating childhood epilepsies have been revealed in a landmark study jointly led by Australian researchers.

Using advanced gene technology researchers have discovered new genes and new genetic mutations that cause severe childhood epilepsy.

The study's co-leader Professor Sam Berkovic, Director of the Epilepsy Research Centre at the University of Melbourne and Melbourne's Austin Hospital, said as well as providing a pathway to treating epilepsy the research provides answers to patients and families who previously had little or no idea where epilepsy had come from.

"Parents often have a belief that they've done something wrong that caused this disease," Prof Berkovic said.

"Not knowing why has been one of the most frustrating things ... we've never really had the answer. Now we do.

"This also stops the need for further searching and refines the treatments."

A key aspect of the research has been the ability to sequence the entire human genome, Prof Berkovic said.

"Until now we've had these complex patients and we didn't know what was going on," he said.

"Now all the genes are known and the jigsaw can be completed"

As well as using the latest genetic techniques to sequence and analyse DNA from 4000 epilepsy patients and their relatives, the study known as Epi4Ks shared DNA sequences and patient information among dozens of research institutions.

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Aug. 11, 2013 A decade ago, gene expression seemed so straightforward: genes were either switched on or off. Not both. Then in 2006, a blockbuster finding reported that developmentally regulated genes in mouse embryonic stem cells can have marks associated with both active and repressed genes, and that such genes, which were referred to as "bivalently marked genes," can be committed to one way or another during development and differentiation.

This paradoxical state -- akin to figuring out how to navigate a red and green traffic signal -- has since undergone scrutiny by labs worldwide. What has been postulated is that the control regions (or promoters) of some genes, particularly those critical for development during the undifferentiated state, stay "poised" for plasticity by communicating with both activating and repressive histones, a state biologists term "bivalency."

A study by researchers at the Stowers Institute for Medical Research now revisits that notion. In this week's advance online edition of the journal Nature Structural and Molecular Biology, a team led by Investigator Ali Shilatifard, Ph.D., identifies the protein complex that implements the activating histone mark specifically at "poised" genes in mouse embryonic stem (ES) cells, but reports that its loss has little effect on developmental gene activation during differentiation. This suggests that there is more to learn about interpreting histone modification patterns in embryonic and even cancer cells.

"There has been a lot of excitement over the idea that promoters of developmentally regulated genes exhibit both the stop and go signals," explains Shilatifard. "That work supports the idea that histone modifications could constitute a code that regulates gene expression. However, we have argued that the code is not absolute and is context dependent."

Shilatifard has a historic interest in gene regulation governing development and cancer. In 2001, his laboratory was the first to characterize a complex of yeast proteins called COMPASS, which enzymatically methylates histones in a way that favors gene expression. Later, he discovered that mammals have six COMPASS look-alikes -- two SET proteins (1A and 1B) and four MLL (Mixed-Lineage Leukemia) proteins, the latter so named because they are mutant in some leukemias. The group has since focused on understanding functional differences among the COMPASS methylases. The role of mouse Mll2 in establishing bivalency was the topic of the latest study.

Comprehending the results of the paper requires a brief primer defining three potential methylation states of histone H3. If the 4th amino acid, lysine (K), displays three methyl groups (designated H3K4me3), then this mark is a sign of active transcription from that region of the chromosome. If the 27th residue of histone H3 (also a lysine) is trimethylated (H3K27me3), this mark is associated with the silencing of that region of the chromosome. But if both histone H3 residues are marked by methylation (H3K4me3 and H3K27me3 marks), that gene is deemed poised for activation in the undifferentiated cell state.

The team already knew that an enzyme complex called PRC2 implemented the repressive H3K27me3 mark. To identify which COMPASS family member is involved in this process, the group genetically eliminated all possibilities and came up with Mll2 as the responsible factor. Mll2-deficient cells indeed show H3K4me3 loss, not at all genes, but at the promoters of developmentally regulated genes, such as the Hox genes.

The revelation came when the researchers evaluated behaviors of Mll2-deficient mouse embryonic stem cells. First, the cells continued to display the defining property of a stem cell, the ability to "self-renew," meaning that genes that permit stem cell versatility were undisturbed by Mll2 loss. But remarkably, when cultured with a factor that induces their maturation, Mll2-deficient mouse ES cells showed no apparent abnormalities in gene expression. In fact, expression of the very Hox genes that normally exhibit bivalent histone marks was as timely in Mll2-deficient cells as it was in non-mutant cells.

"This means that Mll2-deficient mouse ES cells that receive a differentiation signal can still activate genes required for maturation, even though they have lost the H3K4me3 mark on bivalent regions" says Deqing Hu, Ph.D., the postdoctoral fellow who led the study. "This work paves the way for understanding what the real function of bivalency is in pluripotent cells and development."

The study's findings also potentially impact oncogenesis, as tumor-initiating "cancer stem cells" exhibit bivalent histone marks at some genes. "Cancer stem cells are resistant to chemotherapy, making them difficult to eradicate," says Hu. "Our work could shed light on how cancer stem cells form a tumor or suggest a way to shut these genes down."

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Rethinking the genetic code

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Public release date: 12-Aug-2013 [ | E-mail | Share ]

Contact: Kathryn Ruehle kruehle@liebertpub.com 914-740-2100 Mary Ann Liebert, Inc./Genetic Engineering News

New Rochelle, NY, August 5, 2013Violent and abusive behavior against women, which can be both physically and emotionally harmful, gain societal acceptance when they are glamorized and normalized in popular culture such as books and movies. The main characters' relationship in the best-selling novel Fifty Shades of Grey, for example, helps perpetuate the problem of intimate partner violence against women, according to an article in Journal of Women's Health, a peer-reviewed publication from Mary Ann Liebert, Inc., publishers. To obtain a copy of the article, press contacts should email journalmarketing1@liebertpub.com.

In "'Double Crap!' Abuse and Harmed Identity in Fifty Shades of Grey," Amy Bonomi, PhD, MPH, Lauren Altenburger, BS, and Nicole Walton, MSW from The Ohio State University, Columbus, conducted a systematic analysis of the novel to elucidate patterns consistent with Centers for Disease Control and Prevention (CDC) definitions of interpersonal violence and associated reactions known to occur in abused women. They conclude that the female partner, Anastasia, suffers harm as a result of her relationship with Christian. Specifically, the couple's interactions are emotionally abusive, characterized by stalking, intimidation, and isolation. Sexual violence is pervasive in the novel, including the use of alcohol to impair Anastasia's consent and the use of intimidation. Anastasia suffers stress, altered identity, and disempowerment/entrapment.

At least 25% of women are victims of violence by intimate partners.

"We must be attuned to the way women are treated in books and movies, as such popular culture can perpetuate dangerous violence standards toward women," says Susan G. Kornstein, MD, Editor-in-Chief of Journal of Women's Health, Executive Director of the Virginia Commonwealth University Institute for Women's Health, Richmond, VA, and President of the Academy of Women's Health.

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About the Journal

Journal of Women's Health, published monthly, is a core multidisciplinary journal dedicated to the diseases and conditions that hold greater risk for or are more prevalent among women, as well as diseases that present differently in women. The Journal covers the latest advances and clinical applications of new diagnostic procedures and therapeutic protocols for the prevention and management of women's healthcare issues. Complete tables of content and a sample issue may be viewed on the Journal of Women's Health website at http://www.liebertpub.com/jwh. Journal of Women's Health is the Official Journal of the Academy of Women's Health and the Society for Women's Health Research.

About the Academy

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Fifty Shades of Grey romanticizes sexual violence and emotional abuse of women

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