IMAGE:Laboratory fruit flies live in special glass containers. view more

Credit: Photo: Michael Bernkopf/Vetmeduni Vienna

The information encoded in the DNA of an organism is not sufficient to determine the expression pattern of genes. This fact has been known even before the discovery of epigenetics, which refers to external modifications to the DNA that turn genes "on" or "off". These modifications do not change the DNA sequence, but instead, they affect how genes are expressed. Another, less known mechanism called canalization keeps organisms robust despite genetic mutations and environmental stressors. If an organism experiences environmental or genetic perturbations during its development, such as extreme living conditions or genetic mutations, canalization acts as a way of buffering these disturbances. The organism remains stable and can continue to develop without recognizable changes.

A comfort zone in the fly genome

Christian Schltterer at the Institute of Population Genetics and his colleagues studied the mechanism of canalisation in fruit flies. The researchers subjected two genetically distinct strains of fruit flies, Oregon and Samarkand, to different temperatures (13C, 18C, 23C and 29C). Subsequently, they analysed the variation in gene expression in response to the different temperatures. The results revealed a homogenous pattern of gene expression among the two strains at 18C. No matter whether the flies were from the Oregon or to the Samarkand strain, their gene expression was almost indistinguishable.

"The flies' genetic comfort zone appears to be located at 18C. "As soon as the flies leave the comfort zone, move to either higher or lower temperatures, the gene expression of the two strains varies dramatically" Schltterer explains.

Buffering the genotype

The effect of canalization was first described in 1942, when researchers pointed out that organisms remain stable in their external appearance despite different environmental circumstances or genetic mutations. This sort of developmental buffering helps to stabilize organismal growth.

"If an organism develops along the canalization pathway, or along the comfort zone, mutations can accumulate without being expressed. Once an organisms leaves the canalized range, those hidden genetic variations can be expressed and become visible. The phenomenon is called decanalization", Schltterer explains.

Decanalization as the origin of complex genetic disease

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Living in the genetic comfort zone

Washington, DC (PRWEB) February 26, 2015

Today, the National Alliance for Hispanic Health, in collaboration with the U.S. Food and Drug Administration, released the report Genes, Culture, and Health: Ensuring the Best Health Outcomes for All. The report reviewed available research and found that while dramatic advances are being made in genetics and their clinical applications, the promise of personalized medicine is not being realized by all.

A lack of inclusion in genetic research is creating a genomic divide putting the frontiers of science and medicine at risk. Without a dramatic reversal in the quality of genetic studies, the benefits of personalized medicine will not be realized by all, said Dr. Jane L. Delgado, President and CEO of the Alliance.

Ensuring that all patients benefit from discoveries in genetic science and personalized medicine is critical to our nations health. The FDA is committed to working with diverse partners on the road forward for access to the best science and treatment, said Dr. Jonca Bull, Director of the U.S. Food and Drug Administrations (FDA) Office of Minority Health. Dr. Bull added, The report issued today is an important update on the status of genetic research and personalized medicine. It calls on all of us to do a better job on inclusion to improve our understanding of how medical products will work in the populations intended to use them.

Among the key findings of the report released today

Downloadable copies of the Genes, Culture, and Health report and key findings are available online at the Alliance website (http://www.hispanichealth.org) and consumers can get information on how to have a discussion with their health provider on the role of genetics in their and their familys health by calling the Alliances bilingual Su Familia Helpline at 1-866-783-2645.

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The National Alliance for Hispanic Health is the nation's foremost science-based source of information and trusted non-partisan advocate for the best health outcomes for all. The Alliance represents thousands of Hispanic health providers across the nation providing services to more than 15 million each year. For more information, visit http://www.hispanichealth.org, call the Alliances Su Familia Helpline at 1-866-783-2645, or find us on Facebook at healthyamericas or on Twitter at health4americas.

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FDA and National Alliance for Hispanic Health Release Genes, Culture, and Health Report

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Newswise The therapeutic promise of human stem cells is indisputably huge, but the process of translating their potential into effective, real-world treatments involves deciphering and resolving a host of daunting complexities.

Writing in the February 25 online issue of the journal PLOS ONE, researchers at University of California, San Diego School of Medicine, with collaborators from The Scripps Research Institute (TSRI), have definitively shown for the first time that the culture conditions in which stem cells are grown and mass-produced can affect their genetic stability.

Since genetic and epigenetic instability are associated with cancers, we worry that similar alterations in stem cells may affect their safety in therapeutic transplants. Certain mutations might make transplanted stem cells more likely to form tumors, introducing the risk of cancer where it didnt exist before, said co-corresponding author Louise Laurent, MD, PhD, assistant professor and director of perinatal research in the Department of Reproductive Medicine at UC San Diego School of Medicine.

This study shows the importance of quality control, added Jeanne F. Loring, PhD, professor and director of the Center for Regenerative Medicine at TSRI, and adjunct professor in the UC San Diego Department of Reproductive Medicine and the studys other co-corresponding author. Its almost certain these cells are safe, but we want to make sure they are free from any abnormalities.

To exploit the transformative powers of human pluripotent stem cells, which include embryonic stem cells and induced pluripotent stem cells, requires producing them in large numbers for transplantation into patients.

During this culturing process, mutations can occur, and mutations that increase cell survival or proliferation may be favored, such that the cells carrying such mutations could take over the culture, said Laurent.

Human pluripotent stem cells are cultured in several different ways. Key variables are the surfaces upon which the cells are cultured, called the substrate, and the methods used to transfer cells from one culture dish into another as they grow, called the passage method.

Originally, scientists determined that stem cells grew best when cultured atop of a feeder layer that included other types of cells, such as irradiated mouse embryonic fibroblasts. For reasons not fully understood, these cells provide stem cells with factors that support their growth. However, concerns about the feeder cells also introducing undesirable materials into stem cells has prompted development of feeder-free cultures.

Excerpt from:

Culture Clash: How Stem Cells Are Grown Affects Their Genetic Stability

Boston, MA (PRWEB) February 25, 2015

Anyone familiar with the founding principles of Asymmetrex, LLC will appreciate the new editorial from its director and the collection of authors he assembled as Associate Editor for the Frontiers Research Topic, titled Stem Cell Genetic Fidelity. Both the introductory editorial and the individual articles are currently available online, ahead of issue in the form of the Frontiers e-book later this year.

Central to the stem cell mechanisms investigated and reviewed by the nine articles is the still controversial proposal of immortal strands in adult tissue stem cells. Based on the experimental observations of K. Gordon Lark in the 1960s, John Cairns predicted the existence of immortal strands of the DNA genetic material about a decade later.

In studies with cultured mouse tissues and plant root tips, Lark had noted that when some cells divided, they seemed to violate well-established genetic laws. These were the Mendelian laws of inheritance, name after Gregor Mendel, who laid their foundation. Each of the 46 human chromosomes has two complementary strands of DNA. One DNA strand is older than the other, because it was used as the template for copying the other. As a result of this inherent age difference in chromosome DNA strands, when the two DNA strands are split to make two new chromosomes before cell division to produce two new cells one chromosome in each of the 46 pairs of new chromosomes has the oldest DNA strand.

Mendels laws maintain that each new sister cell should randomly get a similar number of chromosomes with the oldest DNA strands. But Cairns hypothesized that adult tissue stem cells had a mechanism to ignore Mendels laws. Instead, one of the two cells produced by an asymmetric stem cell division retained all, and only, the chromosomes with the oldest DNA strands. Cairns called these immortal strands. By continuously retaining the same complete set of oldest template DNA strands, Cairns envisioned that tissue stem cells could significantly reduce their rate of accumulation of carcinogenic mutations, which primarily occur by chance when DNA is being copied.

Cairns presented his concept of immortal strands in tissue stem cells in a 1975 report to account for a large discrepancy that he had noted between human cancer rates and human cell mutation rates. He estimated that human cancer rates, though still undesirable, fell far short of expectations based on generally known rates of human cell mutation.

Whereas some scientists continue to view Cairns immortal strand hypothesis as folly, others consider it genius. In the last decade, progress in evidence for immortal strands in stem cells of diverse animal tissues and animal species accelerated greatly. However, little progress has occurred in defining their role in normal tissue stem cells or diseases like cancer.

In his new editorial, Sherley reveals that he is firmly in the camp that views the immortal strand hypothesis as genius. Before founding Asymmetrex, as a laboratory head in two different independent research institutes Fox Chase Cancer Center and Boston Biomedical Research Institute and at the Massachusetts Institute of Technology he developed new tools and approaches for investigating immortal strand functions, which are now a focus for commercial development in the new company. Immortal strands and cellular factors associated with them have significant potential to provide specific biomarkers for tissue stem cells. There is a significant unmet need for such invaluable tools in stem cell research, drug development, and regenerative medicine.

About Asymmetrex (http://asymmetrex.com/)

Asymmetrex, LLC is a Massachusetts life sciences company with a focus on developing technologies to advance stem cell medicine. Asymmetrexs founder and director, James L. Sherley, M.D., Ph.D. is an internationally recognized expert on the unique properties of adult tissue stem cells. The companys patent portfolio contains biotechnologies that solve the two main technical problems production and quantification that have stood in the way of successful commercialization of human adult tissue stem cells for regenerative medicine and drug development. In addition, the portfolio includes novel technologies for isolating cancer stem cells and producing induced pluripotent stem cells for disease research purposes. Currently, Asymmetrexs focus is employing its technological advantages to develop facile methods for monitoring adult stem cell number and function in clinically important human tissues.

Originally posted here:

New Commentary from Asymmetrex LLC Director Anticipates Forthcoming E-Book on Stem Cell Genetic Fidelity

LEADING experts are hosting a special event to highlight pioneering genetic work carried out at Newcastle University, including the controversial three-parent IVF technique.

Genetic Matters will focus on a series of high-profile talks, including mitochondrial donation, the future of genetic diagnostics and life after being diagnosed with a rare illness.

Newcastle Universitys 100,000 Genome Project will also be discussed. The world-leading scheme aims to map 100,000 complete genetic codes to uncover DNA data that can be used to develop personalised diagnostic procedures and drugs.

Dr Katarzyna Pirog, from the Institute of Genetic Medicine, said: Genetics Matters is an event designed specifically for members of the public, and is an exciting opportunity to meet scientists and learn about the state-of-the-art genetic research that happens at Newcastle University.

With a series of high profile talks, presentations from patient groups and charity organisations, and hands on research tables, it is a packed day giving everyone a chance to talk to real scientists and ask them any questions to do with genetic research.

Prof Sir John Burn, head of Newcastle Universitys Institute of Human Genetics, will close the event with a talk about the future of rare disease research.

He said: There are more than 8,000 rare diseases, mostly due to faults in one or more genes and the number grows as sequencing gets cheaper and faster. One in 17 people has a rare genetic disorder and providing their care is a major health cost.

As we learn how these rare diseases are caused we gain new insights into the causes of common diseases and can use this to develop new treatments.

Genetic Matters will take place on Friday, February 27, from 10:45am until 5pm, at the Great North Museum: Hancock in Newcastle.

To book a place at the event visit: forms.ncl.ac.uk/view.php?id=7501

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Genetic medicine under the spotlight

Mutation of one gene is all it takes to get cystic fibrosis (CF), but disease severity depends on many other genes and proteins. For the first time, researchers at the UNC School of Medicine have identified genetic pathways -- or clusters of genes -- that play major roles in why one person with CF might never experience the worse kinds of symptoms while another person will battle severe airway infection for a lifetime.

The finding, published in the American Journal of Human Genetics, opens avenues of research toward new personalized or precision treatments to lessen pulmonary symptoms and increase life expectancy for people with cystic fibrosis.

"Right now, there are drugs being developed to fix the function of the CFTR protein that is disrupted in cystic fibrosis, but even then, some patients will respond very well to therapy and some won't," said Michael Knowles, MD, professor of pulmonary and critical care medicine and senior author of the paper. "Why is that? We think it's the genetic background -- the pathways that we identified contain genes that likely interact with the main CFTR gene mutation."

Knowles's team found that when these pathways or groups of genes are highly expressed, CF patients have less severe symptoms. When these pathways are expressed in lower amounts, patients experience a more severe form of the disease and are more likely to be hospitalized.

Wanda O'Neal, PhD, associate professor of medicine and first author, said, "Now that we've found these pathways, we need to dig into the biology to see how specific genes within them influence disease severity. This could help us not only to predict which patients will respond to a given therapy but it may also provide drug targets to lessen the severity of disease for all patients."

The CFTR gene was discovered in 1989, and since then researchers have found about 1,800 different mutations in the CFTR gene that cause cystic fibrosis. There is a new drug that works very well to correct a mutation found in about 4 percent of CF patients. There is still no FDA approved drug to correct the mutation found in about 70 percent of patients (called the DF508 mutation), though a drug company has recently shown that a combination therapy of two new drugs modestly improved lung function in some CF patients. Still, this combination therapy may not work or wouldn't work well enough for some patients, and the reason could be the complex interaction between the CFTR gene and the genetic pathways uncovered by Knowles, O'Neal, and co-senior author Fred Wright, PhD, a professor of bioinformatics and director of the bioinformatics program at North Carolina State University.

In a normal epithelial cell, the CFTR gene creates the protein that transits from the cell nucleus to the cell membrane, where it then works to maintain proper lung function. As the protein transits, there are many genes that interact with it in various ways so that it can complete the journey to the membrane and work properly in the end. In CF patients with the DF508 mutation, the CFTR gene does not fold into its correct form and cannot make it to the cell surface. In order for CF patients to be out of the woods, the DF508 protein would need help from a complex network of genes and proteins to get to the membrane.

Over the past decade, Knowles has teamed with scientists from the United States and Canada to gather thousands of genetic and blood cell samples from CF patients. One of the research goals has been to identify genes and cellular proteins that often have subtle effects inside cells but that can produce dramatic differences in disease severity. Decades of research on protein functions has allowed genes to be grouped into pathways based on common biological roles.

For this current study, Knowles and O'Neal used gene expression data from the cells collected from 750 patients gathered over the past decade from 40 sites across the United States. Along with Wright and other authors, they analyzed data on more than 4,000 pathways to find pathways that identified severe CF patients as compared to mild CF patients. They found significant genetic variation in only broad types of pathways: endomembrane pathways and HLA pathways.

This finding was telling because endomembrane genes are responsible for transporting the DF508 protein from the cell nucleus to the cell membrane and for regulating the way that proteins such as CFTR are folded into the proper functioning form. The HLA genes are widely known to have roles in immune function; they're important for protection against pathogens, such as Pseudomonas -- the commonly seen bacteria that causes pneumonia in CF patients.

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Genetic pathways linked to CF disease severity pinned down

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Newswise CHAPEL HILL, NC Mutation of one gene is all it takes to get cystic fibrosis (CF), but disease severity depends on many other genes and proteins. For the first time, researchers at the UNC School of Medicine have identified genetic pathways or clusters of genes that play major roles in why one person with CF might never experience the worse kinds of symptoms while another person will battle severe airway infection for a lifetime.

The finding, published in the American Journal of Human Genetics, opens avenues of research toward new personalized or precision treatments to lessen pulmonary symptoms and increase life expectancy for people with cystic fibrosis.

Right now, there are drugs being developed to fix the function of the CFTR protein that is disrupted in cystic fibrosis, but even then, some patients will respond very well to therapy and some wont, said Michael Knowles, MD, professor of pulmonary and critical care medicine and senior author of the paper. Why is that? We think its the genetic background the pathways that we identified contain genes that likely interact with the main CFTR gene mutation.

Knowless team found that when these pathways or groups of genes are highly expressed, CF patients have less severe symptoms. When these pathways are expressed in lower amounts, patients experience a more severe form of the disease and are more likely to be hospitalized.

Wanda ONeal, PhD, associate professor of medicine and first author, said, Now that weve found these pathways, we need to dig into the biology to see how specific genes within them influence disease severity. This could help us not only to predict which patients will respond to a given therapy but it may also provide drug targets to lessen the severity of disease for all patients.

The CFTR gene was discovered in 1989, and since then researchers have found about 1,800 different mutations in the CFTR gene that cause cystic fibrosis. There is a new drug that works very well to correct a mutation found in about 4 percent of CF patients. There is still no FDA approved drug to correct the mutation found in about 70 percent of patients (called the DF508 mutation), though a drug company has recently shown that a combination therapy of two new drugs modestly improved lung function in some CF patients. Still, this combination therapy may not work or wouldnt work well enough for some patients, and the reason could be the complex interaction between the CFTR gene and the genetic pathways uncovered by Knowles, ONeal, and co-senior author Fred Wright, PhD, a professor of bioinformatics and director of the bioinformatics program at North Carolina State University.

In a normal epithelial cell, the CFTR gene creates the protein that transits from the cell nucleus to the cell membrane, where it then works to maintain proper lung function. As the protein transits, there are many genes that interact with it in various ways so that it can complete the journey to the membrane and work properly in the end. In CF patients with the DF508 mutation, the CFTR gene does not fold into its correct form and cannot make it to the cell surface. In order for CF patients to be out of the woods, the DF508 protein would need help from a complex network of genes and proteins to get to the membrane.

Over the past decade, Knowles has teamed with scientists from the United States and Canada to gather thousands of genetic and blood cell samples from CF patients. One of the research goals has been to identify genes and cellular proteins that often have subtle effects inside cells but that can produce dramatic differences in disease severity. Decades of research on protein functions has allowed genes to be grouped into pathways based on common biological roles.

Continued here:

Researchers Pin Down Genetic Pathways Linked to CF Disease Severity

This post is sponsored by the MidAmerica Healthcare Venture Forum.

The table is set for jaw-dropping growth in the genomics/personalized medicine/precision medicine space. Pick your favorite news item. Is it the presidents new plan? The big investments out of JP Morgan? Or, most recently, the breakthrough decision by the FDA around 23andMe and other genetic testing kits?

Its not about whether personalized medicine has arrived. Its here. Now its about not getting lost in the hype and focusing on what matters.

Thats why weve assembled a strong cast of clinicians and innovators at the MidAmerica Healthcare Venture Forum on March 10-11 in Chicago who will keep us on track and explain how to maximize the potential of personalized medicine. MedCitys Meghana Keshavan will lead a discussion exploring not only what the next milestones are for the industry but also where the biggest opportunities are and what areas of personalized medicine need the most support.

Join us in Chicago and youll hear from the following panelists:

New funding and fresh attention bring new opportunities. The worst-case scenario for precision medicine is for investors, entrepreneurs and other healthcare leaders to squander it by getting lost amidst the hype and euphoria.

Our panel at the MidAmerica Healthcare Venture Forum will help keep everyone on track by sharing their hands-on knowledge on what it will take to deliver real success in personalized medicine. I hope you can join us March 10-11 in Chicago to participate in the discussion.

[Photo from Flickr user Craig Cloutier]

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Personalized medicines potential grows. But what signals real progress?

Researchers from Yale University have found new evidence for a link between obsessive compulsive spectrum disorder and pathological gambling, perhaps due to genetic factors.

Building off of previous research that suggested a link between addictive behavior and pathological gambling, this study is part of an ongoing effort to further classify gambling addiction on an impulse-to-compulsion spectrum. The central question of the debate is: To what extent do pathological gamblers have impulse-control problems as opposed to a compulsion to gamble? This study adds evidence that there is an element of compulsive behavior for some pathological gamblers.

We were trying to understand the relation between pathological gambling and other disorders, said Yale professor of psychiatry at the School of Medicine and the papers senior author Marc Potenza. There has been some debate in the literature about how best to consider pathological gambling whether it might fall along the impulsive-compulsive spectrum or be thought of as an addiction without the drug.

The researchers performed a twin study, using the Vietnam Era Twin Registry a compiled list of male twin veterans of the Vietnam War to study both genetic explanations of pathological gambling and its connection with latent obsessive-compulsive behavior. Twin studies allow researchers to better disentangle the complex relationship between environmental and genetic factors at play in disorders, diseases and behaviors. The researchers found a correlation between latent obsessive-compulsive behavior and pathological gambling. In addition, they found behavioral correlations between twins, suggesting a genetic component to compulsive behavior and pathological gambling.

It was unusual that the researchers decided to use a twin study, as opposed to conducting genetic testing, Potenza said. The methodology allowed the researchers to ascertain a genetic component, but without the genetic testing, they were unable to identify which genes cause this effect. That second question, Potenza said, may lead to further research.

But clinical professor at the Stanford School of Medicine Alan Ringold, an expert on OCD who is unaffiliated with the study, said he does not believe pathological gambling is related to OCD, which is an extreme enough form of obsessive behavior that it is classified as a disorder in the Diagnostic and Statistical Manual, which classifies psychiatric disorders.

Gambling is an impulse control disorder. Its not OCD, Ringold said, highlighting the controversy within the medical community about whether gambling is compulsion-based or impulse control-based.

Because the researchers only used male participants, it is unknown to what extent the results generalize to the entire population.

This is an example of being persistent, said Jeffrey Scherrer, professor in the department of family and community medicine at Saint Louis University School of Medicine. This gambling study data collection was completed around 2003, and we began some preliminary analysis. We werent able to get back together on this until many years later, so the lesson is dont give up on an idea.

Between 5 and 7 percent of Americans have a problem with gambling.

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Addiction can also be compulsion, gambling study shows

Precision Medicine: How our Genes Can Help Determine Our Risk and Treatment for Disease
Esteban Burchard, Director, Center for Genes, Environments Health Professor of Bioengineering Therapeutic Sciences Medicine University of California Sa...

By: CalChannel

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Precision Medicine: How our Genes Can Help Determine Our Risk and Treatment for Disease - Video

Keck Medicine of the University of Southern California (USC) scientists have found a promising new therapeutic target for prostate cancer. The findings offer evidence that a newly discovered member of a family of cell surface proteins called G-protein coupled receptors (GPCRs) promotes prostate cancer cell growth. The protein, GPR158, was found while the researchers were looking for new drug targets for glaucoma.

Prostate cancer is the second most common cancer in American men, after skin cancer, according to the American Cancer Society (ACS). The ACS projects more than 27,000 deaths from prostate cancer in 2015 and is the second leading cause of cancer death in American men, behind lung cancer. One man in seven will be diagnosed with prostate cancer during his lifetime.

"When a prostate cancer tumor is in its early stages, it depends on hormones called androgens to grow," said Nitin Patel, Ph.D., research scientist at the Institute for Genetic Medicine at the Keck School of Medicine of USC, and corresponding author on the research. "Eventually it progresses to a more lethal form, called castration-resistant prostate cancer (CRPC), and is resistant to drugs that block androgen receptors. We found that GPR158, unlike other members of the GPCR family, is stimulated by androgens, which in turn stimulates androgen receptor expression, leading to tumor growth."

The team also discovered that GPR158 is associated with neuroendocrine transdifferentiation (NED) of epithelial prostate tumor cells, which plays a critical role in development of resistance to contemporary androgen receptor-target therapies. The scientists found that prostate cancer patients with elevated GPR158 expression experienced recurrence of prostate cancer. The GPR158 protein is a likely target for new prostate cancer drugs.

The researchers used a conditional Pten knockout mouse model of prostate cancer in collaboration with Keck School of Medicine of USC researchers Mitchell Gross, Chun-Peng Liao and Pradip Roy-Burman.

The team is now exploring the molecular pathways involved in the functional role of GPR158 in NED in the development of CRPC and exploring GPR158-targeted antibody therapeutics.

Story Source:

The above story is based on materials provided by University of Southern California - Health Sciences. Note: Materials may be edited for content and length.

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New target for prostate cancer treatment discovered

Researchers are beginning to understand how DNA makes some athletes more likely to get hurt.

Injury is a fact of life for most athletes, but some professionalsand some weekend warriors, for that matterjust seem more injury-prone than others. But what is it about their bodies that makes the bones, tendons, and ligaments so much more likely to tear or strainbad luck, or just poor preparation?

A growing body of research suggests another answer: that genetic makeup may play an important role in injury risk.

A review article recently published in the Clinical Journal of Sports Medicine emphasizes that research on the genetics of sports injuries holds great potential for injury prevention for athletes at every level. The authors, from Stanford Universitys department of developmental biology and genetics, believe that genetic testing also gives athletes valuable information that might increase their competitive edge.

Stuart Kim, one of the studys authors and a professor of genetics at Stanford, says his interest in sports injuries began almost by accident. I initially intended to study the genes associated with the large size of NFL lineman, but the athletes werent really interested in finding out the genetic reasons why they were so big, Kim says. But they were extremely interested in figuring out what injuries they were more likely to sustain.

Genetic information can be valuable for amateur athletes, tooregardless of skill level, someone about to join a recreational basketball league or a tennis club would be well-served to know if theyre at risk of blowing out an ACL or tearing an Achilles. Each year, around 2 million adults go to the emergency room for sports-related injuries, many of them acquired during pickup games or matches in recreational leagues.

Within the field of sports-injury genetics, some studies have focused on variations in the genes that control the production of collagen, the main component of tendons and ligaments. Collagen proteins also form the backbone of tissues and bones, but in some people, structural differences in these proteins may leave the bodys structures weaker or unable to repair themselves properly after injury. In a study published in the British Journal of Sports Medicine in 2009, South African researchers found that specific variations of a collagen gene named COL1A1 were under-represented in a group of recreational athletes who had suffered traumatic ACL injuries. Those who had torn their ACL were four times as likely as the uninjured study subjects to have a blood relative who had suffered the same injury, suggesting that genetics are at least partially responsible for the strength of the ligament.

The same COL1A1 gene has also been linked to other soft-tissue injuries, like Achilles-tendon ruptures and shoulder dislocations. In a review article that combined the results of multiple studies on the COL1A1 gene, published in the British Journal of Sports Medicine in 2010, researchers concluded that those with the TT genotypeone of three potential variants of the gene, found only in 5 percent of the populationare extremely unlikely to suffer a traumatic ligament or tendon injury.

However, because of the vast complexity of the human genome, its highly improbable that a single variant within a gene can determine a persons genetic risk for a given soft-tissue injury. Researchers agree its much more likely that these injuries, like complex conditions such as obesity or type 2 diabetes, are influenced by multiple genes.

The COL5A1 gene, another one associated with collagen production, has been linked to a higher risk of injury of the ACL and Achilles tendon, as well as greater susceptibility to exercise-induced muscle cramping. A 2013 study in the Clinical Journal of Sports Medicine found that specific variants of COL5A1 were strongly correlated with muscle cramping among runners in the Two Oceans Marathon in South Africa.

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The Genetics of Being Injury-Prone

How can we keep more people from joining the ranks of the 29 million Americans already diagnosed with diabetes? What if we could tell with precision who has the highest risk of developing the disease, and figure out which preventive steps are most likely to help each of them individually?

Researchers have just released a "precision medicine" approach to diabetes prevention that could do just that -- using existing information like blood sugar levels and waist-to-hip ratios, and without needing new genetic tests.

Their newly published model examined 17 different health factors, in an effort to predict who stands to gain the most from a diabetes-preventing drug, or from lifestyle changes like weight loss and regular exercise. Seven of those factors turned out to matter most.

The model is published in the British Medical Journal by a team from the University of Michigan, VA Ann Arbor Healthcare System and Tufts Medical Center in Boston.

They hope to turn it into a tool for doctors to use with patients who have "pre-diabetes," currently defined by abnormal results on a test of blood sugar after fasting. They also hope their approach could be used to develop similar precise prediction models for other diseases and treatments.

"Simply having pre-diabetes is not everything," says lead author Jeremy Sussman, M.D., M.S. "This really shows that within the realm of pre-diabetes there's a lot of variation, and that we need to go beyond single risk factors and look holistically at who are the people in whom a particular approach works best." Sussman is an assistant professor of general medicine at the U-M Medical School and a research scientist at the VA Center for Clinical Management Research.

The team developed the model using data from a gold-standard clinical trial of diabetes prevention: the Diabetes Prevention Program, which randomly assigned people with an elevated risk of diabetes to placebo, the drug metformin, or a lifestyle-modification program.

The team developed and tested their model by carefully analyzing data from more than 3,000 people in the study, all of whom had a high body mass index and abnormal results on two fasting blood sugar tests. Most also had a family history of diabetes, and more than a third were African American or Latino -- all known to be associated with higher risks of diabetes. In all, they looked at 17 factors that together predicted a person's risk of diabetes -- and his or her chance of benefiting from diabetes-preventing steps. They found seven factors were most useful.

The seven were: fasting blood sugar, long-term blood sugar (A1C level), total triglycerides, family history of high blood sugar, waist measurement, height, and waist-to-hip ratio. They developed a scoring scale using the clinical trial data, assigning points to each measure to calculate total score.

Fewer than one in 10 of trial participants who scored in the lowest quarter would develop diabetes in the next three years, while almost half of those in the top quarter would develop diabetes in that time. Then, the team looked at what impact the two diabetes-preventing approaches had.

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Precision medicine to prevent diabetes? Researchers develop personalized way to steer prevention efforts

Tucson, AZ. (PRWEB) February 19, 2015

Could genetic codedetermine someones coffee habit? Apparently so, according to a new study by researchers at the Harvard T.H. Chan School of Public Health (HSPH).

Produced with the support of the Coffee and Caffeine Genetics Consortium and published in the journal Molecular Psychiatry this past fall, the studyone of several recent HSPH investigations of the popular beverageinvolved a meta-analysis of genomic data from more than 120,000 regular coffee drinkers of European and African ancestry. The researchers analyzed their subjects genetic makeup through DNA sequencing, and compared those results to self-reported coffee-drinking figures, in an effort to understand why some people need more of the stimulant than others to feel the same effect. Their data suggest that people instinctively regulate their coffee intake in order to experience the optimal effects of caffeine.

Lead author Marilyn Cornelis, a former research associate in the HSPH nutrition department who is now assistant professor in preventive medicine at Northwestern, says their findings provide insight not only on why caffeine affects people differently, but also on how these effects influence coffee-drinking behavior. One individual, for example, may need three cups of coffee to feel invigorated, while another may need only one. If that one-cup-a-day person consumes four cups instead, Cornelis explains, any jitters or other ill effects that result may discourage that level of consumption in the future.

Given coffees widespread consumption, its effects on health have been the subject of continuing interest and debate. The newest edition of The Diagnostic and Statistical Manual of Mental Disorders, for example, lists both caffeine intoxication and withdrawal as disorders. On the other hand, a study released in January by other investigators at HSPH found that drinking up to six cups of coffee a day showed no association with any increased risk of death (including from cancer or cardiovascular disease). Going back several yearscoffee often had a bad rap, Cornelis says. I hope to finally account for those genetic variants and possibly other risk factors that might modify our response to coffee or caffeine.

Her team identified six new genetic variants associated with habitual coffee drinking, including twoPOR and ABCG2related to caffeine metabolism, and another two that may influence the psychological boost and possible physical health benefits of caffeine. The most surprising aspect of the study, Cornelis reports, was the discovery that two genes involved in glucose and lipid metabolismGCKR and MLXIPLare also linked for the first time to the metabolic and neurological effects of caffeine.

Coffee is possibly protective, Cornelis says. Eventually, she hopes to account for those genetic variants and possibly other risk factors that might modify our response to coffee or caffeine. We know coffee is one of the primary sources of antioxidants of the American diet. If some individuals can metabolize caffeine quickly, then theyre potentially getting rid of the adverse effects of caffeine yet still experiencing the beneficial effects of other coffee constituents.

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Enhancing the Caffeine Experience and How Coffee Habits Relate to Our Genetic Code

For the first time, scientists have mapped out the molecular "switches" that can turn on or silence individual genes in the DNA in more than 100 types of human cells, an accomplishment that reveals the complexity of genetic information and the challenges of interpreting it.

Researchers unveiled the map of the "epigenome" in the journal Nature on Wednesday, alongside nearly two dozen related papers. The mapping effort is being carried out under a 10-year, $240 million U.S. government research program, the Roadmap Epigenomics Project, which was launched in 2008.

The human genome is the blueprint for building an individual person. The epigenome can be thought of as the cross-outs and underlinings of that blueprint: For example, if someone's genome contains DNA associated with cancer, but that DNA is "crossed out" by molecules in the epigenome, the DNA is unlikely to lead to cancer. As sequencing individuals' genomes to infer the risk of disease becomes more common, it will become all the more important to figure out how the epigenome is influencing that risk.

Sequencing genomes is the centerpiece of President Barack Obama's "precision medicine" initiative. "The only way you can deliver on the promise of precision medicine is by including the epigenome," said MIT's Manolis Kellis, who led the mapping project.

Because scientists involved in the project have been depositing their findings in a public database as they went along, other researchers have been analyzing the information even before the map was formally published. One of the resulting studies shows, for instance, that brain cells from people who died with Alzheimer's disease had epigenetic changes in DNA involved in immune response.

First published February 18 2015, 7:38 PM

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Scientists Map the Epigenome, Our Second Genetic Code

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Newswise BOSTON President Barack Obama is requesting an increase of $215 million in the 2016 federal budget to launch the Precision Medicine Initiative. This boost in funding for research will give genetic causes of cancer a national focus specifically around precision or personalized treatments for cancer in the future.

Here are some facts about precision medicine:

1) What is precision or personalized medicine?

Physicians have long recognized that the same disease can behave differently from one patient to another, and that there is no one-size-fits-all treatment. Precision medicine makes diagnosis and treatment of cancer and other diseases more accurate, using the specific genetic makeup of patients (and, in cancer, of their tumors) to select the safest and most effective treatments for them.

In cancer, precision medicine involves testing DNA from patients tumors to identify the mutations or other changes that drive their cancer. Then a treatment for a particular patients cancer that best matches, or targets, the culprit mutations in the tumor DNA is used. While such therapies are not widespread yet, many cancer specialists believe precision treatments will be central to the future of cancer care.

2) Do all patients receive precision or targeted treatment?

Not all patients need targeted therapy to treat their type of cancer. The use of targeted therapies is meant for patients whose tumors have specific gene mutations that can be blocked by available drug compounds. Patients who have mutations in certain types of genes, who have mutations that are beyond the reach of available drugs, or whose tumor cells lack identifiable mutations generally would not be candidates for personalized medicine treatments.

According to the National Cancer Institute, a patient is a candidate for a targeted therapy only if he or she meets specific criteria, which vary depending on the disease. These criteria are set by the Federal Drug Administration (FDA) when it approves a specific targeted therapy.

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Dana-Farber Experts Share Five Things You Should Know About Precision Medicine

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Newswise While genomics is the study of all of the genes in a cell or organism, epigenomics is the study of all the genomic add-ons and changes that influence gene expression but arent encoded in the DNA sequence. A variety of new epigenomic information is now available in a collection of studies published Feb. 19 in Nature by the National Institutes of Health (NIH) Roadmap Epigenomics Program. This information provides a valuable baseline for future studies of the epigenomes role in human development and disease.

Two of these studies, led by researchers at University of California, San Diego School of Medicine and Ludwig Cancer Research, address the differences between chromosome pairs (one inherited from mom, the other from dad) and how chromosome folding influences gene expression.

Both of these studies provide important considerations for clinicians and researchers who are developing personalized medicines based on a patients genomic information, said Bing Ren, PhD, professor of cellular and molecular medicine at UC San Diego, Ludwig Cancer Research member and senior author of both studies.

The first paper by Rens group takes a look at differences in our chromosome pairs. Each of us inherits one set from our mother and the other from our father. Chromosome pairs are often thought to be identical, one just a backup for the other. But this study found widespread differences in how genes are regulated (turned on and off) between the two chromosomes in a pair. It turns out that we all have biases in our chromosomes. In other words, different traits have a stronger contribution from one parent than the other. The study also suggests that these biases are rooted in inherited sequence variations and that they are not randomly distributed. These findings help explain why, for example, all kids in a family may have their fathers hair but their mothers eyes.

The second paper by Rens group tackles how the genome is organized and how it changes as stem cells differentiate (specialize). DNA strands in every cell are tightly wound and folded into chromosomes. Yet chromosomal structures, and how they influence gene expression, are not well understood. In this study, Ren and team mapped chromosomal structures in stem cells and several different differentiated cell types derived from stem cells. First, they induced differentiation in the stem cells. Then they used molecular tools to examine how the structure of the cells chromosomes changed and how that change is associated with gene activity. The team found that chromosomes are partitioned into relatively stable structural units known as topologically associating domains (TADs), and that TAD boundaries remain constant in different cell types. Whats more, the researchers found that the changes in chromosomal architecture mostly take place within the TADs in a way that correlates with changes in the epigenome.

The epigenome chemical modifications to chromosomes and 3D chromosomal structure is not just a linear object, Ren said. The epigenome is a 3D object, folded in a hierarchical way, and that should affect how we think about many aspects of human development, health and disease.

Co-authors on the paper Integrative Analysis of Haplotype-Resolved Epigenomes Across Human Tissues include Danny Leung, Inkyung Jung, Nisha Rajagopal, Anthony Schmitt, Siddarth Selvaraj, Ah Young Lee, Chia-An Yen, Yunjiang Qiu, Samantha Kuan, Lee Edsall, Ludwig Cancer Research; Shin Lin, Yiing Lin, Stanford University and Washington University School of Medicine; Wei Xie, formerly at Ludwig Cancer Research and now at Tsinghua University; Feng Yue, formerly at Ludwig Cancer Research and now at Pennsylvania State University; Manoj Hariharan, Joseph R. Ecker, Howard Hughes Medical Institute and Salk Institute for Biological Studies; Pradipta Ray, University of Texas; Hongbo Yang, Neil C. Chi, UC San Diego; and Michael Q. Zhang, University of Texas, Dallas and Tsinghua University.

Co-authors on the paper Chromatin Architecture Reorganization during Stem Cell Differentiation include Jesse R. Dixon, Siddarth Selvaraj, Ludwig Cancer Research and UC San Diego; Inkyung Jung, Yin Shen, Ah Young Lee, Zhen Ye, Audrey Kim, Nisha Rajagopal, Yarui Diao, Ludwig Cancer Research; Jessica E. Antosiewicz-Bourget, Morgridge Institute for Research; Wei Xie, Tsinghua University; Jing Liang, Huimin Zhao, University of Illinois at Urbana-Champaign; Victor V. Lobanenkov, National Institute of Allergy and Infectious Diseases; Joseph R. Ecker, Howard Hughes Medical Institute and Salk Institute for Biological Studies; James Thomson, Morgridge Institute for Research, University of Wisconsin and University of California, Santa Barbara.

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New Insights into 3D Genome Organization and Genetic Variability

DUBLIN, Feb .17, 2015 /PRNewswire/ --Research and Markets

(http://www.researchandmarkets.com/research/sqhzfm/personalized) has announced the addition of the "Personalized Medicine, Targeted Therapeutics and Companion Diagnostic Market 2015: Strategic Analysis of Industry Trends, Technologies, Participants, and Environment" report to their offering.

Personalized Medicine, Targeted Therapeutics and Companion Diagnostic Market 2015 - Strategic Analysis of Industry Trends, Technologies, Participants, and Environment is a cutting-edge comprehensive report on the personalized medicine industry and its impact on the health system. This report tackles the growing market interest in pharmacogenomics, companion diagnostics and the associated market environment.

Individualized, targeted or personalized medicine aims to increase the efficacy of therapeutics via genetic testing and companion diagnostics. Personalized therapeutics and associated companion diagnostics will be more specific and effective thereby giving pharma/biotech companies a significant advantage to recuperate R&D costs. Personalized medicine will reduce the frequency of adverse drug reactions and therefore have a dramatic impact on health economics. Developmental and diagnostic companies will benefit from lower discovery and commercialization costs and more specific market subtypes.

This report describes the current technologies that are propelling the personalized medicine and companion diagnostic market. It examines the current genetic diagnostic tests and companion diagnostic assays that are in use by the medical and pharmaceutical industry today. Current developments in personalized medicine and the pharmacogenomics revolution are discussed. The emerging trends that appear in key markets such as the US, UK, Germany and France are elucidated and analysed. This study reveals market figures of the overall personalized medicine market and also sub-market figures. Forecast projections and future growth rates are provided to give the reader a forthcoming perspective of this growing industry.

The study also provides a comprehensive financial and product review of key players in the personalized medicine industry. Strategic drivers and restraints of this market are revealed and market opportunities and challenges are identified.

In summary, the personalized medicine and associated companion diagnostic market have huge opportunities for growth. This industry will revolutionize the healthcare system and will improve therapeutic effectiveness and reduce the severity of adverse effects. It has enormous potential for investment and the emergence of genetic-based in vitro diagnostics.

This report highlights a number of significant pharmacos and gives details of their operations, products, financials and business strategy.

- 23andMe - Affymetrix - Astex Pharmaceuticals - Atossa Genetics - CuraGen - Celera Corporation (Quest Diagnostics) - Celldex Therapeutics - deCode Genetics (Amgen) - Illumina - Genelex - Myriad - Nodality - Qiagen

Key Topics Covered:

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Personalized Medicine, Targeted Therapeutics and Companion Diagnostic Market 2015: Strategic Analysis of Industry ...

As obesity becomes an increasingly prominent health condition in the United States, University researchers have made new discoveries about the biological pathways that cause it.

In the largest genome-wide study ever, the Genetic Investigation of Anthropometric Traits consortium of researchers analyzed more than 300,000 genetic samples and found 97 new genetic locations across the genome that are associated with obesity and body mass index triple the number of previously known sites.

This finding led researchers to believe obesity is much more related to ones genes than was previously thought.

Elizabeth Speliotes, assistant professor of internal medicine and a senior author of the GIANT study, said if scientists can pinpoint the specific gene variants or proteins that contribute to obesity, then therapeutic interventions can directly target them.

Speliotes said the study could lead to a new era of tailored obesity care.

We are realizing that many of the common diseases we aim to treat are caused by multiple different underlying causes, Speliotes said. So now we can understand what those causes are and better define them. And then hopefully in the future we can sub-classify people into what they are at risk for versus what the general population is at risk for.

Currently, therapeutic interventions are often generalized to diseases. For example, the same medications are often prescribed to all patients suffering from the same disease. Outcomes from these interventions have not been very successful.

Right now we dont know what the exact causes are for different diseases, so a lot of the stuff we do is like shooting in the dark, Speliotes said.

In a companion study, an international consortium of researchers led by Karen Mohlke, professor of genetics at the University of North Carolina School of Medicine, identified 49 sites in the human genome associated with the human waist-to-hip ratio.

Mohlke said the waist-to-hip ratio is often associated with obesity because most people with waistlines larger than their hip circumference have more visceral fat around their abdominal organs, making them susceptible to diseases such as type 2 diabetes and cardiovascular diseases.

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Research uncovers additional pathways that cause obesity

Health care professionals nationwide are tangled in a discussion regarding the ethics and regulations of the growing field of precision medicine.

Also known as personalized medicine, the field aims to analyze patients genes so doctors can home in on treatments specific to each person.

As the talks have intensified in recent years, concerns over privacy and insurance discrimination are colliding with benefits like predicting disease contraction and better, more-personalized treatment.

The debate hit the University of Minnesota campus on Thursday with the start of a lecture series focusing on the standardization and policies of precision medicine.

Heidi Rehm, a Harvard University pathology professor, gave the first in a three-part lecture in the Universitys Consortium on Law and Values in Health, Environment and Life Sciences series.

Her lecture comes soon after President Barack Obamas announcement of a plan late last month that calls for a major biomedical research initiative that would create a biobank, or a collection of genetic data, on one million Americans.

If Congress approves Obamas proposal, it would put individualized medicine more easily within doctors reach.

Rehm, who studies precision medicine, said how the technology is used and the way results are interpreted should become more standardized than they currently are.

University law professor and consortium chair Susan Wolf said the difference in technology and interpretation of genomes needs standardization.

Right now its kind of a tower of Babel, Wolf said. And thats really tough on patients that may get different answers from different labs.

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Precision medicine debate hits University campus