Award honors fundamental research that is expected to be of considerable significance for medicine

IMAGE:This is professor Emmanuelle Charpentier, recipient of the Louis-Jeantet-Prize for Medicine 2015. view more

Credit: Helmholtz / Hallbauer&Fioretti

Prof Emmanuelle Charpentier from the Helmholtz Centre for Infection Research (HZI) in Braunschweig is one of the two recipients of the 2015 Louis-Jeantet-Prize for Medicine. The prize money of 700,000 Swiss francs is mostly attributed for the continuation of the awardees work. Charpentier receives the prize for harnessing an ancient immune defense system in bacteria - CRISPR-Cas9 - into a genome editing tool largely exploited by biologists and promising for curing human diseases.

Bacterial pathogens also possess an immune system that defends them against predators, and particularly viruses. When studying this system, Charpentier while she was a group leader at the Laboratory for Molecular Infection Medicine Sweden (MIMS) at Ume University and her team unravelled a unique mechanism - CRISPR-Cas9 - a pair of molecular scissors composed of a duplex of two RNAs linked to a protein. In collaboration with the team of her colleague Prof Jennifer Doudna, University of California, Berkeley, it was demonstrated that the mechanism could be harnessed into a powerful tool for genome engineering. The system is celebrated as a revolution for biology, and used by laboratories all over the world for different purposes.

"The CRISPR-Cas9 system has already breached boundaries and made genetic engineering much more versatile, efficient and easy", says Charpentier, who is the head of the department "Regulation in Infection Biology" at the HZI, Alexander von Humboldt Professor affiliated at the Hannover Medical School and a guest Professor at the Laboratory for Molecular Infection Medicine, Ume University, Sweden. The system can be used in various areas of biology and medicine and curing genetic disorders is only one possible application. The system also shows promises in areas like agriculture and the development of therapeutics for the or when it comes to developing treatment of chronical diseases such as HIV or cancer.

Established in 1986, the Louis-Jeantet-Prize for medicine has already been awarded to 82 researchers. Ten of the awardees subsequently won the Nobel Prize for Physiology or Medicine, or the Nobel Prize for Chemistry. As one of the best-endowed awards in Europe, the Louis-Jeantet Prize for Medicine fosters scientific excellence. It finances the continuation of innovative research projects of more or less immediate practical significance for the treatment of diseases rather than honouring completed work.

"I feel extremely honoured receiving this prestigious award", says Charpentier. "I see it as a motivation for my team to continue our work and will use the prize money to conduct further research on the mechanisms governing the pathogenicity of Streptococcus pyogenes".

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Louis-Jeantet-Prize for Medicine goes to Emmanuelle Charpentier

By Dennis Thompson HealthDay Reporter

WEDNESDAY, Jan. 14, 2015 (HealthDay News) -- Researchers have uncovered a major genetic risk for heart failure -- a mutation affecting a key muscle protein that makes the heart less elastic.

The mutation increases a person's risk of dilated cardiomyopathy. This is a form of heart failure in which the walls of the heart muscle are stretched out and become thinner, enlarging the heart and impairing its ability to pump blood efficiently, a new international study has revealed.

The finding could lead to genetic testing that would improve treatment for people at high risk for heart failure, according to the report published Jan. 14 in the journal Science Translational Medicine.

The mutation causes the body to produce shortened forms of titin, the largest human protein and an essential component of muscle, the researchers said in background information.

"We found that dilated cardiomyopathy due to titin truncation is more severe than other forms and may warrant more proactive therapy," said study author Dr. Angharad Roberts, a clinical research fellow at Imperial College London. "These patients could benefit from targeted screening of heart rhythm problems and from implantation of an internal cardiac defibrillator."

About 5.1 million people in the United States suffer from heart failure. One in nine deaths of Americans include heart failure as a contributing cause. And about half of people who develop heart failure die within five years of diagnosis, according to the U.S. Centers for Disease Control and Prevention.

In this study, researchers studied more than 5,200 people, including both healthy people and people suffering from dilated cardiomyopathy. The researchers performed genetic sequencing on all these people, examining the specific gene that the body uses to create titin.

Prior research had found that genetically shortened titin is the major genetic cause of dilated cardiomyopathy, accounting for about 25 percent of severe cases, according to the paper.

However, there are numerous mutations of the titin gene and many never lead to heart failure, so the researchers focused on those variations that occur most often in people with dilated cardiomyopathy.

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Scientists Spot Mutation Behind Genetic Form of Heart Failure

Autism spectrum disorders (ASD) affect 1 to 2 percent of children in the United States. Hundreds of genetic and environmental factors have been shown to increase the risk of ASD. Researchers at UC San Diego School of Medicine previously reported that a drug used for almost a century to treat trypanosomiasis, or sleeping sickness, reversed environmental autism-like symptoms in mice.

Now, a new study published in this week's online issue of Molecular Autism, suggests that a genetic form of autism-like symptoms in mice are also corrected with the drug, even when treatment was started in young adult mice.

The underlying mechanism, according to Robert K. Naviaux, MD, PhD, the new study's principal investigator and professor of medicine at UC San Diego, is a phenomenon he calls the cellular danger response (CDR). When cells are exposed to danger in the form of a virus, infection, toxin, or even certain genetic mutations, they react defensively, shutting down ordinary activities and erecting barriers against the perceived threat. One consequence is that communication between cells is reduced, which the scientists say may interfere with brain development and function, leading to ASD.

Researchers treated a Fragile X genetic mouse model, one of the most commonly studied mouse models of ASD, with suramin, a drug long used for sleeping sickness. The approach, called antipurinergic therapy or APT, blocked the CDR signal, allowing cells to restore normal communication and reversing ASD symptoms.

"Our data show that the efficacy of APT cuts across disease models in ASD. Both the environmental and genetic mouse models responded with a complete, or near complete, reversal of ASD symptoms," Naviaux said. "APT seems to be a common denominator in improving social behavior and brain synaptic abnormalities in these ASD models."

Weekly treatment with suramin in the Fragile X genetic mouse model was started at nine weeks of age, roughly equivalent to 18 years in humans. Metabolite analysis identified 20 biochemical pathways associated with symptom improvements, 17 of which have been reported in human ASD. The findings of the six-month study also support the hypothesis that disturbances in purinergic signaling - a regulator of cellular functions, and mitochondria (prime regulators of the CDR) - play a significant role in ASD.

Naviaux noted that suramin is not a drug that can be used for more than a few months without a risk of toxicity in humans. However, he said it is the first of its kind in a new class of drugs that may not need to be given chronically to produce beneficial effects. New antipurinergic medicines, he said, might be given once or intermittently to unblock metabolism, restore more normal neural network function, improve resilience and permit improved development in response to conventional, interdisciplinary therapies and natural play.

"Correcting abnormalities in a mouse is a long way from a cure in humans," cautioned Naviaux, who is also co-director of the Mitochondrial and Metabolic Disease Center at UC San Diego, "but our study adds momentum to discoveries at the crossroads of genetics, metabolism, innate immunity, and the environment for several childhood chronic disorders. These crossroads represent new leads in our efforts to understand the origins of autism and to develop treatments for children and adults with ASD."

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Co-authors include Jane C. Naviaux, Lin Wang, Kefeng Li, A. Taylor Bright, William A. Alaynick, Kenneth R. Williams and Susan B. Powell, all at UC San Diego.

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Century-old drug reverses autism-like symptoms in fragile X mouse model

In three recent deals, drugmakers are betting that personal genetic maps will finally fulfill their early promise to unlock secrets and cure diseases.

At the same time, the agreements revived questions about privacy protections and how useful personal genetic data will prove to be.

Roche Holding AG (RHHBY) committed $1 billion to take control of Foundation Medicine Inc. (FMI), which sequences genes of cancer patients, aiming to customize treatment. Roches Genentech unit said it would pay as much as $60 million for access to 23andMe Inc.s data on customers with Parkinsons disease. And Pfizer Inc. (PFE) reached a deal that will allow the drugmaker to analyze personal genetic information from 650,000 23andMe customers, without giving terms.

The pacts, together with 23andMes announcement that it will enter into partnerships with eight other companies this year, boosted confidence in the commercial value of gene mapping. Since the first draft of a full human genome was deciphered in 2001, researchers have predicted breakthroughs in understanding the origins of disease, only to be frustrated as business developed slowly and regulatory issues cropped up.

Foundation Medicine and 23andMe were created to serve consumers directly and are not developing medicines. Foundation Medicines clients pay to have more than 300 genes in their tumors sequenced, and then receive counseling about voluntarily entering trials of drugs that may address genetic abnormalities in their cancers. Customers of 23andMe, on the other hand, are encouraged to learn about yourself through genetics.

Now drugmakers are seeing research value in the genetic databases the companies have created.

Core to our mission is making data available to other researchers to advance genetic discoveries, and we are committed to doing so in the most responsible way possible, said Angela Calman-Wonson, a spokeswoman for Mountain View, California-based 23andMe.

Genentech will ask 23andMe customers with Parkinsons disease to consent to participate in having their full genomes - - all 6 billion chemical units of their DNA -- sequenced and analyzed. The company will look in those anonymous results for clues to how Parkinsons arises and how to treat it, said Alex Schuth, director of development for technology innovation and diagnostics.

After Genentech has completed its drug discovery work, the genome data will be put into a public database where other researchers and companies can freely study it, Schuth said.

We have no intention to further sell this data to anyone else, he said in telephone interview.

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Deals For Genetic Data Raise Issues of Privacy, Sharing

Mutations in a gene that helps repair damaged chromosome ends may make smokers -- especially female smokers -- more susceptible to emphysema, according to results of a new study led by Johns Hopkins Kimmel Cancer Center researchers.

The mutations are one of a few genetic factors directly linked to chronic obstructive pulmonary disease (COPD), including emphysema, since the 1960s, says Mary Armanios, M.D., associate professor of oncology at the Johns Hopkins University School of Medicine.

Specifically, the alteration occurs in the telomerase reverse transcriptase (TERT) gene, which helps produce an enzyme called telomerase. Telomerase maintains and repairs the "caps" that protect the ends of chromosomes from degradation during cell division. Telomeres gradually shorten with age and act as a sort of cellular clock in cells. Mutations in TERT lead to excessively shortened telomeres.

Using genetic data gathered in COPD studies funded by the National Institutes of Health, Armanios and colleagues found TERT mutations in three of 292 smokers with emphysema. The researchers then looked at a sample of 50 Johns Hopkins patients with syndromes linked to telomere shortening. Among 39 nonsmokers, there were no cases of emphysema. Among smokers, seven of 11 patients, including all six female smokers, had emphysema. Armanios says this suggests that female smokers with telomerase-related mutations may be more susceptible to emphysema.

A report on the research was published Dec. 22 in the Journal of Clinical Investigation. Lung disease is the third leading cause of death in the U.S., and the main risk factors are aging and smoking. However, only about 10 percent of smokers develop COPD, according to Armanios. "Not everyone who smokes gets emphysema, so our study is part of a bigger effort to find out why some people get it and others do not," says Armanios, who notes that other studies have shown that young women who smoke may be more susceptible to emphysema.

The researchers had some clues about telomerase genes from earlier studies, including one in which Armanios and her colleagues identified the impact of shortened telomeres in mice as a risk factor for emphysema after being exposed to cigarette smoke. The scientists previously had noted a link between telomerase mutations and a severe hereditary lung disease called idiopathic pulmonary fibrosis.

Patients with emphysema often suffer from other health problems, including osteoporosis, liver disease and cancer. These disorders are common in people with shortened telomeres as well. The new study, says Armanios, "may now give us an explanation for why people with emphysema have these systemic problems. If we know that they have a telomerase mutation, it may help us take care of them in a more sophisticated way and delay the onset of those diseases."

Armanios and colleagues published a study last year showing that telomerase mutations may lead to more complications during lung transplants for people with idiopathic pulmonary fibrosis.

In the current study, only 1 percent of the smokers with severe emphysema carried the TERT mutation, but Armanios says this is comparable to the percentage who carry another known genetic factor related to COPD -- a mutation in the alpha-1 antitrypsin gene.

The researchers only looked at mutations in two telomerase genes but will now search for mutations in other telomere-regulating genes that might also predispose people to lung disease. "There are many genes that regulate the telomere, so it's likely that more than 1 percent could be impacted by these predisposing factors," says Armanios.

Go here to read the rest:

Mutations linked to repair of chromosome ends may make emphysema more likely in smokers

Researchers at the Montreal Heart Institute announced today results showing that patients with cardiovascular disease and the appropriate genetic background benefit greatly from the new medication dalcetrapib, with a reduction of 39% in combined clinical outcomes including heart attacks, strokes, unstable angina, coronary revascularizations and cardiovascular deaths. These patients also benefit from a reduction in the amount of atherosclerosis (thickened walls) in their vessels. The detailed results are published in the Journal Circulation Cardiovascular Genetics. This discovery may also pave the way for a new era in cardiovascular medicine, with personalized or precision drugs.

The team led by Drs Jean-Claude Tardif and Marie-Pierre Dub performed the analysis of 5749 patients who received dalcetrapib or placebo and provided DNA in a clinical study. A strong association was discovered between the effects of dalcetrapib and a specific gene called ADCY9 (adenylate cyclase 9) on chromosome 16, particularly for a specific genetic variant (rs1967309). In patients with the genetic profile AA at rs1967309, there was a 39% reduction in the composite cardiovascular endpoint with dalcetrapib compared to placebo. Supporting evidence was also obtained from a second study, which showed that patients with the favourable genetic profile also benefited from a reduction in the thickness of their carotid artery walls with dalcetrapib.

"These results will lead to a genetics-guided clinical study in patients with the appropriate genetic background to allow review by health regulatory agencies and to provide personalized therapy with dalcetrapib. It also offers great hope for precision treatments for patients with cardiovascular diseases and for curbing atherosclerosis, the first cause of mortality in the world" said lead investigator Jean-Claude Tardif MD, director of the Research Center at the Montreal Heart Institute and professor of medicine at the University of Montreal.

The investigators tested multiple genetic markers across the entire genome in a procedure called genome-wide association study. "We used state-of-the-art genetic and statistical techniques to demonstrate that the effect of the patient's genetic profile was only observed in those treated with dalcetrapib and not placebo. We want to provide patients with additional personalized cardiovascular therapies in the years to come, for more efficacious and safer medicines," commented Marie-Pierre Dub PhD, director of the Beaulieu-Saucier Pharmacogenomics Center at the Montreal Heart Institute and professor of medicine at the University of Montreal.

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The above story is based on materials provided by Montreal Heart Institute. Note: Materials may be edited for content and length.

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Personalized therapy for cardiovascular disease

Important reduction in events including heart attacks and deaths in patients with the appropriate genetic background to respond to a new medication

IMAGE:This is Dr. Jean-Claude Tardif. view more

Credit: MHI

This news release is available in French.

Montreal, January 12 2015 - Researchers at the Montreal Heart Institute announced today results showing that patients with cardiovascular disease and the appropriate genetic background benefit greatly from the new medication dalcetrapib, with a reduction of 39% in combined clinical outcomes including heart attacks, strokes, unstable angina, coronary revascularizations and cardiovascular deaths. These patients also benefit from a reduction in the amount of atherosclerosis (thickened walls) in their vessels. The detailed results are published in the prestigious Journal Circulation Cardiovascular Genetics. This discovery may also pave the way for a new era in cardiovascular medicine, with personalized or precision drugs.

The team led by Drs Jean-Claude Tardif and Marie-Pierre Dub performed the analysis of 5749 patients who received dalcetrapib or placebo and provided DNA in a clinical study. A strong association was discovered between the effects of dalcetrapib and a specific gene called ADCY9 (adenylate cyclase 9) on chromosome 16, particularly for a specific genetic variant (rs1967309). In patients with the genetic profile AA at rs1967309, there was a 39% reduction in the composite cardiovascular endpoint with dalcetrapib compared to placebo. Supporting evidence was also obtained from a second study, which showed that patients with the favourable genetic profile also benefited from a reduction in the thickness of their carotid artery walls with dalcetrapib.

"These results will lead to a genetics-guided clinical study in patients with the appropriate genetic background to allow review by health regulatory agencies and to provide personalized therapy with dalcetrapib. It also offers great hope for precision treatments for patients with cardiovascular diseases and for curbing atherosclerosis, the first cause of mortality in the world" said lead investigator Jean-Claude Tardif MD, director of the Research Center at the Montreal Heart Institute and professor of medicine at the University of Montreal.

The investigators tested multiple genetic markers across the entire genome in a procedure called genome-wide association study. "We used state-of-the-art genetic and statistical techniques to demonstrate that the effect of the patient's genetic profile was only observed in those treated with dalcetrapib and not placebo. We want to provide patients with additional personalized cardiovascular therapies in the years to come, for more efficacious and safer medicines", commented Marie-Pierre Dub PhD, director of the Beaulieu-Saucier Pharmacogenomics Center at the Montreal Heart Institute and professor of medicine at the University of Montreal.

###

Dr. Jean-Claude Tardif is available for interviews.

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World first at the Montreal Heart Institute -- personalized therapy for cardiovascular disease

New research provides insights into the ties between certain genetic variants and kidney disease in African Americans. The genetic association is one of the strongest ever reported for a common disease, and these latest findings may help improve diagnosis and treatment. The study appears in an upcoming issue of the Journal of the American Society of Nephrology (JASN).

African Americans have a 4-fold increased risk for chronic kidney disease compared with European Americans. Recent work from several research groups has shown that much of this risk is due to genetic variations in a gene called apolipoprotein L1 (APOL1), which creates a protein that is a component of HDL, or good cholesterol. These variants arose tens of thousands of years ago in sub-Saharan Africa, and so are present in individuals who have recent sub-Saharan African ancestry. Approximately 5 million African Americans carry APOL1 risk variants, placing them at increased risk for kidney disease.

Jeffrey Kopp, MD (National Institutes of Health) and his colleagues investigated the role of APOL1 variants in a particular form of kidney disease called focal segmental glomerulosclerosis (FSGS). The team studied information on 94 patients with FSGS and found that patients who had APOL1 variants tended to have more advanced disease when they were diagnosed, which fits with prior observations that this genetic form of FSGS progresses rapidly. Previous research has shown that patients with two APOL1 variants respond to glucocorticoids with reductions in urinary protein excretion, but they nonetheless may experience progressive loss of kidney function. The present study showed a similar pattern with cyclosporine and mycophenolate mofetil. "New therapies targeting APOL1 injury pathways are needed, as standard therapies do not work for many people with this gene variant," said Dr. Kopp.

The investigators also found that 72% of self-identified African Americans in the study had APOL1 risk variants, similar to earlier findings. "We also found the APOL1 risk genotype in 2 individuals of Hispanic descent, which is well known, and in 2 individuals who self-identified as White, or European American, which has not been reported before. This last finding suggests that APOL1 risk variants can be present in individuals who self-identify in various ways," said Dr. Kopp.

In an accompanying editorial, Christopher Larsen, MD (Nephropath) and Barry Freedman, MD, PhD (Wake Forest School of Medicine) write that "the report by Kopp et al. enhances our understanding of a common etiology of the FSGS lesion seen on kidney biopsy in African Americans." They note, however, that the findings from the trial, although informative, are not encouraging due to the poor outcomes that patients with APOL1 variants often ultimately experience.

Story Source:

The above story is based on materials provided by American Society of Nephrology (ASN). Note: Materials may be edited for content and length.

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Insights into role of genetic variants in kidney disease

PITTSBURGH, January 8, 2015 - Genetic mutations may link smoking and alcohol consumption to destruction of the pancreas observed in chronic pancreatitis, according to a 12-year study led by researchers at the University of Pittsburgh School of Medicine. The findings, published today in Nature Publishing Group's online, open-access journal Clinical and Translational Gastroenterology, provides insight into why some people develop this painful and debilitating inflammatory condition while most heavy smokers or drinkers do not appear to suffer any problems with it.

The process appears to begin with acute pancreatitis, which is the sudden onset of inflammation causing nausea, vomiting and severe pain in the upper abdomen that may radiate to the back, and is typically triggered by excessive drinking or gallbladder problems, explained senior investigator David Whitcomb, M.D., Ph.D., chief of gastroenterology, hepatology and nutrition, Pitt School of Medicine. Up to a third of those patients will have recurrent episodes of acute pancreatitis, and up to a third of that group develops chronic disease, in which the organ becomes scarred from inflammation.

"Smoking and drinking are known to be strong risk factors for chronic pancreatitis, but not everyone who smokes or drinks damages their pancreas," Dr. Whitcomb said. "Our new study identifies gene variants that when combined with these lifestyle factors make people susceptible to chronic pancreatitis and may be useful to prevent patients from developing it."

In the North American Pancreatitis Study II consortium, researchers evaluated gene profiles and alcohol and smoking habits of more than 1,000 people with either chronic pancreatitis or recurrent acute pancreatitis and an equivalent number of healthy volunteers. The researchers took a closer look at a gene called CTRC, which can protect pancreatic cells from injury caused by premature activation of trypsin, a digestive enzyme inside the pancreas instead of the intestine, a problem that has already been associated with pancreatitis.

They found that a certain variant of the CTRC gene, which is thought to be carried by about 10 percent of Caucasians, was a strong risk factor for alcohol- or smoking-associated chronic pancreatitis. It's possible that the variant fails to protect the pancreas from trypsin, leaving the carrier vulnerable to ongoing pancreatic inflammation and scarring.

"This finding presents us with a window of opportunity to intervene in the diseases process," Dr. Whitcomb said. "When people come to the hospital with acute pancreatitis, we could screen for this gene variant and do everything possible to help those who have it quit smoking and drinking alcohol, as well as test new treatments, because they have the greatest risk of progressing to end-stage chronic pancreatitis."

Whitcomb's team has been implementing more personalized approaches to pancreatic diseases in the Pancreas Center of Excellence within the Digestive Disorders Center at UPMC and hopes to learn whether use of genetic information can, in fact, reduce the chances of chronic disease in high-risk patients.

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The study team includes Jessica LaRusch, Ph.D., Antonio Lozano-Leon, Ph.D., Kimberly Stello, Amanda Moore, Venkata Muddana, M.D., Michael O'Connell, Ph.D., Brenda Diergaarde, Ph.D., and Dhiraj Yadav, M.D., all of the University of Pittsburgh.

The project was funded by National Institutes of Health grants DK061451, DK077906 and DK063922, and the Conselleria de Industria e Innovacin, Xunta de Galicia, Spain.

Read the original here:

Smoking, alcohol, gene variant interact to increase risk of chronic pancreatitis

Highlights

Washington, DC (January 8, 2015) -- New research provides insights into the ties between certain genetic variants and kidney disease in African Americans. The genetic association is one of the strongest ever reported for a common disease, and these latest findings may help improve diagnosis and treatment. The study appears in an upcoming issue of the Journal of the American Society of Nephrology (JASN).

African Americans have a 4-fold increased risk for chronic kidney disease compared with European Americans. Recent work from several research groups has shown that much of this risk is due to genetic variations in a gene called apolipoprotein L1 (APOL1), which creates a protein that is a component of HDL, or good cholesterol. These variants arose tens of thousands of years ago in sub-Saharan Africa, and so are present in individuals who have recent sub-Saharan African ancestry. Approximately 5 million African Americans carry APOL1 risk variants, placing them at increased risk for kidney disease.

Jeffrey Kopp, MD (National Institutes of Health) and his colleagues investigated the role of APOL1 variants in a particular form of kidney disease called focal segmental glomerulosclerosis (FSGS). The team studied information on 94 patients with FSGS and found that patients who had APOL1 variants tended to have more advanced disease when they were diagnosed, which fits with prior observations that this genetic form of FSGS progresses rapidly. Previous research has shown that patients with two APOL1 variants respond to glucocorticoids with reductions in urinary protein excretion, but they nonetheless may experience progressive loss of kidney function. The present study showed a similar pattern with cyclosporine and mycophenolate mofetil. "New therapies targeting APOL1 injury pathways are needed, as standard therapies do not work for many people with this gene variant," said Dr. Kopp.

The investigators also found that 72% of self-identified African Americans in the study had APOL1 risk variants, similar to earlier findings. "We also found the APOL1 risk genotype in 2 individuals of Hispanic descent, which is well known, and in 2 individuals who self-identified as White, or European American, which has not been reported before. This last finding suggests that APOL1 risk variants can be present in individuals who self-identify in various ways," said Dr. Kopp.

In an accompanying editorial, Christopher Larsen, MD (Nephropath) and Barry Freedman, MD, PhD (Wake Forest School of Medicine) write that "the report by Kopp et al. enhances our understanding of a common etiology of the FSGS lesion seen on kidney biopsy in African Americans." They note, however, that the findings from the trial, although informative, are not encouraging due to the poor outcomes that patients with APOL1 variants often ultimately experience.

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Study co-authors include Cheryl Winkler, PhD, Xiongce Zhao, PhD, Milena Radea, PhD, Jennifer Gassman, PhD, Vivette D'Agati, MD, Cynthia Nast, MD, Changli Wei, MD, Jochen Reiser, MD, PhD, Lisa Guay Woodford, MD, Friedhelm Hildebrandt, MD, Marva Moxie-Mims, MD, Debbie Gipson, MD, Aaron Friedman, MD, and Frederick Kaskel, MD.

Disclosures: The authors reported no financial disclosures.

The article, entitled "Clinical Features and Histology of Apolipoprotein L1-Associated Nephropathy in the FSGS Clinical Trial," will appear online at http://jasn.asnjournals.org/ on January 8, 2015.

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Study provides insights into the role of genetic variants in kidney disease

Published on January 7th, 2015 | by LedgerOnline

By Diana Burmistrovich/JNS.org

One in four Jews is a carrier of one or more of the 19 known preventable Jewish genetic diseases, according to the Center for Jewish Genetics. Although Sephardic Jews and non-Jews can carry these diseases, they appear twice as often for Ashkenazi Jews as they do for the rest of the population. When both spouses are carriers for a particular genetic disease, the couple has a 25 percent chance of passing the disease on to their children.

Launched in September through the Emory University School of Medicines Department of Human Genetics, the goal of the JScreen not-for-profit health initiative is to make those statistics appear less daunting.

A carrier-screening program for Jewish genetic diseases, JScreen aims to give families with Jewish ancestry easy access to information and to provide convenient testing. Employing an easy-to-use kit, JScreen allows individuals to test for the 19 known preventable Jewish genetic diseaseswhich among others include Tay-Sachs, Canavan, and Gaucherin their own homes.

While testing for genetic disorders is nothing new, JScreens accessibility is. The kit is easily acquired through the initiatives website atwww.JScreen.org, and the test allows a saliva sample to be sentdirectly for analysis. Theprogram works closely with the individual,obtaining doctors orders when needed andproviding updates on the status of the sample until results are sent out approximately four weeks later.

Touting the initiative as community-oriented, JScreens website provides resources that aim to make couples feel comfortable in proceeding with their family-planning efforts. This includes explaining the reasons for getting tested, as well as statistics.

JScreen hopes to act as a resource for the community to do genetic testing and make a big impact in growing healthy families, JScreen spokesperson Patricia Page told JNS.org.

The program grew out of the work of Randy and Caroline Gold, who were surprised to find out that their daughter, Eden, had the genetic disease Mucolipidosis Type IV (ML4), despite their having both undergone genetic testing before starting a family.

When they learned that their genetic test had screened for less than half the conditions common in people of Jewish descent, the Golds made it their mission to spread the word about expanded Jewish genetic disease screening. They launched the Atlanta Jewish Gene Screen, an organization thatpartneredwith the Victor Center for Prevention of Jewish Genetic Diseases at Einstein Medical Center in Philadelphia, and Emory Geneticsfrom 2010 to 2012.

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Jewish genetic screening becomes more accessible through at-home testing kits

Listen Story audio 37min 24sec Susan Wolf: Professor of law, medicine and public policy at the University of Minnesota Robert Green: Medical geneticist at Harvard Medical School and Brigham & Women's Hospital

Genetic tests are giving patients unprecedented insights into conditions that they could inherit, but should this information be made available to other family members who might also be susceptible?

On The Daily Circuit, we discuss the tension between awareness and privacy in genetic testing.

Susan Wolf, professor of law, medicine and public policy at the University of Minnesota joins the discussion along with Dr. Robert Green, a medical geneticist at Harvard Medical School.

From Science Friday:

That's even true when information can be vital for for the health of family members. "Let's say a researcher is doing a genetic study ... and they discover that their participant has a variant of the BRCA gene, associated with higher risk of breast and ovarian cancer," says Susan M. Wolf, the McKnight Presidential Professor of Law, Medicine and Public Policy at the University of Minnesota. "They go to that person and say, 'We think it's important for you to know this, but we're also concerned about your sister, or your brother, and other members of your family.'"

Do you think your genetic information is private? Does that change when a serious and inheritable disease turns up? Leave your comments below.

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Genetic privacy: Who should know what your tests reveal?

A new study of twins suggests that insomnia in childhood and adolescence is partially explained by genetic factors.

Results show that clinically significant insomnia was moderately heritable at all stages of the longitudinal study. Genetic factors contributed to 33 to 38 percent of the insomnia ratings at the first two stages of the study, when participants had an average age of 8 to 10 years. The heritability of insomnia was 14 to 24 percent at the third and fourth follow-up points, when the average age of participants was 14 to 15 years. The remaining source of variance in the insomnia ratings was the non-shared environment, with no influence of shared, family-wide factors. Further analysis found that genetic influences around age 8 contributed to insomnia at all subsequent stages of development, and that new genetic influences came into play around the age of 10 years.

"Insomnia in youth is moderately related to genetic factors, but the specific genetic factors may change with age," said study author Philip Gehrman, PhD, assistant professor in the Department of Psychology at the University of Pennsylvania in Philadelphia. "We were most surprised by the fact that the genetic factors were not stable over time, so the influence of genes depends on the developmental stage of the child."

Study results are published in the January issue of the journal Sleep.

Insomnia involves difficulty initiating or maintaining sleep, or waking up earlier than desired, according to the American Academy of Sleep Medicine. Children with insomnia may resist going to bed on an appropriate schedule or have difficulty sleeping without intervention by a parent or caregiver. An insomnia disorder results in daytime symptoms such as fatigue, irritability or behavioral problems.

According to the authors, the results suggest that genes controlling the sleep-wake system play a role in childhood insomnia. Therefore, molecular genetic studies are needed to identify this genetic mechanism, which could facilitate the development of targeted treatments.

"These results are important because the causes of insomnia may be different in teens and children, so they may need different treatment approaches," said Gehrman.

The study group comprised 1,412 twin pairs who were between the ages of 8 and 18 years: 739 monozygotic pairs, 672 dizygotic pairs and one pair with unknown zygosity. Participants were followed up at three additional time points. Average ages at each of the four waves of the study were 8, 10, 14 and 15 years. Results were interpreted in terms of the progression across time, rather than differences between discrete age groups. Clinical ratings of insomnia symptoms were assessed by trained clinicians using the Child and Adolescent Psychiatric Assessment and rated according to the Diagnostic and Statistical Manual of Mental Disorders, 3rd Edition.

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The above story is based on materials provided by American Academy of Sleep Medicine. Note: Materials may be edited for content and length.

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Genetic factors contribute to insomnia in children, teens, twin study suggests

(PRWEB) January 06, 2015

Sequencing the genomes, or entire DNA codes, of individuals to better diagnose and treat disease is a burgeoning area of research. From identifying specific genetic mistakes highly associated with certain cancers to applying effective treatments to mitigate a wayward genes effects, personalized genomic medicine is increasingly finding its way into patient care.

Harnessing the power of whole genome analysis and further defining the role of pathologists in this new era of medicine is the topic of the 2015 Benjamin Highman Lecture, sponsored by the Department of Pathology and Laboratory Medicine at UC Davis Health System.

The lecture, entitled Moving to Genomic Medicine, will be held from 5 p.m. to 6 p.m. on Thursday, Jan. 22 at the Education Building, 4610 X Street in auditorium #2222 in Sacramento. A reception will follow the presentation. Participants can register at Eventbrite.

The lecture will be presented by Debra G. B. Leonard, a leading expert in molecular pathology and genomic medicine and in applying genomic information for diagnosis and treatment of human diseases, including inherited disorders, cancers and infectious diseases.

During her presentation, Leonard will highlight the current applications for genomics and describe the various online genomic medicine resources for testing and for making patient-care decisions. She has spoken widely on various molecular pathology testing services, the future of molecular pathology and the impact of gene patents on molecular pathology practice. Leonard is professor and chair of pathology and laboratory medicine at the University of Vermont Medical Center and Physician Leader of Pathology and Laboratory Medicine at Fletcher Allen Health Care.

Making use of the massive amount of data that results from whole genome testing is an ongoing challenge for practicing physicians across disciplines, said Lydia Howell, professor and chair of pathology and laboratory medicine at UC Davis Health System. While we have the technology to quickly identify an individuals entire genetic code, which includes some three million genetic sequences, its less easy to know which genetic mistakes actually cause disease. Pathologists, with their expertise in molecular diagnostic testing, are in a unique position to lead the current movement of genomic medicine from the research bench to applications in the clinic.

The Highman Symposium is an annual lectureship in honor of Benjamin Highman, who spent almost 40 years in the U.S. Public Health Service as medical director and as chief of Pathologic Anatomy at the National Institutes of Health. He was awarded the Willey Medallion and a special citation by the U.S. Food and Drug Administration. In 1985, Highman retired and joined the volunteer faculty at the UC Davis School of Medicine.

The Department of Pathology and Laboratory Medicine includes 40 faculty and 400 academic and clinical staff who develop and deliver comprehensive diagnostic services in the fields of pathology and laboratory medicine through established and novel diagnostic modalities. Its Clinical Laboratory is home to one of the most technologically advanced testing facilities in California, providing many unique diagnostic tests unavailable elsewhere. The department processes 5 million clinical tests and 20,000 surgical pathology and 20,000 cytology specimens each year.

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UC Davis presents 2015 Benjamin Highman Lecture on genomic medicine

Comparison of fat cells in mice and men hints at how genes and environment conspire to produce disease

IMAGE:Researchers compared epigenetic "tags " on fat cells of lean and obese mice. view more

Credit: Oak Ridge National Laboratory

An analysis of the genomes and epigenomes of lean and obese mice and humans has turned up a wealth of clues about how genes and the environment conspire to trigger diabetes, Johns Hopkins researchers say. Their findings reveal that obesity-induced changes to the epigenome -- reversible chemical "tags" on DNA -- are surprisingly similar in mice and humans, and might provide a new route to prevention and treatment of the disease, which affects hundreds of millions worldwide. A report on the study appears Jan. 6 in the journal Cell Metabolism.

"It's well known that most common diseases like diabetes result from a combination of genetic and environmental risk factors. What we haven't been able to do is figure out how, exactly, the two are connected," says Andrew Feinberg, M.D., M.P.H. , Gilman Scholar and director of the Center for Epigenetics in the Institute for Basic Biomedical Sciences at the Johns Hopkins University School of Medicine. "This study takes a step in that direction."

Feinberg has long studied the epigenome, which he compares to "software" that runs on DNA's "hardware." Epigenetic chemical tags affect whether and how much genes are used without changing the genetic code itself.

Feinberg wondered whether epigenetics might partly explain the skyrocketing worldwide incidence of type 2 diabetes. Obesity is a well-established risk factor for the disease, so Feinberg's research group teamed with that of a group led by G. William Wong, Ph.D. , an associate professor of physiology in the Center for Metabolism and Obesity Research at Johns Hopkins, to study the epigenetics of otherwise identical mice that were fed either normal or high-calorie diets.

Analyzing epigenetic marks at more than 7 million sites in the DNA of the mice's fat cells, the researchers found clear differences between the normal and obese mice. Some sites that bore chemical tags called methyl groups in the lean mice were missing them in the obese mice, and vice versa. The methyl groups prevent genes from making proteins.

With colleagues at Sweden's Karolinska Institutet, Feinberg and his team then tested whether the same pattern of differences held in fat cells from lean and obese people, and found, to their surprise, that it did. "Mice and humans are separated by 50 million years of evolution, so it's interesting that obesity causes similar epigenetic changes to similar genes in both species," Feinberg says. "It's likely that when food supplies are highly variable, these epigenetic changes help our bodies adapt to temporary surges in calories. But if the high-calorie diet continues over the long term, the same epigenetic pattern raises the risk for disease."

The research team also found that some of the epigenetic changes associated with obesity affect genes already known to raise diabetes risk. Others affect genes that had not been conclusively linked to the disease, but that turned out to have roles in how the body breaks down and uses nutrients, a process called metabolism. "This study yielded a list of genes that previously have not been shown to play a role in diabetes," says Wong. "In further tests, we showed that at least some of these genes indeed regulate insulin action on sugar uptake; they offer insights into new potential targets for treating type 2 diabetes."

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Researchers identify new genetic and epigenetic contributors to diabetes

DARIEN, IL - A new study of twins suggests that insomnia in childhood and adolescence is partially explained by genetic factors.

Results show that clinically significant insomnia was moderately heritable at all stages of the longitudinal study. Genetic factors contributed to 33 to 38 percent of the insomnia ratings at the first two stages of the study, when participants had an average age of 8 to 10 years. The heritability of insomnia was 14 to 24 percent at the third and fourth follow-up points, when the average age of participants was 14 to 15 years. The remaining source of variance in the insomnia ratings was the non-shared environment, with no influence of shared, family-wide factors. Further analysis found that genetic influences around age 8 contributed to insomnia at all subsequent stages of development, and that new genetic influences came into play around the age of 10 years.

"Insomnia in youth is moderately related to genetic factors, but the specific genetic factors may change with age," said study author Philip Gehrman, PhD, assistant professor in the Department of Psychology at the University of Pennsylvania in Philadelphia. "We were most surprised by the fact that the genetic factors were not stable over time, so the influence of genes depends on the developmental stage of the child."

Study results are published in the January issue of the journal Sleep.

Insomnia involves difficulty initiating or maintaining sleep, or waking up earlier than desired, according to the American Academy of Sleep Medicine. Children with insomnia may resist going to bed on an appropriate schedule or have difficulty sleeping without intervention by a parent or caregiver. An insomnia disorder results in daytime symptoms such as fatigue, irritability or behavioral problems.

According to the authors, the results suggest that genes controlling the sleep-wake system play a role in childhood insomnia. Therefore, molecular genetic studies are needed to identify this genetic mechanism, which could facilitate the development of targeted treatments.

"These results are important because the causes of insomnia may be different in teens and children, so they may need different treatment approaches," said Gehrman.

The study group comprised 1,412 twin pairs who were between the ages of 8 and 18 years: 739 monozygotic pairs, 672 dizygotic pairs and one pair with unknown zygosity. Participants were followed up at three additional time points. Average ages at each of the four waves of the study were 8, 10, 14 and 15 years. Results were interpreted in terms of the progression across time, rather than differences between discrete age groups. Clinical ratings of insomnia symptoms were assessed by trained clinicians using the Child and Adolescent Psychiatric Assessment and rated according to the Diagnostic and Statistical Manual of Mental Disorders, 3rd Edition.

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The study was supported by funding from the Mid-Atlantic Twin Registry and the National Center for Advancing Translational Sciences of the National Institutes of Health. Additional support was provided by the Virginia Retirement System and the U.S. Department of Social Security. Data analyses were performed at Northumbria University in the U.K., and data were collected at the Virginia Commonwealth University School of Medicine in Richmond.

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Twin study suggests genetic factors contribute to insomnia in children, teens

TIME Health Infectious Disease Health Workers See Promise in Software to Tackle Drug-Resistant Bacteria Getty Images New software may predict genetic changes in bacteria before they occur

Researchers have developed a new software that predicts changes in bacteria that can make them drug-resistant.

Drug resistance happens when disease-causing bacteria adapts to antibiotics and becomes less responsive to treatment. Antibiotic-resistant bacteria cause at least 2 million infections and 23,000 deaths in the United States each year, but because the bacteria are constantly reproducing, its hard to determine what changes and mutations will occur.

Concern about drug resistance has caused doctors to prescribe bacteria-killing drugs more sparingly.

Now a team of researchers at Duke University may have alighted on a solution. In a recently published study in the journal Proceedings of the National Academy of Sciences, the researchers software, OSPREY, was able to predict the most likely mutations to come out of certain bacteria.

Researchers were able to then test treatment with drugs that are still in the experimental phase. Identifying the most likely mutations while drugs are still under development, the team believes, means the medicine is better positioned for success when it hits the market.

If we can somehow predict how bacteria might respond to a particular drug ahead of time, we can change the drug, or plan for the next one, or rule out therapies that are unlikely to remain effective for long, said study co-author Pablo Gainza-Cirauqui in a statement.

The scientists looked specifically at a common drug-resistant bacteria called methicillin-resistant Staphylococcus aureus, or MRSAa common cause of infections in health care settings like hospitals. They used their software to successfully predict that genetic changes that would occur in the bacteria when treated with drugs.

The researchers are now testing their software on other bacteria, but have made the software open for use by any researcher. The hope is that with time and practice the software algorithm will be able to predict genetic changes more than one mutation ahead.

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Health Workers See Promise in Software to Tackle Drug-Resistant Bacteria

TWO thirds of adult cancer cases were the result of genetic bad luck rather than unhealthy living, according to groundbreaking new research from the US.

Johns Hopkins University School of Medicine scientist Dr Bert Vogelstein said random mutations in DNA were the most common cause of cancer, with the rest caused by environment or inherited genes.

But he warned the finding should not be taken as a licence to drink or smoke to excess.

"This study shows that you can add to your risk of getting cancers by smoking or other poor lifestyle factors," Dr Vogelstein said.

"However, many forms of cancer are due largely to the bad luck of acquiring a mutation in a cancer driver gene regardless of lifestyle and heredity factors."

Researchers compared the number of times organ stem cells divided with the risk of cancer in the tissues.

Those with the most divisions were generally more prone to tumours.

They found 22 of 31 cancer types were caused by random cell mutations - really just genetic misfortune which scientists could not otherwise explain.

The remainder, including smoking-related lung cancer and skin cancer, were related to heredity and environmental factors like exposure to harmful chemicals.

"Cancer-free longevity in people exposed to cancer-causing agents, such as tobacco, is often attributed to their 'good genes', but the truth is that most of them simply had good luck," Dr Vogelstein said.

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Two thirds of cancer cases were genetic of bad luck: study

photo courtesy of dr. Radu Kramer

Gabi Popa, Jackie Conti, Santa Crisall, Dr. Radu Kramer, Jossy Breton and Yazmin Rodriguez of Alternative and Integrative Medicine Center in Paramus.

Providing quality care to patients

"The integrative medical approach is probably the most comprehensive way to diagnose and treat a patient," said Dr. Radu Kramer of the Alternative and Integrative Medicine Center in Paramus.

Alternative and integrative medicine relies on performing a thorough evaluation of the patient.

"The medical history, physical examination and the emotional assessment is corroborated with the genetic predispositions and environmental influences," Kramer said. "The diagnostic workup includes up-to-date conventional medicine modalities."

Kramer received his training in nephrology at Mount Sinai Medical Center in New York.

"I spent five years at Keller Army Hospital in West Point, N.Y., prior to starting my private practice," he said. "During that time, I also worked with Dr. Revici, my great uncle and a true pioneer of alternative thinking in medicine, at his Institute of Applied Biology in Manhattan."

A strong belief in alternative and integrative medicine led Kramer to open his own practice.

"I was convinced then, just as I am today, that there's a growing need for a comprehensive approach for patients in general and in particular for those suffering from more complex diseases," he said.

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Alternative and Integrative Medicine Center

Stanford University studies show that those who follow a DNA-based diet lose 2.5 times more weight than those who do not-- BalanceDiet offers a proprietary genetic test for weight management based on clients DNA, then provides a personal lifestyle plan designed using each individuals test results.

Melisa Jakubiec, a BalanceDiet Club Director, tells FOX News, Tampa Bay: By looking at four genes, we can determine if they [BalanceDiet clients] are sensitive to fat or carbohydrates, or a little of both. Then, the diet can be further personalized to facilitate their weight loss. Similar genetic testing programs can be thousands of dollars, what I love about the BalanceDiet program is its simplicity and how affordable it is. For under $200 a client can have insight into their body and a lifetime of wisdom on food and eating strategies tailored to them

Christopher Gardner, Associate Professor of Medicine at Stanford University published a study in April 2013 that looked at 141 women who were following four diets that focus on varying portions of carbohydrates and fats according to national standards. Each woman provided a DNA test sample. After one year, women on average who followed a diet that matched their specific genetic makeup lost 2.5x more weight than those women who did not follow the diet according to their genetic makeup. To put these results in perspective, they lost approximately 13 pounds versus 4 pounds, respectively.

Based on this Stanford University Study as well as multiple other studies, the BalanceDiet genetic weight loss test is designed to determine a persons ideal dietary food identity with a simple cotton swab test.

Rena Anne Apple, client at BalanceDiet, who after losing 70lbs, still attends the center to maintain her weight: I started gaining weight in middle school and I just kept gaining weight up until I went to college, and even after college I topped out at 275lbs...Now that Im on maintenance, I dont have to eliminate all carbs from my diet. I can say Okay, Ill have this potato, but Im going to eliminate bread...I look like a completely different person from when I was [275lbs]... Im a totally different person, and I love it! One of the things that has helped me stick to the plan is how easy it is to follow.

BalanceDiet provides private coaching from highly trained lifestyle experts who customize personal nutrition and wellness plans as a followup to support a clients genetic test results.

Existing and new clients may register for the weight management genetic test at any BalanceDiet Centers nationwide. To learn more, visit: http://www.gobalancediet.com/about/genetic-testing/

About BalanceDiet:

For over 20 years, BalanceDiet has been helping clients meet and exceed their weight loss goals with its proven diet programs, award-winning product lines, and innovative client options such as their proprietary genetic test for weight loss. Known for personalized consulting and highly effective weight loss plans, the company reflects a balanced approach to food, eating, and maintaining a healthy lifestyle. BalanceDiet is a fast-growing wellness brand with more than 30 locations throughout the United States, in addition to the BalanceDiet At Home service offered directly to consumers. The company is expanding internationally and expects to have 40 ground-based operations by year-end, with additional franchise opportunities available. For more information on BalanceDiet, please visit http://www.goBalanceDiet.com.

1. Miles, Kathleen. Fat Genes Determine Obesity, UCLA Study Says, In Addition To Diet And Exercise. Huffingtonpost.com. N.p., 10 Jan. 2013. Web. 10 Jan. 2014. huffingtonpost.com/2013/01/10/fat-genes-obesity-ucla-study-diet-exercise_n_2450108.html.

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Time to Fit Into Your Genes: Scientifically Proven Genetic Tests for Weight Loss