Category Archives: Gene Medicine

A new study shows that a gene discovered 30 years ago and now known to play a fundamental role in cancer development produces five different gene variants (called isoforms), rather than just the one original form, as thought.

The study of the NRAS gene by researchers at The Ohio State University Comprehensive Cancer Center -- Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC -- James) identified four previously unknown variants that the NRAS gene produces.

The finding might help improve drugs for cancers in which aberrant activation of NRAS plays a crucial role. It also suggests that NRAS might affect additional target molecules in cells, the researchers say.

The isoforms show striking differences in size, abundance and effects. For example, the historically known protein (isoform 1) is 189 amino-acids long, while one of the newly discovered variants, isoform 5, is only 20 amino-acids long.

The study is published in the Proceedings of the National Academy of Sciences.

"We believe that the existence of these isoforms may be one reason why NRAS inhibitors have so far been unsuccessful," says corresponding author Albert de la Chapelle, MD, PhD, professor of Medicine and the Leonard J. Immke Jr. and Charlotte L. Immke Chair in Cancer Research.

Co-senior author Clara D. Bloomfield, MD, Distinguished University Professor and Ohio State University Cancer Scholar, notes that one of the newly discovered isoforms might play a greater role in the development of some cancers than the known protein itself.

"Targeting the NRAS pathway may have been unsuccessful in the past because we were unaware of the existence of additional targets of these novel isoforms," says Bloomfield, who is also senior adviser to the OSUCCC -- James and holds the William Greenville Pace III Endowed Chair in Cancer Research.

"The discovery of these isoforms might open a new chapter in the study of NRAS," says first author Ann-Kathrin Eisfeld, MD, a postdoctoral fellow in the laboratories of de la Chapelle and of Bloomfield. "Knowing that these isoforms exist may lead to the development of drugs that specifically decrease or increase the expression of one of them and provide more effective treatment for cancer patients."

For this study, de la Chapelle, Eisfeld and their colleagues analyzed expression of the NRAS isoforms in a variety of normal and matched tumor samples. Key technical findings include:

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Well-known cancer gene NRAS produces 5 variants, study finds

Stanford University researcher Irving Weissman explains how the drug Rituxan, generically called rituximab, improves the cancer-killing effect of a new antibody that renders cancer cells vulnerable to immune attack. He spoke Monday, April 7, at the American Association for Cancer Research meeting in San Diego.

The war on cancer is getting some potent reinforcements, including a potentially broad-spectrum new weapon and genetically engineered immune cells with improved cancer-fighting abilities, speakers said at a major cancer research conference held this week in San Diego.

The American Association for Cancer Research, attended by an estimated 18,000 participants, is being held at the San Diego Convention Center through Wednesday. While it is covering the gamut of research, cancer immunotherapy is a major focus. The field began more than 100 years ago, and has lately scored impressive advances by using gene therapy to its tool kit.

The weapon is an antibody that makes a wide range of cancer cells vulnerable to immune attack. It's close to entering human clinical trials, said Irving L. Weissman, a Stanford University professor leading that project. The antibody neutralizes a chemical signal many cancers exude to decoy the immune system, Weissman said in a Monday morning plenary session.

The antibody is being tested first in acute myeloid leukemia patients, backed by $20 million from the California Institute for Regenerative Medicine, Weissman said. The institute is interested because the target cells are cancer stem cells, the cells that proliferate to spread cancer.

Moreover, research indicates the method can be used against many solid tumors that emit the signal, a protein called CD47. These include breast, ovarian, bladder, pancreatic and colon cancer.

"Every human cancer that we've seen has CD47," Weissman said.

Animal studies show that anti-CD47 antibodies inhibit growth of transplanted patient tumors, he said. And when used against non-Hodgkin's lymphoma along with an existing antibody drug called Rituxan, the result is a potent cancer-killing effect. Immune cells called macrophages actually engulf and destroy the cancer cells.

The CD47 molecule is normally present on young cells, serving as a "don't eat me" signal to immune system cells that might otherwise attack them, Weissman said. Cancer cells have chanced on mutations that cause the protein to be made in exceptionally high amounts. So even when they might be abnormal enough to merit immune system attack, they escape surveillance.

Another approach already in the clinic is to genetically engineer immune cells called T cells to be better at fighting cancer. Carl June, a University of Pennsylvania researcher behind one of the studies, said results continue to be encouraging. This approach targets another protein abnormally made by cancer cells, CD19. Novartis is testing the therapy.

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Gene, immune therapy help cancer war

PUBLIC RELEASE DATE:

6-Apr-2014

Contact: Carrie Strehlau carrie.strehau@stjude.org 901-595-2295 St. Jude Children's Research Hospital

(MEMPHIS, TENN. - April 6, 2014) The St. Jude Children's Research Hospital-Washington University Pediatric Cancer Genome Project has identified new mutations in pediatric brain tumors known as high-grade gliomas (HGGs), which most often occur in the youngest patients. The research appears today as an advance online publication in the scientific journal Nature Genetics.

The discoveries stem from the most comprehensive effort yet to identify the genetic missteps driving these deadly tumors. The results provide desperately needed drug development leads, particularly for agents that target the underlying mutations. This and other studies show these mutations often differ based on patient age. HGGs represent 15 to 20 percent of brain and spinal tumors in children. Despite aggressive therapy with surgery, radiation and chemotherapy, long-term survival for HGG patients remains less than 20 percent.

The study is one of four being published simultaneously in the same issue of Nature Genetics that link recurring mutations in ACVR1 to cancer for the first time. Pediatric Cancer Genome Project researchers found that ACVR1 was mutated in 32 percent of 57 patients diagnosed with a subtype of HGG called diffuse intrinsic pontine glioma (DIPG). While DIPGs are usually found in children ages 5 to 10, ACVR1 mutations occurred most frequently in younger-than-average patients. DIPG occurs in the brainstem, which controls vital functions and cannot be surgically removed.

The investigators also identified alteration in NTRK genes that drove tumor development in young HGG patients whose tumors developed outside the brainstem. This study included 10 patients who were age 3 or younger when they were diagnosed with such non-brainstem HGGs. Of those, 40 percent had tumors with alterations in one of three NTRK genes and few other changes. The alterations occurred when a segment of the NTRK genes involved in regulating cell division fused with part of another gene.

"These results indicate the NTRK fusion genes might be very potent drivers of cancer development that have the ability to generate tumors with few other mutations," said co-corresponding author Suzanne Baker, Ph.D., a member of the St. Jude Department of Developmental Neurobiology. The other corresponding author is Jinghui Zhang, Ph.D., a member of the St. Jude Department of Computational Biology. "We want to see if these tumors might be selectively sensitive to therapies that target the pathways that are disrupted as a result of these fusion genes," Baker said.

Added co-author Richard K. Wilson, Ph.D., director of The Genome Institute at Washington University School of Medicine in St. Louis: "We've made some very exciting discoveries that likely will result in more effective diagnosis and treatment of these particularly nasty tumors."

In this study, researchers analyzed 127 HGGs from 118 pediatric patients, including whole genome sequencing of the complete tumor and normal DNA from 42 patients. More targeted sequencing of additional tumors was conducted to track how instructions encoded in DNA were translated into the proteins that do the work of cells.

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Gene sequencing project discovers mutations tied to deadly brain tumors in young children

PUBLIC RELEASE DATE:

4-Apr-2014

Contact: Allison Hydzik hydzikam@upmc.edu 412-559-2431 University of Pittsburgh Schools of the Health Sciences

SAN DIEGO, April 4, 2014 An examination of the genetic landscape of head and neck cancers indicates that while metastatic and primary tumor cells share similar mutations, recurrent disease is associated with gene alterations that could be exquisitely sensitive to an existing cancer drug. Researchers from the University of Pittsburgh Cancer Institute (UPCI) and Yale University School of Medicine will share their findings during a mini-symposium Sunday at the American Association for Cancer Research Annual Meeting 2014.

About 50 percent of patients diagnosed with head and neck squamous cell cancers already have disease that has spread, or metastasized, to the lymph nodes, explained Jennifer Grandis, M.D., distinguished professor and vice chair of research, Department of Otolaryngology, Pitt School of Medicine, and director of the Head and Neck Program at UPCI, partner with UPMC CancerCenter. About 20 to 30 percent of patients thought to be cured of the disease go on to develop recurrent cancer, which typically doesn't respond to standard treatments.

"We decided to compare the genetic signatures of tumor cells from primary tumors with those from disease that had spread and cancers that were thought cured but then came back in the hopes of getting some clues about how best to guide therapy in these different settings," Dr. Grandis said. "We found that recurrent cancers might have an Achilles' heel we can exploit to kill them."

The team conducted the first whole-exome genetic sequencing study on what Dr. Grandis called its "treasure trove" of frozen patient samples and found similar mutations both in primary tumors and in the lymph nodes to which their cancers had already spread. But there were different mutations in tumors that had recurred after a period of remission that were not found in their original cancers.

"The recurrent tumors carried mutations in a gene area that encodes for DDR2 cell receptors," Dr. Grandis said. "Other studies have shown that DDR2 mutations can confer sensitivity to the cancer drug dasatinib, which could mean that drug has promise in the treatment of recurrent head and neck cancers."

The researchers suggest that further investigation of dasatinib treatment is warranted.

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Recurrent head and neck tumors have gene mutations that could be vulnerable to cancer drug

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Newswise Philadelphia, April 1, 2014 Beverly L. Davidson, Ph.D., a nationally prominent expert in gene therapy, is joining The Childrens Hospital of Philadelphia (CHOP) today.

Dr. Davidson, who investigates gene therapy for neurodegenerative diseases, arrives from the Center for Gene Therapy at the University of Iowa. She served as associate director at that Center, as well as director of the Gene Therapy Vector Core, and held the Roy J. Carver Biomedical Research Chair in Internal Medicine at the University. She also was Vice Chair of the Department of Internal Medicine and was a Professor in Internal Medicine, Neurology, and Physiology & Biophysics.

She has been named to the Arthur V. Meigs Chair in Pediatrics at CHOP and will join the hospitals Department of Pathology and Laboratory Medicine. We heartily welcome Dr. Davidson to our hospital, and are excited that she has chosen to continue her groundbreaking gene therapy research here, said Robert W. Doms, M.D., Ph.D., pathologist-in-chief at The Childrens Hospital of Philadelphia. She will greatly enhance our abilities to translate important biological discoveries into pioneering treatments for deadly diseases.

In addition, Dr. Davidson will serve as the new director of the Center for Cellular and Molecular Therapeutics at CHOP. The mission of the Center is to use pioneering research in cell and gene therapy to develop novel therapeutic approaches for hitherto untreatable illnesses. The inaugural director of the Center, Katherine A. High, M.D., said, I am thrilled that we have been able to recruit one of the premier translational investigators in the U.S. to serve as the next director of the Center. I have led the Center for the last ten years, and I eagerly look forward to the innovations of the next decade, under Dr. Davidsons leadership.

Dr. Davidson has concentrated on inherited genetic diseases that attack the central nervous system, with a particular focus on childhood-onset neurodegenerative diseases such as Batten disease and similar diseases called lysosomal storage disorders. In these disorders, the lack of an enzyme impairs lysosomes, proteins that perform crucial roles in removing unwanted by-products of cellular metabolism. Toxic waste products then accumulate in the brain and cause progressively severe brain damage.

Dr. Davidson has studied the cell biology and biochemistry of these disorders, and has developed novel methods to deliver therapeutic genes to the central nervous system. Her laboratory team has succeeded in reversing neurological deficits in small and large animal models of disease, and is working to advance this approach to treating human diseases.

In addition to lysosomal storage disorders, she has studied other inherited neurological diseases such as Huntingtons disease and spino-cerebellar ataxia. In these studies, she has delivered forms of RNA to the brains of animals to silence the activity of disease-causing genes. She also is collaborating with scientists at Massachusetts General Hospital in animal studies of Alzheimers disease.

Although much of Dr. Davidsons research has centered on delivering beneficial genes to the central nervous system, the viral vectors that she has developed are applicable to other organs and tissuesfor example, in gene therapy directed to the lungs or the liver.

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Gene Therapy Expert to Join The Children's Hospital of Philadelphia

PUBLIC RELEASE DATE:

1-Apr-2014

Contact: Sandy Van sandy@prpacific.com 808-526-1708 Cedars-Sinai Medical Center

LOS ANGELES (April 1, 2014) The Cedars-Sinai Regenerative Medicine Institute has received a $2.5 million grant from the Department of Defense to conduct animal studies that, if successful, could provide the basis for a clinical trial of a gene therapy product for patients with Lou Gehrig's disease, also called amyotrophic lateral sclerosis, or ALS.

The incurable disorder attacks muscle-controlling nerve cells motor neurons in the brain, brainstem and spinal cord. As the neurons die, the ability to initiate and control muscle movement is lost. Patients experience muscle weakness that steadily leads to paralysis; the disease usually is fatal within five years of diagnosis. Several genes have been identified in familial forms of ALS, but most cases are caused by a complex combination of unknown genetic and environmental factors, experts believe.

Because ALS affects a higher-than-expected percentage of military veterans, especially those returning from overseas duties, the Defense Department invests $7.5 million annually to search for causes and treatments. The Cedars-Sinai study, led by Clive Svendsen, PhD, professor and director of the Regenerative Medicine Institute at Cedars-Sinai Medical Center, and Genevive Gowing, PhD, a senior scientist in his laboratory, also will involve a research team at the University of Wisconsin, Madison and a Netherlands-based biotechnology company, uniQure, that has extensive experience in human gene therapy research and development.

The research will be conducted in laboratory rats bred to model a genetic form of ALS. If successful, it could have implications for patients with other types of the disease and could translate into a gene therapy clinical trial for this devastating disease.

It centers on a protein, GDNF, that promotes the survival of neurons. In theory, transporting GDNF into the spinal cord could protect neurons and slow disease progression, but attempts so far have failed, largely because the protein does not readily penetrate into the spinal cord. Regenerative Medicine Institute scientists previously showed that spinal transplantation of stem cells that were engineered to produce GDNF increased motor neuron survival, but this had no functional benefit because it did not prevent nerve cell deterioration at a critical site, the "neuromuscular junction" the point where nerve fibers connect with muscle fibers to stimulate muscle action.

Masatoshi Suzuki, PhD, DVM, assistant professor of comparative biosciences at the University of Wisconsin, Madison, who previously worked in the Svendsen Laboratory and remains a close collaborator, recently found that stem cells derived from human bone marrow and engineered to produce GDNF protected nerve cells, improved motor function and increased lifespan when transplanted into muscle groups of a rat model of ALS.

"It seems clear that GDNF has potent neuroprotective effects on motor neuron function when the protein is delivered at the level of the muscle, regardless of the delivery method. We think GDNF will be able to help maintain these connections in patients and thereby keep the motor neuron network functional," Suzuki said.

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$2.5 million Defense Department grant funds gene therapy study for Lou Gehrig's disease

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Newswise Right now, options are limited for preventing heart attacks. However, the day may come when treatments target the heart attack gene, myeloid related protein-14 (MRP-14, also known as S100A9) and defang its ability to produce heart attack-inducing blood clots, a process referred to as thrombosis.

Scientists at Case Western Reserve School of Medicine and University Hospitals Case Medical Center have reached a groundbreaking milestone toward this goal. They have studied humans and mice and discovered how MRP-14 generates dangerous clots that could trigger heart attack or stroke, and what happens by manipulating MRP-14. This study describes a previously unrecognized platelet-dependent pathway of thrombosis. The results of this research will appear in the April edition of The Journal for Clinical Investigation (JCI).

This is exciting because we have now closed the loop of our original finding that MRP-14 is a heart attack gene, said Daniel I. Simon, MD, the Herman K. Hellerstein Professor of Cardiovascular Research and Medicine at the School of Medicine and director of the University Hospitals Harrington Heart & Vascular Institute. We now describe a whole new pathway that shows clotting platelets have MRP-14 inside them, that platelets secrete MRP-14 and that MRP-14 binds to a platelet receptor called CD36 to activate platelets.

This translational research has moved back and forth from the cardiac catheterization laboratory investigating patients presenting with heart attack to the basic research lab probing mechanisms of disease. The clinical portion of this research yielded a visually stunning elementblood clots extracted from an occluded heart artery loaded with MRP-14 containing platelets.

It is remarkable that this abundant platelet protein promoting thrombosis could have gone undetected until now, Simon said.

In detailed studies using MRP-14-deficient mice, the investigators discovered MRP-14 in action. One key finding is that, while MRP-14 is required for pathologic blood clotting, it does not appear to be involved in the natural, primary hemostasis response to prevent bleeding.

The practical significance of this research is that it may provide a new target to develop more effective and safer anti-thrombotic agents, Simon said. Current anti-clotting drugs are subject to significant bleeding risk, which is associated with increased mortality.

If we could develop an agent that affects pathologic clotting and not hemostasis, that would be a home run, Simon said. You would have a safer medication to treat pathologic clotting in heart attack and stroke.

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Heart Attack Gene, MRP-14, Triggers Blood Clot Formation

For a long time, people thought HIV was incurable. The main reason was that HIV is a retrovirus, meaning that it inserts its own viral DNA into the genome of its host perhaps we could treat the symptoms of HIV, but many doubted it was possible to actually correct the genes themselves.Our techniques for slicing up DNA are very advanced when that DNA sits suspended in a test solution, but nearly useless when we need to accurately edit millions of copies of a gene spread throughout a complex, living animal. Technologies aimed at addressing that problem have been the topic of intense study in recent years, and this week MIT announced that one of the most promising lines of research has achieved its first major goal: researchers have permanently cured a genetic disease in an adult animal.

This is a proof of concept for something medicine has been teasing for decades: useful, whole-body genome editing in fully developed adults. Until recently, most such manipulation was possible only during early development and many genetic diseases dont make themselves known until after birth, or even much later in life. While breakthroughs in whole-genome sequencing are bringing genetic early-warning to awhole new level for parents, there are still plenty of ways to acquire problem DNA later in life most notably, through viruses like HIV. Whether were talking about a hereditary genetic disease like Alzheimers or an acquired one like radiation damage, MITs newest breakthrough has the potential to help.

A simplified schematic of the CRISPR system. RNA guides Cas9 in cutting at the CRISPR sequences.

In this study[doi:10.1038/nbt.2884], researchers attacked a disease called hereditarytyrosinemia, which stops liver cells from being able to process the amino acid tyrosine. It is caused by a mutation in just a single base of a single gene on the mouse (and human) genome, and prior research has confirmed that fixing that mutation cures the disease. The problem is that, until now, such a correction was only possible during early development, or even before fertilization of the egg. An adult body was thought to be simply too complex a target.

The gene editing technology used here is called the CRISPR system, which refers to the Clustered Regularly Interspaced Short Palindromic Repeats that allow its action.As the name suggests, the system inserts short palindromic DNA sequences called CRISPRs that are a defining characteristic of viral DNA. Bacteria have an evolved defense that finds these CRISPRs, treating them (correctly, until now) as evidence of unwanted viral DNA. Scientists insert DNA sequences that code for this bacterial cutting enzyme, along with the healthy version of our gene of interest and some extra RNA for targeting. All scientists need do is design their sequences so CRISPRs are inserted into the genome around the diseased gene, tricking the cell into identifying it as viral from there, the cell handles the excision all on its own, replacing the newly viral gene with the studys healthy version. The whole process plays out using the cells own machinery.

This is how MIT chose to visualize the process.

The experimental material actually enters the body via injection, targeted to a specific cell type.In this study, researchers observed an initial infection rate of roughly 1 in every 250 target cells. Those healthy cells out-competed their unmodified brothers, and within a month the corrected cells made up more than a third of the target cell type. This effectively cured the disease; when the mice were taken off of previously life-saving medication, they survived with little ill effect.

There are other possible solutions to the problem of adult gene editing, but they can be much more difficult to use,less accurate and reliable, and are generally useful in a narrower array of circumstances. CRISPRs offer a very high level of fidelity in targeting, both to specific cells in the body and to very specific genetic loci within each cell.

Tyrosinemia affects only about 1 in every 100,000 people, but the science on display here is very generalizable. While many diseases will require a more nuanced approach than was used here, many will not; wholly replacing genes in adult animals is a powerful tool, capable of curing many, many diseases. Not every cell type will lend itself as well to the CRISPR system, nor every disease; particularly, this study relies on the fact that corrected cells will naturally replace disease cells, improving their initial infection rate. That wont always be possible, unfortunately.

Theres also very little standing between this technique and non-medical applications can you drug test an athlete or academic for the contents of their own genome? These questions and more will become relevant over the next few decades, though their effects should be minuscule when weighed against the positive impacts of the medical applications.

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Gene therapy comes of age: We can now edit entire genomes to cure diseases

New research indicates that obesity in the general population may be genetically linked to how our bodies digest carbohydrates.

Published today in the journal Nature Genetics, the study investigated the relationship between body weight and a gene called AMY1, which is responsible for an enzyme present in our saliva known as salivary amylase. This enzyme is the first to be encountered by food when it enters the mouth, and it begins the process of starch digestion that then continues in the gut.

People usually have two copies of each gene, but in some regions of our DNA there can be variability in the number of copies a person carries, which is known as copy number variation. The number of copies of AMY1 can be highly variable between people, and it is believed that higher numbers of copies of the salivary amylase gene have evolved in response to a shift towards diets containing more starch since prehistoric times.

Researchers from Imperial College London, in collaboration with other international institutions, looked at the number of copies of the gene AMY1 present in the DNA of thousands of people from the UK, France, Sweden and Singapore. They found that people who carried a low number of copies of the salivary amylase gene were at greater risk of obesity.

The chance of being obese for people with less than four copies of the AMY1 gene was approximately eight times higher than in those with more than nine copies of this gene. The researchers estimated that with every additional copy of the salivary amylase gene there was approximately a 20 per cent decrease in the odds of becoming obese.

Professor Philippe Froguel, Chair in Genomic Medicine in the School of Public Health at Imperial College London, and one of the lead authors on the study, said: "I think this is an important discovery because it suggests that how we digest starch and how the end products from the digestion of complex carbohydrates behave in the gut could be important factors in the risk of obesity. Future research is needed to understand whether or not altering the digestion of starchy food might improve someone's ability to lose weight, or prevent a person from becoming obese. We are also interested in whether there is a link between this genetic variation and people's risk of other metabolic disorders such as diabetes, as people with a low number of copies of the salivary amylase gene may also be glucose intolerant."

Dr Mario Falchi, also from Imperial's School of Public Health and first author of the study, said: "Previous genetic studies investigating obesity have tended to identify variations in genes that act in the brain and often result in differences in appetite, whereas our finding is related to how the body physically handles digestion of carbohydrates. We are now starting to develop a clearer picture of a combination of genetic factors affecting psychological and metabolic processes that contribute to people's chances of becoming obese. This should ultimately help us to find better ways of tackling obesity."

Dr Julia El-Sayed Moustafa, another lead author from Imperial's School of Public Health, said: "Previous studies have found rare genetic variations causing extreme forms of obesity, but because they occur in only a small number of people, they explained very little of the differences in body weight we see in the population. On the other hand, research on more common genetic variations that increase risk of obesity in the general population have so far generally found only a modest effect on obesity risk. This study is novel in that it identifies a genetic variation that is both common and has a relatively large effect on the risk of obesity in the general population. The number of copies of the salivary amylase gene is highly variable between people, and so, given this finding, can potentially have a large impact on our individual risk of obesity."

The first step of the study involved the analysis of genetic data from a Swedish family sample of 481 participants, recruited on the basis of sibling-pairs where one was obese and the other non-obese. The researchers used these data to short-list genes whose copy number differences influence body mass index (BMI), and identified the gene coding for the enzyme salivary amylase (AMY1) as the one with the greatest influence on body weight in their analysis. They then investigated the relationship between the number of times the AMY1 gene was repeated on chromosome 1 in each individual and their risk of obesity, by studying approximately 5,000 subjects from France and the UK.

The researchers also expanded their study to include approximately 700 obese and normal-weight people from Singapore, and demonstrated that the same relationship between the number of copies of the AMY1 gene and the risk of obesity also existed in non-Europeans.

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Carbohydrate digestion and obesity strongly linked

WEDNESDAY, March 26, 2014 (HealthDay News) -- Scientists say they've constructed an "atlas" that maps the ways human genes are turned on and off, offering potentially important new insights into health and disease.

The new atlas builds on the achievements of the Human Genome Project -- the mapping of all of the approximately 20,500 human genes, first completed in 2003. Speaking at the time of the Human Genome Project's publication, Francis Collins, director of the U.S. National Human Genome Research Institute, called it "a shop manual, with an incredibly detailed blueprint for building every human cell."

The new gene-activity map describes those networks that govern genes' activity in major cells and tissues in the human body, according to a team of 250 experts from more than 20 countries.

"Now, for the first time, we are able to pinpoint the regions of the genome that can be active in a disease and in normal activity, whether it's in a brain cell, the skin, in blood stem cells or in hair follicles," Winston Hide, an associate professor of bioinformatics and computational biology at Harvard School of Public Health, said in a Harvard news release.

"This is a major advance that will greatly increase our ability to understand the causes of disease across the body," added Hide, who was one of the authors of the main paper in the March 27 issue of Nature.

The findings from the three-year project -- called FANTOM5 -- are described in a series of papers published in Nature and 16 other journals. The project was led by the RIKEN Center for Life Science Technologies in Japan.

In their work, Hide and his colleagues mapped the activity of 224,000 switches that turn human genes on and off. The map includes switches -- which are regions of DNA that manage gene activity -- across a wide range of cell and tissue types.

"We now have the ability to narrow down the genes involved in particular diseases based on the tissue cell or organ in which they work," Hide said. "This new atlas points us to the exact locations to look for the key genetic variants that might map to a disease."

"The FANTOM5 project is a tremendous achievement. To use the analogy of an airplane, we have made a leap in understanding the function of all of the parts. And we have gone well beyond that, to understanding how they are connected and control the structures that enable flight," David Hume, director of The Roslin Institute at the University of Edinburgh, Scotland, and a lead researcher on the project, said in a university news release.

"The FANTOM5 project has identified new elements in the genome that are the targets of functional genetic variations in human populations, and also have obvious applications to other species," he added.

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New Gene 'Atlas' Maps Human DNA Activity