Category Archives: Gene Medicine

Rachel Philipson

Ph.D. student and study co-author Sachi Horibata and Scott Coonrod, associate professor at the Baker Institute for Animal Health, work on research that linked an enzyme to cancer development.

New research on an enzyme linked to cancer development shows that 37 percent of mice that produce excessive quantities of the enzyme developed skin tumors within four to 12 months of birth, and many of these growths progressed to highly invasive squamous cell carcinoma, a common form of skin cancer.

This finding, published online Sept. 11 in the journal Cancer Research, provides the first genetic link between the activity of the enzyme, called PAD2, and cancer progression, and provides important supporting evidence for further studies aimed at using PAD2 inhibitors to block carcinoma progression in humans.

Lead author Scott Coonrod, the Judy Wilpon Associate Professor of Cancer Biology at the Baker Institute for Animal Health in Cornells College of Veterinary Medicine, has studied links between PAD2 and other PAD (peptidylarginine deiminase) enzymes and cancer for some time. Those prior studies suggested that PAD2 plays an important role in regulating genes during cancer progression; however, a direct link between PADs and tumor progression had not yet been proven. Other work from the lab suggested that PAD2 is found at high concentrations in several tumor types, but it was not known whether these elevated levels of the enzyme were causing cancer or merely a consequence of tumor progression.

To directly test for links between PAD2 and cancer, the researchers engineered mice to overexpress PAD2 and then looked to see whether these mice developed cancer.

Coonrod thinks that the reason PAD2 overproduction in the skin may cause cancer is likely due to its ability to promote inflammation.

Inflammation has long been known to play an important role in the development of many types of cancer, he says. Recent studies provide strong evidence that inflammation represents one of the 10 hallmarks of cancer.Its becoming clear that the activity of PAD enzymes seems to be low in most normal tissues, but becomes elevated in a whole range of inflammatory diseases like rheumatoid arthritis, colitis and lupus. PAD activity is very high in the affected tissues and seems to be driving a lot of the inflammatory conditions that cause these diseases.

To test whether PAD2 might be promoting inflammation, Coonrod and his colleagues looked for classical markers of inflammation in the growths and found that a number of these markers were significantly elevated in the mouse tumors. To further test their hypothesis, they overexpressed PAD2 in human cell lines to better understand how the enzyme might behave in human tissue. They found that, similar to the mouse studies, PAD2 overproduction made these human cells more invasive and also enhanced inflammatory marker expression.

Together, these studies suggest that increased PAD activity in human skin, and potentially other tissues, promotes an inflammatory environment that is favorable for cancer development, says Coonrod. His longtime collaborator, Paul Thompson at the University of Massachusetts Memorial Medical Center, has developed a range of new PAD inhibitors, and the team is now testing whether these compounds might suppress carcinoma progression in mouse models of both skin and mammary glands.

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Gene linked to development of skin cancer in mice

PUBLIC RELEASE DATE:

22-Sep-2014

Contact: Katie Marquedant kmarquedant@partners.org 617-726-0337 Massachusetts General Hospital @MassGeneralNews

Analysis of circulating tumor cells (CTCs) in a mouse model of pancreatic cancer identified distinct patterns of gene expression in several groups of CTCs, including significant differences from the primary tumor that may contribute to the ability to generate metastases. In their study reported in the Sept. 25 issue of Cell Reports, investigators from the Massachusetts General Hospital (MGH) Cancer Center identified several different classes of pancreatic CTCs and found unexpected factors that may prove to be targets for improved treatment of the deadly tumor.

"Our ability to combine a novel microfluidic CTC isolation device, developed here at MGH, with single-cell RNA sequencing has given us new biological insights into these cells and revealed novel avenues to try and block the spread of cancer," says lead author David T. Ting, MD, MGH Cancer Center.

Pancreatic cancer is among the most deadly of tumors because it spreads rapidly via CTCs carried in the bloodstream. The earliest technologies for isolating CTCs from blood samples relied on interactions with known tumor-specific marker proteins, potentially missing cells that did not express those particular markers. The device used in the current study, called the CTC-iChip, enables the isolation of all CTCs in a blood sample, regardless of the proteins they express on their surface, by removing all other components. Since the CTCs collected are in solution, unlike with previous CTC capture devices, they are suitable for advanced RNA sequencing techniques to reveal the gene expression patterns of each individual cell.

Using a well-known mouse model of pancreatic cancer, the researchers first isolated 168 single CTCs from the bloodstreams of five individual mice. Analysis of the RNA transcripts of each CTC revealed several different subsets of CTCs, based on gene expression patterns that were different from each other and from the primary tumor. The largest subset, which the authors call 'classic CTCs,' was found to have elevated expression of a stem cell gene called Aldh1 a2, along with genes characteristic of two basic cell types epithelial and mesenchymal transition between which has been associated with tumor metastasis. Another gene expressed by almost all classic CTCs, Igfbp5, is only expressed in primary tumor at locations where epithelial cancer cells interface with the supporting stromal cells that provide a nurturing microenvironment, an observation that suggests that those regions may be the source of CTCs.

The research team was most surprised to observe that extracellular matrix (ECM) genes in general usually expressed primarily in stromal cells were highly expressed in all classic CTCs. Previous studies have suggested that the establishment of metastases depends on the appropriate cellular microenvironment 'soil' in which CTCs can plant themselves as 'seeds' and that the expression of ECM genes is an important aspect of that environment. Expression of ECM genes by CTCs themselves suggests that the blood-borne cells may provide or help prepare their own 'soil.'

Analysis of CTCs from blood samples of human patients with pancreatic, breast or prostate cancer also found elevated expression of several ECM genes. One particular gene, SPARC, was highly expressed in all pancreatic CTCs as well as in 31 percent of breast CTCs. Further experiments revealed that suppressing SPARC expression in human pancreatic cancer cells reduced their ability to migrate and invade tissue, and significantly fewer metastases were generated when SPARC-suppressed pancreatic tumors were implanted into a mouse model, supporting the protein's role in a tumor's metastatic potential.

"Given our limited therapeutic options for pancreatic cancer, understanding the role of the ECM in this tumor seems to be of great importance," says Ting, who is an assistant professor of Medicine at Harvard Medical School. "Much effort has been focused on targeting the microenvironment to improve the efficacy of chemotherapy, and data indicating that environmental stromal cells can enhance a tumor's metastatic ability indicate that ECM proteins are important whether they are produced in stroma or within the tumor cells themselves. Now we need to investigate whether therapeutically targeting ECM can destroy both the tumor microenvironment and CTCs before they have a chance to metastasize."

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Massachusetts General study reveals gene expression patterns in pancreatic CTCs

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Newswise CHAPEL HILL, NC Scientists at the UNC School of Medicine have discovered that knocking out the gene NrCAM leads to an increase of dendritic spines on excitatory pyramidal cells in the brains of mammals. Other studies have confirmed that the overabundance of dendritic spines on this type of brain cell allows for too many synaptic connections to form between neurons a phenomenon strongly linked to autism.

The finding, published in The Journal of Neuroscience, adds evidence that NrCAM is a major player in neurological disorders. Previous UNC studies showed that knocking out the NrCAM gene caused mice to exhibit the same sorts of social behaviors associated with autism in humans.

There are many genes involved in autism, but were now finding out exactly which ones and how theyre involved, said Patricia Maness, PhD, professor of biochemistry and biophysics and senior author of the Journal of Neuroscience paper. Knowing that NrCAM has this effect on dendrites allows us to test potential drugs, not only to observe a change in behaviors linked to autism but to see if we can improve dendritic spine abnormalities, which may underlie autism.

Manesss finding comes on the heels of a report from Columbia University researchers who found an overabundance of the protein MTOR in mice bred to develop a rare form of autism. By using a drug to limit MTOR in mice, the Columbia researchers were able to decrease the number of dendritic spines and thus prune the overabundance of synaptic connections during adolescence. As a result, the social behaviors associated with autism were decreased. However, the drug used to limit MTOR can cause serious side effects, and it is located inside cells, making it a potentially difficult protein to target.

It is too early to tell if NrCAM and MTOR are linked, but Maness is now studying if the decreased amount of the NrCAM protein could trigger activation of MTOR. If so, then NrCAM, which is an accessible membrane-bound protein, might be a preferred therapeutic target for certain autism-related conditions.

In their study, Maness and her colleagues found that the NrCAM protein forms a complex with two other molecules to create a receptor on the membrane of excitatory pyramidal neurons. Manesss team found that this receptor allows dendritic spines to retract, allowing for proper neuron pruning during maturation of the cortex. As a result, excitatory and inhibitory synapses between neurons develop in a balanced ratio necessary for brain circuits to function properly.

Maness, a member of the UNC Neuroscience Center and the Carolina Institute for Developmental Disabilities, also said that there are likely many other proteins downstream of NrCAM that depend on the protein to maintain the proper amount of dendritic spines. Decreasing NrCAM could allow for an increase in the levels of some of these proteins, thus kick starting the creation of dendritic spines.

Basic science in autism is converging in really exciting ways, Maness said. Too many spines and too many excitatory connections that are not pruned between early childhood and adolescence could be one of the chief problems underlying autism. Our goal is to understand the molecular mechanisms involved in pruning and find promising targets for therapeutic agents.

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UNC Researchers Link Gene to Increased Dendritic Spines - a Signpost of Autism

Joint research projects by NUIG and the Mayo Clinic will focus on a number of key strategic areas, including adult stem-cell therapy, gene therapy, biomaterials and biomedical engineering, the two institutes have said. Illustration: Getty

NUI Galway and the Mayo Clinic in the US plan to collaborate on clinical trials using regenerative medicine, following the signing of a memorandum of understanding between the two institutes.

The joint research projects will focus on a number of key strategic areas, including adult stem-cell therapy, gene therapy, biomaterials and biomedical engineering, the two institutes have said.

The Mayo Clinic and NUIGs Regenerative Medicine Institute have worked closely with each other for a number of years.

Both have licensed cell manufacturing facilities, and student and staff exchange programmes between Galway and the US will continue.

Welcoming the agreement, NUIG president Dr Jim Browne has noted that his university has Irelands only facility licensed to produce stem cells for human use.

A new clinical and translational research facility for conducting clinical trials with patients will be complete in early 2015, he said.

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NUI Galway in joint stem cell project with Mayo Clinic

Scientists at the UNC School of Medicine have discovered that knocking out the gene NrCAM leads to an increase of dendritic spines on excitatory pyramidal cells in the brains of mammals. Other studies have confirmed that the overabundance of dendritic spines on this type of brain cell allows for too many synaptic connections to form between neurons a phenomenon strongly linked to autism.

The finding, published in The Journal of Neuroscience, adds evidence that NrCAM is a major player in neurological disorders. Previous UNC studies showed that knocking out the NrCAM gene caused mice to exhibit the same sorts of social behaviors associated with autism in humans.

There are many genes involved in autism, but were now finding out exactly which ones and how theyre involved, said Patricia Maness, PhD, professor of biochemistry and biophysics and senior author of the Journal of Neuroscience paper. Knowing that NrCAM has this effect on dendrites allows us to test potential drugs, not only to observe a change in behaviors linked to autism but to see if we can improve dendritic spine abnormalities, which may underlie autism.

Manesss finding comes on the heels of a report from Columbia University researchers who found an overabundance of the protein MTOR in mice bred to develop a rare form of autism. By using a drug to limit MTOR in mice, the Columbia researchers were able to decrease the number of dendritic spines and thus prune the overabundance of synaptic connections during adolescence. As a result, the social behaviors associated with autism were decreased. However, the drug used to limit MTOR can cause serious side effects, and it is located inside cells, making it a potentially difficult protein to target.

It is too early to tell if NrCAM and MTOR are linked, but Maness is now studying if the decreased amount of the NrCAM protein could trigger activation of MTOR. If so, then NrCAM, which is an accessible membrane-bound protein, might be a preferred therapeutic target for certain autism-related conditions.

In their study, Maness and her colleagues found that the NrCAM protein forms a complex with two other molecules to create a receptor on the membrane of excitatory pyramidal neurons. Manesss team found that this receptor allows dendritic spines to retract, allowing for proper neuron pruning during maturation of the cortex. As a result, excitatory and inhibitory synapses between neurons develop in a balanced ratio necessary for brain circuits to function properly.

Maness, a member of the UNC Neuroscience Center and the Carolina Institute for Developmental Disabilities, also said that there are likely many other proteins downstream of NrCAM that depend on the protein to maintain the proper amount of dendritic spines. Decreasing NrCAM could allow for an increase in the levels of some of these proteins, thus kick starting the creation of dendritic spines.

Basic science in autism is converging in really exciting ways, Maness said. Too many spines and too many excitatory connections that are not pruned between early childhood and adolescence could be one of the chief problems underlying autism. Our goal is to understand the molecular mechanisms involved in pruning and find promising targets for therapeutic agents.

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The above story is based on materials provided by University of North Carolina School of Medicine. Note: Materials may be edited for content and length.

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Gene linked to increased dendritic spines -- a signpost of autism

Mutations in the human retinoblastoma protein gene are a leading cause of eye cancer. Now, Michigan State University scientists have turned to fruit fly eyes to unlock the secrets of this important cancer gene.

In a paper featured on the cover of the current issue of the Journal of Biological Chemistry, Michigan State University researchers provide the first detailed examination of a set of mutations similar to those present in the human cancer gene, said Irina Pushel, MSU undergraduate and co-author.

"By systematically evaluating mutations of increasing severity, we now have a model to better predict how we think the protein will react with each mutation," said Pushel, who co-authored the paper with Liang Zhang, lead author and MSU graduate student, and Bill Henry and David Arnosti, MSU molecular biologists. "We're trying to understand the protein, not even in the specific context of cancer, but rather studying how it interacts within the cell, how it interacts with DNA."

The protein, retinoblastoma, would appear to play a key role in everything. When it's healthy, it helps control cell growth and development. If absent, the organism would die. In its abnormal state cells can overgrow, as seen in cancer, or undergo premature death, as in other human diseases.

Since fruit flies are essentially tiny people with wings, in terms of genetics, these model organisms can play a key role in advancing human medicine.

"If we find one of these mutations in a human, then we can predict what will happen with the protein, such as folding incorrectly," Pushel said. "This isn't going to immediately lead to a new drug to treat cancer. However, we have to know how the protein works before we can develop a drug to fix it. Future medicines will be built upon models such as this, though that is years away."

Previous work has shown that a specific part of this protein plays a role in regulating other genes. In this study, the team modified some of the known important parts of this region of retinoblastoma.

Boosting levels of even standard, or wild-type, protein altered fruit flies eyes and wings. However, when levels of the mutated protein began to climb, deformations were consistent and dramatic.

While a cancer treatment based on this finding may be years away, the insight and understanding into cell development and gene regulation is immediate, Pushel said.

"That's the cool thing about basic research; it may not lead directly to the creation of a new drug, but it helps decipher the genetic code, which for each person controls the unique pattern of how they grow and how they develop -- that's amazing," she said. "It will have many impacts, from understanding development to personalized medicine."

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Abnormal properties of cancer protein revealed in fly eyes

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Newswise Bioluminescence, nanoparticles, gene manipulation these sound like the ideas of a science fiction writer, but, in fact, they are components of an exciting new approach to imaging local and metastatic tumors. In preclinical animal models of metastatic prostate cancer, scientists at Virginia Commonwealth University Massey Cancer Center, VCU Institute of Molecular Medicine and Johns Hopkins Medical Institutions have provided proof-of-principle of a new molecular imaging approach that could revolutionize doctors ability to see tumors that have metastasized to other sites in the body, including the bones.

Recently published in the OnlineFirst edition of the journal Cancer Research, a journal of the American Association for Cancer Research, this multiple institution study is the first to develop in vivo (in animal models) a systemically administered, non-invasive, molecular-genetic technique to image bone metastases resulting from prostate cancer. The new method relies on the detection of a gene known as AEG-1, which was originally discovered by the study's co-lead investigator Paul B. Fisher, M.Ph., Ph.D., and has been shown to be expressed in the majority of cancers but not in normal, healthy cells. In preclinical studies, the researchers were able to image bone metastases with greater accuracy than any clinically approved imaging method.

Currently, we do not have a sensitive and specific non-invasive technique to detect bone metastases, so we are very encouraged by the results of this study says Fisher, Thelma Newmeyer Corman Endowed Chair in Cancer Research and co-leader of the Cancer Molecular Genetics research program at VCU Massey Cancer Center, chairman of the Department of Human and Molecular Genetics at the VCU School of Medicine and director of the VCU Institute of Molecular Medicine. Additionally, because AEG-1 is expressed in the majority of cancers, this research could potentially lead to earlier detection and treatment of metastases originating from a variety of cancer types.

Imaging the expression of a gene in real time is not an easy task. To do it, the scientists used a promoter called AEG-Prom. A promoter is a set of chemical instructions coded in DNA that initiates activity in a gene. The team combined AEG-Prom with imaging agents consisting of a gene that produces firefly luciferase, the bioluminescent substance that makes fireflies glow, and a gene called HSV1tk, which initiates a chemical reaction when specific radioactive compounds are administered. The team then inserted the combination into tiny nanoparticles that are injected intravenously. When exposed to specific proteins that activate the AEG-Prom, including the c-MYC protein that is elevated in many cancer cells, the AEG-Prom initiates activity in the imaging agent, and the location of cancer cells expressing the imaging agent are made visible using sensitive imaging devices.

"The imaging agents and nanoparticle used in this study have already been tested in unrelated clinical trials. Moving this concept into the clinic to image metastasis in patients is the next logical step in the evolution of this research," says co-lead author Martin G. Pomper, M.D., Ph.D., William R. Brody Professor of Radiology at Johns Hopkins Medical Institutions. "My colleagues and I are working toward this goal, and we look forward to opening a study to deploy this technology as soon as possible."

Fisher and Pomper are pioneering the use of cancer-specific and cancer-selective gene promoters to image cancer. Previous studies in melanoma and breast cancer leveraged another gene originally discovered by Fisher called progression elevated gene-3 (PEG-3) using a promoter known as PEG-Prom. In addition to imaging, this approach could also be used to deliver therapeutic agents, such as targeted therapies, directly to local and distant tumors sites and allow physicians to monitor drug delivery in real time. Separate studies are currently under way to examine the therapeutic potential of this strategy.

Fisher and Pomper collaborated on this research with Siddik Sarkar, Ph.D., postdoctoral research scientist in the Department of Human and Molecular Genetics at the VCU School of Medicine, as well as Akrita Bhatnagar, Ph.D., Yuchuan Wang, Ph.D., Ronnie C. Mease, Ph.D., Matthew Gabrielson, M.D., Polina Sysa, M.D., lL Minn, Ph.D., Gilbert Green, Brian Simmons, Ph.D., and Kathleen Gabrielson, D.V.M., Ph.D., all from Johns Hopkins Medical Institutions.

This study was supported by National Cancer Institute grant CA151838, the Prostate Cancer Foundation, the Patrick C. Walsh Foundation, the National Foundation for Cancer Research and, in part, by VCU Massey Cancer Centers NIH-NCI Cancer Center Support Grant P30 CA016059.

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New Non-Invasive Technique Could Revolutionize the Imaging of Metastatic Cancer

Bacteria appear to be having the microbial equivalent of inter-species sex in hospital sinks, swapping chunks of DNA that render them impervious to antibiotics, researchers reported Wednesday.

The findings may help explain the rise in drug-resistant superbugs in hospitals, and they suggest that they may sometimes be breeding on site, as opposed to being carried in by patients.

The team at the National Institutes of Health found carbapenem-resistant Enterobacteriaceae (CRE) that appeared to have exchanged pieces of genetic material called plasmids that gave them resistance to antibiotics. CRE resist most, if not all antibiotics, and they are becoming more common: they are found in about 4 percent of hospitals now and 18 percent of long-term care facilities.

"Over the past decade, there has been a steady and alarming increase in antibiotic-resistant bacteria."

They found the superbugs on patients and in the sinks at the NIH clinical center outside Washington D.C., a large hospital that had a bad outbreak of drug-resistant Klebsiella in 2011 in which 17 patients got badly infected and six died.

They tested all the patients in two wards in 2012 and 2013 - 1,000 in all -- and found 10 patients colonized with CRE. There was clear evidence the germs were getting new plasmids from somewhere. More searching turned them up in sink drains, although theres no direct evidence thats where the patients got them from.

Antibiotic resistance is becoming a huge medical challenge. Antibiotic resistance is caused by resistance genes carried on plasmids, small circles of DNA separate from the chromosomal DNA. Resistance spreads by horizontal gene transfer, in which plasmid genes from a donor bacterial cell spread to a recipient bacterial cell during cell-to-cell contact. When the DNA that is transferred includes antibiotic-resistance genes, the bacterium receiving this DNA becomes antibiotic-resistant too.

It's also not clear where the bacteria are getting the new plasmids, says Julia Segre of the National Human Genome Research Institute, part of NIH.

Bacteria reproduce by splitting in half, but they can also exchange genetic material. This DNA exchange helps them evolve and can help them evolve resistance to antibiotics.

Over the past decade, there has been a steady and alarming increase in antibiotic-resistant bacteria, a trend that poses a serious threat to the U.S. medical system, Segre and colleagues wrote in their report, published in the journal Science Translational Medicine.

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Gene-Swapping Bacteria Are Making New Superbugs

Diagnosing clinical depression in adults is tricky for doctors. That's mostly because assessment is largely reliant on imperfect analysis, like patient observations and interviews. Most laboratory tests are, by and large, of little use in determining if someone is depressed or not.

That could soon change. About three years ago, a team of researchers co-led by Eva Redei, a research professor for psychiatric disease at the Northwestern University Feinberg School of Medicine, published a study finding that certain RNA markers--a short identifiable string in the DNA sequence, which can be read sort of like fingerprints--were associated with clinical depression in teenagers.

In a new study published today, that same team has identified nine RNA blood markers that, at very specific levels, could be used to diagnose major depression in adults. Furthermore, three of those genetic fingerprints could be used to determine who might be receptive to cognitive behavioral therapy as a means to get better; the researchers saw consistent patterns in patients for whom therapy was helpful.

Now, the sample size wasn't huge: The team looked at 32 depressed individual, and another 32 in a control group (the subjects varied greatly in age, from 23 to 83), and put all of them through cognitive behavioral therapy. All the while, researchers kept a close eye on their gene markers.

Of the afflicted, some 40% showed improved mental health after treatment. And after controlling for variables like gender and age, the team found a correlation between nine of the markers in people who were clinically diagnosed as depressed. In the patients who were better after treatment, the team identified three other RNA markers that could be be used for future diagnoses. "We could identify one of those nine, and two others, that were very different between those who got well and those who didnt," Redei tells Fast Company. "That shows clearly the efficacy of cognitive behavioral therapy [for certain individuals]."

The methodology wasn't perfect, but the results were strong enough that "it's very hopeful for the future," Redei says. And the team doesn't yet know how early these gene markers can be detected in, say, children--especially to determine who might be vulnerable to clinical depression as they age. "That's a huge independent study on its own," she says.

But for adults suffering from depression? If you can identify who might be receptive to psychotherapy, for example, there may be other unidentified gene markers that can identify who might be receptive to certain types of antidepressants. "What we hope to do," adds Redei, "is to have an FDA-approved test in the future that any clinical laboratory can do."

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How A Simple Blood Test Can Now Help Diagnose Depression

PUBLIC RELEASE DATE:

16-Sep-2014

Contact: Mary Clarke press.office@sanger.ac.uk 01-223-492-368 Wellcome Trust Sanger Institute @sangerinstitute

Research using data collected from around 4,000 healthy people in the UK has enabled scientists to identify a rare genetic variant that dramatically reduces levels of certain types of lipids in the blood. The study is the first to emerge from the UK10K Project's cohort of samples from the general public and demonstrates the power of whole genome sequencing at scale.

"Until now it has only been possible to look for common variants of small effect in large genome wide association studies," says Dr Nicholas Timpson, first author from the Medical Research Council (MRC) Integrative Epidemiology Unit at the University of Bristol. "Thanks to the quantity of data available through the UK10K Project and because of the relatively large effect of this variant, we have been able to find a rare genetic variant that has clinical relevance."

By looking at whole genome sequences from 4,000 people and comparing this with data about their lipid levels, scientists spotted an association between levels of lipids called triglycerides and the presence of the APOC3 gene variant. The research suggests that people with the rare change (approximately 0.2 per cent of the population carry this) typically have lower levels of triglycerides, which (as shown elsewhere) is associated with reduced risk of cardiovascular disease.

Two studies in the New England Journal of Medicine have recently explored the role of this genetic variant through the examination of APOC3 in a targeted approach, and through coding and analysing only part of the genome. These studies give important context to this finding as they also relate this change to heart disease.

"These three studies independently reporting this finding give us confidence that it is reliable and informative for clinical understanding," says Professor Steve Humphries, a British Heart Foundation-funded senior author from University College London. "Once we can understand the mechanism of the protective function of this variant, we can try to use this information to develop novel therapies to help those at risk of cardiovascular disease."

This is the first in a series of studies that will use whole genome sequences and clinical information about physical characteristics from the UK10K project to find rare genetic variants.

"Extending genome wide association studies to include whole genome sequencing can help us to identify more clinically informative variants," says Dr Nicole Soranzo, senior author from the Wellcome Trust Sanger Institute. "Data collected as part of the UK10K project is essential to this and we are beginning to see its extraordinary value."

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Gene variant that dramatically reduces 'bad' lipids