Researchers have narrowed down the list of genes implicated in autism spectrum disorder, and they appear to point toward a part of the brain that has largely been overlooked.

Most research into the genetic roots of autism, a highly heritable disorder that affects about 1 in 68 children, starts with a kind of inventory of genes. Then, it narrows down this genome-wide survey to prime suspects that appear to be different among those with one or several of the symptoms of autism.

That gene-by-gene approach, however, has unearthed too many suspects, each with somewhat vague relationships to a small sliver of the autism spectrum. That situation has sparked some to abandon the gene-by-gene approach in favor of environmental factors that may alter gene behavior.

Whats special about autism is that it doesnt seem like its a one-gene thing, said Stanford UniversitySchool of Medicinegeneticist Michael Snyder, lead investigator of the study published online Tuesday in the journal Molecular Systems Biology.

Maybe this is a tough way to look at it, Snyder said of the gene-by-gene approach. Maybe a better way to look at it is to see what the normal biological landscape looks like, and see how people who are mutated for autism map onto that.

What followed was a complex computational task that corralled proteins into scores of modules tightly bound by their inter-related functions. Then Snyders team overlaid the map of gene variants implicated in autism.

At first glance, proteins encoded by these 383 suspect genes were scattered among many of these functional modules. But a few of the modules screamed out with autism connections, both from existing data and a genome screening the researchers conducted, Snyder said.

One module involved molecular activity that goes on all over the brain, particularly involving synapses, the tiny spaces where electrochemical signals cross for one neuron to another. This helps explain why so much autism research points toward problems with synapses.

But there was another module just as rich in autism implications, and this one implicated the corpus callosum. That thick band of fibers connects the brains two hemispheres, and its generally smaller among those with autism a disease marked by many anomalies in connectivity.

The corpus callosum is chock full of a different kind of brain cell, oligodendrocytes, which provide a sheath of insulation around the transmission lines of neurons, known as their axons. That greatly aids the propagation of electrochemical signals along the neuron. Defects in this myelin sheathing have been associated with developmentaldisorders.

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Study narrows down genetic suspects in autism

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As comprehensive genetic tests become more widespread, patients and experts mull how to deal with unexpected findings

Skip Sterling

Last spring Laura Murphy, then 28 years old, went to a doctor to find out if a harmless flap of skin she had always had on the back of her neck was caused by a genetic mutation. Once upon a time, maybe five years ago, physicians would have focused on just that one question. But today doctors tend to run tests that pick up mutations underlying a range of hereditary conditions. Murphy learned not only that a genetic defect was indeed responsible for the flap but also that she had another inherited genetic mutation.

This one predisposed her to long QT syndrome, a condition that dramatically increases the risk of sudden cardiac death. In people with the syndrome, anything that startles themsay, a scary movie or an alarm clock waking them from a deep slumbermight kill by causing the heart to beat completely erratically.

Doctors call this second, unexpected result an incidental finding because it emerged during a test primarily meant to look for something else. The finding was not accidental, because the laboratory was scouring certain genes for abnormalities, but it was unexpected.

Murphy, whose name was changed for this story, will most likely have plenty of company very soon. The growing use of comprehensive genetic tests in clinics and hospitals practically guarantees an increasing number of incidental discoveries in coming years. Meanwhile the technical ability to find these mutations has rapidly outpaced scientists understanding of how doctors and patients should respond to the surprise results.

Unknown Unknowns Incidental findings from various medical tests have long bedeviled physicians and their patients. They appear in about a third of all CT scans, for example. A scan of the heart might reveal odd shadows in nearby lung tissue. Further investigation of the unexpected resultseither through exploratory surgery or yet more testscarries its own risks, not to mention triggering intense anxiety in the patient. Follow-up exams many times reveal that the shadow reflects nothing at alljust normal variation with no health consequences.

What makes incidental findings from genetic tests different, however, is their even greater level of uncertainty. Geneticists still do not know enough about how most mutations in the human genome affect the body to reliably recommend any treatments or other actions based simply on their existence. Furthermore, even if the potential effects are known, the mutation may require some input from the environment before it will cause its bad effects. Thus, the presence of the gene does not necessarily mean that it will do damage. Genetics is not destiny. In Murphy's case, her mutation means that she has a roughly 50 to 80 percent chance of developing long QT syndrome, and the presence of the mutation alone is not a sure indicator she will be afflicted, says her physician, Jim Evans, a genetics and medicine professor at the University of North Carolina School of Medicine. To be safe, he has advised her to meet with a cardiac specialist to talk about next steps, including possibly starting beta-blocker drugs to regularize her heart rate.

The incidence of hard-to-interpret results is expected to rise because the cost of surveying large swaths of the genome has dropped so lowto around $1,000. It is typically less expensive to get preselected information about the 20,000 or so genes that make up a person's exomethe section of the genome that provides instructions for making proteinsthan to perform a more precision-oriented test that targets a single gene. As a consequence, scientists and policy makers are now scrambling to set up guidelines for how much information from such testing to share with patients and for how best to help them deal with the inevitable incidental findings.

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What Rare Disorder Is Hiding in Your DNA?

Protein UbcH7 regulates action of 53BP1 gene repair route where cancer cells are met with fatal inhospitality

Case Western Reserve researchers have identified a two-pronged therapeutic approach that shows great potential for weakening and then defeating cancer cells. The team's complex mix of genetic and biochemical experiments unearthed a way to increase the presence of a tumor-suppressing protein which, in turn, gives it the strength to direct cancer cells toward a path that leads to their destruction.

If the laboratory findings are supported by tests in animal models, the breakthrough could hold the promise of increasing the effectiveness of radiation and chemotherapy in shrinking or even eliminating tumors. The key is to build up a "good" protein - p53-binding protein 1 (53BP1) -- so that it weakens the cancer cells, leaving them more susceptible to existing cancer-fighting measures.

The breakthrough detailed appeared in the Nov. 24 online edition of the journal PNAS (Proceedings of the National Academy of Sciences).

"Our discovery one day could lead to a gene therapy where extra amounts of 53BP1 will be generated to make cancer cells more vulnerable to cancer treatment," said senior author Youwei Zhang, PhD, assistant professor of pharmacology, Case Western Reserve University School of Medicine, and member of the Case Comprehensive Cancer Center. "Alternatively, we could design molecules to increase levels of 53BP1 in cancers with the same cancer-killing end result."

The cornerstone of the research involves DNA repair - more specifically, double-stand DNA repair. DNA damage is the consequence of an irregular change in the chemical structure of DNA, which in turn damages and even kills cells. The most lethal irregularity to DNA is the DNA double-strand break in the chromosome. DNA double-strand breaks are caused by everything from reactive oxygen components occurring with everyday bodily metabolism to more damaging assaults such as radiation or chemical agents.

The body operates two repair shops, or pathways, to fix these double strand breaks. One provides rapid, but incomplete repair - namely, gluing the DNA strand ends back together. The problem with the glue method is that it leaves the DNA strands unable to transmit enough information for the cell to function properly - leading to a high cell fatality rate.

The second shop, or pathway, uses information from intact, undamaged DNA to instruct damaged cells on how to mend broken double strands. During his study, Zhang and fellow investigators discovered a previously unidentified function of a known gene, UbcH7, in regulating DNA double-strand break repair. Specifically, they found that depleting UbcH7 led to a dramatic increase in the level of the 53BP1 protein.

"What we propose is increasing the level of 53BP1 to force cancer cells into the error-prone pathway where they will die," Zhang said. "The idea is to suppress deliberately the second accurate repair pathway where cancer cells would prefer to go. It is a strategy that would lead to enhanced effectiveness of cancer therapy drugs."

The next research step for Zhang and his team will be to test their theory in animal models with cancer. Investigators would study the effects of introducing the protein 53BP1 in lab mice with cancer and then applying chemotherapy and radiotherapy as treatment.

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Cancer treatment potential discovered in gene repair mechanism

Every recipe has both instructions and ingredients. So does the human genome. An error in the instructions can raise the risk for disease.

Every cell in your body reads the same genome, the DNA-encoded instruction set that builds proteins. But your cells couldnt be more different. Neurons send electrical messages, liver cells break down chemicals, muscle cells move the body. How do cells employ the same basic set of genetic instructions to carry out their own specialized tasks? The answer lies in a complex, multilayered system that controls how proteins are made.

Frey compares the genome to a recipe that a baker might use. All recipes include a list of ingredientsflour, eggs and butter, sayalong with instructions for what to do with those ingredients. Inside a cell, the ingredients are the parts of the genome that code for proteins; surrounding them are the genomes instructions for how to combine those ingredients.

Just as flour, eggs and butter can be transformed into hundreds of different baked goods, genetic components can be assembled into many different configurations. This process is called alternative splicing, and its how cells create such variety out of a single genetic code. Frey and his colleagues used a sophisticated form of machine learning to identify mutations in this instruction set and to predict what effects those mutations have.

Olena Shmahalo/Quanta Magazine

The researchers have already identified possible risk genes for autism and are working on a system to predict whether mutations in cancer-linked genes are harmful. I hope this paper will have a big impact on the field of human genetics by providing a tool that geneticists can use to identify variants of interest, said Chris Burge, a computational biologist at the Massachusetts Institute of Technology who was not involved in the study.

But the real significance of the research may come from the new tools it provides for exploring vast sections of DNA that have been very difficult to interpret until now. Many human genetics studies have sequenced only the small part of the genome that produces proteins. This makes an argument that the sequence of the whole genome is important too, said Tom Cooper, a biologist at Baylor College of Medicine in Houston, Texas.

The splicing code is just one part of the noncoding genome, the area that does not produce proteins. But its a very important one. Approximately 90 percent of genes undergo alternative splicing, and scientists estimate that variations in the splicing code make up anywhere between 10 and 50 percent of all disease-linked mutations. When you have mutations in the regulatory code, things can go very wrong, Frey said.

People have historically focused on mutations in the protein-coding regions, to some degree because they have a much better handle on what these mutations do, said Mark Gerstein, a bioinformatician at Yale University, who was not involved in the study. As we gain a better understanding of [the DNA sequences] outside of the protein-coding regions, well get a better sense of how important they are in terms of disease.

Scientists have made some headway into understanding how the cell chooses a particular protein configuration, but much of the code that governs this process has remained an enigma. Freys team was able to decipher some of these regulatory regions in a paper published in 2010, identifying a rough code within the mouse genome that regulates splicing. Over the past four years, the quality of genetics dataparticularly human datahas improved dramatically, and machine-learning techniques have become much more sophisticated, enabling Frey and his collaborators to predict how splicing is affected by specific mutations at many sites across the human genome. Genome-wide data sets are finally able to enable predictions like this, said Manolis Kellis, a computational biologist at MIT who was not involved in the study.

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Machine Intelligence Cracks Genetic Controls

Abu Dhabi: A comprehensive new health care strategy for the emirate of Abu Dhabi will focus on reducing critical gaps across medical specialities and improving access to health care, senior health officials announced in the capital on Wednesday.

One of the hallmarks of this plan, launched by the emirates health sector regulator, the Health Authority Abu Dhabi (Haad), is to reduce the prevalence of genetic diseases among residents. In addition, personalised medicine programmes will also be introduced to tailor management of diseases based on each individuals predisposition to health risks, Dr Maha Barakat, director-general at the Health Authority Abu Dhabi, told Gulf News.

Such personalised management of health is the future of medicine, and we are currently in the exploratory phase of implementing it. For example, a simple blood test can be used to extract the genetic profile of an individual, and based on inherent risks towards certain diseases, the individuals future treatment plans can be determined and precautionary measures taken, Dr Maha said.

She was speaking at a press conference held to launch the Haads health care plan for the next five years. The scheme highlights 58 initiatives distributed across seven priority areas, and was recently approved by the Abu Dhabi Executive Council.

While existing initiatives to improve patient satisfaction and to increase the reach of screening programmes have been revamped, new elements have also been introduced to address emerging health care concerns.

For example, the new plan aims to reduce the prevalence of genetic diseases, which were responsible for 2 per cent of all fatalities in 2013.

We understand that many of these congenital malformations and abnormalities occur due to consanguineous marriages. A standing premarital screening programme does address this concern, but we hope to create greater awareness among residents about these risks as well. In addition, we also hope to increase pre-gestational diagnoses and treatment of diseases to limit the number of children born with severe malformations, Dr Maha said.

There is still a shortfall in the provision of certain medical specialities in the emirate, including intensive medicine, neonatology, paediatrics, oncology, psychiatry, orthopaedics and rehabilitation. The Haad strategy aims to attract and retain specialists to fill these, especially Emirati professionals, said Dr Mugheer Al Khaili, the authoritys chairman.

Statistics released on Wednesday (December 24) show that about 4,800 more doctors and 13,000 nurses are required in Abu Dhabi by 2020, which translates into 1,700 additional doctors and 2,900 nurses annually.

In addition, officials are hoping to encourage further private sector investment into health care facilities.

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New health care strategy to introduce personalised medicine

Patients in Greater Manchester are set to spearhead a genetic revolution to help fight cancer and rare diseases.

The citys St Marys Hospital has been named as one of 11 Genomic Medicine Centres, which together will map the complete genetic codes of 100,000 patients.

The three-year project, unveiled by the Prime Minister earlier this year, is a bold bid to transform diagnosis and treatment.

It will allow doctors to learn more about cancer and rare conditions by decoding and exploring human genomes - complete sets of peoples genes.

University of Manchester scientists and doctors at St Marys will work closely with colleagues at Salford Royal, The Christie, Wythenshawe Hospital and the Pennine Acute Hospitals Trust on the project.

Bill Newman, professor of translational Genomic medicine at the Manchester Centre for Genomic Medicine at the University of Manchester and honorary consultant at Central Manchester University Hospitals Trust, said doctors, nurses and scientists at the Manchester Centre for Genomic Medicine, based at St Marys, were delighted to have been selected for the pioneering project.

He said: They plan to work with colleagues to use the new type of genetic testing called whole genome sequencing to find out why some people have certain types of rare health problems and to treat people with cancer more effectively.

The project is expected to revolutionise the future of healthcare. It could improve the prediction and prevention of disease, enable new diagnostic tests, and allow treatments to be personalised.

It could also allow patients with rare conditions to be diagnosed more quickly and unlock the secrets of genetic changes in cancer.

St Marys and The Christie have already been part of a pilot phase of the project.

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St Mary's Hospital to lead genetic revolution in fight against cancer and rare diseases

A new genetics project could help "unlock a series of secrets about devastating diseases", the NHS says.

Under the scheme, 11 Genomics Medicine Centres are being set up in English hospitals to gather DNA samples to help devise targeted treatments for a wide range of diseases.

It is focusing on cancer and rare genetic diseases.

The aim is to sequence 100,000 genomes within three years in order to develop new tests and drugs.

Doctors will offer suitable patients the opportunity to take part in the scheme.

They will have to agree to have their genetic code and medical records - stripped of anything that could identify them - made available to drugs companies and researchers.

Up to 25,000 cancer patients will have the genetic code of their healthy tissue compared to the genetic code of their tumour.

A giant game of spot-the-difference will then take place to identify the precise mutations in DNA that are causing a patient's tumour.

This would allow targeted medicines to be developed.

Genetic code

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NHS DNA Scheme To Fight Cancer And Genetic Diseases

A team of Liverpool scientists have been selected to take part in a genetic revolution.

The group will participate in a world-leading project to tackle the genetic causes of cancer and rare diseases.

The North West Coast NHS Genomic Medicine Centre is a partnership led by Liverpool Womens Hospital which will be helping deliver the 100,000 Genomes Project, a three year scheme launched by David Cameron.

Angela Douglas, scientific director for genetics at Liverpool Womens NHS Foundation Trust and chair of the British Society for Genetic Medicine (BSGM), said: The 100,000 Genome Project is welcomed by the BSGM as an exciting and unprecedented development that offers the UK the opportunity of being a leader in the field of genomic medicine.

The project has the potential to transform the future of healthcare.

It could improve the prediction and prevention of disease, enable new and more precise diagnostic tests, and allow personalisation of drugs and other treatments to specific genetic variants.

The initiative involves collecting and decoding 100,000 human genomes complete sets of peoples genes that will enable scientists and doctors to understand more about specific conditions.

Life Sciences Minister George Freeman said: We want to make the UK the best place in the world to design and discover 21st century medicines which is why we have invested in the 100,000 Genomes Project.

We also want to ensure NHS patients benefit which is why we have now selected NHS hospitals to help us sequence genomes on an unprecedented scale and bring better treatments to people with cancers and rare diseases for generations to come.

It is anticipated that around 75,000 people will be involved in this project which will also include some patients who have life threatening or debilitating diseases.

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Liverpool to lead world in genetic cancer research

Eleven genomic medicine centres (GMC) are the heart of the project, a plan to map 100,000 complete genetic codes of patients. The human genome consists of more than three billion chemical units or "base pairs" that make up the letters of the genetic code - abbreviated to A, T, C, and G. The way the letters pair up on both sides of the double-helix DNA molecule shapes the genome sequence. Mistakes in the pairing can lead to disease.

The project is needed to treat illnesses such as cancer, which can take a variety of forms - breast cancer, for example, has at least 10 - each requiring a different treatment. In the case of breast cancers, more than 70 per cent respond to hormone therapies, but their reaction to the treatment is very varied. The new research centres will create personalised treatment that can be targeted more effectively at each variation of cancer.

The participants in the project will agree to share their genetic code and medical records with drugs companies and researchers. Their DNA will then be examined in order to compare the genetic code of their healthy tissue to the genetic code of their tumour.

It should then be easier to spot the mutations in DNA that are causing the tumour, and so create a more precisely targeted treatment.

Some 15,000 patients with rare diseases will have their genome compared with those of close relatives in order to spot the mutations.

Ultimately the aim is to secure the participation of more than 100 NHS trusts over the project's three-year lifespan. Scientists and doctors hope the 300m initiative will transform medicine by uncovering DNA data that can be used to develop personalised diagnostic procedures and drugs.

More than 100 patients with cancer and rare inherited diseases have already had their genomes sequenced during the project's pilot phase.The first wave of GMCs will be linked to NHS trusts in 11 locations covering London, Manchester, Oxford, Birmingham, Cambridge, Southampton, Exeter and Newcastle.

Professor Mark Caulfield, chief scientist at Genomics England, the Department of Health company set up to deliver the project, strongly defended the decision to let drug companies have access to the data.

"It is absolutely vital if you want to develop maximum benefit from this project that we encourage industry to join us in this," he said. "There's no university in the land that can develop a medicine on its own."

But he pointed out that drug companies would be restricted to using the facility like a reading library. They would be able to work with data, but not take it away.

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How the genomes project could help you

During a conversation I had with a doctor a couple of years ago, the subject of cancer diagnoses came up, in a tangential way. She said that not all that many decades ago, a physician who had established that a patient had cancer often wouldnt bother investigating further: since there werent any effective treatments for any kind of cancer, there wasnt much point in finding out what kind of cancer it was. You could try to cut it out, or you could leave it in and see what happened, and that was about it.

Now, of course, that has changed. It matters what cancer you have, because different cancers respond differently to different treatments. As we get better at treating the disease, it pushes us to get better at differentiating them; as we establish the various kinds, it allows us to target drugs more precisely at the ones they work on, so that the drugs themselves become more effective. There is a virtuous circle between diagnostics and treatment that improves both. Thats why the news that the NHS is to open 11 major genomics centres with more to follow around the country is so hugely positive.

Over the past few years, genomics the study of our genetic code has taken off in spectacular style: while it took decades and billions of pounds to sequence the first human genome, now the information in a human cell can be catalogued in a few days for about a grand. This, obviously, opens up huge possibilities for medicine. It renders it practical to record and analyse the genetic code of thousands of people, and to see how small differences in our DNA change our vulnerability to different diseases.

And thats exactly what the NHS plan, with Genomics England, involves. The centres will take the genetic data of 100,000 people, all suitably anonymised, and analyse and record them, making them available to researchers at universities and drug firms. They will also sequence the DNA of 25,000 cancer sufferers, and the DNA of the cancers themselves. Cancer is a disease of the genes the product of mutations which send the cell into uncontrolled reproduction and establishing which genes are vulnerable to which mutations will be vital in defeating its various incarnations.

This has possibilities far beyond cancer, though. To a startling degree, we are freed from the crippling burden of infectious disease. Thats not the case in developing countries, where more than half of all deaths are caused by infection, according to the World Health Organisation; but in the rich West, nearly nine out of 10 of us will die of a non-communicable disease, when something simply goes wrong with our bodies. Sometimes that something goes wrong because of environmental factors smoking, drinking, obesity and sometimes were just unlucky, but our risk of suffering pretty much any non-communicable disease, from heart disease to diabetes to stroke, is influenced by our genes. If we can see which genes tend to be associated with which diseases, doctors can help those at the greatest risk to take steps to avoid it.

An obvious example is breast cancer, which oncologists now think of as at least 10 different diseases. While the average lifetime risk for a woman in the UK is about 12.5 per cent, according to Cancer Research UK, if they have a particular mutation in a gene called BRCA1, that risk goes up to between 60 and 90 per cent. Angelina Jolie was tested and found to have this mutation, and chose to have a double mastectomy as a preventive measure. Less dramatically, statins could be prescribed specifically to those people who are found to be more susceptible to high blood pressure or heart disease, instead of as now giving them to a huge swath of the population in order to help the minority who actually need them. It is the difference between a sniper rifle and a shotgun.

The trick with the genomics revolution will be tying it in to the everyday business of health care in England, and that is where these centres will become vital. When doctors are able to look at a patients genetic information as easily as they can their height and weight, they will be able to target those patients with the interventions that will work best on them true individualised medicine. But that involves making genome sequencing routine, calming understandable fears about privacy, and convincing people to take that first scary step and look at what their genes hold in store for them.

A year or so after my conversation with the doctor about cancer, a close relative was diagnosed with malignant melanoma. It was a horrible, terrifying time. Skin cancer comes in various forms, many of them relatively benign, but melanoma is a killer. And until recently there were no drugs that were effective against it. If caught early, it could be cut off, and you were usually all right; later, once it had got into your system, you were in real trouble. Like the cancers a century ago, there was little point knowing more about what kind of melanoma it was, because you couldnt do much about it.

Luckily (touch wood) my relatives cancer was caught early, and the prognosis is good. But if, heaven forfend, it comes back, there are now drugs that can be used, with some success and the choice of which drug depends on your genes. The genomic revolution is already transforming medicine, and saving the lives of people right now. This is an extraordinary time for medicine.

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Genomics: the revolution that's transforming medicine

ITV Report 22 December 2014 at 1:26am Credit: Christoph Bock/Max Planck Institute for Informatics

More than ten years since scientists completed the first sequence of the human genome, today the genetic era will make its grand entrance into mainstream clinical care.

This morning, NHS England launched its 100,000 Genomes Project, a three-year plan to sequence the entire genetic code of thousands of patients with cancers and rare diseases.

The latter includes thousands of conditions that are often named after first doctor or scientist to describe the symptoms in a patient and can involve everything from neurological to muscular or behavioural problems. They are debilitating, often inherited and can shorten life but usually defy doctors trying to identify the biological causes.

The potential for all this genetic information is huge. As well as insights into how cancers and rare diseases work and how they progress, knowing which genetic variations a person has will help doctors work out ways to personalise their treatment by giving them drugs, for example, that specifically target particular problematic genetic mutations. This already happens to some extent in the NHS with drugs such as Herceptin for some types of breast cancer but the potential to improve so-called precision medicine using genetic information is vast.

Genomes have always held the promise to be the cornerstone of healthcare in the 21st century, ever since the draft of the first human genome was published in 2000. The international Human Genome Project (HGP) was a staggering achievement, taking hundreds of researchers more than a decade to piece together the 3 billion letters of the human genetic code, at a cost of around $3bn.

Today, we are learning the language in which God created life, said President Bill Clinton on the morning of 26 June 2000, when the draft of the first human genome sequence was formally announced:

We are gaining ever more awe for the complexity, the beauty, the wonder of God's most divine and sacred gift. With this profound new knowledge, humankind is on the verge of gaining immense, new power to heal.

Genome science will have a real impact on all our lives and even more, on the lives of our children. It will revolutionize the diagnosis, prevention and treatment of most, if not all, human diseases.

Bill Clinton

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NHS starts new era of DNA medicine

Cancer treatment could be transformed by project to read our DNA Scientists hope it will lead to faster and more accurate diagnosis Predicted genetic revolution will make chemotherapy obsolete in 20 years Project launched today aims to read genetic blueprint of 75,000 volunteers

By Fiona Macrae, Science Correspondent for the Daily Mail

Published: 19:06 EST, 21 December 2014 | Updated: 19:37 EST, 21 December 2014

Cancer treatment could be transformed by a landmark project to read the DNA of thousands of men, women and children.

Scientists believe that unlocking secrets deep in patients' genetic code will lead to faster and more accurate diagnosis, speed the development of 'wonder' drugs and mean better use is made of existing medicines.

It is even predicted that the genetic revolution will make chemotherapy obsolete within 20 years.

The value of genetic testing is demonstrated by Angelina Jolie's experience. Testing revealed that the Hollywood actress carries a mutation of the BRCA1 gene, meaning she had an 87 per cent risk of developing breast cancer and a 50 per cent risk of ovarian cancer. The data led Miss Jolie, 39, to have a preventative double mastectomy

The treatment of rare genetic diseases is also set to benefit from the 100,000 Genomes Project, which will combine genetic data with information from health records to give Britain 'the greatest healthcare system in the world'.

Sir Bruce Keogh, the NHS's medical director, said the 300million initiative puts the UK in a position to 'unlock a series of secrets about devastating diseases which have remained hidden for centuries and to unlock those on behalf of the whole of humankind'.

Professor Mark Caulfield, the project's chief scientist, said: 'If there was just one medicine that came out of this programme that would be well worth the investment.'

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300m bid to find new cancer cures by mapping our DNA: Unlocking genetic code could lead to faster and more accurate ...

Opening a new chapter in the use of genomic science to fight cancer, the Food & Drug Administration on Friday approved olaparib, a medication for advanced ovarian cancer associated with a defective BRCA gene.

The new drug, to be marketed under the commercial name Lynparza, was found in a preliminary clinical trial to shrink or eliminate ovarian tumors in women whose cancers bore a specific genetic fingerprint and who had undergone at least three prior lines of chemotherapy.

Based on Lynparza's "existing objective response rate and duration of response data," the drug safety agency granted the medication's maker, Astra-Zeneca, an "accelerated" approval. Roughly a third of women with the genetic mutation targeted by Lynparza saw partial shrinkage or complete disappearance of their ovarian tumors over an average of eight months.

At the same time, the FDA granted marketing approval for a "companion diagnostic" that will help identify women whose advanced ovarian cancer is likely to respond to the drug. That test, BRACAnalysis CDx, is made by Myriad Genetics Inc. To be a candidate for Lynparza, a patient must take the test and show positive for a specific mutation of the BRCA gene, which confers a high risk of both breast and ovarian cancer.

"Today's approval constitutes the first of a new class of drugs for treating ovarian cancer," Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research, said in the news release.

Pazdur called Lynparza "an example of how a greater understanding of the underlying mechanisms of disease can lead to targeted, more personalized treatment."

Lynparza is the first of a new class of drugs called poly ADP-ribose polymerase (PARP) inhibitors, which work by blocking the action of an enzyme that helps repair DNA. In certain tumor cells, such as those seen in BRCA1 and BRCA2 mutation carriers, blocking this enzyme can lead to cell death.

"Its really opening a whole new avenue of therapy," said Dr. M. William Audeh, a medical oncologist and geneticist at Cedars-Sinai Medical Center's Samuel Oschin Cancer Institute in Los Angeles. "This drug is working in a fundamentally different way than chemotherapy: This is a cancer treatment thats been designed to hit this kind of inherited genetic weakness in the cancer itself."

Because PARP inhibitors such as Lynparza target a cancer's genetic Achilles' heel, they appear to hold out the particular promise of driving some patients' cancer into remission entirely, said Audeh, an investigator on the Astra-Zeneca-sponsored trial assessed by the FDA.

"All of us whove done these trials over seven years have some patients whove been in long-term remission. Thats not something you see very often with chemotherapy," he added.

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FDA approves new ovarian cancer drug

FRIDAY, Dec. 19, 2014 (HealthDay News) -- The intestinal bacteria that cause inflammatory bowel disease, which includes Crohn's disease and ulcerative colitis, may be inherited, researchers report.

The findings, published recently in the journal Genome Medicine, could help in efforts to prevent the disease and treat the 1.6 million Americans with Crohn's or colitis, the study authors added.

"The intestinal bacteria, or 'gut microbiome,' you develop at a very young age can have a big impact on your health for the rest of your life," lead author Dan Knights, an assistant professor in the department of computer science and engineering and the Biotechnology Institute at the University of Minnesota, said in a journal news release.

"We have found groups of genes that may play a role in shaping the development of imbalanced gut microbes," he explained.

The study of 474 adults with inflammatory bowel disease who live in the United States, Canada and the Netherlands found a link between the participants' DNA and their gut bacteria DNA. The Crohn's and colitis patients also had less variety of gut bacteria and more opportunistic bacteria than the general population.

The findings are an important step in creating new drugs for the treatment of Crohn's and colitis, the researchers said.

The investigators also found that antibiotics can worsen the imbalances in intestinal bacteria associated with inflammatory bowel disease.

"In many cases, we're still learning how these bacteria influence our risk of disease, but understanding the human genetics component is a necessary step in unraveling the mystery," Knights said.

Previous research has identified associations between gut bacteria and increased risks for health problems such as diabetes, autism, heart disease and some types of cancer, the researchers said.

-- Robert Preidt

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Crohn's, Colitis May Have Genetic Underpinnings, Study Finds

This gene accounts for the size of the human brain and potentially our superior cognitive abilities

Scientists at A*STAR's Institute of Medical Biology (IMB) and Institute of Molecular and Cellular Biology (IMCB) have identified a genetic pathway that accounts for the extraordinary size of the human brain. The team led by Dr Bruno Reversade from A*STAR in Singapore, together with collaborators from Harvard Medical School, have identified a gene, KATNB1, as an essential component in a genetic pathway responsible for central nervous system development in humans and other animals.

By sequencing the genome of individuals of normal height but with a very small head size, the international team revealed that these individuals had mutations in the KATNB1 gene, indicating that this gene is important for proper human brain development. Microcephaly (literally meaning "small head" in Latin) is a condition often associated with neurodevelopmental disorders. Measured at birth by calculating the baby's head circumference, a diagnosis of microcephaly is given if it is smaller than average.

Microcephaly may stem from a variety of conditions that cause abnormal growth of the brain during gestation or degenerative processes after birth, all resulting in a small head circumference. In general, individuals with microcephaly have a reduced life expectancy due to reduced brain function which is often associated with mental retardation.

The team also carried out further experiments to determine the function of KATNB1, whose exact mode of action was previously unknown in humans. Using organisms specifically designed to lack this gene, they realised that KATNB1 is crucial for the brain to reach its correct size. Zebrafish and mice embryos without this gene could not live past a certain stage and showed dramatic reduction in brain and head size, similar to the human patients. Their results were published in the 17 December 2014 online issue of Neuron, the most influential journal in the field of Neuroscience.

Sequencing and screening for this particular gene before birth or at birth might also help to detect future neurocognitive problems in the general population. Dr Reversade said, "We will continue to search for other genes important for brain development as they may unlock some of the secrets explaining how we, humans, have evolved such cognitive abilities."

Prof Birgit Lane, Executive Director of IMB, said, "This is one of a small number of genes that scientists have found to be vital for brain development. The work is therefore an important advance in understanding the human brain. The team's findings provide a new platform from which to look further into whether - and how - this gene can be used for targeted therapeutic applications."

Prof Hong Wanjin, Executive Director of IMCB, said, "This coordinated effort shows the increasingly collaborative nature of science. As the complexity and interdisciplinary nature of research evolves, so do the networks of collaborations between research institutes at A*STAR and across continents."

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A*STAR scientists discover gene critical for proper brain development

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17-Dec-2014

Contact: George Hunka ghunka@aftau.org 212-742-9070 American Friends of Tel Aviv University @AFTAUnews

Premature ovarian failure, also known as primary ovarian insufficiency (POI), affects 1% of all women worldwide. In most cases, the exact cause of the condition, which is often associated with infertility, is difficult to determine.

A new Tel Aviv University study throws a spotlight on a previously-unidentified cause of POI: a unique mutation in a gene called SYCE1 that has not been previously associated with POI in humans. The research, published in the Journal of Clinical Endocrinology and Metabolism, was led by Dr. Liat de Vries and Prof. Lina Basel-Vanagaite of TAU's Sackler Faculty of Medicine and Schneider Children's Medical Center and conducted by a team of researchers from both TAU and Schneider.

While the genes involved in chromosome duplication and division had been shown to cause POI in animal models, this is the first time a similar mutation has been identified in humans.

A new insight

"Researchers know that POI may be associated with Turner's syndrome, a condition in which a woman has only one X chromosome instead of two, or could be due to toxins like chemotherapy and radiation therapy," said Dr. de Vries. "However, in 90% of the cases, the exact cause remains a mystery."

The idea for the study surfaced when Dr. de Vries was asked to treat two POI patients, daughters of two sets of Israeli-Arab parents who were related to each other. The girls presented with typical POI symptoms: one had the appearance of puberty but had not gotten her period, and the other one had not started puberty at all. After ruling out the usual suspects (toxins, autoimmune disease, and known chromosomal and genetic diseases), the researchers set out to identify the genetic cause of POI in the two young women.

"One of my main topics of interest is puberty," said Dr. de Vries. "The clinical presentation of the two sisters, out of 11 children of first-degree cousins, was interesting. In each of the girls, POI was expressed differently. One had reached puberty and was almost fully developed but didn't have menses. The second, 16 years old, showed no signs of development whatsoever."

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Genetic mutation found to cause ovarian failure

Alnylam Pharmaceuticals, Inc. ( ALNY ) announced its pipeline growth strategy for the development and commercialization of RNAi therapeutics across three strategic therapeutic areas (STArs) - genetic medicines, cardio-metabolic disease and hepatic infectious disease.

Alnylam's genetic medicine STAr consists of a broad pipeline of RNAi therapeutics including patisiran (phase III - APOLLO) and revusiran (phase III - ENDEAVOUR), being developed for the treatment of transthyretin-mediated amyloidosis. Additionally, the company reported positive initial data from a phase I study on ALN-AT3 last week.

The company is advancing ALN-AT3 for the treatment of hemophilia and rare bleeding disorders. Further, the company plans to initiate a phase I/II study on ALN-CC5 for paroxysmal nocturnal hemoglobinuria.

Meanwhile, Alnylam intends to commercialize its genetic medicine products in the U.S. and EU, while Genzyme, a Sanofi ( SNY ) company, will develop and commercialize in the rest of the world.

In its cardio-metabolic disease STAr, Alnylam recently initiated a phase I study on ALN-PCSsc (RNAi therapeutic targeting PCSK9 for the treatment of hypercholesterolemia) with initial data expected in mid-2015. Alnylam has an agreement with The Medicines Company ( MDCO ) for ALN-PCSsc. Alnylam is also advancing other candidates including ALN-AC3 (hypertriglyceridemia), ALN-ANG (hypertriglyceridemia and mixed hyperlipidemia) and ALN-AGT (hypertensive disorders of pregnancy including preeclampsia) among others.

Finally, Alnylam's hepatic infectious disease STAr includes ALN-HBV for the treatment of hepatitis B viral infection. The company intends to file an investigational new drug (IND) application or an IND equivalent in late 2015.

Alnylam is looking for partnerships for programs in its cardio-metabolic disease and hepatic infectious disease STArs. At the same time it intends to retain significant product commercialization rights in the U.S. and EU.

Alnylam expects to provide additional guidance on pipeline programs in its three STArs in Jan 2015. We expect investor focus to remain on Alnylam's pipeline.

Alnylam currently carries a Zacks Rank #2 (Buy). A better-ranked stock in the health care sector is Amgen Inc. ( AMGN ) carrying a Zacks Rank #1 (Strong Buy).

ALNYLAM PHARMA (ALNY): Free Stock Analysis Report

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Alnylam Provides Pipeline Update, Growth Strategy - Analyst Blog

By Bryan Grossman

Thanks to modern technology, genetic counselors in Colorado Springs now can meet with patients in Durango by two-way live audio/video conferencing. Patients in Durango who seek genetic counseling can schedule appointments with Penrose Cancer Center genetic counselors and meet with them virtually. Penrose is in partnership with Mercy Regional Medical Center.

Appointments physically take place at Mercy Family Medicines Three Springs and Horse Gulch locations in Durango, where a medical assistant sits down with the patient in the clinic room, initiates the video counseling session and introduces the patient. In Colorado Springs, a Penrose Cancer Center genetic counselor logs on simultaneously and meets with the patient as if it were an in-person appointment.

Prior to the start of this program, patients at MRMC didnt have access to local genetic counseling services, saidElena Strait, certified genetic counselor. This telemedicine program allows us to meet a need in a way that makes sense for MRMC patients. They are thrilled to receive this service without leaving home, and Durango medical providers appreciate having us as a resource for their patients.

Genetic counseling services include recording a detailed family history and using family history information to estimate the risk of developing cancer, estimate the risk of an inherited cancer, review the pros and cons of genetic testing and help patients decide if testing is appropriate, coordinate genetic testing, consider ways to screen for and prevent cancer based on risks and explore implications with family members

Genetic counseling is a program that Penrose Cancer Centers parent company, Centura Health, is excited to grow, according to a news release sent by Penrose. The goal is ultimately to involve genetic counselors at other hospitals in the network to reach additional outlying communities throughout Colorado and western Kansas. Centura isalso servicing other rural affiliate hospitals with telemedicine services for pulmonology, outpatient gastrointestinal clinic needs and tumor board consultations.

What is Telemedicine?

Formally defined, it is the use of medical information exchanged from one site to another via electronic communications to improve a patients clinical health status. It includes a growing variety of applications and services using two-way video, email, wireless tools and other forms of telecommunications.

Beginning40years ago with demonstrations of hospitals extending care to patients in remote areas, the use of telemedicine has spread rapidly and is now becoming integrated into the ongoing operations of hospitals, specialty departments, home health agencies, private physician offices as well as consumers homes and workplaces.

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Penrose offers genetic counseling via telemedicine

Bookshelf

A collection of biomedical books that can be searched directly or from linked data in other NCBI databases. The collection includes biomedical textbooks, other scientific titles, genetic resources such as GeneReviews, and NCBI help manuals.

A resource to provide a public, tracked record of reported relationships between human variation and observed health status with supporting evidence. Related information intheNIH Genetic Testing Registry (GTR),MedGen,Gene,OMIM,PubMedand other sources is accessible through hyperlinks on the records.

An archive and distribution center for the description and results of studies which investigate the interaction of genotype and phenotype. These studies include genome-wide association (GWAS), medical resequencing, molecular diagnostic assays, as well as association between genotype and non-clinical traits.

An open, publicly accessible platform where the HLA community can submit, edit, view, and exchange data related to the human major histocompatibility complex. It consists of an interactive Alignment Viewer for HLA and related genes, an MHC microsatellite database, a sequence interpretation site for Sequencing Based Typing (SBT), and a Primer/Probe database.

A searchable database of genes, focusing on genomes that have been completely sequenced and that have an active research community to contribute gene-specific data. Information includes nomenclature, chromosomal localization, gene products and their attributes (e.g., protein interactions), associated markers, phenotypes, interactions, and links to citations, sequences, variation details, maps, expression reports, homologs, protein domain content, and external databases.

A collection of expert-authored, peer-reviewed disease descriptions on the NCBI Bookshelf that apply genetic testing to the diagnosis, management, and genetic counseling of patients and families with specific inherited conditions.

Summaries of information for selected genetic disorders with discussions of the underlying mutation(s) and clinical features, as well as links to related databases and organizations.

A voluntary registry of genetic tests and laboratories, with detailed information about the tests such as what is measured and analytic and clinical validity. GTR also is a nexus for information about genetic conditions and provides context-specific links to a variety of resources, including practice guidelines, published literature, and genetic data/information. The initial scope of GTR includes single gene tests for Mendelian disorders, as well as arrays, panels and pharmacogenetic tests.

A database of known interactions of HIV-1 proteins with proteins from human hosts. It provides annotated bibliographies of published reports of protein interactions, with links to the corresponding PubMed records and sequence data.

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Genetics & Medicine - Site Guide - NCBI

By RTT News, December 12, 2014, 07:18:00 AM EDT

(RTTNews.com) - Alnylam Pharmaceuticals, Inc. ( ALNY ) announced its pipeline growth strategy for development and commercialization of RNAi therapeutics across three Strategic Therapeutic Areas, or STArs: Genetic Medicines, Cardio-metabolic Disease, and Hepatic Infectious Disease. The company said its strategic therapeutic areas will remain focused on liver-expressed and genetically validated or pathogen-derived disease targets, with biomarkers for assessment of clinical activity early in Phase 1 trials.

In Genetic Medicine STAr, Alnylam said it is advancing a broad pipeline of RNAi therapeutics for rare diseases. Across the Genetic Medicine STAr, Alnylam plans on commercializing its products through direct marketing and sales in the U.S. and EU, while leveraging its landmark partnership with Genzyme, a Sanofi company, for commercialization in the rest-of-world.

In Cardio-metabolic Disease STAr, Alnylam is advancing pipeline of RNAi therapeutics toward genetically validated, liver-expressed disease targets for unmet needs in dyslipidemias, hypertension, non-alcoholic steatohepatitis, and type 2 diabetes. The company intends to seek strategic partnership opportunities for programs in Cardio-metabolic Disease STAr, while retaining significant product commercialization rights in the U.S. and EU.

In Hepatic Infectious Disease STAr, Alnylam is advancing a pipeline of RNAi therapeutics that address major global health challenges, including hepatitis B virus and hepatitis D virus infections, amongst other hepatic infectious disease opportunities. The company intends to seek strategic partnership opportunities for programs in its Hepatic Infectious Disease STAr, while retaining significant product commercialization rights in the U.S. and EU.

For comments and feedback: contact editorial@rttnews.com

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Alnylam Pharma Announces Pipeline Growth Strategy For RNAi Therapeutics