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Newswise BIRMINGHAM, Ala. An international group co-led by University of Alabama at Birmingham researcher Mary MacDougall, Ph.D., has unraveled the molecular basis for the rare, inherited genetic disorder, Singleton-Merten Syndrome (SMS). Individuals with SMS develop extreme, life-threatening calcification of the aorta and heart valves, early-onset periodontitis and root resorption of the teeth, decreases in bone density, and loss of bone tissue at the tips of fingers and toes.

The cause of SMS is a missense mutation that changes a single amino acid in the protein MDA5 from arginine to glutamine, MacDougall and colleagues are reporting today (Jan. 22) in the online version of The American Journal of Human Genetics. That change in MDA5 which detects viral double-stranded RNA as part of the innate immunity system causes increased induction of interferon beta. Thus SMS is recognized as an innate autoimmune disease for the first time.

The autoimmunity finding was startling, said MacDougall, associate dean for research, James R. Rosen Chair of Dental Research, and professor in the Department of Oral and Maxillofacial Surgery at the UAB School of Dentistry, and director of UABs Global Center for Craniofacial, Oral and Dental Disorders. She and Frank Rutsch, M.D., Department of General Pediatrics, Muenster University Childrens Hospital, Germany, are co-first authors of the paper, A Specific IFIH1 Gain-of-function Mutation Causes Singleton-Merten Syndrome.

Because of the unusual dental problems in SMS patients, Rutsch had contacted MacDougall 10 years ago to probe the molecular mechanisms of the syndrome. MacDougall is an internationally respected research leader in craniofacial developmental biology and dental genetics, particularly the molecular basis and mechanisms associated with human dental genetic disorders that alter tooth number, formation and hard tissue structure. Such investigations of differentiation during tooth and bone formation have broad applications across medical research.

SMS is an autosomal-dominant disorder, meaning the mutation is not carried on the sex chromosomes, and a single copy of the mutation in the gene IFIH1 that encodes MDA5 can cause disease. Rutsch identified three SMS-affected families, and researchers in Cologne, Germany performed whole-exome DNA sequencing and targeted Sanger sequencing to identify the mutation. The same mutation was found in 10 different patients.

MacDougalls group at UAB analyzed the dental features of patients and created cell lines from SMS individuals and controls. Several of the dental pulp cell lines came from an extracted, forming third-molar that was shipped from Germany to Alabama by FedEx.

Functional studies by the UAB group found that: MDA5 as measured by immunohistochemistry of human heart, skin and cartilage tissue, or demineralized developing mouse teeth was present in all target tissues that are altered in SMS. Presence of the SMS- IFIH1 mutant gene increased interferon beta gene expression by 20-fold, and correcting the single mutation of the SMS-IFIH1 back to normal reduced expression to control levels. The SMS- IFIH1 mutant gene had a greater response, as measured by interferon beta induction, when challenged with double-stranded RNA, as compared with the normal gene. Whole blood of SMS individuals and the cell lines developed from the SMS tooth had higher expression of interferon signature genes, compared with control individuals and cells.

Thus, the altered gene is a gain-of-function mutation. Recently, IFIH1 has been linked to several autoimmune disorders, including Aicardi-Goutieres syndrome, though those individuals show brain and developmental defects.

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UAB Research Probes Molecular Basis of Rare Genetic Disorder

Among the problems people with Autism spectrum disorders (ASD) struggle with are difficulties with social behavior and communication. That can translate to an inability to make friends, engage in routine conversations, or pick up on the social cues that are second nature to most people. Similarly, in a mouse model of ASD, the animals, like humans, show little interest in interacting or socializing with other mice.

One drug, risperidone, works in both humans and mice with ASD to treat other symptoms of the disorder -- including repetitive behaviors--but no medication has been found to help socialization.

Now researchers at UCLA have treated ASD mice with a neuropeptide--molecules used by neurons to communicate with each other--called oxytocin, and have found that it restores normal social behavior. In addition, the findings suggest that giving oxytocin as early as possible in the animal's life leads to more lasting effects in adults and adolescents. This suggests there may be critical times for treatment that are better than others.

The study appears in the January 21 online edition of the journal Science Translational Medicine.

Mouse models of neuropsychiatric diseases provide a platform for understanding the mechanisms behind disorders and development of new therapies, noted Daniel Geschwind, a UCLA professor of psychiatry, neurology and human genetics, and senior author of the study. In 2011, Geschwind and his colleagues developed a mouse model for ASD by knocking out a gene called CNTNAP2 (contactin-associated protein-like 2), which scientists believe plays an important role in the brain circuits responsible for language and speech. Previous research has linked common CNTNAP2 variants to heightened autism risk in the general population, while rare variants can lead to an inherited form of autism called cortical dysplasia-focal epilepsy syndrome (CDFE).

It's known that the oxytocin is involved in regulating various aspects of social behavior. Among its other roles, oxytocin neurons in the brain's hypothalamus interact with several other brain regions, including the amygdala, hippocampus, and frontal cortex, where they influence such behaviors as fear, memory, and social behavior.

"The oxytocin system is a key mediator of social behavior in mammals, including humans, for maternal behavior, mother-infant bonding, and social memory," said Geschwind, who holds UCLA's Gordon and Virginia MacDonald Distinguished Chair in Human Genetics and is the director of the Center for Autism Research and Treatment at the Semel Institute for Neuroscience and Human Behavior at UCLA. "So it seemed like a natural target for us to go after."

In the ASD mice, the researchers found a decrease in the number of oxytocin neurons in the hypothalamus and, overall, a decrease in oxytocin levels throughout the brain. But when they administered oxytocin to the ASD mice, sociability, defined as time spent interacting normally with other mice, was restored. Then, using a second strategy, the researchers also found that by giving the mice melanocortin, an agonist (which binds to specific receptors on a cell to activate it) caused a natural release of oxytocin from brain cells, which also improved social deficits.

"The study shows that a primary deficit in oxytocin may cause the social problems in these mice, and that correcting this deficit can correct social behavior," said Geschwind. "We were surprised as well to discover a relationship between the cntnap2 protein and oxytocin--the absence of cntnap2 effected oxytocin neurons in the hypothalamus."

The biggest surprise, though, said Geschwind, was finding that early postnatal administration of the oxytocin led to longer positive effects upon social behavior when measured several weeks later. "This suggests that there may be critical windows of time for treatment that are better than others."

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Treatment restores sociability in autism mouse model

An international group co-led by University of Alabama at Birmingham researcher Mary MacDougall, Ph.D., has unraveled the molecular basis for the rare, inherited genetic disorder, Singleton-Merten Syndrome (SMS). Individuals with SMS develop extreme, life-threatening calcification of the aorta and heart valves, early-onset periodontitis and root resorption of the teeth, decreases in bone density, and loss of bone tissue at the tips of fingers and toes.

The cause of SMS is a missense mutation that changes a single amino acid in the protein MDA5 from arginine to glutamine, MacDougall and colleagues are reporting today (Jan. 22) in the online version of The American Journal of Human Genetics. That change in MDA5 -- which detects viral double-stranded RNA as part of the innate immunity system -- causes increased induction of interferon beta. Thus SMS is recognized as an innate autoimmune disease for the first time.

"The autoimmunity finding was startling," said MacDougall, associate dean for research, James R. Rosen Chair of Dental Research, and professor in the Department of Oral and Maxillofacial Surgery at the UAB School of Dentistry, and director of UAB's Global Center for Craniofacial, Oral and Dental Disorders. She and Frank Rutsch, M.D., Department of General Pediatrics, Muenster University Children's Hospital, Germany, are co-first authors of the paper, "A Specific IFIH1 Gain-of-function Mutation Causes Singleton-Merten Syndrome.

Because of the unusual dental problems in SMS patients, Rutsch had contacted MacDougall 10 years ago to probe the molecular mechanisms of the syndrome. MacDougall is an internationally respected research leader in craniofacial developmental biology and dental genetics, particularly the molecular basis and mechanisms associated with human dental genetic disorders that alter tooth number, formation and hard tissue structure. Such investigations of differentiation during tooth and bone formation have broad applications across medical research.

SMS is an autosomal-dominant disorder, meaning the mutation is not carried on the sex chromosomes, and a single copy of the mutation in the gene IFIH1 that encodes MDA5 can cause disease. Rutsch identified three SMS-affected families, and researchers in Cologne, Germany performed whole-exome DNA sequencing and targeted Sanger sequencing to identify the mutation. The same mutation was found in 10 different patients.

MacDougall's group at UAB analyzed the dental features of patients and created cell lines from SMS individuals and controls. Several of the dental pulp cell lines came from an extracted, forming third-molar that was shipped from Germany to Alabama by FedEx.

Functional studies by the UAB group found that: MDA5 -- as measured by immunohistochemistry of human heart, skin and cartilage tissue, or demineralized developing mouse teeth -- was present in all target tissues that are altered in SMS. Presence of the SMS- IFIH1 mutant gene increased interferon beta gene expression by 20-fold, and correcting the single mutation of the SMS-IFIH1 back to normal reduced expression to control levels. The SMS- IFIH1 mutant gene had a greater response, as measured by interferon beta induction, when challenged with double-stranded RNA, as compared with the normal gene. Whole blood of SMS individuals and the cell lines developed from the SMS tooth had higher expression of interferon signature genes, compared with control individuals and cells.

Thus, the altered gene is a gain-of-function mutation. Recently, IFIH1 has been linked to several autoimmune disorders, including Aicardi-Goutieres syndrome, though those individuals show brain and developmental defects.

The UAB research team included Changming Lu and Olga Mamaeva, research associates for the Institute of Oral Health Research in the UAB School of Dentistry, and Heidi Erlandsen, a former dental school instructor.

MacDougall is continuing SMS gene research at UAB, including probing the impact of its dysregulation of 30 genes that are involved in tooth formation and dentin mineralization; using it as a paradigm for patients with other diseases, such as periodontitis and aggressive periodontitis; screening glaucoma patients for the mutation, since early-onset glaucoma is one phenotype seen in some SMS individuals; and looking for altered microbiomes and oral biomes in SMS individuals.

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Research probes molecular basis of rare genetic disorder

Mary Lyon's research advanced the understanding of X-linked inherited diseases such as haemophilia. Photograph: Adrian Ford

Mary Lyon, who has died aged 89, was one of the foremost geneticists of the 20th century. She used the mouse as a powerful genetic tool to gain fundamental and profound insights into mammalian genetics and the genetic bases of disease.

Perhaps her greatest achievement was to propose in 1961 the theory of X chromosome inactivation, in which she suggested that one of the two X chromosomes in the cells of female mammals is randomly inactivated during early development. This process is now sometimes referred to as Lyonisation, and the theory has had a fundamental impact on research into mammalian genetics and human medical genetics.

Marys work greatly advanced the understanding of X-linked inherited diseases, including Duchenne muscular dystrophy and haemophilia, and explained why women who are carriers of these diseases can display symptoms. It was an early example of an epigenetic phenomenon, whereby changes in the expression of genes are caused not by alterations in the DNA itself but by non-genetic factors. The theory of X chromosome inactivation provided a compelling insight into the mechanisms of genetic regulation and Marys discovery still resonates with contemporary research into how genes are regulated as we develop and grow.

Born in Norwich, to Louise (nee Kirby), a schoolteacher, and Clifford Lyon, a civil servant working for the Inland Revenue, Mary was the eldest of three children. Because of her fathers job, the family moved around the country, to Yorkshire, then Birmingham, and, at the outbreak of the second world war, to Woking, Surrey. It was the prize that Mary won for an essay competition at King Edward VI grammar school in Birmingham, a set of books on wild flowers, birds and trees, that first sparked her interest in biology.

In 1943, she went on to read zoology, physiology and biochemistry at Girton College, Cambridge. Zoology was her main subject, but she became interested in the concept that genes underlie all embryological development, a relatively new idea at the time. Before 1948 women were not official members of the university, so Mary graduated in 1946 with a titular degree.

She began a PhD in genetics with the eminent geneticist and statistician Sir Ronald Fisher at Cambridge, but completed her research under the supervision of Douglas Falconer in Edinburgh, where she had access to better facilities. On completion of her PhD in 1950, she was offered a position in the group of Toby Carter at Edinburgh to conduct research into the genetic hazards of radiation.

In 1954, Carters group and Mary moved to the Medical Research Council Radiobiological Research Unit at Harwell, Oxfordshire. Reflecting wider concerns about the need to understand the mechanisms of radiation damage in the atomic era, a genetics division was established at MRC Harwell under the leadership of Carter, to assess genetic risks based on the incidence and types of genetic damage caused by radiation.Mary and her colleagues made significant contributions to our understanding of mutagenesis mechanisms. However, given Marys fascination with the genetic variants and anomalies that mutagenesis can produce, it seems inevitable now that she would establish an interest in the mouse mutants arising from these radiation studies.

It was her curiosity and fascination with the humble mouse and the extraordinary collection of mouse variants generated at Harwell that led her to the many discoveries that transformed our understanding of mammalian genetics. She recognised the advantages to biomedical science of cryopreservation of mouse mutants and strains; and the archive of frozen mouse embryos at Harwell, which provides such an important repository for biomedical science worldwide, is testament to her foresight.

Mary took over the stewardship of the genetics division from Carter in 1962. She stepped down in the mid-1980s, and officially retired in 1990, but continued to come to the unit several times a week to do academic work and to attend scientific lectures right up to 2012.

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Mary Lyon obituary

Norway's largest charitable foundation bestows cash prize for TAU cancer geneticist's research on cell survival and DNA stability

IMAGE:This is professor Yosef Shiloh of Tel Aviv University. view more

Credit: American Friends of Tel Aviv University (AFTAU)

Norway's largest charitable organization, the Olav Thon Foundation, which invests heavily in medical research, awarded its first international research award in the medical and natural sciences to Tel Aviv University's Prof. Yosef Shiloh and Prof. Judith Campisi of the Buck Institute for Research on Aging, California. The prize money, NOK 5,000,000 (approximately $660,000), was split between the two winners.

Prof. Shiloh, the Myers Professor of Cancer Genetics and Research Professor of the Israel Cancer Research Fund at TAU's Sackler School of Medicine, was recognized for his pioneering research on the mechanisms that maintain the survival of human cells and the stability of human genetic material.

A member of the Israel National Academy of Sciences and Humanities, Prof. Shiloh was a recipient of the prestigious Israel Prize (considered "Israel's Nobel") in Life Sciences in 2011, the 2011 American Association of Cancer Research G.H.A. Clowes Award, and the 2005 EMET Prize in Life Sciences.

"A prize means scientific recognition," said Prof. Shiloh. "Scientists do not work in order to get prizes or any other monetary benefits, but the award of a prize means that our work is recognized by our colleagues, and this is probably the true reward of a scientist."

Unraveling the genome

Prof. Shiloh has spent much of his career investigating the processes that maintain genome stability and the defense mechanisms against substances that damage our DNA. He has investigated how the harmful effects of such substances can be countered and offered insights into how mammalian cells react to DNA damage produced by environmental factors, such as radiation and carcinogenic chemicals.

According to the Foundation, "The laureates have provided us with new insights into the molecular basis of aging, aging-related diseases, and cellular degenerative processes."

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Tel Aviv University's professor Yosef Shiloh Receives first Olav Thon Foundation Prize

Scientists develop a computational method to estimate the importance of each letter in the human genome

Cold Spring Harbor, NY - There are 3 billion letters in the human genome, and scientists have endlessly debated how many of them serve a functional purpose. There are those letters that encode genes, our hereditary information, and those that provide instructions about how cells can use the genes. But those sequences are written with a comparative few of the vast number of DNA letters. Scientists have long debated how much of, or even if, the rest of our genome does anything, some going so far as to designate the part not devoted to encoding proteins as "junk DNA."

In work published today in Nature Genetics, researchers at Cold Spring Harbor Laboratory (CSHL) have developed a new computational method to identify which letters in the human genome are functionally important. Their computer program, called fitCons, harnesses the power of evolution, comparing changes in DNA letters across not just related species, but also between multiple individuals in a single species. The results provide a surprising picture of just how little of our genome has been "conserved" by Nature not only across species over eons of time, but also over the more recent time period during which humans differentiated from one another.

"In model organisms, like yeast or flies, scientists often generate mutations to determine which letters in a DNA sequence are needed for a particular gene to function," explains CSHL Professor Adam Siepel. "We can't do that with humans. But when you think about it, Nature has been doing a similar experiment on a very large scale as species evolve. Mutations occur across the genome at random, but important letters are retained by natural selection, while the rest are free to change with no adverse consequence to the organism."

It was this idea that became the basis of their analysis, but it alone wasn't enough. "Massive research consortia, like the ENCODE Project, have provided the scientific community with a trove of information about genomic function over the last few years," says Siepel. "Other groups have sequenced large numbers of humans and nonhuman primates. For the first time, these big data sets give us both a broad and exceptionally detailed picture of both biochemical activity along the genome and how DNA sequences have changed over time."

Siepel's team began by sorting ENCODE consortium data based on combinations of biochemical markers that indicate the type of activity at each position. "We didn't just use sequence patterns. ENCODE provided us with information about where along the full genome DNA is read and how it is modified with biochemical tags," says Brad Gulko, a Ph.D. student in Computer Science at Cornell University and lead author on the new paper. The combinations of these tags revealed several hundred different classes of sites within the genome each having a potentially different role in genomic activity.

The researchers then turned to their previously developed computational method, called INSIGHT, to analyze how much the sequences in these classes had varied over both short and long periods of evolutionary time. "Usually, this, kind of analysis is done comparing different species - like humans, dogs, and mice - which means researchers are looking at changes that occurred over relatively long time periods," explains Siepel. But the INSIGHT model considers the changes among dozens of human individuals and close relatives, such as the chimpanzee, which provides a picture of evolution over much shorter time frames.

The scientists found that, at most, only about 7% of the letters in the human genome are functionally important. "We were impressed with how low that number is," says Siepel. "Some analyses of the ENCODE data alone have argued that upwards of 80% of the genome is functional, but our evolutionary analysis suggests that isn't the case." He added, "other researchers have estimated that similarly small fractions of the genome have been conserved over long time evolutionary periods, but our analysis indicates that the much larger ENCODE-based estimates can't be explained by gains of new functional sequences on the human lineage. We think most of the sequences designated as 'biochemically active' by ENCODE are probably not evolutionarily important in humans."

According to Siepel, this analysis will allow researchers to isolate functionally important sequences in diseases much more rapidly. Most genome-wide studies implicate massive regions, containing tens of thousands of letters, associated with disease. "Our analysis helps to pinpoint which letters in these sequences are likely to be functional because they are both biochemically active and have been preserved by evolution." says Siepel. "This provides a powerful resource as scientists work to understand the genetic basis of disease."

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Harnessing data from Nature's great evolutionary experiment

Striving to unravel and comprehend DNAs biological significance, Cornell scientists have created a new computational method that can identify positions in the human genome that play a role in the proper functioning of cells, according to a report published Jan. 19 in the journal Nature Genetics.

The human genome is vast, totaling some three billion base pairs of nucleotides, the subunits of DNA. But only about 1.25 percent of those billions of base pairs account for genes that encode all the proteins we use. A fraction of the rest of that genetic material regulates genes and turns them on and off, but these have yet to be fully identified.

This paper tackles the deep question of how to identify functional non-coding human genomic material controlling human traits and disease, said Brad Gulko, the papers first author and a graduate student in the field of computer science. Gulkos adviser, Adam Siepel, Cornell associate professor of biological statistics and computational biology and professor of computer science at Cold Spring Harbor Laboratory, is a co-author.

What makes our approach unique is the straightforward combination of DNA biochemistry with recent evolutionary pressures," said Gulko. "Our method allows other scientists not only to use the results, but to readily understand them.

Insight into the human genome gained from this new computation method could be applied to personalized medicine and it may be a big step toward developing treatments for diseases like AIDS, malaria, muscular sclerosis, ALS and Alzheimers.

Geneticists identify biologically significant DNA by looking for signals of selective pressure in DNA, genes and genetic material that give individuals in a population advantages and greater fitness, or reproductive success.

The new method combines two previously used techniques to identify selective pressure. One technique looks for divergence, or differences between humans and chimpanzee genomes accumulated over millions of years; a less commonly used method looks for mutations in DNA (polymorphisms) between individual humans.

The new computational method clusters functionally similar markers in the genome into groups, then estimates a probability of whether a group is contributing to the fitness of the species based on associated patterns of divergence and genomic polymorphisms.

In this way, the researchers receive a fitness consequence (fitCons) score that predicts which genetic material might be under selective pressure and therefore biologically significant.

Compared to conventional techniques, fitCons scores demonstrate a much greater power to predict which genetic material regulates the expression of genes.

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New computation method helps identify functional DNA

20.01.2015 - (idw) Universittsklinikum Heidelberg

A gene that influences the communication between nerve cells has a higher mutation rate in schizophrenia patients than in healthy individuals / Previously unknown gene mutations show a functional effect in nerve cells / Parallels between genetic alterations in patients with schizophrenia and autism / Scientists from Heidelberg publish in Molecular Psychiatry Researchers from Heidelberg University Hospital have identified 10 previously unknown genetic alterations (mutations) in schizophrenia patients. The affected gene defines the blueprint for a scaffolding protein, the SHANK2 protein, which plays a determinant role in the structures connecting nerve cells (neurons). These 10 gene variants represent risk factors for schizophrenia, said Prof. Dr. Gudrun Rappold, head of the Department of Molecular Human Genetics at Heidelberg University Hospital and senior author of the article. The alterations have only been found in schizophrenia patients and are not in any healthy individuals. Mutations that are not found in healthy people could have a direct effect on the disease says Dr. Slavil Peykov, researcher and first author of the study. The results have recently been published in the renowned scientific journal Molecular Psychiatry.

The protein SHANK2 is already known to Professor Rappolds research department from another standpoint: in 2010, they identified several alterations in the SHANK2 gene in patients with autism disorders and intellectual disability. The recently identified mutations in schizophrenia patients reside in the same gene but their positions, and thus their detrimental effect, differ from those previously found in autism. Modifications in one gene can lead to very diverse neurobiological disorders, such as autism, intellectual disability or schizophrenia. Apparently the exact nature and position of the alteration influences the resulting neuropsychiatric disease and the gravity of the symptoms explains Prof. Rappold. In the study, experiments with neurons revealed that these mutations alter the connections between neurons (synapses) to varying degrees, in such a way that the communication between these cells is affected.

One percent of the worlds population suffers from schizophrenia

Worldwide, approximately 1% of the population is afflicted with schizophrenia. The disease most commonly develops in early adulthood. The affected patients can rarely lead normal, independent lives without treatment, ranging from needing help with everyday tasks to a complete loss of social and professional functioning. Schizophrenia is classified as a disorder of perception; typical symptoms are delusions and hallucinations, though symptoms and their severity vary from patient to patient. These individuals are also more likely to suffer from other disorders than the general population, such as speech deficits, addiction and depression. The exact causes and triggers of schizophrenia remain to date unknown.

In the most recently published study, the SHANK2 gene was investigated in DNA from 481 affected patients and 659 healthy controls, in collaboration with Professor Marcella Rietschel, Department of Genetic Epidemiology, Central Institute of Mental Health in Mannheim and Professor Markus Noethen, Institute of Human Genetics at the University of Bonn. Approximately twice as many genetic alterations were found in patients with schizophrenia compared to people with no psychiatric disorders. The onset of disease is likely prompted only when further factors are also present, for example, certain environmental risk factors, explains human geneticist Prof. Rappold.

Early diagnosis is paramount to a satisfactory quality of life for the patient; the earlier a patient is treated, both pharmacologically and socially, the less likely they are to relapse and develop further disorders. Therefore, our understanding of the genetic causes of this disorder could, in the future, help doctors distinguish individual patient groups suffering from similar disease courses, and consequently individualize treatment options explains Prof. Rappold. If scientists could find exactly which molecules in which molecular networks are faulty in the brain, precise therapies for that particular disease progression could be developed. For example, in the aforementioned 481 schizophrenia patients, 4 non-related patients were found to have an identical SHANK2 mutation. All four patients developed schizophrenia at similar time points and with similar symptoms. If one mutation could lead to a similar set of symptoms and one treatment could correct the consequences of that mutation, the genetic screening for this mutation in potential candidates could very much improve their treatment plan. The close relationship between geneticists, neurobiologists and clinicians should now lead to a better diagnosis and to the identification of knowledge based treatments.

Contact for journalists: Professor Dr. rer. nat. Gudrun A. Rappold Abteilung Molekulare Humangenetik Institut fr Humangenetik Universittsklinikum Heidelberg Tel.: 06221 / 56 50 59 E-Mail: Gudrun.Rappold@med.uni-heidelberg.de

Heidelberg University Hospital and Medical Faculty: Internationally recognized patient care, research, and teaching

Heidelberg University Hospital is one of the largest and most prestigious medical centers in Germany. The Medical Faculty of Heidelberg University belongs to the internationally most renowned biomedical research institutions in Europe. Both institutions have the common goal of developing new therapies and implementing them rapidly for patients. With about 12,600 employees, training and qualification is an important issue. Every year, around 66,000 patients are treated on a fully or partially inpatient basis and over 1,000,000 patients have been treated on an outpatient basis in more than 50 clinics and departments with 1,900 beds. Currently, about 3,500 future physicians are studying in Heidelberg; the reform Heidelberg Curriculum Medicinale (HeiCuMed) is one of the top medical training programs in Germany. Weitere Informationen:http://www.klinikum.uni-heidelberg.de/Abt-Molekulare-Humangenetik.6096.0.html Department of Molecular Human Genetics

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Schizophrenia: genetic alterations linked to functional changes in nerve cells

The study of the Caernorhabditis elegans worm will aid researchers understanding of the genetics of human disease, whilst reducing the need for animal testing

IMAGE:Dr Tarja Kinnunen will study the benefits of the worm, named Caernorhabditis elegans or C. elegans, which will offer a better understanding of the genetic basis for many human diseases... view more

Credit: University of Huddersfield

THE study of tiny worms that are barely visible to the naked eye could lead to new treatments for ailments such as kidney disease and to the development of drugs designed to slow down the effects of ageing on human health.

Now, a University of Huddersfield scientist has received major funding that will enable her to develop her work in this field and to recruit and train a new researcher.

Also, Dr Tarja Kinnunen is poised to deliver a free public lecture (January 21) that will describe the benefits of studying the worm, named Caernorhabditis elegans or C. elegans. These include a better understanding of the genetic basis for many human diseases.

Another advantage is that by using the worms for fundamental scientific discoveries, the need to carry out research using animals such as rodents and primates can be greatly reduced. This factor has led to Dr Kinnunen being awarded 90,000 doctoral training studentship by the National Centre for the Refinement and Reduction of Animals in Research (NC3RS).

The money will enable the appointment of a new doctoral student, supervised by Dr Kinnunen, who will use C. elegans in order to understand the important role played by a recently-discovered protein molecule named Klotho on physiology, including the effects of ageing.

Research involving animals

Most research into Klotho involves animals. But Dr Kinnunen and her researchers, via genetics and microscopy, use the worms, which are about a millimetre in length. It was almost 50 years ago that the Cambridge-based geneticist Sydney Brenner pioneered the use of C. elegans as an organism that was ideal for experiments, enabling scientists to link genetic analysis to animal development, following the process under the microscope. Since then, three Nobel prizes have been won by scientists who deployed C. elegans in their research.

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90,000 research project of tiny garden compost worms for new research on human diseases

Annunaki, Elohim and Human Genetics: Basis, Bias, or BS? Please Share!
This video covers the HARD SCIENCE behind the properties observed in DNA and various aspects of the Origins of Life. We will cover various concepts of geneti...

By: Cullen Smith Lifting The Veil

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Annunaki, Elohim and Human Genetics: Basis, Bias, or BS? Please Share! - Video

Largest genome-wide study of parasite provides clearest picture yet of genetic changes driving artemisinin resistance

The largest genome-wide association study to date of the malaria parasite Plasmodium falciparum unveils a complex genetic architecture that enables the parasite to develop resistance to our most effective antimalarial drug, artemisinin. The results could help to improve early detection of emerging artemisinin resistance.

The global research collaboration analysed 1612 samples from 15 locations in Southeast Asia and Africa finding 20 mutations in the kelch13 gene, a known artemisinin resistance marker, that appear to work in concert with a set of background mutations in four other genes to support artemisinin resistance.

"Our findings suggest that these background mutations emerged with limited impact on artemisinin resistance -- until mutations occurred in the kelch13 gene," explains Dr Roberto Amato, a first author and Research Associate in Statistical Genomics at the Wellcome Trust Sanger Institute and Oxford University's Wellcome Trust Centre for Human Genetics. "It's similar to what we see with pre-cancerous cells which accumulate genetic changes but only become malignant when they acquire critical driver mutations that kick-off growth."

The variety of kelch13 mutations associated with artemisinin resistance, with new variants continually emerging, makes it difficult to use this gene alone as a marker for genetic surveillance.

Monitoring parasite populations for a specific genetic background - in this case, a fixed set of four well-defined mutations in the fd, arps10, mdr2, and crt genes - could allow researchers to assess the likelihood of new resistance-causing mutations emerging in different locations, helping to target high-risk regions even before resistant parasites take hold.

"We are at a pivotal point for malaria control. While malaria deaths have been halved, this progress is at risk if artemisinin ceases to be effective," says Nick Day, Director of the Mahidol-Oxford Tropical Medicine Research Unit (MORU) in Bangkok, Thailand. "We need to use every tool at our disposal to protect this drug. Monitoring parasites for background mutations could provide an early warning system to identify areas at risk for artemisinin resistance."

Researchers also uncovered new clues about how artemisinin resistance has evolved in Southeast Asia. By comparing parasites from Cambodia, Vietnam, Laos, Thailand, Myanmar and Bangladesh, scientists found that the distribution of different kelch13 mutations are localised within relatively well-defined geographical areas.

Whilst artemisinin resistant parasites do appear to have migrated across national borders, this only happened on a limited scale and, in fact, the most widespread kelch13 mutation, C580Y, appeared to have emerged independently on several occasions. Notably parasites along the Thailand-Myanmar border appear to have acquired this mutation separately from those in Cambodia and Vietnam. Crucially, parasite populations in both regions possess the genetic background mutations, even though they are clearly genetically distinct.

There remain many unanswered questions. "We don't yet know the role of these background mutations," says Dr Olivo Miotto, a first author and Senior Informatics Fellow at MORU and the Centre for Genomics and Global Health. "Some may not affect drug resistance directly, but rather provide an environment where drug resistance mutations are tolerated. Since kelch13 has hardly changed in 50 million years of Plasmodium evolution, we can assume that this gene is essential to parasite survival. Therefore, kelch13 mutations may severely handicap mutant parasites, compromising their survival unless some other change can counteract this negative effect."

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Genetics underpinning antimalarial drug resistance revealed

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Newswise ANN ARBOR, Mich. A new analysis opens the door to discovery of thousands of potential new cancer biomarkers.

Researchers at the University of Michigan Comprehensive Cancer Center analyzed the global landscape of a portion of the genome that has not been previously well-explored long non-coding RNAs. This vast portion of the human genome has been considered the dark matter because so little is known about it. Emerging new evidence suggests that lncRNAs may play a role in cancer and that understanding them better could lead to new potential targets for improving cancer diagnosis, prognosis or treatment.

We know about protein-coding genes, but that represents only 1-2 percent of the genome. Much less is known about the biology of the non-coding genome in terms of how it might function in a human disease like cancer, says senior study author Arul M. Chinnaiyan, M.D., Ph.D., director of the Michigan Center for Translational Pathology and S.P. Hicks Professor of Pathology at the University of Michigan Medical School.

The researchers pulled together 25 independent datasets totaling 7,256 RNA sequencing samples. The data was from public sources such as The Cancer Genome Atlas project, as well as from the Michigan Center for Translational Pathologys archives. They applied high-throughput RNA sequencing technology to identify more than 58,000 lncRNA genes across normal tissue and a range of common cancer types.

Results of the study appear online in Nature Genetics.

We used all of this data to decipher what the genomic landscape looks like in different tissues as well as in cancer, Chinnaiyan says. This opens up a Pandoras box of all kinds of lncRNAs to investigate for biomarker potential.

The complete dataset, named the MiTranscriptome compendium, has been made available on a public website, http://www.mitranscriptome.org, for the scientific community to explore.

The researchers also identified one lncRNA, SChLAP1, as a potential biomarker for aggressive prostate cancer. SChLAP1 was more highly expressed in metastatic prostate cancer than in early stage disease. SChLAP1 was found primarily in prostate cancer cells, not in other cancers or normal cells, which gives researchers hope that a non-invasive test could be developed to detect SChLAP1. Such a test could be used to help patients and their doctors make treatment decisions for early stage prostate cancer.

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Researchers Open 'Pandora's Box' of Potential Cancer Biomarkers

DCDC14 | The Human Genetics Historical Library: collecting for the future
Karen Pierce, Cardiff University Discovering Collections, Discovering Communities 2014 was a collaborative conference hosted by The National Archives and Research Libraries UK, in partnership...

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DCDC14 | The Human Genetics Historical Library: collecting for the future - Video

NVIDIA GPUshave been used to uncover the inner workings of the human genome, finding that it works in folds in the same way as origami.

Researchers from Baylor College of Medicine, Rice University, MIT and Harvard University said they used the graphics processors to map in unprecedented detail how the human genome folds.

This new information might provide new clues for cell function as well as new approaches to combat cancer and other complex diseases, Nvidia said.

Led by Erez Aiden, assistant professor of genetics at Baylor and assistant professor of computer science and computational and applied mathematics at Rice, the project found that the human genome is folded into around 10,000 loops.

These loops form when two widely separated bits of DNA come into contact in the folded version of the genome in a cell's nucleus.

The researchers learned that these loops and other genome folding patterns are an essential part of genetic regulation.

Genes can be switched on or off just by folding the genome into different shapes, allowing cells to take on a wide range of functions.

The research team relied on high-performance computer clusters and custom algorithms via the Nvidia GPUs to analyse large quantities of genome data.

"We faced a real challenge because we were asking how each of the millions of pieces of DNA in the database interact with each of the other millions of pieces," said Miriam Huntley, a doctoral student at Harvard's School of Engineering and Applied Sciences.

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Nvidia GPUs could help combat cancer in human genome research

Largest study to date of rare genetic variants and asthma risk finds few associations

Despite a strong suspected link between genetics and asthma, commonly found genetic mutations account for only a small part of the risk for developing the disease - a problem known as missing heritability.

Rare and low frequency genetic mutations have been thought to explain missing heritability, but it appears they are unlikely to play a major role, according to a new study led by scientists from the University of Chicago. Analyzing the coding regions of genomes of more than 11,000 individuals, they identified mutations in just three genes that were associated with asthma risk. Each was associated with risk in specific ethnicities. Their findings, published in Nature Communications on Jan. 16, suggest gaps in the current understanding of asthma genetics.

"Previous studies have likely overestimated the heritability of asthma," said study senior author Carole Ober, PhD, Blum-Riese Professor and chair of the Department of Human Genetics at the University of Chicago. "This could be because those estimates are based on correlations between family members that share environment as well as genes, which could inflate the heritability. Gene-environment interactions are not considered in these large scale association studies, and we know that these are particularly important in establishing individual risks for asthma."

Asthma affects more than 25 million adults and children of all ages and ethnicities in the US. Due to the widespread nature of the disease, most studies of its genetic underpinnings have focused on commonly occurring mutations, referred to as genetic variants. However, while numerous such variants have been identified, they are able to account for only a small proportion of the risk for inheriting or developing asthma. Rare mutations, found in less than five percent of the population, have been hypothesized to explain this disparity.

Graduate student Catherine Igartua led the analysis under the supervision of co-senior author Dan Nicolae, PhD, Professor in the Departments of Medicine, Statistics and Human Genetics. She evaluated nearly 33,000 rare or low frequency mutations in more than 11,000 individuals of a variety of ethnicities representing European, African and Latino backgrounds. She analyzed mutations jointly across subjects, using a technique that allowed them to study mutations common in one ethnicity, but rare in others.

Only mutations in the genes GRASP, GSDMB and MTHFR showed a statistical link to asthma risk. Mutations in the first two genes were found primarily in Latino individuals, and mutations in the last gene in those with African ancestry. These genes, involved in protein scaffolding, apoptosis regulation and vitamin B9 metabolism respectively, have as yet unknown roles in asthma. The rarity and ethnic-specificity of these genes is insufficient to account for the widespread prevalence of asthma.

Although rare mutations might not contribute much to population asthma risk, these genes still have the potential to serve as targets for therapeutic development. Ober points to the discovery of rare mutations in the LDL receptor that eventually led to the development of statins to treat high cholesterol. She also notes that it is possible, but unlikely, that there are mutations with large effects on asthma risk outside of their screen as it looked at approximate 60 percent of mutations in coding regions of the genome.

"It was assumed that there would be rare mutations with larger effect sizes than the common variants we have been studying," Ober said. "Surprisingly, we found that low frequency mutations explain only a very small amount of asthma risk."

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Rare mutations do not explain 'missing heritability' in asthma

HOUSTON -- (Jan. 15, 2015) - Alteration of lipid metabolism in brain cells promotes the formation of lipid droplets that presage the loss of neurons, said researchers from Baylor College of Medicine and the Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital in a report that appears online in the journal Cell.

Neuroscience graduate student Lucy Liu, and Dr. Hugo Bellen, professor of molecular and human genetics, neuroscience, a Howard Hughes Medical Institute investigator and director of the Graduate Program in Developmental Biology at Baylor connected the presence of lipid droplet accumulation in the glia of specific mutants as a harbinger of neurodegeneration.

Fruit fly genetics

The Bellen lab uses fruit fly mutants of evolutionarily conserved genes that lead to neurodegeneration in human patients to dissect the molecular mechanisms that underlie the demise of neurons. The fruit flies carry mutations in genes that have human homologs that cause Leigh syndrome, Charcot-Marie-Tooth type 2A2 and ARSAL (autosomal recessive spastic ataxia with leukoencephalopathy). All of these mutations affect the function of the mitochondria, the powerhouse of the cell.

Lipid droplets and energy

Lipid droplets are organelles that serve as energy storage depots. They accumulate in the brain support cells (glia) when defects in the mitochondria of neurons lead to elevated levels of reactive oxygen species (ROS). Working with three independent fruit fly models and a mouse model, Liu et al., revealed a novel pathway leading to this accumulation through the inappropriate activation of two proteins: c-Jun-N-terminal Kinase (JNK) and Sterol Regulatory Element Binding Protein (SREBP). These lipid droplets accumulate in glial cells before signs of neurodegeneration appeared.

"This is the first documentation of lipid droplet accumulation in glial cell" said Liu, first author of the study. The authors show that elevated reactive oxygen species in the neurons promotes synthesis of lipids leading to the formation of lipid droplets in glia. This accumulation affects the glia's ability to support the neurons when the lipid droplets become peroxidated, completing a negative feedback loop.

Not enough for neurodegeneration

"ROS or lipid droplets alone do not lead to the rapid onset of neurodegeneration," said Bellen, senior author on the study. "The synergism of ROS with lipid droplets is key. Reducing one or the other delays neurodegeneration."

Upon further investigation, Liu and her colleagues showed that reducing many of the components of this pathway can delay neurodegeneration. For example, treatments with a blood-brain-barrier penetrating antioxidant delay the onset of neurodegeneration in flies and mice developed by their collaborator Dr. Albert Quintana at University of Washington in Seattle.

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Baylor College of Medicine scientist identify a novel precursor to neurodegeneration

Kansas City, Mo. -- January 15, 2015 -- A new study published in the American Journal of Human Genetics demonstrates the continued important contributions from the Center for Pediatric Genomic Medicine at Children's Mercy Hospital in Kansas City, Mo. The study describes a new pediatric mitochondrial syndrome and discovery of the responsible gene, called CLPB. Dr. Carol Saunders and her team partnered with collaborators in Denmark to report their collective findings based on gene mapping and exome sequencing in five children with CLPB-related disease. These patients had strikingly similar clinical findings including cataracts, severe psychomotor regression during febrile episodes, epilepsy, neutropenia with frequent infections, urinary excretion of 3-methylglutaconic aciduria, and death in early childhood.

"This research once again highlights the power of genomic medicine in the diagnosis and discovery of rare pediatric conditions," said Saunders, clinical laboratory director of the Center for Pediatric Genomic Medicine "In this case, we have identified one of the many genes, CLPB, involved in mitochondrial diseases. These findings emphasize the importance of basic research into the characterization of human CPLB gene function and will pave the way for the diagnosis of other patients."

The Center for Pediatric Genomic Medicine at Children's Mercy was the first genome center in the world inside a children's hospital, and the center's STAT-Seq test for critically ill newborns was one of TIME magazine's Top 10 Medical Breakthroughs of 2012. Learn more at http://www.childrensmercy.org/genomics.

About Children's Mercy Kansas City

Children's Mercy, located in Kansas City, Mo., is one of the nation's top pediatric medical centers. The 354-bed, not-for-profit hospital provides care for children from birth through the age of 21, and has been ranked by U.S. News & World Report as one of "America's Best Children's Hospitals." For the third time in a row, Children's Mercy has achieved Magnet nursing designation, awarded to fewer than seven percent of all hospitals nationally, for excellence in quality care. Its faculty of 600 pediatricians and researchers across more than 40 subspecialties are actively involved in clinical care, pediatric research, and educating the next generation of pediatric subspecialists.

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FOR INTERVIEWS WITH DR. CAROL SAUNDERS, CONTACT JAKE JACOBSON AT JAJACOBSON@CMH.EDU

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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Discovery of CLPB gene associated with a new pediatric mitochondrial syndrome

Software and silicon are sometimes the poor relations of the science world, their advances eclipsed by more glamorous breakthroughs in physics, genetics, and space exploration. Progress in AI and robotics, in particular, is often greeted with as much with trepidation as praise. Yet some amazing leaps were made in 2014 alone, from a robotic hand which an amputee can "feel" to a realistic virtual universe.

Here's our nine best new advances:

In April, electronic artist Squarepusher released an EP called Music for Robots, which was played by actual robots with musical superpowers. The guitarist of Z-machines, Mach, plays two guitars with the aid of 78 fingers and 12 picks. Cosmos triggers notes on his keyboard with lasers and drummer Ashura uses his six arms to wield 21 drumsticks. Z-Machines were created at the University of Tokyo by CGI artist Yoichiro Kawaguchi, robotics engineer Naofumi Yonetsuka, and media artist Kenjiro Matsuo.

Squarepushers objective was to see if robot musicians could play emotionally engaging music. "Part of what interests me is when we listen to a robot, do we listen to it as if we're listening to a human?" he said. "I wasn't trying to make it emulate a human being, but I was trying to make it do something which I wanted to hear. Now the question remains, is the thing which I want to hear a human being?"

Chips inspired by the billions of neurons in the human brain made a splash this year. Current hardware architectures separate computation and storage of information and operate sequentially, limiting the amount of data which can be processed and synthesized. So neuromorphic chips integrate data storage and processing and can operate in parallel, mimicking the way the human brain processes sensory information like images and sound in a massively parallel manner. Such chips could recognize patterns in large amounts of data more efficiently than current linear or "left-brained" architectures.

IBM announced in August that it had packed the largest number of chips ever on to its latest chip, the TrueNorth processor. Powered by a million artificial neurons and 256 million synapses (in the brain a synapse allows electrical charge to pass between neurons) the chip is laid out in a network of 4,096 neurosynaptic cores which integrate memory and computation and operate in parallel in an event-driven fashion. TrueNorth uses a mere 70 milliwatts in operation, giving it a power density (power consumption per cm2) 10,000 lower than most microprocessors. This allows it to efficiently perform power-hungry tasks like detecting and classifying objects in a video stream.

In June, a chatbot program called Eugene Goostman persuaded 33% of human interrogators that it was actually a 13-year-old boy, making it the first piece of software to pass the Turing test. Alan Turing predicted in a 1950 paper that by the year 2000 a computer would play the imitation game well enough that "an average interrogator will not have more than 70% chance of making the right identification after five minutes of questioning." Developers Vladimir Veselov and Eugene Demchenko gave Eugene the personality of a teenage Ukrainian boy in order to make gaps in his knowledge seem more plausible.

In October Australian researchers claimed a quantum computing breakthrough when they created two new types of quantum bit, or "qubit". A bit is always in one of two states0 or 1 while a qubit can be in superpositions, i.e., in both of its possible states at once. Once a qubit is measured, however, it has one known state. A quantum computer maintains a sequence of qubits which can be in every possible combination of 1s and 0s at once, giving it the potential to perform complex calculations exponentially faster than classical computers.

The first type of qubit created by the researchers exploits an atom made of phosphorous, which achieved 99.99% accuracy in quantum operations, while the second relies on an artificial atom made of conventional silicon transistors. Both qubits were housed in a very thin layer of silicon from which magnetic isotopes had been removed to eliminate noise in the quantum calculations. (Quantum states are very fragile and prone to interference, a fact that has proved to be one of the major obstacles to the development of a practical quantum computer.) The team also set a new world record by preserving a quantum state for a full 35 seconds.

In September Akamai announced that the average global Internet connection speed had smashed the 4 megabit-per-second broadband threshold for the first time, hitting 4.6 Mbps during the second quarter of 2014. The global average peak connection speed also increased 20% to 25.4 Mbps between the first and second quarter of 2014.

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9 Things Computers Can Do Now That They Couldn't Do A Year Ago

An international research team finds a link between retinal degeneration and lipid metabolism

IMAGE:Dr. Robert Koenekoop examines a child's eyes and vision at the McGill Ocular Genetics Laboratory. view more

Credit: McGill University Health Centre

This news release is available in French.

Finding genes for retinal degenerations has immediate benefits for people living with blindness and vision loss, their families, and their physicians. Establishing a genetic cause confirms the clinical diagnosis at the molecular level, helps predict the future visual prognosis, suggests therapies, and allows some patients to join clinical trials. While more than 200 genes for retinal degenerations have been identified, approximately 40-50% of cases remain a mystery.

When 11 year old Naomi Lalandec walked into Dr. Robert Koenekoop's clinic at the Montreal Children's Hospital of the McGill University Health Centre (MUHC) with blindness and dwarfism due to Oliver McFarlane Syndrome (OMS), her unknown mutation sparked an international gene hunt. Comparing her genome to others with OMS and Leber congenital amaurosis (LCA), another form of childhood blindness, uncovered a new gene that is critical for vision. What makes this breakthrough exceptional is that it opens up new treatment avenues for OMS and LCA and potentially other retinal degenerative diseases.

"It was like finding a needle in a haystack," said Dr. Koenekoop, who is also a researcher at the Research Institute of the MUHC and a Professor of Human Genetics, Paediatric Surgery and Ophthalmology at McGill University. "It was so obvious to all of us that this was big; a new gene, a possible new disease pathway, a new treatment avenue." With ongoing support from the Foundation Fighting Blindness (FFB), Canada's largest charity supporting vision research, Dr. Koenekoop has spent more than a decade searching for genes linked to blindness. This search brought together an international team of scientists, including Dr. Michel Cayouette at the Institut de recherches cliniques de Montral (IRCM), Dr. Doris Kretzschmar at the Oregon Health and Science University, Dr. Jacek Majewski from the McGill University and Gnome Qubec Innovation Centre and more than 30 others from around the world. Together, the team identified mutations in the PNPLA6 gene in families with retinal degeneration. This is the 20th gene associated with LCA and the first associated with OMS.

Although we've known about the PNLPA6 gene for more than 45 years, no one had identified that mutations in this gene can lead to retinal degeneration - until now. To better understand the role of this gene, the team studied how it functions in fruit flies. They learned that the PNPLA6 gene is expressed and located in photoreceptors (which are the light-sensing cells in the eye) and that mutating the gene causes photoreceptors to die.

To determine what PNPLA6 was doing in photoreceptors, the team did a variety of experiments. They observed that some lipids were elevated in fruit flies with the PNPLA6 mutation, which led them to conclude that PNPLA6 affects phospholipid metabolism. Phospholipids are located in our cell membranes where they influence the membrane's shape and functioning. They also influence how cells communicate with each other by determining the signals that are able to pass through cell membranes. When phospholipids stop doing what they are supposed to do, important signals get lost and cells can no longer maintain their structures or respond to their environment.

This novel insight about the role of phospholipid metabolism in photoreceptor biology paves the way for new sight-saving treatments. These potentially game-changing results were published on January 9, 2015 in the prestigious journal Nature Communications.

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Genetic discovery about childhood blindness paves the way for new treatments

By RTT News, January 12, 2015, 08:18:00 AM EDT

(RTTNews.com) - Seattle Genetics, Inc. ( SGEN ) and Bristol-Myers Squibb Co. ( BMY ) Monday said they have entered into a clinical trial collaboration agreement to evaluate the investigational combination of Seattle Genetics' antibody-drug conjugate, or ADC, Adcetris (brentuximab vedotin) and Bristol-Myers Squibb's immunotherapy Opdivo (nivolumab) in two planned Phase 1/2 clinical trials.

The first trial will evaluate the combination of Adcetris and Opdivo as a potential treatment option for patients with relapsed or refractory Hodgkin lymphoma or HL, and the second trial will focus on patients with relapsed or refractory B-cell and T-cell non-Hodgkin lymphomas, including diffuse large B-cell lymphoma.

Adcetris is an ADC directed to CD30, a defining marker of classical HL, which combines the targeting ability of a monoclonal antibody with the potency of a cell-killing agent. Opdivo is a human programmed death receptor-1 blocking antibody that binds to the PD-1 receptor expressed on activated T-cells.

The studies are expected to begin in 2015, with Seattle Genetics conducting the HL trial and Bristol-Myers Squibb conducting the NHL trial.

Adcetris is approved in relapsed HL and systemic anaplastic large cell lymphoma, but is not currently approved for the treatment of relapsed, transplant eligible HL or for the treatment of other types of NHL. Opdivo is currently not approved for the treatment of lymphoma.

For comments and feedback: contact editorial@rttnews.com

http://www.rttnews.com

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Seattle Genetics, Bristol-Myers Report Clinical Trial Collaboration