Category Archives: Human Genetics

Science has helped us understand how blue eyes or baldness as well as other inherited traits both harmless and harmful can run in a family. In the past few decades, largely due to the Human Genome Project and other scientific endeavors, knowledge has exploded in the field of human genetics.

Genetic services available in New Jersey include direct clinical care services as well as activities such as screening programs and laboratory services, educational activities and birth defects surveillance. The State of New Jersey partially funds a network of Genetic Centers [see the list at bottom of page] that provide testing, diagnosis, and ongoing management and comprehensive care of genetic conditions. Physicians specially trained in medical genetics, along with genetic counselors, nurses, social workers and other medical specialists provide comprehensive care to patients with genetic concerns.

Services may include some or all of the following: a review of your family and medical history; physical examination; laboratory testing; genetic counseling/education; and management or referral to other specialists experienced in treating or managing rare disorders. These services can provide information on certain disorders that you or your child may have inherited, how genetic conditions may be passed from one generation to another in a family, and what the risks are that certain conditions will affect you, your present or future pregnancies, or other members of your family.

Genetic counseling translates the science of genetics into practical information. Anyone who has unanswered questions about diseases or traits in their family should consider genetic counseling. People who might be especially interested are:

Resources:

American College of Medical Genetics (ACMG) http://www.acmg.net

Genetic Alliance http://www.geneticalliance.org/

Genetics Home Reference http://ghr.nlm.nih.gov/

Human Genetics Association of New Jersey (HGANJ) http://www.hganj.org

National Newborn Screening & Genetic Resource Center (NNSGRC) http://genes-r-us.uthscsa.edu/

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NJDOH - New Born Screening & Genetic Services

A single gene that coordinates a network of about 400 genes involved in epilepsy could be a target for new treatments, according to research.

Epilepsy is a common and serious disease that affects around 50 million people worldwide. The mortality rate among people with epilepsy is two to three times higher than the general population. It is known that epilepsy has a strong genetic component, but the risk is related to multiple factors that are 'spread' over hundreds of genes. Identifying how these genes are co-ordinated in the brain is important in the search for new anti-epilepsy medications. This requires approaches that can analyse how multiple genes work in concert to cause disease.

Instead of studying individual genes, which has been the usual approach in epilepsy to date, researchers from Imperial College London developed novel computational and genetics techniques to systematically analyse the activity of genes in epilepsy. Published in Nature Communications, the study is the first to apply this 'systems genetics' approach to epilepsy.

The researchers studied samples of brain tissue removed from patients during neurosurgery for their epilepsy. Starting from these samples, they identified a gene network that was highly active in the brain of these patients, and then discovered that an unconnected gene, Sestrin 3 (SESN3), acts as a major regulator of this epileptic gene network. This is the first time SESN3 has been implicated in epilepsy and its co-ordinating role was confirmed in studies with mice and zebrafish.

Dr Enrico Petretto, from the Medical Research Council (MRC) Clinical Sciences Centre at Imperial College London and co-senior author of the study, said: "Systems genetics allows us to understand how multiple genes work together, which is far more effective than looking at the effect of a gene in isolation. It's a bit like trying to tackle a rival football team. If you want to stop the team from playing well, you can't just target an individual player; you first need to understand how the team plays together and their strategy. Likewise in systems genetics we don't look at just one gene at a time, but a network or team of genes and the functional relationships between them in disease.

"After understanding how the team plays together, a possible approach to beating a strong side is then to identify a major control point- say the captain or the coach - who co-ordinates the players. This is like our 'master regulator gene', which in this case is SESN3. If we can develop medication to target this gene in the brain, then the hope is that we could influence the whole epileptic gene network rather than individual parts and in turn achieve more effective treatments."

Using surgical samples of brain tissue provides a unique opportunity to study how genes are coordinated in the brains of people with epilepsy. Patients with severe temporal lobe epilepsy who do not respond to medication can undergo surgery to remove part of the brain to relieve their seizures. Our research was able to use brain tissue samples donated by 129 patients to analyse the genetic and functional activity underlying their epilepsy.

Co-senior author of the paper, Dr Michael Johnson from Imperial's Department of Medicine, said: "This study is proof-of-concept for a new scientific approach in epilepsy. Existing epilepsy medications are symptomatic treatments only; that is they act to supress the seizures but they don't treat the underlying disease.

Consequently, we find that existing medications don't work in about one-third of people with epilepsy. Here we have taken a new approach, and identified a network of genes underlying the epilepsy itself in these patients and mapped its control to a single gene, SESN3. This offers hope that new disease-modifying therapies can be developed for the treatment of epilepsy itself.

"Imperial has pioneered the systems genetics approach to common human disease and by applying its specialism in epilepsy and working in collaboration with pharmaceutical companies and other institutes worldwide, we have identified SESN3 as a new 'master regulatory' gene of key inflammatory processes in the brain that could be a potential target for new and more effective treatments."

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New 'systems genetics' study identifies possible target for epilepsy treatment

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."

Originally posted here:
Treatment restores sociability in autism mouse model

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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.

Original post:
UAB Research Probes Molecular Basis of Rare Genetic Disorder

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

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

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