TAG: "Genetics"

Study pinpoints two genes that increase risk for PTSD


Heredity may influence people’s predisposition for post-traumatic stress disorder.

Armen Goenjian, UCLA

By Elaine Schmidt, UCLA

Why do some people develop post-traumatic stress disorder while others who suffered the same ordeal do not? A new UCLA discovery may shed light on the answer.

UCLA scientists have linked two genes to the debilitating mental disorder, suggesting that heredity influences a person’s risk of developing PTSD. Published in the February 2015 edition of the Journal of Affective Disorders, the findings could provide a biological basis for diagnosing and treating PTSD more effectively in the future.

“Many people suffer with post-traumatic stress disorder after surviving a life-threatening ordeal like war, rape or a natural disaster,” explained lead author Dr. Armen Goenjian, a researcher at the Semel Institute for Neuroscience and Human Behavior at UCLA. “But not everyone who experiences trauma suffers from PTSD. We investigated whether PTSD has genetic underpinnings that make some people more vulnerable to the syndrome than others.”

In 1988, Goenjian, an Armenian American, rushed to Spitak, Armenia, after a 6.8 magnitude earthquake devastated the country. The temblor leveled entire towns and cities, killing more than 25,000 people, two-thirds of them children.

With support from the Armenian Relief Society, Goenjian and his colleagues helped establish a pair of psychiatric clinics that treated earthquake survivors for 21 years. A dozen multigenerational families in northern Armenia agreed to allow their blood samples to be sent to UCLA, where Goenjian and his colleagues combed the DNA of 200 individuals for genetic clues to psychiatric vulnerability.

In 2012, his team discovered that PTSD was more common in survivors who carried two gene variants associated with depression. In the current study, Goenjian and first author Julia Bailey, an adjunct assistant professor of epidemiology at the UCLA Fielding School of Public Health, focused on two genes, COMT and TPH-2, which play important roles in brain function.

COMT is an enzyme that degrades dopamine, a neurotransmitter that controls the brain’s reward and pleasure centers and helps regulate mood, thinking, attention and behavior. Too much or too little dopamine can influence various neurological and psychological disorders.

TPH-2 controls the production of serotonin, a neurotransmitter that regulates mood, sleep and alertness — all of which are disrupted in PTSD. Serotonin is the target of a group of drugs called selective serotonin reuptake inhibitors, or SSRIs, which were designed to treat depression. Now, more physicians are prescribing SSRIs to treat disorders beyond depression, including PTSD.

“We found a significant association between variants of COMT and TPH-2 with PTSD symptoms, suggesting that these genes contribute to the onset and persistence of the disorder,” Goenjian said. “Our results indicate that people who carry these genetic variants may be at higher risk of developing PTSD.”

The team used the most recent PTSD criteria from the American Psychiatric Association’s diagnostic manual to measure genes’ role in predisposing someone to the disorder. The new criteria increased estimates of the degree to which PTSD is genetic to 60 percent; estimates based on older criteria reached only 41 percent.

“Assessments of patients based upon the latest diagnostic criteria may boost the field’s chances of finding new genetic markers for PTSD,” Goenjian said. “We hope our findings will lead to molecular methods for screening people at risk for this disorder and identify new drug therapies for prevention and treatment.”

Goenjian cautioned that PTSD is likely caused by multiple genes, and that more research must be done to find more of the genes involved.

PTSD affects about 7 percent of Americans. It has been a pressing health issue for many veterans returning from tours in Iraq and Afghanistan.

The study’s co-authors were Ernest Noble and Sugandha Dandekar, both of UCLA; Alan Steinberg of the UCLA–Duke National Childhood Center for Traumatic Stress; David Walling of the Collaborative Neuroscience Network; and Sofia Stepanian of UC Riverside.

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Iron overload disease causes rapid growth of potentially deadly bacteria


Deficiency of the hormone hepcidin makes people vulnerable to Vibrio vulnificus.

By Amy Albin, UCLA

Every summer, the news reports on a bacterium called Vibrio vulnificusfound in warm saltwater that causes people to get sick, or die, after they eat raw tainted shellfish or when an open wound comes in contact with seawater.

People with a weakened immune system, chronic liver disease or iron overload disease are most at risk for severe illness. Vibrio vulnificus infections in high-risk individuals are fatal 50 percent of the time.

Now, researchers at UCLA have figured out why those with iron overload disease are so vulnerable. People with the common genetic iron overload disease called hereditary hemochromatosis have a deficiency of the iron-regulating hormone hepcidin and thus develop excess iron in their blood and tissue, providing prime growth conditions for Vibrio vulnificus.

The study also found that minihepcidin, a medicinal form of the hormone hepcidin that lowers iron levels in blood, could cure the infection by restricting bacterial growth.

The early findings were reported online today (Jan. 14) in the journal Cell Host and Microbe.

“This is the first time that the association of hepcidin deficiency and susceptibility to Vibrio vulnificus infection was tested,” said senior author Dr. Yonca Bulut, a clinical professor of pediatrics at Mattel Children’s Hospital at UCLA and a researcher with the UCLA Children’s Discovery and Innovation Institute. “The dramatic effectiveness of the new treatment, even after the infection was established, was impressive.”

To conduct the study, researchers compared the fatality of Vibrio vulnificus infection in healthy mice with mice that lacked hepcidin, modeling human hereditary hemochromatosis. The results showed that the infection was much more lethal in hepcidin-deficient mice because they could not decrease iron levels in the blood in response to infection, a process mediated by hepcidin in healthy mice.

Giving minihepcidin to susceptible hepcidin-deficient mice to lower the amount of iron in the blood prevented infection if the hormone was given before the Vibrio vulnificus was introduced. Additionally, mice given minihepcidin three hours after the bacterium was introduced were cured of any infection.

Hereditary hemochromatosis is a genetic disease that causes the body to absorb and store too much iron. It affects as many as 1 in every 200 people in the United States. Since it can take decades for the body to store damaging levels of iron, many people may not be aware that they have the disease until signs of the condition begin to appear later in life.

The co-directors of the UCLA Center for Iron Disorders, Dr. Tomas Ganz, a professor of medicine and pathology at the David Geffen School of Medicine at UCLA, and Elizabeta Nemeth, a professor of medicine at UCLA, led the invention of minihepcidins at UCLA. Minihepcidins are being developed for treatment of iron-overload disorders, such as hereditary hemochromatosis and Cooley’s anemia. The use of minihepcidin to treat potentially lethal infections is a possible new application.

“We found that hepcidin is required for resistance to a Vibrio vulnificus infection,” said the study’s lead author Joao Arezes, a visiting graduate student from the University of Porto in Portugal. “The development of the treatment tested in mouse models could reduce the high mortality rate of this disease.”

The next stage of research is to understand why Vibrio vulnificus bacteria become so lethal when iron levels are high, and to learn which other microbes respond similarly to excess iron.

The research was conducted at the UCLA Center for Iron Disorders.

Other study authors were Grace Jung, Victoria Gabayan, Erika Valore, Piotr Ruchala, Ganz and Nemeth, all of UCLA, and Paul Gulig of the University of Florida.

The study was funded by the UCLA Today’s and Tomorrow’s Children Fund, the UCLA Stein/Oppenheimer Endowment Award, the UCLA Children’s Discovery and Innovation Institute and the National Institutes of Health (grant R01 DK090554).

The Regents of the University of California is the owner of patents and patent applications directed at minihepcidins and methods of use thereof, which are managed by UCLA’s Office of Intellectual Property and Industry Sponsored Research. This intellectual property is licensed to Merganser Biotech, for which authors Ruchala, Ganz and Nemeth are scientific advisors and equity holders. Other disclosures are available in the manuscript.

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New therapy holds promise for restoring vision


It has several advantages over other sight restoration therapies now under investigation.

Benjamin Gaub and John Flannery observing a mouse in a water maze, in which the mouse swims to a platform designated by bright flashing lights. (Photo by Mervi Kuronen)

By Robert Sanders, UC Berkeley

A new genetic therapy not only helped blind mice regain enough light sensitivity to distinguish flashing from non-flashing lights, but also restored light response to the retinas of dogs, setting the stage for future clinical trials of the therapy in humans.

The therapy employs a virus to insert a gene for a common ion channel into normally blind cells of the retina that survive after the light-responsive rod and cone photoreceptor cells die as a result of diseases such as retinitis pigmentosa. Photoswitches – chemicals that change shape when hit with light – are then attached to the ion channels to make them open in response to light, activating the retinal cells and restoring light sensitivity.

Afflicting people of all ages, retinitis pigmentosa causes a gradual loss of vision, akin to losing pixels in a digital camera. Sight is lost from the periphery to the center, usually leaving people with the inability to navigate their surroundings. Some 100,000 Americans suffer from this group of inherited retinal diseases.

In a paper appearing online this week in the early edition of the journal Proceedings of the National Academy of Sciences, University of California, Berkeley, scientists who invented the photoswitch therapy and vision researchers at the School of Veterinary Medicine of the University of Pennsylvania (PennVet) report that blind mice regained the ability to navigate a water maze as well as normal mice.

The treatment worked equally well to restore light responses to the degenerated retinas of mice and dogs, indicating that it may be feasible to restore some light sensitivity in blind humans.

“The dog has a retina very similar to ours, much more so than mice, so when you want to bring a visual therapy to the clinic, you want to first show that it works in a large animal model of the disease,” said lead researcher Ehud Isacoff, professor of molecular and cell biology at UC Berkeley. “We’ve now showed that we can deliver the photoswitch and restore light response to the blind retina in the dog as well as in the mouse, and that the treatment has the same sensitivity and speed of response. We can reanimate the dog retina.”

The therapy has several advantages over other sight restoration therapies now under investigation, says vision scientist John Flannery, UC Berkeley professor of vision science and of molecular and cell biology. It uses a virus already approved by the Food and Drug Administration for other genetic therapies in the eye; it delivers an ion channel gene similar to one normally found in humans, unlike others that employ genes from other species; and it can easily be reversed or adjusted by supplying new chemical photoswitches. Dogs with the retinal degeneration provide a key test of the new therapy.

“Our ability to test vision is very, very limited in mice because, even in the healthy state, they are not very visual animals, their behaviors are largely driven by their other senses,” he says. “Dogs have a very sophisticated visual system, and are being used already for testing ophthalmic gene therapy.”

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How stem cells can be activated to help immune system fight infection


UCLA scientists show crucial role of genes Scalloped and Yorkie.

UCLA researchers have discovered that the Scalloped (above) and Yorkie genes play a key role in how progenitor stem cells are activated to fight infection. (Image by Dr. Julian Martinez-Agosto Lab, UCLA)

By Peter Bracke, UCLA

In a study led by Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research member Dr. Julian Martinez-Agosto, UCLA scientists have shown that two genes not previously known to be involved with the immune system play a crucial role in how progenitor stem cells are activated to fight infection.

This discovery lays the groundwork for a better understanding of the role progenitor cells can play in immune system response and could lead to the development of more effective therapies for a wide range of diseases.

The two-year study was published in the current issue of the journal Current Biology.

Progenitor cells are the link between stem cells and fully differentiated cells of the blood system, tissues and organs. This maturation process, known as differentiation, is determined in part by the original environment that the progenitor cell came from, called the niche. Many of these progenitors are maintained in a quiescent state or “standby mode” and are ready to differentiate in response to immune challenges such as stress, infection or disease.

Dr. Gabriel Ferguson, a postdoctoral fellow in Martinez-Agosto’s lab and first author of the study, built upon the lab’s previous research that utilized the blood system of the fruit fly species Drosophila to show that a specific set of signals must be received by progenitor cells to activate their differentiation into cells that can work to fight infection after injury. Ferguson focused on two genes previously identified in stem cells but not in the blood system, named Yorkie and Scalloped, and discovered that they are required in a newly characterized cell type called a lineage specifying cell. These cells then essentially work as a switch, sending the required signal to progenitor cells.

The researchers further discovered that when the progenitor cells did not receive the required signal, the fly would not make the mature cells required to fight infection. This indicates that the ability of the blood system to fight outside infection and other pathogens is directly related to the signals sent by this new cell type.

“The beauty of this study is that we now have a system in which we can investigate how a signaling cell uses these two genes, Yorkie and Scalloped, which have never before been shown in blood, to direct specific cells to be made,” said Martinez-Agosto, associate professor of human genetics. “It can help us to eventually answer the question of how our body knows how to make specific cell types that can fight infection.”

The researchers said that they hope future studies will examine these genes beyond Drosophila and extend to mammalian models, and that the system will be used by the research community to study the role of the genes Yorkie and Scalloped in different niche environments.

“At a biochemical level, there is a lot of commonality between the molecular machinery in Drosophila and that in mice and humans,” Ferguson said. “This study can further our shared understanding of how the microenvironment can regulate the differentiation and fate of a progenitor or stem cell.”

Martinez-Agosto noted, “Looking at the functionality of these genes and their effect on the immune response has great potential for accelerating the development of new targeted therapies.”

Ferguson’s research on this project was supported by a Cellular and Molecular Biology National Institutes of Health predoctoral training grant. Additional funding was provided by the David Geffen School of Medicine at UCLA.

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Statins reverse learning disabilities caused by Noonan syndrome


UCLA mouse study shows drugs overcome mutation, even in adult brain.

Alcino Silva, UCLA

UCLA scientists have discovered that statins, a popular class of cholesterol drugs, reverse the learning disabilities caused by a genetic disorder called Noonan syndrome.

Their findings were published online Nov. 10 by the journal Nature Neuroscience.

The disorder, which is caused by a genetic mutation, can disrupt a child’s development in many ways. It often causes unusual facial features, short stature, heart defects and developmental delays, including learning disabilities. No treatment is currently available.

“Noonan syndrome affects 1 in 2,000 people, and up to half of these patients struggle with learning disabilities,” said Alcino Silva, the study’s principal investigator and a professor of neurobiology, psychiatry and psychology at the David Geffen School of Medicine at UCLA. “Our approach identified the mechanism causing the disease, as well as a treatment that reversed its effects in adult mice. We are excited about these findings because they suggest that the treatment we developed may help the millions of Noonan patients with intellectual disabilities.”

While many genes contribute to Noonan syndrome, there is one gene that causes about half of all cases. This gene encodes for a protein that regulates another protein called Ras, which controls how brain cells talk to each other, enabling learning to take place.

Working with first author Young-Seok Lee, Silva studied mice that were genetically engineered to develop Noonan syndrome. They discovered that the predominant mutation that leads to Noonan creates hyperactive Ras, which disrupts cellular conversations and undermines the learning process.

“The act of learning creates physical changes in the brain, much like grooves on a record,” said Silva, who also is a member of the UCLA Brain Research Institute and UCLA Integrative Center for Learning and Memory. “Surplus Ras tips the balance between switching signals on and off in the brain. This interrupts the delicate cell communication needed by the brain to record learned information.”

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New genetic links in autism revealed


For answers, UC San Diego researchers turn to mice, stem cells and the ‘tooth fairy.’

Alysson Muotri, UC San Diego

With the help of mouse models, induced pluripotent stem cells (iPSCs) and the “tooth fairy,” researchers at the UC San Diego School of Medicine have implicated a new gene in idiopathic or non-syndromic autism. The gene is associated with Rett syndrome, a syndromic form of autism, suggesting that different types of autism spectrum disorder (ASD) may share similar molecular pathways.

The findings are published in today’s (Nov. 11) online issue of Molecular Psychiatry.

“I see this research as an example of what can be done for cases of non-syndromic autism, which lack a definitive group of identifying symptoms or characteristics,” said principal investigator Alysson Muotri, Ph.D., associate professor in the UC San Diego departments of pediatrics and cellular and molecular medicine. “One can take advantage of genomics to map all mutant genes in the patient and then use their own iPSCs to measure the impact of these mutations in relevant cell types. Moreover, the study of brain cells derived from these iPSCs can reveal potential therapeutic drugs tailored to the individual. It is the rise of personalized medicine for mental/neurological disorders.”

But to effectively exploit iPSCs as a diagnostic tool, Muotri said researchers “need to compare neurons derived from hundreds or thousands of other autistic individuals.” Enter the “Tooth Fairy Project,” in which parents are encouraged to register for a “Fairy Tooth Kit,” which involves sending researchers like Muotri a discarded baby tooth from their autistic child. Scientists extract dental pulp cells from the tooth and differentiate them into iPSC-derived neurons for study.

“There is an interesting story behind every single tooth that arrives in the lab,” said Muotri.

The latest findings, in fact, are the result of Muotri’s first tooth fairy donor. He and colleagues identified a de novo or new disruption in one of the two copies of the TRPC6 gene in iPSC-derived neurons of a non-syndromic autistic child. They confirmed with mouse models that mutations in TRPC6 resulted in altered neuronal development, morphology and function. They also noted that the damaging effects of reduced TRPC6 could be rectified with a treatment of hyperforin, a TRPC6-specific agonist that acts by stimulating the functional TRPC6 in neurons, suggesting a potential drug therapy for some ASD patients.

The researchers also found that MeCP2 levels affect TRPC6 expression. Mutations in the gene MeCP2, which encodes for a protein vital to the normal function of nerve cells, cause Rett syndrome, revealing common pathways among ASD.

“Taken together, these findings suggest that TRPC6 is a novel predisposing gene for ASD that may act in a multiple-hit model,” Muotri said. “This is the first study to use iPSC-derived human neurons to model non-syndromic ASD and illustrate the potential of modeling genetically complex sporadic diseases using such cells.”

For more information on the Tooth Fairy Project, visit http://muotri.ucsd.edu.

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Genetic damage caused by asthma also shows up in circulating blood stream


Study finds disease harms more than lungs, may be more dangerous than previously thought.

Robert Schiestl, UCLA

Asthma may be more harmful than was previously thought, according to UCLA researchers who found that genetic damage is present in circulating, or peripheral, blood. Doctors previously thought that the genetic damage it caused was limited to the lungs.

In the study, researchers looked for the overexpression of a cytokine called interleukin 13 (IL-13), which is known to mediate inflammation, a critical problem for people with asthma.

The study, which was conducted in an animal model that mimicked human asthma, was the first to assess the role of IL-13 in genetic damage to cells, or genotoxicity, said its senior author, Robert Schiestl, a professor of pathology and radiation oncology at the David Geffen School of Medicine at UCLA.

“Asthma is a very widespread disease, and we show for the first time an association between asthma and genotoxicity in peripheral blood,” said Schiestl, who also is a professor of environmental health sciences at the Fielding School of Public Health at UCLA. “This is important because it shows a whole-body effect from asthma, not just damage in the lungs.”

The findings were published today in the peer-reviewed journal Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis.

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Environmental carcinogens leave genetic imprints in tumors


Chemically induced tumors bear signatures that differentiate them from genetically engineered cancers.

Genetically engineering tumors in mice, a technique that has dominated cancer research for decades, may not replicate important features of cancers caused by exposure to environmental carcinogens, according to a new study led by UC San Francisco scientists. In addition to pointing the way to better understanding of environmental causes of cancer, the findings may help explain why many patients do not benefit from, or develop resistance to, targeted drug therapies.

In the new research, reported Nov. 2 in the advance online edition of Nature, a team led by UCSF graduate student Peter M.K. Westcott found that chemically induced lung tumors in mice carry hundreds of point mutations — deleterious alterations of single “letters” in the genome — that are not present in tumors induced by genetic engineering. The researchers demonstrated that chemically induced tumors display a starkly different “mutational landscape” even when chemicals cause a tumor-initiating mutation that is identical to that created by direct genetic manipulation.

“Since the 1980s, when genetic engineering came along, the mouse model community has been working on genetically engineered cancer—you put a gene in or take a gene out, and you get a tumor,” said Allan Balmain, Ph.D., the Barbara Bass Bakar Distinguished Professor in Cancer Genetics at UCSF and senior author of the study. “But it’s only now that we’re beginning to analyze what has happened between that first engineered change and the ultimate development of an aggressive tumor.”

The new work made use of next-generation sequencing (NGS) technology, which allows researchers to analyze the genomic sequence of tumors or of normal tissue letter-by-letter. For the Nature study, the group used a form of NGS known as whole-exome sequencing, which comprehensively analyzes the portion of the genome that contains the code for producing proteins.

The findings dovetail well with those from NGS-based studies of human tumors, such as The Cancer Genome Atlas (TCGA) initiative spearheaded by the National Cancer Institute and National Human Genome Research Institute, which have revealed mutational “signatures,” some of which can be definitively tied to environmental exposures. For example, distinctive patterns of point mutations are now known to differentiate lung cancer in smokers from that affecting non-smokers.

The results are also consistent with observations that tumors arising in human organs that are most directly exposed to environmental carcinogens — the skin, gastrointestinal system and lungs — are more prone to point mutations than more “protected” organs such as the brain, breast and prostate gland.

“We humans smoke cigarettes, drink alcohol and spend too much time in the sun, all of which cause us to accumulate point mutations that are major determinants of the behavior of tumors, especially of how a tumor responds to therapy,” said Balmain, co-leader of the Cancer Genetics Program at UCSF’s Helen Diller Family Comprehensive Cancer Center. “All this heterogeneity is being missed with genetically engineered tumors, because they don’t reflect these environmental effects.”

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Nobel laureates to gather at symposium honoring Frederick Sanger


His genetics research left a legacy written in A-T-G-C.

Frederick Sanger

After a visit to UC San Diego in the early 1980s to give a lecture, the famed British biochemist Frederick Sanger was rewarded with a homemade T-shirt emblazoned with the letters DNA in sequins. It was the sort of joke only a person who studied genetics might immediately appreciate: DNA sequence, get it?

Sanger, of course, got the joke and reportedly wore the shirt often, telling friends he thoroughly enjoyed his visit to San Diego.

Alas, it was a one-time visit. Sanger never returned to UC San Diego, but his impact upon the university — indeed upon the science of genetics and its rippling, massive impact on society and life — have not been forgotten.

On Nov. 5, a daylong symposium in honor of Sanger will be held in the auditorium of the Medical Education/Telemedicine building on the School of Medicine campus. Sanger is best known for winning the Nobel Prize for chemistry twice, one of only two laureates to win in the same category. (The other was John Bardeen in physics.) He is only the fourth person to garner two Nobel Prizes (joining Bardeen, Marie Curie and Linus Pauling) and just the third to win two Prizes in the sciences (with Bardeen and Curie). [See list of UC Nobel laureates.]

The list of symposium speakers reflects Sanger’s celebrated status. Three fellow Nobel laureates – David Baltimore (1975, physiology or medicine); Hamilton Smith (1978, physiology or medicine) and Roger Kornberg (2006, chemistry) will be in attendance, along with Stanley Norman Cohen, who is credited with co-inventing DNA cloning and recombinant DNA technologies.

There will be speakers from the Swedish Royal Academy, which awards the Nobel Prize; the University of Cambridge where Sanger worked and taught; and closer to home, the Salk Institute for Biological Studies and the J. Craig Venter Institute.

The UC San Diego symposium is one of just a handful of events worldwide celebrating Sanger’s life (he died Nov. 19, 2013, at the age of 95) and his scientific legacy, which has profoundly affected UC San Diego’s rise as a leading research university in biological sciences.

“Fred did not have a close relationship with UC San Diego, but much of the scientific strength of this university and our sister institutions in La Jolla is built upon his work,” said Dr. Theodore Friedmann, a UC San Diego professor of pediatrics, a former student of Sanger’s, a pioneer himself in gene therapy and one of the symposium organizers. (It was Friedmann’s wife, Ingrid, who designed and made Sanger’s sequined DNA T-shirt.)

“We would not be where we are without Fred’s work. He has certainly been one of the principal inspirations of my own career. Our symposium pays homage not so much to any particular connection to UC San Diego, but to his service to the entire world of science.”

His first Nobel Prize, awarded in 1958, honored Sanger’s research describing the structure of proteins, in particular how amino acids linked together to form insulin.

In 1980, he shared half of the Nobel Prize for chemistry with American molecular biologist Walter Gilbert for their invention of a method to decipher the sequences of bases — adenine, thymine, guanine and cytosine, the A-T-G-C molecules essential to all life — in nucleic acids, most famously deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). Paul Berg was awarded the other half for his research involving recombinant DNA.

Sanger’s twin Nobels augured the broader ramifications of his achievements.

By piecing together the chain of 51 amino acids that comprise insulin, Sanger showed scientists how to determine the sequences of other proteins.

By creating a method to read DNA simply and effectively, Sanger and colleagues made it possible to decode entire genomes. In 1977, Sanger decoded the genome of a virus – a first. Subsequent improvements and technological advances eventually made it possible for scientists in 2003 to successfully decipher the 3 billion letters that spell out the human genetic code.

“Sanger invented most of what underlies modern genetics and genomic science,” said Friedmann. “Fred was to genetics what Michelangelo and Picasso were to art, what Einstein is to physics and Darwin to evolutionary science. He was a giant among giants to whom most of us owe our careers.”

Scientific progress in biomedical research at institutions throughout the world has benefitted enormously from Fred’s revolutionary technologies, said Tony Hunter, a renowned Salk biologist who is an adjunct professor at UC San Diego and symposium co-organizer with Friedmann and Susan Taylor, professor of chemistry, biochemistry and pharmacology at UC San Diego.

“Rapid DNA sequencing is now pivotal in all areas of biology and medicine, but very few scientists who use this technology every day remember the crucial role that Fred Sanger played in making this a reality,” he said. “Perhaps it is a testament to the importance of what he did that his methods live on, but the man is largely forgotten!”

Sanger, who retired in 1983 to tend to his much-loved garden of roses and dahlias, would likely be a little dismayed by the symposium. Not the science, just the celebration. He was notably averse to publicity and never sought fame. He refused a knighthood from the Queen and, in his obituary, was quoted as describing himself as “just a chap who messed about in a lab.”

Maybe so, but his achievements are writ large in the letters of our DNA.

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Researchers seek middle-aged and older men for aging study


UC Davis study will follow groups of men with and without the fragile X premutation.

David Hessl, UC Davis

How alterations in a single gene on the X chromosome affects neurological and psychological functioning in men as they age is the subject of a new study by UC Davis MIND Institute researchers.

The gene is FMR1 (fragile X mental retardation 1), and those with an alteration in this gene, known as a “premutation,” are at risk for a range of psychological and medical conditions including decreased cognitive capacity and anxiety. In older adults with the premutation it can cause fragile X-associated tremor/ataxia syndrome (FXTAS), a neurodegenerative disorder that has motor symptoms that are similar to Parkinson’s disease and dementia and psychiatric symptoms that are similar to Alzheimer’s disease.

Researchers with the MIND Institute’s Fragile X Research and Treatment Center are seeking individuals the fragile X premutation who will participate in the study over five years, allowing researchers to track their brain changes, motor functioning, thinking and memory skills, as well as their emotional well‐being. They also are seeking healthy men of the same age, who will act as controls.

The study is co‐led by David Hessl, professor of psychiatry and behavioral sciences, and Susan Rivera, professor in the Department of Psychology.

“This study will follow groups of men with and without the fragile X premutation. It will examine the trajectory of change in their cognitive and emotional functioning, and the structure and function of their brains, in an effort to determine which factors are important for predicting the disease process that will occur in some of these men,” Hessl said.

Healthy male control participants must be between 40 and 75 and live in Northern California. Fragile X premutation carriers of the same age may travel to the MIND Institute from their homes anywhere in North America. Participation involves three two‐day study visits over five years. Compensation of $200, as well as travel reimbursement, will be provided for each two-day visit.

Once enrolled, individuals will receive tests to assess their ability to think and their memory skills. They will be interviewed and fill out questionnaires about their health history. They also will be asked to provide blood samples and will have brain scans taken while engaged in a variety of tasks.

For further information, please contact Jessica Famula, recruitment coordinator, (916) 703‐0470 or email jessica.famula@ucdmc.ucdavis.edu.

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Better education about prenatal testing leads to fewer tests


UCSF study shows importance of clear information on all prenatal testing options.

Miriam Kuppermann, UC San Francisco

A clinical trial led by UC San Francisco has found that when pregnant women are educated about their choices on prenatal genetic testing, the number of tests actually drops, even when the tests are offered with no out-of-pocket costs.

The findings underscore the need for clear information on all prenatal testing options and their possible outcomes, including the option of no testing, before pregnant women decide whether or not to have genetic testing, the authors said.

The study also suggests that some women may have undergone prenatal screening for Down syndrome without having full information about the implications of testing, the authors said.

The article is published in today’s (Sept. 24) issue of JAMA.

“Our findings show that prenatal testing is not appropriate for everyone, and that all women need information that is readily understood and unbiased to enable them to make informed choices reflecting their own preferences and values,” said lead author Miriam Kuppermann, Ph.D., M.P.H., professor and vice chair for clinical research at the UCSF Department of Obstetrics, Gynecology and Reproductive Sciences.

“Decisions about prenatal testing are personal and should be reflective of the patient’s own values and preferences, not those of her health care providers,” said Kuppermann.

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How to delay the aging process by ‘remote control’


UCLA biologists ID gene that can slow the aging process.

David Walker, UCLA

UCLA biologists have identified a gene that can slow the aging process throughout the entire body when activated remotely in key organ systems.

Working with fruit flies, the life scientists activated a gene called AMPK that is a key energy sensor in cells; it gets activated when cellular energy levels are low.

Increasing the amount of AMPK in fruit flies’ intestines increased their lifespans by about 30 percent — to roughly eight weeks from the typical six — and the flies stayed healthier longer as well.

The research, published Sept. 4 in the open-source journal Cell Reports, could have important implications for delaying aging and disease in humans, said David Walker, an associate professor of integrative biology and physiology at UCLA and senior author of the research.

“We have shown that when we activate the gene in the intestine or the nervous system, we see the aging process is slowed beyond the organ system in which the gene is activated,” Walker said.

Walker said that the findings are important because extending the healthy life of humans would presumably require protecting many of the body’s organ systems from the ravages of aging — but delivering anti-aging treatments to the brain or other key organs could prove technically difficult. The study suggests that activating AMPK in a more accessible organ such as the intestine, for example, could ultimately slow the aging process throughout the entire body, including the brain.

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