Posts Tagged ‘genetics’


Sixty trays can contain the entire human genome as 23,040 different fragments of cloned DNA. Credit James King-Holmes/Science Source

By ANDREW POLLACK

Scientists are now contemplating the fabrication of a human genome, meaning they would use chemicals to manufacture all the DNA contained in human chromosomes.

The prospect is spurring both intrigue and concern in the life sciences community because it might be possible, such as through cloning, to use a synthetic genome to create human beings without biological parents.

While the project is still in the idea phase, and also involves efforts to improve DNA synthesis in general.

Organizers said the project could have a big scientific payoff and would be a follow-up to the original Human Genome Project, which was aimed at reading the sequence of the three billion chemical letters in the DNA blueprint of human life. The new project, by contrast, would involve not reading, but rather writing the human genome — synthesizing all three billion units from chemicals.

But such an attempt would raise numerous ethical issues. Could scientists create humans with certain kinds of traits, perhaps people born and bred to be soldiers? Or might it be possible to make copies of specific people?

“Would it be O.K., for example, to sequence and then synthesize Einstein’s genome?” Drew Endy, a bioengineer at Stanford, and Laurie Zoloth, a bioethicist at Northwestern University, wrote in an essay criticizing the proposed project. “If so how many Einstein genomes should be made and installed in cells, and who would get to make them?”

The project was initially called HGP2: The Human Genome Synthesis Project, with HGP referring to the Human Genome Project. An invitation to the meeting at Harvard said that the primary goal “would be to synthesize a complete human genome in a cell line within a period of 10 years.”

But by the time the meeting was held, the name had been changed to “HGP-Write: Testing Large Synthetic Genomes in Cells.”

The project does not yet have funding, Dr. Church said, though various companies and foundations would be invited to contribute, and some have indicated interest. The federal government will also be asked. A spokeswoman for the National Institutes of Health declined to comment, saying the project was in too early a stage.

Besides Dr. Church, the organizers include Jef Boeke, director of the institute for systems genetics at NYU Langone Medical Center, and Andrew Hessel, a self-described futurist who works at the Bay Area software company Autodesk and who first proposed such a project in 2012.

Scientists and companies can now change the DNA in cells, for example, by adding foreign genes or changing the letters in the existing genes. This technique is routinely used to make drugs, such as insulin for diabetes, inside genetically modified cells, as well as to make genetically modified crops. And scientists are now debating the ethics of new technology that might allow genetic changes to be made in embryos.

But synthesizing a gene, or an entire genome, would provide the opportunity to make even more extensive changes in DNA.

For instance, companies are now using organisms like yeast to make complex chemicals, like flavorings and fragrances. That requires adding not just one gene to the yeast, like to make insulin, but numerous genes in order to create an entire chemical production process within the cell. With that much tinkering needed, it can be easier to synthesize the DNA from scratch.

Right now, synthesizing DNA is difficult and error-prone. Existing techniques can reliably make strands that are only about 200 base pairs long, with the base pairs being the chemical units in DNA. A single gene can be hundreds or thousands of base pairs long. To synthesize one of those, multiple 200-unit segments have to be spliced together.

But the cost and capabilities are rapidly improving. Dr. Endy of Stanford, who is a co-founder of a DNA synthesis company called Gen9, said the cost of synthesizing genes has plummeted from $4 per base pair in 2003 to 3 cents now. But even at that rate, the cost for three billion letters would be $90 million. He said if costs continued to decline at the same pace, that figure could reach $100,000 in 20 years.

J. Craig Venter, the genetic scientist, synthesized a bacterial genome consisting of about a million base pairs. The synthetic genome was inserted into a cell and took control of that cell. While his first synthetic genome was mainly a copy of an existing genome, Dr. Venter and colleagues this year synthesized a more original bacterial genome, about 500,000 base pairs long.

Dr. Boeke is leading an international consortium that is synthesizing the genome of yeast, which consists of about 12 million base pairs. The scientists are making changes, such as deleting stretches of DNA that do not have any function, in an attempt to make a more streamlined and stable genome.

But the human genome is more than 200 times as large as that of yeast and it is not clear if such a synthesis would be feasible.

Jeremy Minshull, chief executive of DNA2.0, a DNA synthesis company, questioned if the effort would be worth it.

“Our ability to understand what to build is so far behind what we can build,” said Dr. Minshull, who was invited to the meeting at Harvard but did not attend. “I just don’t think that being able to make more and more and more and cheaper and cheaper and cheaper is going to get us the understanding we need.”

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By Marlene Cimons

Mary Harada’s father lived to 102, healthy and sharp to the end. She wouldn’t mind living that long, if she could stay as mentally and physically fit as he was. “He died sitting in his chair,’’ says Harada, 80, a retired history professor who lives in West Newbury, Mass. “He was in excellent shape until his heart stopped.’’

She may, in fact, have a good chance of getting there. Longevity experts believe that extreme old age — 100 or older — runs in families, and often is strikingly apparent in families where there are several siblings or other close relatives who have reached that milestone. (Harada’s great-aunt — her father’s aunt — also lived an extremely long life, to 104.)

Moreover, researchers are finding that many of those who live to extreme old age remain in remarkably good condition, delaying the onset of such chronic and debilitating age-related illnesses as cancer, heart disease and diabetes until close to the end of their lives, and a certain percentage don’t get them at all.

“It’s one thing to live to be 100 and quite another to live to be 100 and be in good shape,’’ says Winifred K. Rossi, deputy director of the Division of Geriatrics and Clinical Gerontology at the National Institute on Aging. The institute is sponsoring an ongoing study of more than 500 families with long-lived members that involves nearly 5,000 individuals. “Something is going on that has protected them from the bad stuff that causes problems for other people earlier in life.’’

Experts attribute healthy longevity to a combination of good genes and good behaviors. Good behaviors play a greater role than genes in getting you to your mid-to-late 80s — don’t smoke or drink alcohol, exercise regularly and eat healthfully — while getting beyond 90, and to 100 or even older, probably depends more heavily on genes, they say. Families with a cluster of members with exceptional longevity don’t occur by chance, they say, but probably from familial factors they all share.

Growing numbers

Centenarians have become a fast-growing group in this country. In 1980, there were 32,194 Americans age 100 or older. By 2010, the number had grown to 53,364, or 1.73 centenarians per 10,000 people, according to the Census Bureau. This represents a 65.8 percent increase during that period, compared with a 36.3 percent rise in the general population.

Moreover, the number of Americans 90 and older nearly tripled during the past three decades, reaching 1.9 million in 2010, and is expected to more than quadruple between 2010 and 2050, according to the bureau. Globally, the number of centenarians is expected to increase tenfold during that time, according to the aging institute.

This is probably due to numerous factors, among them improved health care, dietary changes and reduced rates of smoking.

“When I started practicing, it was rare to see someone of 100, but now it’s not that strange at all,’’ says Anne B. Newman, director of the Center for Healthy Aging at the University of Pittsburgh. “More people have had the opportunity to get there,’’ largely because of advances in public health and medicine.

But as the numbers of very old have increased and the examination of human genetics has become more sophisticated, researchers have been trying to discover the genetic and biological factors that contribute to a life span of 100 or older and why some centenarians stay healthy for so long. Not surprisingly, what they are finding is complicated and far from a one-size-fits-all answer.

“Aging is not simple,’’ says Thomas Perls, a professor of medicine at Boston University and director of the New England Centenarian Study at Boston Medical Center. “There are many different biological mechanisms involved in aging, so it makes sense that there are different genes involved. We are still in the infancy of figuring this out.’’

Nir Barzilai, director of the Institute for Aging Research at the Albert Einstein College of Medicine in New York, has been conducting several studies that focus on inherited genetic and biological influences that promote longevity.

In 2003, for example, his team discovered that centenarians, especially women, and their offspring have significantly higher HDL, or good cholesterol, which protects against heart disease, hypertension and metabolic syndrome, a series of risk factors that raise the chances of heart disease, diabetes and stroke.

Health & Science
Do you think you’ll live to be 100? The answer may be in your genes.
By Marlene Cimons December 14, 2015
Mary Harada’s father lived to 102, healthy and sharp to the end. She wouldn’t mind living that long, if she could stay as mentally and physically fit as he was. “He died sitting in his chair,’’ says Harada, 80, a retired history professor who lives in West Newbury, Mass. “He was in excellent shape until his heart stopped.’’

She may, in fact, have a good chance of getting there. Longevity experts believe that extreme old age — 100 or older — runs in families, and often is strikingly apparent in families where there are several siblings or other close relatives who have reached that milestone. (Harada’s great-aunt — her father’s aunt — also lived an extremely long life, to 104.)

Moreover, researchers are finding that many of those who live to extreme old age remain in remarkably good condition, delaying the onset of such chronic and debilitating age-related illnesses as cancer, heart disease and diabetes until close to the end of their lives, and a certain percentage don’t get them at all.

[Tech Titan’s Latest Project: Defying Death]

“It’s one thing to live to be 100 and quite another to live to be 100 and be in good shape,’’ says Winifred K. Rossi, deputy director of the Division of Geriatrics and Clinical Gerontology at the National Institute on Aging. The institute is sponsoring an ongoing study of more than 500 families with long-lived members that involves nearly 5,000 individuals. “Something is going on that has protected them from the bad stuff that causes problems for other people earlier in life.’’

( Martin Tognola for The Washington Post)
Experts attribute healthy longevity to a combination of good genes and good behaviors. Good behaviors play a greater role than genes in getting you to your mid-to-late 80s — don’t smoke or drink alcohol, exercise regularly and eat healthfully — while getting beyond 90, and to 100 or even older, probably depends more heavily on genes, they say. Families with a cluster of members with exceptional longevity don’t occur by chance, they say, but probably from familial factors they all share.

Growing numbers
Centenarians have become a fast-growing group in this country. In 1980, there were 32,194 Americans age 100 or older. By 2010, the number had grown to 53,364, or 1.73 centenarians per 10,000 people, according to the Census Bureau. This represents a 65.8 percent increase during that period, compared with a 36.3 percent rise in the general population.

Moreover, the number of Americans 90 and older nearly tripled during the past three decades, reaching 1.9 million in 2010, and is expected to more than quadruple between 2010 and 2050, according to the bureau. Globally, the number of centenarians is expected to increase tenfold during that time, according to the aging institute.

This is probably due to numerous factors, among them improved health care, dietary changes and reduced rates of smoking.

“When I started practicing, it was rare to see someone of 100, but now it’s not that strange at all,’’ says Anne B. Newman, director of the Center for Healthy Aging at the University of Pittsburgh. “More people have had the opportunity to get there,’’ largely because of advances in public health and medicine.

But as the numbers of very old have increased and the examination of human genetics has become more sophisticated, researchers have been trying to discover the genetic and biological factors that contribute to a life span of 100 or older and why some centenarians stay healthy for so long. Not surprisingly, what they are finding is complicated and far from a one-size-fits-all answer.

“Aging is not simple,’’ says Thomas Perls, a professor of medicine at Boston University and director of the New England Centenarian Study at Boston Medical Center. “There are many different biological mechanisms involved in aging, so it makes sense that there are different genes involved. We are still in the infancy of figuring this out.’’

The average American can expect to live for about 80 years. But that may change as scientists develop new ways to prolong human life. In this game, you will have access to seven promising tools. Play to learn more. Can you make it to 100 years or beyond? VIEW GRAPHIC
Nir Barzilai, director of the Institute for Aging Research at the Albert Einstein College of Medicine in New York, has been conducting several studies that focus on inherited genetic and biological influences that promote longevity.

In 2003, for example, his team discovered that centenarians, especially women, and their offspring have significantly higher HDL, or good cholesterol, which protects against heart disease, hypertension and metabolic syndrome, a series of risk factors that raise the chances of heart disease, diabetes and stroke.

The results, which found HDL levels of 60 and higher within this group — anything lower than 50 raises the risk of heart disease — suggest a heritable trait “that promotes healthy aging,’’ he says. This isn’t surprising, considering that women outlive men overall and — in 2010 — nearly 83 percent of centenarians were female, according to the Census Bureau.

Unusual chemistry

The Einstein researchers also have found that centenarians and their offspring often make unusually large amounts of a peptide (a short chain of amino acids) called humanin, which declines with age in most people and whose loss contributes to the development of Type 2 diabetes and Alzheimer’s disease. This may help explain why those who produce higher levels of humanin enjoy greater protection against those diseases and experience exceptionally long lives. For these individuals, humanin diminishes as they age, too, but the levels are much higher to start with than those of average people.

Barzilai believes the propensity for high levels of both HDL and humanin is heritable: “Offspring of centenarians have higher levels of humanin than their parents. Same with HDL. It declines with age, so it’s more apparent in the offspring.’’

Perls and his colleagues, in a study released almost four years ago, concluded there is no single common gene variant responsible for exceptional longevity. Rather, after examining about 280 gene variations, they discovered a series of gene combinations — nearly two dozen, in fact — that they believe contribute to long lives, “meaning there are different ways to get to these old ages,’’ Perls says. “It’s like playing the lottery. If you get all seven numbers, you’ll hit the jackpot.’’

These genetic groupings also seem to be involved in protecting against developing age-related diseases, since the scientists did not find an absence of disease-causing genes in their study group. “They have just as many as everybody else, which was a big surprise to us,’’ Perls says.

Also, the researchers found that the children of these healthy centenarians stay healthy longer than their same-age counterparts. The offspring of centenarians show 60 percent less heart disease, stroke, diabetes and hypertension, and 80 percent fewer overall deaths when they are in their early 70s, than those who were born at the same time but who do not have longevity in their families.

“They remain incredibly healthy into their 70s and 80s, and their mortality rate is very low, compared to others born at the same time,’’ Perls says.

Perls has studied 2,300 centenarians since 1995, including “super-centenarians’’ of 110 or older, and their offspring. He says about 45 percent of those who reach 100 manage to delay chronic age-related diseases until after they turn 80, and about 15 percent never get them at all.

Furthermore, he found that “semi-super-centenarians’’ — that is, those who are 105 to 109 — and super-centenarians don’t develop those diseases until roughly the final 5 percent of their very long lives. “They are dealing with diseases much better than the average person,’’ he says, who is more likely to develop these diseases in the 60s and 70s.

Many eventually die from the same diseases as non-centenarians, “but they do it 30 years later,’’ Barzilai says.

‘An additional 10 years’

Perls says that if you want to know whether you will live to 100, “you don’t have to do all this complicated genetic testing. Just look at your family and your health-related behaviors.’’ If you engage in healthful practices, you could reach your late 80s. “If you have the genes for longevity and you fight them [with risky behaviors], you will chop time off,’’ he says. “But if there is longevity in your family and you don’t do those things, you might get an additional 10 years past 90.’’

Newman agrees. “Don’t underestimate how powerful lifestyle is in longevity,’’ she says. “Even if longevity runs in your family, your life expectancy still will be more influenced by how you take care of yourself. If you have a centenarian parent, don’t count on living to 100 if you smoke, drink, eat a high-fat diet, and are sedentary and sleep-deprived.’’

Mary Harada thinks less about her genes and more about the unexpected event — breaking a bone, for example — that could make her a burden to her adult children.

“I don’t spend much time thinking about how long I’m going to live,’’ she says. “Whatever happens, happens. I spend more time thinking about how long I’m going to stay in my current house.’’

She has no age-related diseases and always has taken good care of herself. She has been a runner for 47 years, and she lifts weights. She shuns smoking and avoids most processed foods. She lives alone — her husband died last year — and she does most of the maintenance in and around her four-bedroom house, including leaf removal, routine yard work and spending two hours every 10 days in spring and summer mowing a very hilly lawn.

“I’ve lived here for 40 years, and I like living in this house and in this town,’’ she says. “If I could be like my father, and not break anything, I would stay here another five to 10 years. That would be wonderful.’’

https://www.washingtonpost.com/national/health-science/do-you-have-genes-that-will-let-you-live-to-age-100/2015/12/09/1460f234-953d-11e5-a2d6-f57908580b1f_story.html

Excessive activity in complement component 4 (C4) genes linked to the development of schizophrenia may explain the excessive pruning and reduced number of synapses in the brains of patients with schizophrenia, according to a study published in Nature.

The study, co-funded by the Office of Genomics Research Coordination at the National Institute of Mental Health and the Stanley Center for Psychiatric Research at the Broad Institute in Cambridge, Massachusetts, analyzed various structurally diverse versions of the C4 gene.

Led by Steve McCarroll, PhD, of the Broad Institute of Harvard and MIT, researchers analyzed the genomes of 65 000 study participants and 700 postmortem brains, detecting a link between specific gene versions and the biological process that causes some cases of schizophrenia.

The team—including Beth Stevens, PhD; Michael Carroll, PhD; and Aswin Sekar, BBS— determined that C4 genes generate varying levels of C4A and C4B proteins; the more C4A found in a person, the higher his or her risk of developing schizophrenia. The researchers found that during critical periods of brain maturation, C4 identifies synapses for pruning. Overexpression of C4 results in higher amounts of C4A, which could cause excessive pruning during the late teens and early adulthood, “conspicuously corresponding to the age-of-onset of schizophrenia symptoms,” the researchers noted.

“It has been virtually impossible to model [schizophrenic] disorder in cells or animals,” said Dr McCarroll. “The human genome is providing a powerful new way into this disease. Understanding these genetic effects on risk is a way of prying open that black box, peering inside, and starting to see actual biological mechanisms.”

Research suggests that future schizophrenia treatments may be developed to target and suppress excessive levels of pruning, halting a process that has the potential to develop into psychotic illness.

Reference

Sekar A, Bialas AR, de Rivera H, et al. Schizophrenia risk from complex variation of complement component 4. Nature. 2016; doi: 10.1038/nature16549.

With the pressure for a certain body type prevalent in the media, eating disorders are on the rise. But these diseases are not completely socially driven; researchers have uncovered important genetic and biological components as well and are now beginning to tease out the genes and pathways responsible for eating disorder predisposition and pathology.

As we enter the holiday season, shoppers will once again rush into crowded department stores searching for the perfect gift. They will be jostled and bumped, yet for the most part, remain cheerful because of the crisp air, lights, decorations, and the sound of Karen Carpenter’s contralto voice ringing out familiar carols.

While Carpenter is mainly remembered for her musical talents, unfortunately, she is also known for introducing the world to anorexia nervosa (AN), a severe life-threatening mental illness characterized by altered body image and stringent eating patterns that claimed her life just before her 33rd birthday in 1983.

Even though eating disorders (ED) carry one of the highest mortality rates of any mental illness, many researchers and clinicians still view them as socially reinforced behaviors and diagnose them based on criteria such as “inability to maintain body weight,” “undue influence of body weight or shape on self-evaluation,” and “denial of the seriousness of low body weight” (1). This way of thinking was prevalent when Michael Lutter, then an MD/PhD student at the University of Texas Southwestern Medical Center, began his psychiatry residency in an eating disorders unit. “I just remember the intense fear of eating that many patients exhibited and thought that it had to be biologically driven,” he said.

Lutter carried this impression with him when he established his own research laboratory at the University of Iowa. Although clear evidence supports the idea that EDs are biologically driven—they predominantly affect women and significantly alter energy homeostasis—a lack of well-defined animal models combined with the view that they are mainly behavioral abnormalities have hindered studies of the neurobiology of EDs. Still, Lutter is determined to find the biological roots of the disease and tease out the relationship between the psychiatric illness and metabolic disturbance using biochemistry, neuroscience, and human genetics approaches.

We’ve Only Just Begun

Like many diseases, EDs result from complex interactions between genes and environmental risk factors. They tend to run in families, but of course, for many family members, genetics and environment are similar enough that teasing apart the influences of nature and nurture is not easy. Researchers estimate that 50-80% of the predisposition for developing an ED is genetic, but preliminary genome-wide analyses and candidate gene studies failed to identify specific genes that contribute to the risk.

According to Lutter, finding ED study participants can be difficult. “People are either reluctant to participate, or they don’t see that they have a problem,” he reported. Set on finding the genetic underpinnings of EDs, his team began recruiting volunteers and found 2 families, 1 with 20 members, 10 of whom had an ED and another with 5 out of 8 members affected. Rather than doing large-scale linkage and association studies, the team decided to characterize rare single-gene mutations in these families, which led them to identify mutations in the first two genes, estrogen-related receptor α (ESRRA) and histone deacetylase 4 (HDAC4), that clearly associated with ED predisposition in 2013 (1).

“We have larger genetic studies on-going, including the collection of more families. We just happened to publish these two families first because we were able to collect enough individuals and because there is a biological connection between the two genes that we identified,” Lutter explained.

ESRRA appears to be a transcription factor upregulated by exercise and calorie restriction that plays a role in energy balance and metabolism. HDAC4, on the other hand, is a well-described histone deacteylase that has previously been implicated in locomotor activity, body weight homeostasis, and neuronal plasticity.

Using immunoprecipitation, the researchers found that ESRRA interacts with HDAC4, in both the wild type and mutant forms, and transcription assays showed that HDAC4 represses ESRRA activity. When Lutter’s team repeated the transcription assays using mutant forms of the proteins, they found that the ESRRA mutation seen in one family significantly reduced the induction of target gene transcription compared to wild type, and that the mutation in HDAC4 found in the other family increased transcriptional repression for ESRRA target genes.

“ESRRA is a well known regulator of mitochondrial function, and there is an emerging view that mitochondria in the synapse are critical for neurotransmission,” Lutter said. “We are working on identifying target pathways now.”

Bless the Beasts and the Children

Finding genes associated with EDs provides the groundwork for molecular studies, but EDs cannot be completely explained by the actions of altered transcription factors. Individuals suffering these disorders often experience intense anxiety, intrusive thoughts, hyperactivity, and poor coping strategies that lead to rigid and ritualized behaviors and severe crippling perfectionism. They are less aware of their emotions and often try to avoid emotion altogether. To study these complex behaviors, researchers need animal models.

Until recently, scientists relied on mice with access to a running wheel and restricted access to food. Under these conditions, the animals quickly increase their locomotor activity and reduce eating, frequently resulting in death. While some characteristics of EDs—excessive exercise and avoiding food—can be studied in these mice, the model doesn’t allow researchers to explore how the disease actually develops. However, Lutter’s team has now introduced a promising new model (3).

Based on their previous success with identifying the involvement of ESRRA and HDAC4 in EDs, the researchers wondered if mice lacking ESRRA might make suitable models for studies on ED development. To find out, they first performed immunohistochemistry to understand more about the potential cognitive role of ESRRA.

“ESRRA is not expressed very abundantly in areas of the brain typically implicated in the regulation of food intake, which surprised us,” Lutter said. “It is expressed in many cortical regions that have been implicated in the etiology of EDs by brain imaging like the prefrontal cortex, orbitofrontal cortex, and insula. We think that it probably affects the activity of neurons that modulate food intake instead of directly affecting a core feeding circuit.”

With these data, the team next tried providing only 60% of the normal daily calories to their mice for 10 days and looked again at ESRRA expression. Interestingly, ESRRA levels increased significantly when the mice were insufficiently fed, indicating that the protein might be involved in the response to energy balance.

Lutter now believes that upregulation of ESRRA helps organisms adapt to calorie restriction, an effect possibly not happening in those with ESRRA or HDAC4 mutations. “This makes sense for the clinical situation where most individuals will be doing fine until they are challenged by something like a diet or heavy exercise for a sporting event. Once they start losing weight, they don’t adapt their behaviors to increase calorie intake and rapidly spiral into a cycle of greater and greater weight loss.”

When Lutter’s team obtained mice lacking ESRRA, they found that these animals were 15% smaller than their wild type littermates and put forth less effort to obtain food both when fed restricted calorie diets and when they had free access to food. These phenotypes were more pronounced in female mice than male mice, likely due to the role of estrogen signaling. Loss of ESRRA increased grooming behavior, obsessive marble burying, and made mice slower to abandon an escape hole after its relocation, indicating behavioral rigidity. And the mice demonstrated impaired social functioning and reduced locomotion.

Some people with AN exercise extensively, but this isn’t seen in all cases. “I would say it is controversial whether or not hyperactivity is due to a genetic predisposition (trait), secondary to starvations (state), or simply a ritual that develops to counter the anxiety of weight related obsessions. Our data would suggest that it is not due to genetic predisposition,” Lutter explained. “But I would caution against over-interpretation of mouse behavior. The locomotor activity of mice is very different from people and it’s not clear that you can directly translate the results.”

For All We Know

Going forward, Lutter’s group plans to drill down into the behavioral phenotypes seen in their ESRRA null mice. They are currently deleting ESRRA from different neuronal cell types to pair individual neurons with the behaviors they mediate in the hope of working out the neural circuits involved in ED development and pathology.

In addition, the team has created a mouse line carrying one of the HDAC4 mutations previously identified in their genetic study. So far, this mouse “has interesting parallels to the ESRRA-null mouse line,” Lutter reported.

The team continues to recruit volunteers for larger-scale genetic studies. Eventually, they plan to perform RNA-seq to identify the targets of ESRRA and HDAC4 and look into their roles in mitochondrial biogenesis in neurons. Lutter suspects that this process is a key target of ESRRA and could shed light on the cognitive differences, such as altered body image, seen in EDs. In the end, a better understanding of the cells and pathways involved with EDs could create new treatment options, reduce suffering, and maybe even avoid the premature loss of talented individuals to the effects of these disorders.

References

1. Lutter M, Croghan AE, Cui H. Escaping the Golden Cage: Animal Models of Eating Disorders in the Post-Diagnostic and Statistical Manual Era. Biol Psychiatry. 2015 Feb 12.

2. Cui H, Moore J, Ashimi SS, Mason BL, Drawbridge JN, Han S, Hing B, Matthews A, McAdams CJ, Darbro BW, Pieper AA, Waller DA, Xing C, Lutter M. Eating disorder predisposition is associated with ESRRA and HDAC4 mutations. J Clin Invest. 2013 Nov;123(11):4706-13.

3. Cui H, Lu Y, Khan MZ, Anderson RM, McDaniel L, Wilson HE, Yin TC, Radley JJ, Pieper AA, Lutter M. Behavioral disturbances in estrogen-related receptor alpha-null mice. Cell Rep. 2015 Apr 21;11(3):344-50.

http://www.biotechniques.com/news/Exploring-the-Biology-of-Eating-Disorders/biotechniques-361522.html

A multinational team of researchers has sequenced the nuclear genome of the aurochs (Bos primigenius), an extinct species of ox that inhabited Europe, Asia and North Africa.

“This is the first complete nuclear genome sequence from the extinct Eurasian aurochs,” said Dr David MacHugh of University College Dublin, Ireland, corresponding author of a paper published online in the journal Genome Biology.

Domestication of the now-extinct wild aurochs gave rise to the two major domestic extant cattle species – Bos taurus and B. indicus.

While previous genetic studies have shed some light on the evolutionary relationships between European aurochs and modern cattle, important questions remain unanswered, including the phylogenetic status of aurochs, whether gene flow from aurochs into early domestic populations occurred, and which genomic regions were subject to selection processes during and after domestication.

To build a clearer picture of the ancestry of European cattle breeds, Dr MacHugh and his colleagues from the United States, the UK, China and Ireland, extracted genetic material from a bone of a 6,750 year old wild aurochs discovered in a cave in Derbyshire, England.

The scientists then sequenced its complete genome and compared it with the genomes of 81 domesticated Bos taurus and B. indicus animals, and DNA marker information from more than 1,200 modern cows.

They discovered clear evidence of breeding between wild British aurochs and early domesticated cattle.

“Our results show the ancestors of modern British and Irish breeds share more genetic similarities with this ancient specimen than other European cattle,” Dr MacHugh said.

“This suggests that early British farmers may have restocked their domesticated herds with wild aurochs.”

“Genes linked to neurobiology and muscle development were also found to be associated with domestication of the ancestors of European cattle, indicating that a key part of the domestication process was the selection of cattle based on behavioral and meat traits.”

The study contradicts earlier simple models of cattle domestication and evolution that researchers proposed based on mitochondrial DNA or Y chromosomes.

“What now emerges from high-resolution studies of the nuclear genome is a more nuanced picture of crossbreeding and gene flow between domestic cattle and wild aurochs as early European farmers moved into new habitats such as Britain during the Neolithic,” Dr MacHugh concluded.

_____

Stephen D.E. Park et al. 2015. Genome sequencing of the extinct Eurasian wild aurochs, Bos primigenius, illuminates the phylogeography and evolution of cattle. Genome Biology 16: 234; doi: 10.1186/s13059-015-0790-2

http://www.sci-news.com/genetics/science-genome-eurasian-wild-aurochs-bos-primigenius-03377.html?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+BreakingScienceNews+%28Breaking+Science+News%29


Results imply creative people are 25% more likely to carry genes that raise risk of bipolar disorder and schizophrenia. But others argue the evidence is flimsy.

The ancient Greeks were first to make the point. Shakespeare raised the prospect too. But Lord Byron was, perhaps, the most direct of them all: “We of the craft are all crazy,” he told the Countess of Blessington, casting a wary eye over his fellow poets.

The notion of the tortured artist is a stubborn meme. Creativity, it states, is fuelled by the demons that artists wrestle in their darkest hours. The idea is fanciful to many scientists. But a new study claims the link may be well-founded after all, and written into the twisted molecules of our DNA.

In a large study published on Monday, scientists in Iceland report that genetic factors that raise the risk of bipolar disorder and schizophrenia are found more often in people in creative professions. Painters, musicians, writers and dancers were, on average, 25% more likely to carry the gene variants than professions the scientists judged to be less creative, among which were farmers, manual labourers and salespeople.

Kari Stefansson, founder and CEO of deCODE, a genetics company based in Reykjavik, said the findings, described in the journal Nature Neuroscience, point to a common biology for some mental disorders and creativity. “To be creative, you have to think differently,” he told the Guardian. “And when we are different, we have a tendency to be labelled strange, crazy and even insane.”

The scientists drew on genetic and medical information from 86,000 Icelanders to find genetic variants that doubled the average risk of schizophrenia, and raised the risk of bipolar disorder by more than a third. When they looked at how common these variants were in members of national arts societies, they found a 17% increase compared with non-members.

The researchers went on to check their findings in large medical databases held in the Netherlands and Sweden. Among these 35,000 people, those deemed to be creative (by profession or through answers to a questionnaire) were nearly 25% more likely to carry the mental disorder variants.

Stefansson believes that scores of genes increase the risk of schizophrenia and bipolar disorder. These may alter the ways in which many people think, but in most people do nothing very harmful. But for 1% of the population, genetic factors, life experiences and other influences can culminate in problems, and a diagnosis of mental illness.

“Often, when people are creating something new, they end up straddling between sanity and insanity,” said Stefansson. “I think these results support the old concept of the mad genius. Creativity is a quality that has given us Mozart, Bach, Van Gogh. It’s a quality that is very important for our society. But it comes at a risk to the individual, and 1% of the population pays the price for it.”

Stefansson concedes that his study found only a weak link between the genetic variants for mental illness and creativity. And it is this that other scientists pick up on. The genetic factors that raise the risk of mental problems explained only about 0.25% of the variation in peoples’ artistic ability, the study found. David Cutler, a geneticist at Emory University in Atlanta, puts that number in perspective: “If the distance between me, the least artistic person you are going to meet, and an actual artist is one mile, these variants appear to collectively explain 13 feet of the distance,” he said.

Most of the artist’s creative flair, then, is down to different genetic factors, or to other influences altogether, such as life experiences, that set them on their creative journey.

For Stefansson, even a small overlap between the biology of mental illness and creativity is fascinating. “It means that a lot of the good things we get in life, through creativity, come at a price. It tells me that when it comes to our biology, we have to understand that everything is in some way good and in some way bad,” he said.

But Albert Rothenberg, professor of psychiatry at Harvard University is not convinced. He believes that there is no good evidence for a link between mental illness and creativity. “It’s the romantic notion of the 19th century, that the artist is the struggler, aberrant from society, and wrestling with inner demons,” he said. “But take Van Gogh. He just happened to be mentally ill as well as creative. For me, the reverse is more interesting: creative people are generally not mentally ill, but they use thought processes that are of course creative and different.”

If Van Gogh’s illness was a blessing, the artist certainly failed to see it that way. In one of his last letters, he voiced his dismay at the disorder he fought for so much of his life: “Oh, if I could have worked without this accursed disease – what things I might have done.”

In 2014, Rothernberg published a book, “Flight of Wonder: an investigation of scientific creativity”, in which he interviewed 45 science Nobel laureates about their creative strategies. He found no evidence of mental illness in any of them. He suspects that studies which find links between creativity and mental illness might be picking up on something rather different.

“The problem is that the criteria for being creative is never anything very creative. Belonging to an artistic society, or working in art or literature, does not prove a person is creative. But the fact is that many people who have mental illness do try to work in jobs that have to do with art and literature, not because they are good at it, but because they’re attracted to it. And that can skew the data,” he said. “Nearly all mental hospitals use art therapy, and so when patients come out, many are attracted to artistic positions and artistic pursuits.”

http://www.theguardian.com/science/2015/jun/08/new-study-claims-to-find-genetic-link-between-creativity-and-mental-illness