Category: gene

Creating a Synthetic Human Genome

On By A.P.In DNA, gene, The FutureLeave a comment


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.”

Chinese researchers report first-ever gene editing of human embryos

On By A.P.In DNA, gene, Medicine, Michael Moore, Science, The FutureLeave a comment

In an ethically charged first, Chinese researchers have used gene editing to modify human embryos obtained from an in-vitro fertilization clinic.

The 16-person scientific team, based at the Sun Yat-Sen University in Guangzhou, China, set out to see whether it could correct the gene defect that causes beta-thalassemia, a blood disease, by editing the DNA of fertilized eggs.

The team’s report showed the method is not yet very accurate, confirming scientific doubts around whether gene editing could be practical in human embryos, and whether genetically engineered people are going to be born anytime soon.

The authors’ report appeared on April 18 in a low-profile scientific journal called Protein & Cell. The authors, led by Junjiu Huang, say there is a “pressing need” to improve the accuracy of gene editing before it can be applied clinically, for instance to produce children with repaired genes.

The team did not try to establish a pregnancy and say for ethical reasons they did their tests only in embryos that were abnormal.

“These authors did a very good job pointing out the challenges,” says Dieter Egli, a researcher at the New York Stem Cell Foundation in Manhattan. “They say themselves this type of technology is not ready for any kind of application.”

The paper had previously circulated among researchers and had provoked concern by highlighting how close medical science may be to tinkering with the human gene pool.

n March, an industry group called for a complete moratorium on experiments of the kind being reported from China, citing risks and the chance they would open the door to eugenics, or changing nonmedical traits in embryos, such as stature or intelligence.

Other scientists recommended high-level meetings of experts, regulators, and ethicists to debate if there are acceptable uses for such engineering.

The Chinese team reported editing the genes of more than 80 embryos using a technology called CRISPR-Cas9. While in some cases they were successful, in others the CRISPR technology didn’t work or introduced unexpected mutations. Some of the embryos ended up being mosaics, with a repaired gene in some cells, but not in others.

Parents who are carriers of beta-thalassemia could choose to test their IVF embryos, selecting those that have not inherited the disease-causing mutation. However, gene editing opens the possibility of germline modification, or permanently repairing the gene in an embryo, egg, or sperm in a way that is passed onto the offspring and to future generations.

That idea is the subject of intense debate, since some think the human gene pool is sacrosanct and should never be the subject of technological alteration, even for medical reasons. Others allow that germline engineering might one day be useful, but needs much more testing. “You can’t discount it,” says Egli. “It’s very interesting.”

The Chinese team performed the gene editing in eggs that had been fertilized in an IVF clinic but were abnormal because they had been fertilized by two sperm, not one. “Ethical reasons precluded studies of gene editing in normal embryos,” they said.

Abnormal embryos are widely available for research, both in China and the U.S. At least one U.S. genetics center is also using CRISPR in abnormal embryos rejected by IVF clinics. That group described aspects of its work on the condition that it would not be identified, since the procedure remains controversial.

Making repairs using CRISPR harnesses a cell’s own DNA repair machinery to correct genes. The technology guides a cutting protein to a particular site on the DNA molecule, chopping it open. If a DNA “repair template” is provided—in this case a correct version of the beta-globin gene—the DNA will mend itself using the healthy sequence.

The Chinese group says that among the problems they encountered, the embryo sometimes ignored the template, and instead repaired itself using similar genes from its own genome, “leading to untoward mutations.”

Huang said he stopped the research after the poor results. “If you want to do it in normal embryos, you need to be close to 100 percent,” Huang told Nature News. “That’s why we stopped. We still think it’s too immature.”

http://www.technologyreview.com/news/536971/chinese-team-reports-gene-editing-human-embryo/

Thanks to Michael Moore for bringing this to the It’s Interesting community.

Protein That Can Edit Other Proteins Without DNA Blueprint Discovered

On By A.P.In DNA, gene, Kebmodee, protein, ScienceLeave a comment

In our cells, proteins are the tiny machines that do most of the work. And the instructions for making proteins — and for piecing together their building blocks, called amino acids — are laid out by DNA, then relayed through RNA. But now, researchers show for the first time that amino acids can be assembled by another protein — without genetic instructions. These surprising findings were published in Science this week.

If a cell is an automobile-making factory, then ribosomes are the machines on the protein assembly line that links together amino acids in an order specified by DNA and messenger RNA (mRNA), an intermediate template. If something goes awry and a ribosome stalls, the quality control team shows up to disassemble the ribosome, discard that bit of genetic blueprint, and recycle the partially-made protein.

Turns out, that assembly line can keep going even if it loses its genetic instructions, according to a large U.S. team led by University of Utah, University of California, San Francisco, and Stanford researchers. They discovered an unexpected mechanism of protein synthesis where a protein, and not the normal genetic blueprint, specifies which amino acids are added.

“In this case, we have a protein playing a role normally filled by mRNA,” UCSF’s Adam Frost says in a news release. “I love this story because it blurs the lines of what we thought proteins could do.”

Frost and colleagues found a never-before-seen role for one member of the quality control team: a protein named Rqc2, which helps recruit transfer RNA (tRNA) to sites of ribosomal breakdowns (tRNA is responsible for bringing amino acids to the protein assembly line). Before the incomplete protein gets recycled, Rqc2 prompts the stalled ribosomes to add two amino acids — alanine and threonine — over and over. And that’s because the Rqc2–ribosome complex binds tRNAs that carry those two specific amino acids. In the auto analogy, the assembly line keeps going despite having lost its instructions, picking up whatever it can and attaching it in no particular order: horn-wheel-wheel-horn-wheel-wheel-wheel-wheel-horn, for example.

Pictured above, Rqc2 (yellow) binds tRNAs (blue and teal), which add amino acids (bright sot in the middle) to a partially-made protein (green). The complex binds the ribosome (white). A truncated protein with a seemingly random sequence of alanines and threonines probably doesn’t work properly, and that tail could be a code that signals for the malformed protein to be destroyed.

http://www.iflscience.com/health-and-medicine/protein-directs-protein-synthesis-without-dna-blueprint

Thanks to Kebmodee for bringing this to the attention of the It’s Interesting community.

Genetically Modified Mosquitos Could Eradicate Wild Populations By Only Producing Male Offspring

On By A.P.In Andrea Crisanti, Anopheles gambiae, cloning, DNA, gene, genetic modification, genetically modified, Imperial College London, Lisa Winter, malaria, Medicine, mosquito, Nature, Nature Communications, Nikolai Windbichler, Roberto Galizi, Science1 Comment

by Lisa Winter

Over 200 million people are infected by malaria each year, and the majority of the 627,000 deaths per year are children younger than five. The disease is carried by mosquitos who act as vectors for the parasite. It’s only transmitted to humans by female mosquitoes, as they’re the only ones who bite. A team of researchers led by Andrea Crisanti of the Imperial College London managed to genetically modify mosquitos to produce 95% male offspring, eliminating mosquito populations along with the risk of malaria. The results of the study were published in Nature Communications.

In most species of mosquito, the females need a blood meal in order to acquire the nutrients to create viable eggs. When she does, she can lay about 200 eggs at a time in water, and up to 3,000 eggs over the course of her lifetime. About half of those offspring will be daughters, many of whom will live long enough to produce that amount of offspring also. For humans living near mosquitos carrying the parasite that causes malaria, those numbers of female mosquitos present a very real threat.

But what if the numbers could be skewed so that the sex ratio favors males, who are harmless to humans? This is exactly what Crisanti’s team set out to do with Anopheles gambiae, a species of mosquito endemic to sub-Saharan Africa, where 95% of malaria deaths occur. The researchers modified the males with the enzyme I-Ppol, which excises the X chromosome during spermatogenesis. This renders sperm that would produce daughters to be non-functional, while the sperm that will create male offspring are unaffected. As a result, about 95% of the resulting offspring are male.

Next, modified males were introduced to five caged wild-type populations. As the males mated with the females, they passed along the same mutation until it dominated the population. For four of the five populations, it took only six generations for the mosquitos to die out due to a lack of females.

“What is most promising about our results is that they are self-sustaining,” co-author Nikolai Windbichler said in a press release. “Once modified mosquitoes are introduced, males will start to produce mainly sons, and their sons will do the same, so essentially the mosquitoes carry out the work for us.”

This study was the first to successfully manipulate mosquito sex ratios, and it was done in a big way. The researchers hope that this information will be used to develop genetic mutations to be used in the wild, bringing large populations of mosquitos to their knees.

“The research is still in its early days, but I am really hopeful that this new approach could ultimately lead to a cheap and effective way to eliminate malaria from entire regions,” added lead author Roberto Galizi. “Our goal is to enable people to live freely without the threat of this deadly disease.”

Of course, while eradicating the mosquitos would be fantastic for eliminating the threat of malaria, what other affects would it have? Wouldn’t there be harsh consequences for the ecosystem? After all, mosquitos have been on the planet for about 100 million years and represent 3,500 species. As it turns out, mosquitos wouldn’t really be missed if they were to disappear (http://www.nature.com/news/2010/100721/pdf/466432a.pdf). While mosquitos can act as pollinators as well as a food source for other animals, their absence would be merely a temporary setback before another species filled the niche. Of course, there is a gamble in assuming the replacement organism would be harmless.

“Malaria is debilitating and often fatal and we need to find new ways of tackling it. We think our innovative approach is a huge step forward. For the very first time, we have been able to inhibit the production of female offspring in the laboratory and this provides a new means to eliminate the disease,” Crisanti explained.

Each year, sub-Saharan Africa loses about $12 billion in economic productivity due to malarial infections. Considering developed areas in these countries have per capita incomes of about US$1500, this would have very real implications for the quality of life for people in those areas. Eliminating that disease would also allow doctors and hospitals to address other health concerns, and the environment would likely benefit from not having to use insecticides.

http://www.iflscience.com/health-and-medicine/gm-mosquitos-could-eradicate-wild-populations-only-producing-male-offspring

Termite Genome Reveals Details of “Caste System”

On By A.P.In Arizona State University, caste system, DNA, gene, Hymenoptera, Jürgen Liebig, LiveScience, Nature, Nature Communications, Science, termiteLeave a comment

The genome of the termite has just been sequenced, and it is revealing several clues about how the pests create their rigid social order.

For instance, the new genome, detailed today (May 20) in the journal Nature Communications, uncovers some of the underpinnings of termites’ caste system, as well as the roots of the males’ sexual staying power.

Like other social insects— such as ants, honeybees and some wasps — termites live in highly structured “caste systems,” with each creature programmed to perform a rigidly defined job. A select few termite kings and queens reproduce, while drones and soldiers work, defend the colony or care for young.

Yet termites evolved their social structure independently from ants and bees, which belong to an order known as Hymenoptera.

To understand how this happened, Jürgen Liebig, a behavioral biologist at Arizona State University, and his colleagues collected dampwood termites(Zootermopsis nevadensis nuttingi) that lived in Monterey, California. The researchers then sequenced the genome of the insects and measured how those genes were expressed, or turned on and off.

The research revealed several insights about termite sexual and social behavior.

Termite society is roughly half males and half females. Termites have sexually active kings as well as queens, and kings make sperm throughout their lifetimes. Dampwood termite males also have testes that shrivel and grow seasonally.

Ants and honeybees, in contrast, live in predominantly female societies, and ant sex is a one-time affair.

“Their societies generally consist of females — the males are only there to fly out, mate and die,” Liebig told Live Science.

Sure enough, the termites had more gene variants associated with sperm production and degradation, and those genes were expressed to a greater extent than in ants, Liebig said. That finding suggested those genetic differences contributed to male termites’ sexual longevity.

The termite genome also contains a high fraction of genes that are turned off by chemical tags, or methyl groups, the researchers found. In honeybees, this process of methylation sets the fate of individual animals, determining their place in the caste system. The new findings suggest a similar process may be at play in termites.

In addition, both ants and termites communicate via chemical smell signals sensed by receptors on their antennas.

But while ants venture out for food, these particular termites spend their whole lives dining on one piece of wood.

The new analysis revealed that the termites have far fewer cell types for recognizing individual chemicals, probably because they rarely face off against foreign termites or search for food. They simply don’t need to recognize as many smells, Liebig said.

However, some termite species, such as Australian mound-building termites, do forage and encounter foreigners along the way, so as a follow-up, the team would like to see if those termites can detect a greater array of chemicals, Liebig said.

http://www.scientificamerican.com/article/termite-genome-reveals-details-of-caste-system/

New research shows that whales and dolphins can’t taste anything except salt

On By A.P.In bitter, cetacean, China, Danielle Reed, DNA, dolphin, Dolphins, Dr. Rajadhyaksha, Evolution, Evolutionary Biology, gene, Genome Biology and Evolution, Huabin Zhao, Jianzhi Zhang, Monell Chemical Senses Center, Nature, raoellid, Salt, salty, savory, Science, sour, sweet, taste, taste receptor, umami, University of Michigan, whale, Whales, Wuhan University, zoologyLeave a comment

Tastes are a privilege. The oral sensations not only satisfy foodies, but also on a primal level, protect animals from toxic substances. Yet cetaceans—whales and dolphins—may lack this crucial ability, according to a new study. Mutations in a cetacean ancestor obliterated their basic machinery for four of the five primary tastes, making them the first group of mammals to have lost the majority of this sensory system.

The five primary tastes are sweet, bitter, umami (savory), sour, and salty. These flavors are recognized by taste receptors—proteins that coat neurons embedded in the tongue. For the most part, taste receptor genes present across all vertebrates.

Except, it seems, cetaceans. Researchers uncovered a massive loss of taste receptors in these animals by screening the genomes of 15 species. The investigation spanned the two major lineages of cetaceans: Krill-loving baleen whales—such as bowheads and minkes—were surveyed along with those with teeth, like bottlenose dolphins and sperm whales.

The taste genes weren’t gone per se, but were irreparably damaged by mutations, the team reports online this month in Genome Biology and Evolution. Genes encode proteins, which in turn execute certain functions in cells. Certain errors in the code can derail protein production—at which point the gene becomes a “pseudogene” or a lingering shell of a trait forgotten. Identical pseudogene corpses were discovered across the different cetacean species for sweet, bitter, umami, and sour taste receptors. Salty tastes were the only exception.

“The loss of bitter taste is a complete surprise, because natural toxins typically taste bitter,” says zoologist Huabin Zhao of Wuhan University in China who led the study. All whales likely descend from raccoon-esque raoellids, a group of herbivorous land mammals that transitioned to the sea where they became fish eaters. Plants range in flavors—from sugary apples to tart, poisonous rhubarb leaves—and to survive, primitive animals learned the taste cues that signal whether food is delicious or dangerous. Based on the findings, taste dissipated after this common ancestor became fully aquatic—53 million years ago—but before the group split 36 million years ago into toothed and baleen whales.

“Pseudogenes arise when a trait is no longer needed,” says evolutionary biologist Jianzhi Zhang of the University of Michigan, Ann Arbor, who was not involved in the study. “So it still raises the question as to why whales could afford to lose four of the five primary tastes.” The retention of salty taste receptors suggests that they have other vital roles, such as maintaining sodium levels and blood pressure.

But dulled taste perception might be dangerous if noxious substances spill into the water. Orcas have unwittingly migrated into oil spills, while algal toxins created by fertilizer runoff consistently seep into the fish prey of dolphins living off the Florida coast.

“When you have a sense of taste, it dictates whether you swallow or not,” says Danielle Reed, a geneticist at the Monell Chemical Senses Center in Philadelphia, Pennsylvania. She was not involved with the current work, but co-authored a 2012 paper that found the first genetic inklings that umami and sweet taste receptors were missing in cetaceans, albeit in only one species—bottlenose dolphins.

Flavors are typically released by chewing, but cetaceans tend to swallow their food whole. “The message seems clear. If you don’t chew your food and prefer swallowing food whole, then taste really becomes irrelevant,” Reed says.

http://news.sciencemag.org/biology/2014/05/whales-cant-taste-anything-salt

Thanks to Dr. Rajadhyaksha for bringing this to the attention of the It’s Interesting community.

DNA mugshot: Computer sketch program can reconstruct faces from DNA

On By A.P.In computer, Crime, DNA, DNA mugshot, facial morphology, gene, New Scientist, Philip Ross, PLoS Genetics, Science, The Future1 Comment


Workflow for 3D face scan processing, including the A) original surface, B) trimmed to exclude non-face parts, C) reflected to make mirror image, D) anthropometric mask of quasi-landmarks, E) remapped, F) reflected remapped, G) symmetrized and H) reconstructed.

By Philip Ross

Could a single hair be used to make an accurate 3D model of a criminal suspect’s face? Researchers from the U.S. and Belgium have developed a computer program that renders a crude genetic “mugshot” from a small sample of DNA.

Forensics can already predict eye and hair color relatively easily. Io9 notes that criminal investigators can even use maggots to extract a victim’s DNA from their unidentifiable body or find hidden faces by zooming into hi-res photos of eyes. But the face is a complex structure that’s more difficult to map from just one DNA sample.

According to New Scientist, researchers used a stereoscopic camera to make 3D images of roughly 600 volunteers with mixed European and West African ancestry. They identified more than 7,000 distinct points on the face to see how sex and racial ancestry affect the position of these points. The variations were used to develop a statistical model that reconstructs the overall shape of a person’s face.

The team also isolated 24 genetic variants, called single nucleotide polymorphisms, which play a role in shaping a face, such as those that shape the head during embryonic development. Lastly, researchers had volunteers rate the 600 faces on perceived ethnicity as well as on a scale of masculinity and femininity.

The new study, published in the journal PLOS Genetics, says this process could allow investigators to make computer-generated mugshots from genetic material left at a crime scene.

“We show that facial variation with regard to sex, ancestry, and genes can be systematically studied with our methods, allowing us to lay the foundation for predictive modeling of faces,” the authors note. “Such predictive modeling could be forensically useful; for example, DNA left at crime scenes could be tested and faces predicted in order to help to narrow the pool of potential suspects. Further, our methods could be used to predict the facial features of descendants, deceased ancestors, and even extinct human species. In addition, these methods could prove to be useful diagnostic tools.”

Any 3D renderings created using the new technology wouldn’t be used in a court of law – any person identified via the DNA mugshots would still have his DNA compared to the crime scene sample – but it could at least narrow the search for a suspected criminal. And there are still a few kinks to work out in the process before the technology is ever used in the field.

“I believe that in five to 10 years’ time, we will be able to computationally predict a face,” Peter Claes of the Catholic University of Leuven in Belgium told New Scientist.

http://www.ibtimes.com/dna-mugshot-how-crime-fighting-computer-sketch-program-can-predict-face-your-genes-1563049

Thanks to Da Brayn for bringing this to the attention of the It’s Interesting community.

‘Jumping Genes’ Linked to Schizophrenia

On By A.P.In DNA, Dr. Rajadhyaksha, gene, Japan, jumping gene, line element, Medicine, mental health, mental illness, neural activity, neurogenesis, neurologist, Neurology, Neuron, neuroplasticity, Neuropsychiatric Disease, Neuroscience, neuroscientist, neurotransmitter, RIKEN Brain Science Institute, schizophrenia, Science, Tadafumi KatoLeave a comment

sn-schizophrenia

Roaming bits of DNA that can relocate and proliferate throughout the genome, called “jumping genes,” may contribute to schizophrenia, a new study suggests. These rogue genetic elements pepper the brain tissue of deceased people with the disorder and multiply in response to stressful events, such as infection during pregnancy, which increase the risk of the disease. The study could help explain how genes and environment work together to produce the complex disorder and may even point to ways of lowering the risk of the disease, researchers say.

Schizophrenia causes hallucinations, delusions, and a host of other cognitive problems, and afflicts roughly 1% of all people. It runs in families—a person whose twin sibling has the disorder, for example, has a roughly 50-50 chance of developing it. Scientists have struggled to define which genes are most important to developing the disease, however; each individual gene associated with the disorder confers only modest risk. Environmental factors such as viral infections before birth have also been shown to increase risk of developing schizophrenia, but how and whether these exposures work together with genes to skew brain development and produce the disease is still unclear, says Tadafumi Kato, a neuroscientist at the RIKEN Brain Science Institute in Wako City, Japan and co-author of the new study.

Over the past several years, a new mechanism for genetic mutation has attracted considerable interest from researchers studying neurological disorders, Kato says. Informally called jumping genes, these bits of DNA can replicate and insert themselves into other regions of the genome, where they either lie silent, doing nothing; start churning out their own genetic products; or alter the activity of their neighboring genes. If that sounds potentially dangerous, it is: Such genes are often the culprits behind tumor-causing mutations and have been implicated in several neurological diseases. However, jumping genes also make up nearly half the current human genome, suggesting that humans owe much of our identity to their audacious leaps.

Recent research by neuroscientist Fred Gage and colleagues at the University of California (UC), San Diego, has shown that one of the most common types of jumping gene in people, called L1, is particularly abundant in human stem cells in the brain that ultimately differentiate into neurons and plays an important role in regulating neuronal development and proliferation. Although Gage and colleagues have found that increased L1 is associated with mental disorders such as Rett syndrome, a form of autism, and a neurological motor disease called Louis-Bar syndrome, “no one had looked very carefully” to see if the gene might also contribute to schizophrenia, he says.

To investigate that question, principal investigator Kazuya Iwamoto, a neuroscientist; Kato; and their team at RIKEN extracted brain tissue of deceased people who had been diagnosed with schizophrenia as well as several other mental disorders, extracted DNA from their neurons, and compared it with that of healthy people. Compared with controls, there was a 1.1-fold increase in L1 in the tissue of people with schizophrenia, as well as slightly less elevated levels in people with other mental disorders such as major depression, the team reports today in Neuron.

Next, the scientists tested whether environmental factors associated with schizophrenia could trigger a comparable increase in L1. They injected pregnant mice with a chemical that simulates viral infection and found that their offspring did, indeed, show higher levels of the gene in their brain tissue. An additional study in infant macaques, which mimicked exposure to a hormone also associated with increased schizophrenia risk, produced similar results. Finally, the group examined human neural stem cells extracted from people with schizophrenia and found that these, too, showed higher levels of L1.

The fact that it is possible to increase the number of copies of L1 in the mouse and macaque brains using established environmental triggers for schizophrenia shows that such genetic mutations in the brain may be preventable if such exposures can be avoided, Kato says. He says he hopes that the “new view” that environmental factors can trigger or deter genetic changes involved in the disease will help remove some of the disorder’s stigma.

Combined with previous studies on other disorders, the new study suggests that L1 genes are indeed more active in the brain of patients with neuropsychiatric diseases, Gage says. He cautions, however, that no one yet knows whether they are actually causing the disease. “Now that we have multiple confirmations of this occurring in humans with different diseases, the next step is to determine if possible what role, if any, they play.”

One tantalizing possibility is that as these restless bits of DNA drift throughout the genomes of human brain cells, they help create the vibrant cognitive diversity that helps humans as a species respond to changing environmental conditions, and produces extraordinary “outliers,” including innovators and geniuses such as Picasso, says UC San Diego neuroscientist Alysson Muotri. The price of such rich diversity may be that mutations contributing to mental disorders such as schizophrenia sometimes emerge. Figuring out what these jumping genes truly do in the human brain is the “next frontier” for understanding complex mental disorders, he says. “This is only the tip of the iceberg.”

Thanks to Dr. Rajadhyaksha for bringing this to the attention of the It’s Interesting community.

http://news.sciencemag.org/biology/2014/01/jumping-genes-linked-schizophrenia

Study reveals gene expression changes with meditation

On By A.P.In Center for Investigating Healthy Minds, DNA, Dr. D, epigenetics, gene, IIBB-CSIC-IDIBAPS, Medicine, Meditation, mindfullness, National Center for Complementary and Alternative Medicine, Perla Kaliman, Psychoneuroendocrinology, Richard J. Davidson, Science, Spain, The Brain, University of Wisconsin, University of Wisconsin-MadisonLeave a comment

meditation

With evidence growing that meditation can have beneficial health effects, scientists have sought to understand how these practices physically affect the body.

A new study by researchers in Wisconsin, Spain, and France reports the first evidence of specific molecular changes in the body following a period of mindfulness meditation.

The study investigated the effects of a day of intensive mindfulness practice in a group of experienced meditators, compared to a group of untrained control subjects who engaged in quiet non-meditative activities. After eight hours of mindfulness practice, the meditators showed a range of genetic and molecular differences, including altered levels of gene-regulating machinery and reduced levels of pro-inflammatory genes, which in turn correlated with faster physical recovery from a stressful situation.

“To the best of our knowledge, this is the first paper that shows rapid alterations in gene expression within subjects associated with mindfulness meditation practice,” says study author Richard J. Davidson, founder of the Center for Investigating Healthy Minds and the William James and Vilas Professor of Psychology and Psychiatry at the University of Wisconsin-Madison.

“Most interestingly, the changes were observed in genes that are the current targets of anti-inflammatory and analgesic drugs,” says Perla Kaliman, first author of the article and a researcher at the Institute of Biomedical Research of Barcelona, Spain (IIBB-CSIC-IDIBAPS), where the molecular analyses were conducted.

The study was published in the journal Psychoneuroendocrinology.

Mindfulness-based trainings have shown beneficial effects on inflammatory disorders in prior clinical studies and are endorsed by the American Heart Association as a preventative intervention. The new results provide a possible biological mechanism for therapeutic effects.

The results show a down-regulation of genes that have been implicated in inflammation. The affected genes include the pro-inflammatory genes RIPK2 and COX2 as well as several histone deacetylase (HDAC) genes, which regulate the activity of other genes epigenetically by removing a type of chemical tag. What’s more, the extent to which some of those genes were downregulated was associated with faster cortisol recovery to a social stress test involving an impromptu speech and tasks requiring mental calculations performed in front of an audience and video camera.

Perhaps surprisingly, the researchers say, there was no difference in the tested genes between the two groups of people at the start of the study. The observed effects were seen only in the meditators following mindfulness practice. In addition, several other DNA-modifying genes showed no differences between groups, suggesting that the mindfulness practice specifically affected certain regulatory pathways.

However, it is important to note that the study was not designed to distinguish any effects of long-term meditation training from those of a single day of practice. Instead, the key result is that meditators experienced genetic changes following mindfulness practice that were not seen in the non-meditating group after other quiet activities — an outcome providing proof of principle that mindfulness practice can lead to epigenetic alterations of the genome.

Previous studies in rodents and in people have shown dynamic epigenetic responses to physical stimuli such as stress, diet, or exercise within just a few hours.

“Our genes are quite dynamic in their expression and these results suggest that the calmness of our mind can actually have a potential influence on their expression,” Davidson says.

“The regulation of HDACs and inflammatory pathways may represent some of the mechanisms underlying the therapeutic potential of mindfulness-based interventions,” Kaliman says. “Our findings set the foundation for future studies to further assess meditation strategies for the treatment of chronic inflammatory conditions.”

Study funding came from National Center for Complementary and Alternative Medicine (grant number P01-AT004952) and grants from the Fetzer Institute, the John Templeton Foundation, and an anonymous donor to Davidson. The study was conducted at the Center for Investigating Healthy Minds at the UW-Madison Waisman Center.

http://www.news.wisc.edu/22370

Thanks to Dr. D for bringing this to the attention of the It’s Interesting community.

How the Whale Became the Whale

On By A.P.In DNA, Dr. Rajadhyaksha, gene, marine biology, Science, WhalesLeave a comment

whale

About 54 million years ago, a semiaquatic deerlike creature headed into the water for good, giving rise to whales and their relatives. The newly sequenced genome of the minke whale, a baleen whale found worldwide, tells the story of how stressful this move to live underwater was. An international team has decoded the genomes of four minke whales, a fin whale, a bottlenose dolphin, and a finless porpoise, comparing these cetaceans’ genes to the equivalent genes in other mammals. It found whale-specific mutations in genes important for the regulation of salt and of blood pressure and for antioxidants that get rid of charged oxygen molecules that can harm cells. These molecules increase in number as the whale uses up its oxygen supply during dives. Whales also had larger numbers of related genes, called gene families, for dealing with sustained dives, the team reports online today in Nature Genetics. Overall, 1156 gene families had expanded, and several increased the number of enzymes that help the whale cope with low-to-no oxygen conditions. A few of those expanded families are also expanded in naked mole rats, which live underground where oxygen is scarce. But the numbers of genes for body hair and for taste and smell had decreased. And of course, there were genes and gene families that help explain why whales look the way they do.

http://news.sciencemag.org/biology/2013/11/scienceshot-how-whale-became-whale

Thanks to Dr. Rajadhyaksha for bringing this to the attention of the It’s Interesting community.