Daily Archives: June 28, 2017

Whole genomes may hold clues to autism, but patience is key – Spectrum

Posted: June 28, 2017 at 5:50 am

Bernie Devlin

Professor, University of Pittsburgh

Associate professor, Harvard University

Professor, University of Pittsburgh

Associate professor, Harvard University

Its been 14 years since scientists spelled out most of the more than 3 billion letters of the human genome. The feat, which took 13 years and cost just under $3 billion to complete, signaled a new era in biomedical research.

Much of human genetic research has focused on the roughly 2 percent of the genome that makes up genes, called the exome. Amino acids, the building blocks of proteins, are encoded in three-letter triplets throughout the exome. This triplet code has allowed us to predict which mutations are likely to alter the function of a protein, and which are likely to be silent.

The most severe mutations are those that disrupt the proteins critical to health and development. Natural selection acts against these changes. Some of the mutations seen in people with autism are severe and rarely seen in the general population. We have used this information to identify genes that are likely relevant to the condition.

We know relatively little, however, about the 98 percent of the genome that does not code for genes. These sweeping swaths of DNA, once blown off as junk, are now known to contain important sequences that switch genes on and off and fine-tune their expression.

Its reasonable to assume that a small subset of the mutations that occur in the noncoding genome contribute to autism. And now that the cost of sequencing a genome has dropped to about $1,500, we can finally test that assumption.

One of the enticing things about mutations in the noncoding genome is their frequency in all of us: Each of our exomes carries perhaps 1 new mutation, whereas our noncoding genomes carry around 100. But most of these mutations are surely benign, and we lack a decoder that allows us to predict which mutations are harmful.

If finding mutations tied to autism in the exome is like finding a needle in a haystack, then finding mutations in the noncoding genome is like finding a peculiar piece of hay in that stack without knowing the properties that distinguish it from the rest. If we are going to be successful in our search, we need to understand what were looking for.

It is possible that some noncoding mutations are as damaging as those in the exome. For instance, they might disrupt a stretch of DNA that regulates the expression of a key gene for brain development. But we have no way to interpret which DNA letters are crucial for the function of these regulatory regions and may therefore affect gene function when mutated.

So how can we approach this daunting problem? History suggests that we must scour the noncoding genome for mutations tied to autism agnostically, without any preconceived notions about where these mutations may be hiding. This unbiased approach has served us well in previous efforts to analyze the genome.

We expect our initial results using this approach to be lean, but we will avoid the pitfalls of a past era of human genetics when many investigators focused on candidate genes they assumed played a role in a particular condition. The record of replication from the candidate-gene approach was abysmal, and in the end very little was learned about the conditions at all. Indeed, several decades of research have taught us that scientists as a whole are not terribly prescient when it comes to predicting the genetic causes of human conditions.

We have begun the search using whole-genome sequencing data from 519 families that have one child with autism but unaffected parents and siblings. To explore these data, we have assembled a consortium of scientists with extensive expertise in many facets of human genetics, genomics, statistical genetics and computer science. Perhaps we can best liken our initial analysis to Alfred Tennysons poem The Charge of the Light Brigade, in which a confluence of circumstances led a British light cavalry unit into a battle against impossible odds.

Figuratively, like the plight of Light Brigade, the outcome of our initial advance into the noncoding genome was likely predetermined. The data from only 519 families are no match for the complexity of the noncoding genome and the sheer number of tests required to properly evaluate it. Only a strong and focused noncoding signal could overcome this testing burden, and if such a signal were present, its likely we would have seen it with other methods.

We detected a small increase in the burden of noncoding variation in individuals with autism compared with their unaffected siblings, but the risk associated with these regulatory variants does not approach the risk associated with protein-coding mutations.

We plan to continue to develop new statistical and bioinformatics methods to interpret the impact of mutations that alter gene regulation. As we amass additional whole-genome sequences, we will continue our unbiased search, and eventually, reliable insights will emerge.

It is not reasonable to expect breakthroughs at this early stage. Instead, we expect to learn much about the nature of the noncoding genome and how to analyze it. As sample sizes and knowledge increases, we will soon transition from this era of initial exploration to one of true biological discovery.

When that transition will occur is impossible to say at this point. Our proverbial haystack will not change in size, content or complexity. However, with many scientists committed to searching together, we will eventually discover the peculiar features of those pieces of hay we seek.

Bernie Devlin is professor of psychiatry at the University of Pittsburgh. Michael Talkowski is associate professor of neurology at the Center for Genomic Medicine at Massachusetts General Hospital.

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Macrauchenia: DNA solves animal riddle that Darwin couldn’t – CNN … – CNN

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Macrauchenia patachonica lived during the last ice age. It resembled a bulky camel without a hump, with a long neck like that of a llama and a short trunk for a nose.

The long neck would enable the herbivore to reach leaves on plants and bushes across what is now South America and the open landscapes of Patagonia.

"It was a fairly bulky quadruped, probably not very fleet of foot," said Ross MacPhee, study co-author and curator at the American Museum of Natural History. "Its outstanding feature, however, was its nose. We have no soft tissue fossils, so we don't know whether the nose was developed into an actual trunk, like an elephant's, or was something more like a big fleshy appendage, resembling the tapir's proboscis. It would not have looked very much like anything alive today."

The nasal opening is right between the eye sockets, rather than just above the teeth.

Legendary British scientist Darwin found the first fossil of this creature, as well as those of other extinct animals that fall under the "South American native ungulates" category, in 1834. The fossils were given to Richard Owen, a British paleontologist, to study. Neither Owen or Darwin could clarify the Macrauchenia's combination of features to a modern-day counterpart or a distinct mammal lineage. But they had only a few limb bones and vertebrae to study.

The ungulates group itself is puzzling to researchers because some of them seem elephant-like, while others are more like aardvarks and moles. Owen even used an old name for the llama to come up with the genus Macrauchenia.

"What we knew for quite some time is that there is a large number of species that are put into this group, and many of them looked quite peculiar," said Michi Hofreiter, lead author of the new study and paleogenomics expert at the University of Potsdam. "They are all extinct, and we do not even know if they represent a single group or belong to different phylogenetic groups."

A previous study tried to place Macrauchenia on the tree of life by using ancient collagen. The new study, led by MacPhee and Hofreiter, built on the 2015 collagen study by extracting mitochondrial DNA from a fossil found in South America. The researchers also used a new approach to recovering Macrauchenia's genome, even without a modern analog.

"I'm pleased to see that our ancient protein results for Macrauchenia are verified using this advancement in ancient DNA alignments of a deeply diverged mammal without close modern relatives," said Frido Welker, author of the 2015 collagen study. "Overcoming the absence of a close relative while achieving a near-complete mitochondrial genome is impressive."

Before these studies using protein and DNA, arguments for where the animal belonged were derived from bone morphology, leading to a variety of possibilities.

Macrauchenia now belongs to a sister group of Perissodactyla, which includes horses, rhinos and tapirs. The two groups split about 66 million years ago, around the time a mass extinction occurred when an asteroid struck the Earth.

"We now have found a place in the tree of life for this group, so we can now also better explain how the peculiarities of these animals evolved," Hofreiter said. "And we lost a pretty old branch on the mammalian tree of life when the last member of this group went extinct."

The new study "finally settles who it is closely related to," MacPhee added. "Finally settles that its lineage had already diverged from that of modern perissodactyls as early as the close of the age of dinosaurs."

Next, the researchers want to solve the mystery of what Darwin dubbed "the strangest animal ever discovered": Toxodon. This giant animal is thought to have looked something like a fur-covered rhinoceros, with the head of a hippopotamus .

They tried to extract Toxodon DNA from fossil samples for this study, but it wasn't possible, as is often the case with fossils found in temperate climates rather than cold ones. However, solving the riddle of Macrauchenia has given them hope.

They will also use these techniques to look at fossils of ancient sloths, armadillos, anteaters and their extinct relatives, MacPhee said. The benefit of ancient proteins like collagen is that they contain genetic information and break down slowly.

Without having to rely on close living relatives of ancient, extinct creatures, researchers can use the latest technology to push their fields forward.

"We will eventually be able to recover complete genomes from many kinds of fossil species," MacPhee said. "Then, we can start comparing genes from different species and make inferences about functional differences in gene products. This will have a profound effect on the study of evolution, because it will be fully empirical, not inferential."

Filling in the gaps that these strange creatures left behind also answers basic questions about the history of our planet.

"The vast majority of all species that ever lived on Earth are now extinct," Hofreiter said. "So if we want to understand the history of life on Earth, we also need to study the extinct species."

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How African Americans Use DNA Testing to Connect With Their Past – The Atlantic

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In 1977, Alondra Nelson remembers lying stomach-down, head-in-hands, in front of the television, watching Alex Haleys miniseries Roots with her parents. I knew that something special was happening because my parents didnt let us watch TV in the evenings, and here, they were letting us watch eight nights in a row, she told a crowd at the Aspen Ideas Festival, which is co-hosted by the Aspen Institute and The Atlantic. They wanted us to see it for its historic nature.

The miniseries, which traced Haleys genealogy back to the Gambia, spurred many African Americans to start tracing their own ancestries. And it inspired Nelsons own interest in genealogy and the social consequences of learning about ones roots. Now, as the dean of social science at Columbia University, Nelson has spent more than a decade studying what she describes as a new groundswell of root-seekingone propelled by genetic testing.

Today, there are dozens of companies that will sequence segments of a customers DNA and tell them about their ancestry. When Nelson asked the audience how many had made use of such services, at least a dozen people raised their hands. But in 2002, the industry was a nascent one. To find its early customers, Nelson had to go to old-fashioned genealogy clubs and societies.

The history of genetics as a field is steeped in eugenics and scientific racism. And yet, Nelson says that for many African Americans, DNA testing held a special appeal because many of the traditional methods of genealogy had been complicated by the history of slavery. Records disappeared. Names changed. People were trafficked across state lines. Stories were verboten because they were too traumatic. Ancestry testing offered a way of circumventing these obstacles, and airing stories that might never otherwise have come to light. Its an interesting story about race and genetics, Nelson says. When we talk about African Americans in science, its often a story of skepticism and distrust. But this ancestry-testing story is one of pioneering early adopters who are willing to do something different.

One such pioneer was Rick Kittles, a geneticist and cancer researcher who founded a company called African Ancestry Inc. His service provided only broad inferences about where people came from, but for many customers, that was enough. It definitely wasnt perfect, but many people said that if its a choice between no information or an inference that might be slightly off, Ill take the inference, Nelson says.

As tests became more precise, those inferences often proved to be unexpectedly moving. Nelson once met a group of African Americans whose DNA suggested that they had Sierra Leonean ancestry. They met for a ceremony of remembrance on the Ashley River in South Carolina, at a ferry landing where slaves were disembarked from ships and auctioned off. The actor Isaiah Washington was there. A man cast soil and stones from Sierra Leone into the river and said a prayer.

We talk about the history of slavery in this country and it feels so abstract. But genetic ancestry testing can make it very personal, she says. The ceremony allowed for a social practice of healing, where people didnt just have to sit with the knowledge. Many of the folks I talked to tell very moving stories about new relationships they began in their communities with their genetic test results.

Nelson expands on this theme in her recent book, The Social Life of DNA. In it, she argues that DNA is more than a molecule that defines our identity; it also takes a social life beyond its influence within individual bodies. The communities that can arise from ancestry testing are a far cry from the cutesy images often used to sell ancestry tests, in which bemused people swap lederhosen for tartan. This test was not just about identity in a narcissistic way, but about people trying to reconcile the history of slavery, and scaling up from their ancestry test to what it means for the history of the U.S., says Nelson.

When Nelson first looked at ancestry tests, they were mainly of interest to the 50-plus crowd. But theyre now capturing the interest of a younger demographic who are drawn to the quantified-self movement, and the power of dramatically revealing where you came from, reality TV-style. Nelson knows that power first-hand. I didnt want to do the test, but I thought if I was going to do it, it would be with a big reveal, she says.

It happened in an Atlanta ballroom, with Rick Kittles and Isaiah Washington MCing. At the event, Martin Luther King III learned his ancestry on his mothers side traced back to Africa, while his fathers line traced to Scotland and Ireland. He told a story about how were all related in the end, and spoke about his desire to go to Europe. Marcus Garvey Jr.s son heard similar resultsa mothers line that descended from Africa and a fathers line that came from the Iberian Peninsula. He told a story that highlighted the horrors of slavery. It was an example about how these results, even when theyre very similar, get taken up into these stories that are important to us, says Nelson.

She learned that her mitochondrial DNA (which passes down the female line) traced back to the Bamileke people of Cameroona fact that delighted her mother. She couldnt wait to tell everyone, Nelson says. And then soon after, she developed a close relationship with a woman from Cameroon, whose family would spend holidays with us. Her son had grandparents day at school, and since his grandparents are in Cameroon, he invited my motherthe DNA Cameroonianto be his grandparent for the day.

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Could Shift Work Damage Your DNA? – WebMD

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By Amy Norton

HealthDay Reporter

TUESDAY, June 27, 2017 (HealthDay News) -- When people work the night shift, their bodies might have less capacity to repair everyday damage to cells' DNA, a small study hints.

The research found that people excreted lower levels of a chemical called 8-OH-dG when they worked at night. That might be a sign that the body's ability to repair DNA damage is diminished.

While this is all theoretical, a number of studies have tied shift work to higher risks of obesity, diabetes, heart disease and certain cancers.

The new findings might point to one reason for those risks, said lead researcher Parveen Bhatti, of the Fred Hutchinson Cancer Research Center, in Seattle.

He explained that 8-OH-dG is excreted in the urine when the body repairs DNA damage that occurs during normal body processes.

"So we think lower clearance [of 8-OH-dG] likely reflects a reduced ability to repair DNA damage," Bhatti said.

"Over time, such DNA damage might contribute to cancer or other diseases," Bhatti added.

And, he said, the whole process might be due to insufficient levels of melatonin -- a hormone that helps regulate the body's internal "clock."

The brain churns out melatonin in response to darkness, and night-shift workers tend to have lower melatonin levels compared to people who work days.

However, a researcher who reviewed the study was cautious about interpreting it.

"The results are interesting," said Kathryn Reid, who studies sleep and circadian rhythms at Northwestern University Feinberg School of Medicine, in Chicago.

"But they didn't link shift work to actual DNA damage," Reid said. And it's not really clear, she added, how melatonin fits in.

"This doesn't show that it's cause-and-effect," Reid noted.

The findings, reported June 26 in the journal Occupational & Environmental Medicine, are based on 50 men and women who worked the night shift in health care jobs.

Overall, Bhatti's team found, the workers had lower levels of 8-OH-dG in their urine when they worked at night, versus nights where they were able to sleep.

Bhatti said the results bolster an earlier study in which his team followed 223 workers -- including the 50 in this one. There, the researchers found that workers' 8-OH-dG levels were lower during daytime sleep, versus nighttime sleep.

The researchers also saw evidence that lower melatonin levels correlated with lower 8-OH-dG. (The 50 workers in the latest study were those who'd shown the biggest drop in melatonin during night work versus night sleep.)

"We think melatonin might be driving this," Bhatti said.

He acknowledged, though, that his findings so far don't prove that.

"I'd like to do a trial where we give melatonin to shift workers with low melatonin levels, then see if it affects this biomarker," Bhatti said, referring to 8-OH-dG.

But until more research is done, he does not suggest shift workers use melatonin supplements in the hopes of preventing DNA damage.

"I'm cautious about melatonin supplements," Bhatti said. "They're not regulated by the Food and Drug Administration. You don't know how much melatonin you're getting, or what kinds of fillers are being used."

Plus, Reid added, melatonin can make people feel groggy, which is probably not a good idea for workers who need to be alert at night.

For now, Bhatti suggested that shift workers be "extra vigilant" about maintaining a healthy lifestyle -- eating a balanced diet, not smoking and getting regular exercise.

Unfortunately, he added, eating well and exercising can be challenging for shift workers.

"That's where I think employers can help," Bhatti said. "They can try to provide access to healthy food and more opportunities for employees to exercise."

WebMD News from HealthDay

SOURCES: Parveen Bhatti, Ph.D., associate member, epidemiology, Fred Hutchinson Cancer Research Center, Seattle; Kathryn Reid, Ph.D., research associate professor, neurology, Northwestern University Feinberg School of Medicine, Chicago; June 26, 2017 Occupational & Environmental Medicine online

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I Tried A Diet And Fitness Plan Based On My DNA And Couldn’t Believe The Results – BuzzFeed News

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1. My suspicion was correct. Genetically, I do have a slower metabolism. Dr. Dan described this in scientific terms as an "efficient metabolism," meaning that I store energy more than someone with a fast or "inefficient metabolism."

2. I also have a gene variation for the FTO gene that is linked to a hormone called ghrelin, which controls hunger. My gene variation implies that I am someone who becomes hungry very easily, therefore creating a higher risk of overeating. Dan said that eating small frequent meals throughout the day to control hunger would be important.

3. I also have a gene variation in the APOA2 gene, indicating that I am sensitive to saturated fats, meaning that it sticks to me more easily! I asked Dr. Dan what foods have saturated fats and he said things like animal products, butter, dairy products, palm oil and coconut oil. Coconut oil?! I ate so much coconut oil because of how often it's promoted as a healthy oil. No wonder I was having trouble.

4. I am someone who would benefit from working out later in the day because my CLOCK gene variations imply that I am a night owl. This made perfect sense because I am definitely not a morning person.

5. I am someone who responds well to "high volume training," meaning high sets and reps of weight training. I always thought that lots of cardio would be the key to losing weight. It turns out that it was going to take a lot of strength training. Dan said that the more muscle I built, the more fat I would burn.

6. I am someone who does not switch from burning carbohydrates to burning fat easily. This would mean that I would need to be eating the right balance of macronutrients: Carbs, protein and fat.

7. Dan also said that I have a gene variation that indicates I metabolize caffeine slowly. This means that I would benefit by having a cup of green tea about 30 minutes prior to a workout for optimal energy.

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Mold discovered on DNA kits – Story | KTBC – FOX 7 Austin – FOX 7 Austin

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After the Austin Police Department was notified of mold on a sexual assault kit, it led to the discovery of more mold in a storage refrigerator that held DNA cases, according to a memo from the City of Austin.

Signature Science, one of the labs Austin hired for DNA analysis while the Austin Police DepartmentDNA lab is suspended, reached out to APD on April 25, 2017 after they found at least one sexual assault kit with mold, the memo read.

The discovery led to an inspection of the storage refrigeratorand more boxes were found with mold on them. The moldy boxes contained cases mostly dating back to the 1990s and early 2000s.

849 DNA cases had some sign of mold on them. A total of 1,629 were inspected, according to the memo.

On June 21, Signature Science concluded "no issues were observed with the samples processed from the case originally reported to have mold."

APDis further researching mold remediation.

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Cancer Cells Found To Streamline Their Genome To Replicate Themselves Quicker – IFLScience

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Cancer cells may be streamlining their genome in order to replicate themselves quicker. A new study has found that the cells remove large repetitive chunks of their DNA, which may explain how some drugs work in the battle against certain cancers. The study is published inPLOS Genetics.

As both human and mouse cancer cells grow, the researchers found that they startto extricate large pieces of repetitive sequences known as ribosomal DNA, the bits thathappen to code forthe ribosomes that aid in copying the genome. As this basically shortens the genome, it means that the cancer cells can simply replicate their entire genome much quicker, allowing the cancer to grow and spread at an accelerated speed.

But this removal of DNA sections comes with a cost. Studies have suggested that these portions of repetitive sequences, rather than being a mistake or meaningless, play an important role in allowing cells to survive DNA damage. By taking them out of the genome, it could go some way to explain why certaincancers are sensitive to DNA-damaging treatments.

Drugs that damage DNA are often used to treat cancer, but it's not clear why they would selectively kill cancer cells, explainsteam lead Jennifer L Gerton, an investigator at the Stowers Institute, in a statement.Our results suggest that off-loading copies of ribosomal DNA could create instability in the genome that makes cells particularly susceptible to chemotherapy with DNA-damaging drugs.

It may seem odd that the cancer cells are shedding DNA that codes for such vital components of the cell, particularly when the team expected they would increasecopies of ribosomal DNA as a way to speed up the copying of the genome. However, it turns out that the pressure exerted on the cancerous cells to proliferate is causing changes to the ribosomal DNA, making the cells get rid of the replications.

In experiments on yeast cells, getting rid of these extra copies has been found to makethe genome more sensitive to DNA damage. The team of researchers now plan tosee if this holds true with human cancer cells as well, and if so, whether it could help lead to new chemotherapy treatments in the battle against the disease.

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Genome’s ‘dark’ side steps into spotlight of autism research – Spectrum

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Given that genes make up a paltry 2 percent of the genome, theyve received a disproportionate amount of attention from autism researchers. Slowly, however, the other 98 percent of the genome the so-called dark matter is emerging from the shadows.

Once considered nonfunctional or junk DNA, these non-gene regions are now known to contain instructions for making pieces of RNA that fine-tune the activity of genes. The RNA segments control when and where genes are active. Autism researchers have looked at the role of these RNAs for only about a decade, but they already have tantalizing clues that the segments seem to be involved in the condition.

Its an important field that hasnt really been studied very much yet, says Daniel Campbell, assistant professor of psychiatry at the University of Southern California in Los Angeles.

Evidence so far suggests that some noncoding RNAs are unusually scarce and others unusually abundant in people with autism. A few of the RNAs regulate autism genes or signaling pathways implicated in the condition.

Because of this, noncoding RNAs could also lead to treatments for autism.

When the cause of a disorder is in the regulation of genes, then it might be a better target for intervention than having to repair a gene, says Dorret Boomsma, professor of genetics and psychology at Vrije University in Amsterdam.

There are two major types of noncoding RNA: short stretches called microRNAs, which are roughly 20 nucleotides in length; and so-called long noncoding RNAs (lncRNAs), which have more than 200 nucleotides.

Both types typically turn genes off, but do so in different ways. microRNAs bind to messenger RNA (mRNA), the template for a protein thats created from a gene, and either destabilize it or block the machinery that translates it into protein. lncRNAs target mRNAs, but they can also bind and block microRNAs. And they can influence gene expression by interacting either with proteins that turn genes on or off or with those that control how tightly DNA is packed in the nucleus.

Some noncoding RNAs are more abundant in the brain than in other tissues, and seem to be needed for forming neurons and the connections, or synapses, between them.

Changes to the levels of these RNAs can have serious consequences for brain development and function, says Boryana Stamova, associate adjunct professor of neurology at the University of California, Davis.

For example, altered levels of noncoding RNA in the brains of people with autism track with a drop in the expression of genes important for brain signaling, and a rise in the expression of genes in the immune system. Both pathways are implicated in autism.

However, each study generates a different list of noncoding RNAs linked to autism, and few RNAs have consistently been tied to the condition. Some of these inconsistencies could be due to variable methods for detecting noncoding RNAs. Also, noncoding RNA expression patterns vary with age, sex, brain region and even cell type all factors that could contribute to the inconsistencies.

Some preliminary genetic evidence hints at how the levels of noncoding RNAs may be altered in autism.

For example, large deletions or duplications in the genome often overlap with noncoding RNAs. Roughly 40 such mutations with strong ties to autism contain known microRNAs1.

Smaller mutations can also involve noncoding RNAs. A 2009 study pinpointed a stretch of chromosome 5 as a site for common variants linked to autism. Campbells team explored this region and found that it encodes a lncRNA called MSNP1AS. MSNP1AS turned out to be unusually abundant in the brains of people with autism who carry common variants in this genetic region2.

Campbells team discovered that MSNP1AS turns off a gene called MSN that is involved in brain development. Last year, they reported that excess MSNP1AS decreases the number of signal-receiving branches on cultured neurons3. When the researchers tamped down the levels of MSNP1AS, they found changes in the expression of genes involved in the immune system, protein production and DNA packaging4.

All three of those pathways have been implicated by people looking at protein-coding genes that are mutated in autism, Campbell says.

Campbells team has also reported that CHD8, one of the strongest autism candidate genes, controls the quantity of noncoding RNAs in a cell5.

Some researchers are comprehensively scanning noncoding regions for mutations linked to autism. They are sequencing the whole genomes of people with autism and their unaffected relatives to find spontaneous mutations. Some of the mutations in noncoding RNAs may turn out to contribute to autism, says Ivan Iossifov, associate professor at Cold Spring Harbor Laboratory in New York. Once we get more data, this will become a very important focus, he says.

Other teams are working out the role of noncoding RNAs in animal models.

For example, researchers have found enhanced levels of AK081227, a lncRNA, in a mouse model of Rett syndrome, a condition related to autism. The researchers found that this lncRNA controls the expression of a receptor for gamma-aminobutyric acid, a chemical messenger implicated in autism.

Another study, published in April, showed that Rett mice have increased levels of two microRNAs that impair neuron formation in utero6. Blocking these microRNAs returns neuron formation to normal.

Studies like these hint that manipulating the RNAs might treat autism although that strategy is not straightforward.

You can use specific RNA sequences to overexpress or inhibit microRNAs in a mouse, says Nikolaos Mellios, assistant professor of neuroscience at the University of New Mexico in Albuquerque. But this is difficult for the clinic.

The primary hurdle is delivering the RNAs to the brain, because they typically cannot cross the blood-brain barrier. Even if they could, researchers would need to ensure that the RNAs affect only the intended regions.

There are several clinical trials underway using noncoding RNAs to treat cancer and diabetes. Last year, the U.S. Food and Drug Administration approved an RNA-based treatment for spinal muscular atrophy, which is otherwise fatal. The drug must be injected repeatedly into infants spinal fluid, and so is unlikely to be adopted for less severe conditions. Still, the approval supports the idea that RNAs can be used to treat neurological conditions.

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The Moral Question That Stanford Asks Its Bioengineering Students – The Atlantic

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When students in Stanford Universitys Introduction to Bioengineering course sit for their final exams, the first question that they have to answer is about our ability to write DNA.

Scientists have fully sequenced the genomes of humans, trees, octopuses, bacteria, and thousands of other species. But it may soon become possible to not just read large genomes but also to write themsynthesizing them from scratch. Imagine a music synthesizer with only four keys, said Stanford professor Drew Endy to the audience at the Aspen Ideas Festival, which is co-hosted by the Aspen Institute and The Atlantic. Each represents one of the four building blocks of DNAA, C, G, and T. Press the keys in sequence and you can print out whatever stretch of DNA you like.

In 2010, one group did this for a bacterium with an exceptionally tiny genome, crafting all million or so letters of its DNA and implanting it into a hollow cell. Another team is part-way through writing the more complex genome of bakers yeast, with 12 million letters. The human genome is 300 times bigger, and as I reported last month, others are trying to build the technology that will allow them to create genomes of this size.

For now, thats prohibitively expensive, but it wont always be that way. In 2003, it cost 4 dollars to press one of the keys on Endys hypothetical synthesizer. This month, it costs just two centsa 200-fold decrease in price in just 14 years. In the same time frame, the cost of tuition at Stanford has doubled, and is now around $50,000. Given all of that, the first question that Stanfords budding bioengineers get is this:

At what point will the cost of printing DNA to create a human equal the cost of teaching a student in Stanford?

And the answer is: 19 years from today.

There are a lot of assumptions built into that answer. It will take a lot of technological advances to print the complex genomes of humans and to keep the costs falling at the same pace as they have done. But bearing those assumptions in mind, the problem is a mathematical one, and the students are graded on their ability to solve it. But the follow-up question is a little more complicated:

If you and your future partner are planning to have kids, would you start saving money for college tuition, or for printing the genome of your offspring?

The question tends to split students down the line, says Endy. About 60 percent say that printing a genome is wrong, and flies against what it means to be a parent. They prize the special nature of education and would opt to save for the tuition. But around 40 percent of the class will say that the value of education may change in the future, and if genetic technology becomes mature, and allows them to secure advantages for them and their lineage, they might as well do that.

There is clearly no right answer to the second question, and students are graded on their reasoning rather than their conclusion. But when both questions are considered together, they suggest, Endy says, that in the order of a human generation, well have to face possibilities that are much stranger than what were prepared for.

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Patient education: Atopic dermatitis (eczema) (Beyond the Basics)

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ECZEMA OVERVIEW

Atopic dermatitis, also known as eczema, is a skin problem that causes dry, itchy, scaly, red skin. It can occur in infants, children, and adults, and seems more common in certain families. Eczema can be treated with moisturizers and prescription ointments.

More detailed information about atopic dermatitis is available by subscription. (See "Treatment of atopic dermatitis (eczema)" and "Management of severe refractory atopic dermatitis (eczema)".)

ECZEMA CAUSES

The cause of eczema is not completely understood, although hereditary factors appear to play a strong role. In most people, atopic dermatitis is caused by a genetic dysfunction in the outermost layer of the skin (the epidermis). The epidermis is the first line of defense between the body and the environment. When the epidermis is intact, it keeps environmental irritants, allergens, and microbes from entering the body.

Despite popular belief, in children, eczema is rarely linked to food allergies. If a food allergy is suspected, the child should be evaluated by an allergy specialist. (See "Patient education: Food allergy symptoms and diagnosis (Beyond the Basics)" and "Role of allergy in atopic dermatitis (eczema)".)

ECZEMA SYMPTOMS

Most people with eczema develop their first symptoms before age five. Intense itching of the skin, patches of redness, small bumps, and skin flaking are common. Scratching can cause additional skin inflammation, which can further worsen the itching. The itchiness may be more noticeable at nighttime.

Features of eczema vary from one individual to another, and can change over time. Although eczema is usually confined to specific areas of the body, it may affect multiple areas in severe cases:

In infants, there may be red, scaly, and crusted areas on the front of the arms and legs, cheeks, or scalp. The diaper area is not usually affected.

In children and adults, eczema commonly affects the back of the neck, the elbow creases, and the backs of the knees (picture 1). Other affected areas may include the face, wrists, and forearms (picture 2). The skin may become thickened and darkened, or even scarred, from repeated scratching.

The skin can also become infected as a result of scratching. Signs of infection include painful red bumps that sometimes contain pus; a healthcare provider should be consulted if this occurs.

Other findings in people with eczema can include:

Dry, scaly skin

Plugged hair follicles causing small bumps to develop, usually on the face, upper arms, and thighs

Increased skin creasing on the palms and/or an extra fold of skin under the eye

Darkening of the skin around the eyes

ECZEMA DIAGNOSIS

There is no specific test used to diagnose eczema. The diagnosis is usually based upon a person's medical history and physical examination.

Factors that strongly suggest eczema include long-standing and recurrent itching, a personal or family history of allergic conditions, and an early age when symptoms began. Other factors include worsened symptoms after exposure to certain triggers or any of the skin findings noted above.

ECZEMA TREATMENT

Eczema is a chronic condition; it typically improves and then flares (worsens) periodically. Some people have no symptoms for several years. Eczema is not curable, although symptoms can be controlled with a variety of self-care measures and drug therapy.

Who treats eczema?Many patients with atopic dermatitis can initially be treated by their primary care provider. However, a skin specialist (dermatologist) may be recommended in certain situations, such as if the condition does not improve with treatment, if certain areas of the body are affected (face or skin folds), and if another condition could be causing symptoms.

Eliminate aggravating factorsEliminating factors that worsen eczema can help to control the symptoms. Aggravating factors may include:

Heat, perspiration, dry environments

Emotional stress or anxiety

Rapid temperature changes

Exposure to certain chemicals or cleaning solutions, including soaps and detergents, perfumes and cosmetics, wool or synthetic fibers, dust, sand, and cigarette smoke

Keep the skin hydrated

EmollientsEmollients are creams and ointments that moisturize the skin and prevent it from drying out. The best emollients for people with atopic dermatitis are thick creams (such as Eucerin, Cetaphil, and Nutraderm) or ointments (such as petroleum jelly, Aquaphor, and Vaseline), which contain little to no water. Emollients are most effective when applied immediately after bathing. Emollients can be applied twice a day or more often if needed. Lotions contain more water than creams and ointments and are less effective for moisturizing the skin.

BathingIt is not clear if showers or baths are better for keeping the skin hydrated. Lukewarm baths or showers can hydrate and cool the skin, temporarily relieving the itching of eczema. An unscented, mild soap or nonsoap cleanser (such as Cetaphil) should be used sparingly. An emollient should be applied immediately after bathing or showering to prevent the skin from drying out as a result of water evaporation.

However, hot or long baths (greater than 10 to 15 minutes) and showers should be avoided since they can dry out the skin.

In some cases, healthcare providers may recommend dilute bleach baths for people with eczema. These baths help to decrease the number of bacteria on the skin that can cause infections or worsen symptoms. To prepare a bleach bath, to cup of bleach is placed in a full bathtub (about 40 gallons) of water. Bleach baths are usually taken for five to ten minutes twice per week.

Treat skin irritation

Topical steroidsPrescription steroid (corticosteroid) creams and ointments may be recommended to control mild to moderate atopic dermatitis. Steroid creams and ointments are available in a variety of strengths (potencies); the least potent are available without a prescription (eg, hydrocortisone 1% cream). More potent formulations require a prescription.

Steroid creams or ointments are usually applied to the skin once or twice per day. These help to reduce symptoms and moisturize the skin. As the skin improves, a non-medicated emollient can be resumed. Strong topical steroids may be needed to control severe flares of eczema; however, these should be used for only short periods of time to prevent thinning of the skin.

Other skin treatmentsNewer skin treatments for eczema include tacrolimus (Protopic) and pimecrolimus (Elidel). These are effective in controlling eczema, although they do not work as quickly as topical steroids. They are useful in sensitive areas such as the face and groin, and can be used in children over age two. Due to safety concerns, these treatments should only be used as instructed by a healthcare provider.

Oral steroidsOral steroids (eg, prednisone) occasionally are used to treat a severe flare of eczema, although this treatment is not usually recommended on a regular basis because of potential side effects.

Ultraviolet light therapy (phototherapy)Ultraviolet light therapy (phototherapy) can effectively control atopic dermatitis. However, this therapy is expensive, may increase a person's risk for skin cancer, and is therefore recommended only for people with severe eczema who do not respond to other treatments.

Immunosuppressive drugsDrugs that weaken the immune system may be recommended for people with severe eczema who do not improve with other treatments. Treatment with these drugs can cause serious side effects, including an increased risk for infection.

Injectable medicationsThe injectable "biologic" medication dupilumab (brand name: Dupixent), which targets the immune system, may be beneficial for treating atopic dermatitis. Due to its high cost and potential side effects, this drug is reserved for adults with moderate to severe atopic dermatitis that has not responded to other treatments.

Control itching

Oral antihistaminesOral antihistamines sometimes help relieve the itching of eczema. The over-the-counter antihistamine diphenhydramine (Benadryl), and prescription antihistamines, such as hydroxyzine (Atarax) and cyproheptadine, are most effective for itching caused by eczema, although these drugs can cause drowsiness.

The nonsedating antihistamines such as cetirizine (Zyrtec) and loratadine (Claritin) may relieve symptoms, and both are available without a prescription in the United States.

Wet dressingsWet dressings help soothe and hydrate the skin, reduce itching and redness, loosen crusted areas, and prevent skin injury from scratching. Dampened cotton garments may be worn over the affected area and covered with a dry garment. The person may wear these dressings overnight or change them every eight hours during the day.

Can eczema be prevented?Babies who have a parent, brother, or sister with eczema have a high risk of developing atopic eczema. In these babies, the use of moisturizing creams or ointments from the first week of life may prevent eczema during the first year. However, it is uncertain whether this measure is effective in preventing eczema later in life.

WHERE TO GET MORE INFORMATION

Your healthcare provider is the best source of information for questions and concerns related to your medical problem.

This article will be updated as needed on our website (www.uptodate.com/patients). Related topics for patients, as well as selected articles written for healthcare professionals, are also available. Some of the most relevant are listed below.

Patient level informationUpToDate offers two types of patient education materials.

The BasicsThe Basics patient education pieces answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials.

Patient education: Eczema (atopic dermatitis) (The Basics) Patient education: Seborrheic dermatitis (The Basics) Patient education: Giving your child over-the-counter medicines (The Basics) Patient education: Melasma (The Basics) Patient education: Peanut allergy (The Basics)

Beyond the BasicsBeyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are best for patients who want in-depth information and are comfortable with some medical jargon.

Patient education: Food allergy symptoms and diagnosis (Beyond the Basics)

Professional level informationProfessional level articles are designed to keep doctors and other health professionals up-to-date on the latest medical findings. These articles are thorough, long, and complex, and they contain multiple references to the research on which they are based. Professional level articles are best for people who are comfortable with a lot of medical terminology and who want to read the same materials their doctors are reading.

Approach to the patient with a scalp disorder Pathogenesis, clinical manifestations, and diagnosis of atopic dermatitis (eczema) Introducing formula to infants at risk for allergic disease Primary prevention of allergic disease: Maternal diet in pregnancy and lactation The impact of breastfeeding on the development of allergic disease Treatment of atopic dermatitis (eczema) Management of severe refractory atopic dermatitis (eczema) Role of allergy in atopic dermatitis (eczema)

The following organizations also provide reliable health information.

National Library of Medicine

(www.nlm.nih.gov/medlineplus/healthtopics.html)

National Institute on Arthritis and Musculoskeletal and Skin Diseases

(www.niams.nih.gov/hi/index.htm)

American Academy of Dermatology

(www.aad.org)

American Academy of Allergy, Asthma and Immunology

(www.aaaai.org)

EczemaNet

(www.skincarephysicians.com/eczemanet/)

National Eczema Association

(www.nationaleczema.org)

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Literature review current through: May 2017. | This topic last updated: Tue Apr 18 00:00:00 GMT+00:00 2017.

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Patient education: Atopic dermatitis (eczema) (Beyond the Basics)

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