'Junk DNA' Plays Crucial Role In Human Diseases

A lot more of our genome is biologically active than previously thought - about 80% - an international team involving over 400 scientists revealed yesterday. The researchers explained that only approximately 1% of our genome has gene regions that code for proteins, which has made them wonder what is going on with the rest of the DNA. Now that we know that four-fifths of the genome is biochemically active, in a way that regulates the expression of nearby genes, geneticists realize that much less of our genome consists of junk DNA as once believed.

9 Experts believe these new findings will help us better understand how several diseases develop and behave, which may lead to more effective and targeted treatments.

The human genome has twice as many genes than previously thought. Many of the previously unknown genes play a role in cellular control, which may impact on the development of human diseases.

The international consortium of scientists analyzed and experimented on sequencing data from 140 different types of human cells and identified thousands of DNA regions that help direct our genes' activities.

Manolis Kellis, an associate professor of computer science at MIT, and co-author of a report that has appeared in several scientific journals, including Nature, said:

"Humans are 99.9 percent identical to each other, and you only have one difference in every 300 to 1,000 nucleotides. What ENCODE allows you to do is provide an annotation of what each nucleotide of the genome does, so that when it's mutated, we can make some predictions about the consequences of the mutation."

What is ENCODE?

ENCODE (Encyclopedia of DNA Elements) is a public research conglomerate launched by the NHGRI (National Human Genome Research Institute) in the USA, and the EMBL-European Bioinformatics Institute (EMBL-EBI) in the UK, in 2003. Its aim is to identify all the functional components of the human genome. The NHGRI and EMBL-EBI pledged to release all project data immediately into public databases.

What scientists initially thought was junk DNA is actually biochemically active.

One of the aims of ENCODE was to better understand the human genome beyond protein-coding genes. Scientists can do this by examining the chemical changes that occur in individual stretches of DNA - these stretches control when specific genetic regions become active. The chemical modifications vary by cell type, and can change the DNA directly, or just the histone proteins that DNA surrounds.

A pilot project was published in 2007, which had looked at 1% of the human genome.

To map these epigenomes (modifications), the researchers gathered data from various cell types. While some laboratories measured DNA histone modifications, others gauged the accessibility of various DNA stretches by cutting them into fragments with enzymes.

ENCODE is a collaboration of 442 scientists from 32 laboratories in Japan, Singapore, Spain, the USA and UK. Together, they generated and examined over 15 terabytes of raw data - all this data is now publicly available. They have used approximately 300 years' worth of computer time, focusing on 147 tissue types to find out what turns certain genes on and off, and the specific characteristics of switches in different cell types.

The ENCODE scientists found that about 80% of the human genome is involved in some type of biochemical event, such as protein binding, specifically binding to proteins that impact on how neighboring genes are used. They also found that the very same regulatory regions have different roles to play, depending on what kind of cell they are acting in.

The scientists analyzed the conservation of the A, T, C and G nucleotides in the new regulatory regions they had identified. Nucleotides are conserved if they stay the same over long periods during our evolution. This can be examined by either comparing how variations occur between different species, or among individuals of the same species.

In an online communiqué, the European Bioinformatics Institute, wrote:

"On 5 September, an international team of researchers reveal that much of what has been called 'junk DNA' in the human genome is actually a massive control panel with millions of switches regulating the activity of our genes. Without these switches, genes would not work - and mutations in these regions might lead to human disease."

Three Billion Pairs of Genetic Code

So far, all three billion pairs of genetic code that make up human DNA have been analyzed by ENCODE. Scientists at the European Bioinformatics Institute explained that they have identified the genome function of 4 million gene switches, which will help researchers hone-in on specific areas of human disease, and hopefully find ways to better treat or cure them. They added that the switches are frequently a long way along the genome from the gene they regulate.

Ewan Birney of the European Bioinformatics Institute, lead analysis coordinator for ENCODE, said: "Our genome is simply alive with switches: millions of places that determine whether a gene is switched on or off. The Human Genome Project showed that only 2% of the genome contains genes, the instructions to make proteins. With ENCODE, we can see that around 80% of the genome is actively doing something. We found that a much bigger part of the genome - a surprising amount, in fact - is involved in controlling when and where proteins are produced, than in simply manufacturing the building blocks."

Ian Dunham, also of European Bioinformatics Institute, said that ENCODE is a useful research tool for any researcher looking into human diseases. Scientists investigating diseases often have a good idea about which genes are involved, but need data on which switches play a role. In some cases the locations of these switches are not where they expected them to be. Dunham said "ENCODE gives us a set of very valuable leads to follow to discover key mechanisms at play in health and disease. Those can be exploited to create entirely new medicines, or to repurpose existing treatments."

A principal investigator on ENCODE, Dr Michael Snyder, professor and chair at Stanford University, explained that ENCODE provides us with the knowledge required so that we can look beyond the genome's linear structure to how the whole network is connected. Genome-wide association studies are helping us understand where certain genes are located, as well as which sequences control them. Snyder said "Because of the complex, three-dimensional shape of our genome, those controls are sometimes far from the gene they regulate and looping around to make contact. Were it not for ENCODE, we might never have looked in those regions. This is a major step toward understanding the wiring diagram of a human being. ENCODE helps us look deeply into the regulatory circuit that tells us how all of the parts come together to make a complex being."

Before, generating and storing enormous volumes of data was a problem in biomedical research. However, as productivity of genome sequencing has improved and become more economical, the focus has moved to analysis, i.e. interpreting data generated from genome-wide association studies. Cambridge University scientists said "ENCODE partners have been working systematically through the human genome, using the same computational and wet-lab methods and reagents in laboratories distributed throughout the world."

Ewan Birney said:

"Getting the best people with the best expertise together is what this is all about. ENCODE has really shown that leading life scientists are very good at collaborating closely on a large scale to produce excellent foundational resources that the whole community can use."

The scientists emphasized that it will be several years before doctors and patients see any tangible benefits from ENCODE.

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Popular Kids Smoke More

A new study shows heart disease, lung cancer, and emphysema may be more prevalent in popular youths. The University of California and the University of Texas collaborated on a study which found that popular students in seven different California high schools were more likely to smoke cigarettes than unpopular students.

This research, published online in the Journal of Adolescent Health, supports previous USC-led studies of pupils in the sixth through twelfth grades throughout Mexico and the United States.

"That we're still seeing this association more than 10 years later, despite marginal declines in smoking, suggests that popularity is a strong predictor of smoking behavior," said Thomas W. Valente, Ph.D., professor of preventive medicine at the Keck School of Medicine of USC and lead author of three prior studies on the subject.

In the most recent study, Valente and his team surveyed 1,950 students in the ninth and tenth grades in October of 2006 and 2007. Students were asked if they had ever smoked, how many students their age they believed to be smokers, how often in the last 30 days they had smoked, how they believed their close friends felt about smoking, and who their five best friends were. Popularity was calculated by how often participants mentioned a student as a friend.

Results found that pupils who believed their friends smoked were more likely to smoke, even if this assumption was incorrect. Popular students started to smoke earlier than non-popular students. Kids that became smokers between ninth and tenth grade were more likely to befriend other smokers. To the researchers surprise, student perception of the norm, (how often and how many of their peers smoked) was less likely to encourage smoking than the perceived behavior of their close friends.

In a separate study in 2012, published in a journal called Salud Publica de Mexico, Valente and a team of researchers surveyed 399 teens at a high school in Jalisco. In 2005, 1,486 youths in the sixth and seventh grades in Southern California were measured and in 2001, 2,525 high school students across the United States were also surveyed. Both studies appeared in the Journal of Adolescent Health.

Valente concluded that consistent samples have come from four different areas, and therefore, it is easy to see adolescents turn to their close friends when choosing what is important in their lives.

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Acupuncture Provides Relief For Chronic Pain, Say Researchers

Acupuncture for the treatment of chronic pain is better than placebo acupuncture (sham acupuncture) or no acupuncture at all, researchers from the Memorial Sloan-Kettering Cancer Center, New York, wrote in the JAMA journal Archives of Internal Medicine. This was their conclusion after gathering and analyzing data from 29 randomized controlled human studies.

The authors explained that acupuncture is used extensively for the treatment of chronic pain. However, its acceptance is mixed and there is controversy regarding its efficacy and value.

Several studies have shown that acupuncture can have a pain-lowering effect when administered by a qualified practitioner. In 2011, a German pain specialist, Dr. Winfried Meissner, found that acupuncture can help reduce pain in patients after surgery.

Other studies, however, have had unfavorable findings. In 2011, researchers from the Universities of Exeter & Plymouth, UK, and the Korea Institute of Oriental Medicine, found that there was very little compelling evidence that acupuncture reduces pain. They added that acupuncture was associated with some serious adverse events.

Andrew J. Vickers, D.Phil., and team carried out individual data meta-analyses, using information from several published randomized control studies from the USA, UK, Germany, Sweden and Spain involving 17,922 patients. Their aim was to find out what effect acupuncture has on some chronic pain conditions.

The authors wrote:

"We found acupuncture to be superior to both no-acupuncture control and sham acupuncture for the treatment of chronic pain. Although the data indicate that acupuncture is more than a placebo, the differences between true and sham acupuncture are relatively modest, suggesting that factors in addition to the specific effects of needling are important contributors to therapeutic effects."

An acupuncturist inserting needles into a patient's skin

Placebo acupuncture involved pretending to stick needles into the patient with retractable needles that did not really perforate the skin, or ones that just went slightly into the surface, rather than penetrating deeper as occurs in proper acupuncture. Proper acupuncture was also compared to deactivated electrical simulation or detuned laser.

The people who were administered real acupuncture had pain scores 0.23, 0.16 and 0.15 lower (SDs, standard deviations) than those receiving the pretend acupuncture for back and neck pain.

The scientists concluded:

"Our results from individual patient data meta-analyses of nearly 18,000 randomized patients in high-quality RCTs provide the most robust evidence to date that acupuncture is a reasonable referral option for patients with chronic pain."

Accompanying Commentary in the Same Journal

In the same journal, Andrew L. Avins, M.D., M.P.H., of Kaiser-Permanente, Northern California Division of Research, Oakland, wrote that there is still an ambiguous relationship between conventional allopathic medical care and alternative and complementary medicine.

Dr. Avins wrote:

"At the end of the day, our patients seek our help to feel better and lead longer and more enjoyable lives. It's ideal to understand the mechanism of action, which carries the potential for developing more and better interventions. But the ultimate questions is: does this intervention work (or, more completely, do its benefits outweigh its risks and justify its costs)?.

"At least in the case of acupuncture, Vickers et al have provided some robust evidence that acupuncture seems to provide modest benefits over usual care for patients with diverse sources of chronic pain. Perhaps a more productive strategy at this point would be to provide whatever benefits we can for our patients, while we continue to explore more carefully all mechanisms of healing."

What is acupuncture?

Acupuncture started off in China thousands of years ago. There are some records showing that some acupuncture was practiced in Europe a few hundred years ago, however, it did not really enter what we know as Western Society until after the 1950s, after which it spread rapidly throughout Western Europe, Canada and the USA.

Acupuncture involves inserting thin needles through the skin at carefully located points of the body at varying depths. Neurologists and other medical specialists are not sure how acupuncture works scientifically.

Most practitioners, even conventional medicine practitioners, have mostly accepted that acupuncture does provide some pain relief, as well as alleviating symptoms of other conditions, such as nausea caused by chemotherapy, or insomnia.

Chinese medical theory says there are meridian points in the body through which "Chi" vital energy runs - these are the acupuncture points. However, there is no anatomical, histological or scientific proof to back up this theory.

Because of the invasive nature of acupuncture, creating case studies with proper scientific controls is extremely difficult. A clinical study involved a placebo (sham product) which is compared to the targeted treatment.

Acupuncture involves the insertion of needles and advice on self-care. The qualified acupuncturist will also carry out a physical exam and make an assessment of the patient's condition. A session lasts about 30 minutes. In most cases, treatment is carried out in weekly or fortnightly sessions.

The acupuncturist uses single-use disposable sterile needles, which are inserted into the skin. When the needle reaches its target depth, there may be some slight pain. Some needles are stimulated with electric currents or heated up after insertion. They remain in their targeted positions for approximately 20 minutes.

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New Discovery Offers Hope For People Who Can't Smell

A recent study by researchers at the University of Michigan Medical School and their team from other universities and published online in Nature Medicine reports that gene therapy could help people restore their sense of smell. The research, conducted on mice, is a sign of hope for people who were born without the ability to smell or who have lost it due to some unfortunate reason.

The experts believe that fixing congenital anosmia, which is medical language for not being able to smell anything, may eventually lead to curing similar medical issues which also come from the cilia or small hair-like pieces which reside on the outside of cells and are present in diseases involving the kidneys, eyes, and other parts of the body.

According to the report, it may take a while for the evidence to be able to help humans and it will eventually be extremely significant for individuals who have lost the ability to smell because of some type of medical problem, and not so much for people who can't smell because of trauma to the nose, or simply old age. However, the new findings help researchers to understand anosmia on the cellular level, which gives hope to anyone who does not have a sense of smell that someday their ability to smell may be restored.

Jeffery Martens, Ph.D., senior author of the study commented:

"Using gene therapy in a mouse model of cilia dysfunction, we were able to rescue and restore olfactory function, or sense of smell. Essentially, we induces the neurons that transmit the sense of smell to regrow the cilia they'd lost."

The rodents involved in the study possessed some genetic defect that affected a protein named IFT88. This defect made the individuals have less- than-normal amounts of cilia in their bodies. When this problem occurs in mice, it results in early death and poor feeding habits, while for humans it can be fatal.

IFT88 genes were implanted into the cells in the mice when the researchers gave them a common cold virus which had plenty of normal DNA. This made it easy for the virus to infect them, and therefore, the researchers could insert the virus into the cells of the mice.

After this, the experts were able to analyze the feeding habits of the mice, as well as how they were growing, and the neuron signals which assist in the smelling process.

14 days after the mice were treated with 3 day therapy, the researchers found the mice to have increased in body weight by 60%, which meant their feeding habits had improved. When the mice were exposed to amyl acetate, or banana oil, the experts were able to see that their neurons were also working correctly.

Martens said: "At the molecular level, function that had been absent was restored.

First author Jeremy McIntyre, Ph.D., added:

"By restoring the protein back into the olfactory neurons, we could give the cell the ability to regrow and extend cilia off the dendrite knob, which is what the olfactory neuron needs to detect odorants."

People who have ciliopathies, diseases caused by the dysfunction of cilia, may benefit greatly from these findings. Examples of ciliopathies include:

• nephronopthisis
• dyskinesia
• primary ciliary
• Alström syndrome
• Bardet-Biedl syndrome

The scientists say that almost all cells in the body have the ability to grow one or more cilia. For the olfactory system, more than one cilia come from the olfactory sensory neurons. These are sensory cells which are present in the olfactory epithelium, the tissue of the nasal cavity. When loss of smell occurs, receptors the connect odorants are restrained on the cilia, resulting the loss of cilia, and the loss of sense of smell.

Martens concludes:

"We hope this stimulates the olfactory research community to look at asnosmia caused by other factors, such as head trauma and degenerative diseases. We know a lot about how this system works - now have to look at how to fix it when it malfunctions."

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Our Brains Make Men And Women See Things Differently

According to a new study, published in BioMed Central's open access journal Biology of Sex Differences, men and women have different ways of using the visual centers of their brains. Experts suggest that while females are better at distinguishing colors, males are more sensitive to fine detail and rapidly moving stimuli.

There are high concentrations of the male sex hormone (androgen) receptors throughout the cerebral cortex in the brain, particularly in the visual cortex, which is in charge of processing images.

Guys have 25% more neurons in the visual cortex than females because, during embryogenesis, androgens are responsible for controlling the development of those neurons.

The vision of men and women was compared by a team of researchers from Brooklyn and Hunter Colleges of the City University of New York. The experts observed people over the age of 16 from both college and high school, including students and faculty. Both sexes needed to have normal color vision and 20/20 sight (with glasses or contacts was considered fine), in order to participate.

Scientists learned that the color vision of men was shifted, after they asked the volunteers to describe colors shown to them across the visual spectrum. It also became clear that male subjects needed a slightly longer wavelength to experience the same hue as the female subjects.

It was not as easy for men to discriminate between colors as it was for women, meaning that the males had a broader ranger in the center of the spectrum.

In order to measure contrast-sensitivity functions (CSF) of vision, the researchers used an image of light and dark bars that were either horizontal or vertical, asking the participants to decide which one they saw. When the light and dark bars were alternated in each image, the image appeared to flicker.

The investigators found, by varying how quickly the bars alternated or how close together they were, that at moderate rates of image change, volunteers lost sensitivity for bars that were close together, and gained sensitivity when the bars were farther apart.

Both males and females had a harder time resolving the images over all bar widths when the image change was faster. However, men had an easier time resolving more rapidly changing images that were closer together than the women.

Professor Israel Abramov, lead author, explained:

"As with other senses, such as hearing and the olfactory system, there are marked sex differences in vision between men and women. The elements of vision we measured are determined by inputs from specific sets of thalamic neurons into the primary visual cortex.

We suggest that, since these neurons are guided by the cortex during embryogenesis, that testosterone plays a major role, somehow leading to different connectivity between males and females. The evolutionary driving force between these differences is less clear."

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