Tag Archives: human genome

Hand-held device for extracting DNA. (c) UW/NanoFacture/KNR

New, tiny device can extract clean DNA material within minutes

Hand-held device for extracting DNA. (c) UW/NanoFacture/KNR

Hand-held device for extracting DNA. (c) UW/NanoFacture/KNR

The human genome has been sequenced a mere few years ago, and since then a great deal of advancements have been made in the field. This is extremely important since in the future, personalized medicine needs each individual’s genetic markup such that treatment may get the most effective punch or diseases and afflictions might be avoided altogether.

The DNA sequencing industry is growing rapidly, having turned into a multi-billion dollar industry. Since the turn of the new millennium, however, a lot of companies have seen rapid growth, only to plummet at the hand of counter effective technology.

Collecting and sequencing DNA is still expensive, too expensive for gross use at least. That may soon change. For instance, University of Washington engineers and NanoFacture, a Bellevue, Wash., company, have recently unveiled a small, light-weight device that can allegedly collect viable DNA material for samples in mere minutes, instead of hours – all without risking damaging the DNA itself as is the case with current methods.

“It’s very complex to extract DNA,” said Jae-Hyun Chung, a UW associate professor of mechanical engineering who led the research. “When you think of the current procedure, the equivalent is like collecting human hairs using a construction crane.”

Chung isn’t overreacting at all. Current methods rely on centrifuges and chemical solutions, some of which are toxic, to extract DNA. Micro-filters that strain DNA from the bulk fluid is also commonly used. These methods are slow and expensive, however.

The UW device is comprised of tiny, microscopic probing tips that dip into a fluid sample – saliva, sputum or blood – and apply an electric field within the liquid. The field guides particles towards the surface of the probing tips, however larger ones bounces away while DNA molecules stick. Using this method, it takes only 2-3 minutes to purify and separate DNA. The researchers claim they can scale the technology to analyse 96 samples at a time, which is standard for large-scale handling.

A miniature version, the size and shape of a pen, has also been developed which patients can use to swipe saliva at home and ship them to hospitals where their DNA is readily separated and collected for analysis, without having to leave their homes.

Combined with other recent efforts geared towards cheap sequencing, the technology developed by Chung and colleagues might lend a great hand in the strive to form a huge medical DNA database to battle diseases.

[source University of Washington]

Researchers have shown that four-stranded 'quadruple helix' DNA structures -- known as G-quadruplexes -- exist within the human genome. (Credit: Jean-Paul Rodriguez and Giulia Biffi)

Quadruple helix DNA proven to exist in human cells

Exactly 50 years ago, Cambridge researchers Watson and Crick published a monumental paper that for the first time described the intertwined double helix DNA structure which carries the fundamental genetic code for life. The discovery led to an explosion of advancements in the fields of genetics and health, but also in chemistry or computing. Now, researchers, coincidentally or not from the same Cambridge University, have proven that a quadruple helix structure, first discovered some ten years ago, does in fact also exist in human cells.

Researchers have shown that four-stranded 'quadruple helix' DNA structures -- known as G-quadruplexes -- exist within the human genome. (Credit: Jean-Paul Rodriguez and Giulia Biffi)

Researchers have shown that four-stranded ‘quadruple helix’ DNA structures — known as G-quadruplexes — exist within the human genome. (Credit: Jean-Paul Rodriguez and Giulia Biffi)

These rather peculiar DNA structures are called G-quadruplexes, since they form in regions of DNA that are rich in the building block guanine. For over ten years, scientists have been able to replicate the quadruple helix in lab tubes, but only recently did they show that these can found in living human cells too, after they arrived at the end of their research stream from hypothetical model, to computer simulation to human cell identification.

In the new study, chemist Shankar Balasubramanian, grad student Giulia Biffi, and coworkers at Cambridge University developed antibodies that are highly specific for G-quadruplex binding.

Four strands of DNA – still human

The scientists generated antibody proteins, based on previous research, that detect and bind to areas in a human genome rich in quadruplex-structured DNA. Rather ingeniously, these proteins were also tagged  with a florescence marker so the emergence of the structures in the cell could be tracked and imaged, similar to how modern biopsy-bypass techniques employ florescence markers to image cancer cells.

While quadruplex DNA is found fairly consistently throughout the genome of human cells and their division cycles, a marked increase was shown when the fluorescent staining grew more intense during the ‘s-phase’ — the point in a cell cycle where DNA replicates before the cell divides.

With this new found proof, drugs that target quadruplexes with synthetic molecules that trap these DNA structures – consequently preventing cell division – might become effective against cancer proliferation.

“We are seeing links between trapping the quadruplexes with molecules and the ability to stop cells dividing, which is hugely exciting,” said Professor Shankar Balasubramanian from the University of Cambridge’s Department of Chemistry and Cambridge Research Institute, whose group produced the research.

“The research indicates that quadruplexes are more likely to occur in genes of cells that are rapidly dividing, such as cancer cells. For us, it strongly supports a new paradigm to be investigated — using these four-stranded structures as targets for personalised treatments in the future.”

Findings were published in the journal Nature Chemistry.



Nobody’s perfect: we all carry genetic variants that may cause diseases

For the first time ever, researchers at at Cambridge and Cardiff, have identified and compiled a list of damaging or disease associated DNA variants in the human genome. The researchers found that an average healthy individual carries 400 potentially damaging DNA variants. Most such variants should be found as genetic research provides more refined results.

dna-variantScientists have known for a long time that each of us carries genetic variants that when exposed to certain “ideal” conditions cause various illnesses. This is the first time however that researchers have been able to quantify how many such variants each of us has, and list them.

“For over half a century, medical geneticists have wanted to establish the magnitude of the damage caused by harmful variants in our genomes,” says Dr Yali Xue, lead author from the Wellcome Trust Sanger Institute. “Our study finally brings us closer to understanding the extent of these damaging mutations.”

“We measured the number of potentially damaging variants in the genomes of apparently normal healthy humans by comparing two different datasets: whole genome sequences from 179 people in the 1000 Genomes Pilot Project, who were unlikely to have any overt genetic disease at the time of sampling, and information from the Human Gene Mutation Database (HGMD), a detailed catalogue of human disease-causing mutations that have been reported in the scientific literature.”

Exposing our genetic flaws

Don’t look so alarmed, though. Most of these disease or damaged variants were single, ‘recessive’ genetic variants that typically do not cause harm to the carrier. These genes end up to cause the illness they’ve been programmed to carry when two copies – one in each chromosome – are present or if the variant is dominant. Dominant disease genetic variants can give rise to a disease trait when even a single copy is present. The researchers claim one in ten people studied is expected to develop a genetic disease as a consequence of carrying these variants, either because they carry two copies or they have dominant variant.

Specifically, the researchers showed that each individual carried 281–515 missense substitutions, 40–85 of which were homozygous, predicted to be highly damaging. They also carried 40–110 variants classified by the HGMD as disease-causing mutations (DMs), 3–24 variants in the homozygous state, and many polymorphisms putatively associated with disease.

“In the majority of people we found to have a potential disease-causing mutation, the genetic condition is actually quite mild, or would only become apparent in the later decades of life,” says Professor David Cooper, lead author of the study from Cardiff University. “We now know that normal healthy people can possess many damaged or even completely inactivated proteins without any noticeable impact on their health. It is extremely difficult to predict the clinical consequences of a given genetic variant, but databases such as HGMD promise to come into their own as we enter the new era of personalized medicine.”

Findings were reported in the American Journal of Human Genetics.

[story source / image source]

(a–c) Shrinkage of a ∼3.3-nm-diameter nanopore, indicated by circles, and (d–f) enlargement of a ∼6-nm-diameter nanopore in a graphene sheet at 1200 °C.

Cheap DNA sequencing is a step closer with graphene nanopores

Graphene is the strongest material ever discovered by man, and naturally its applications has been extended to a variety of fields – most recently genetics.  University of Texas at Dallas scientists have used advanced manipulation techniques to shrink a sheet of graphene to the point that it’s small enough to read DNA. This successful attempt now opens doors for the possible introduction of graphene based, cheap DNA sequencing devices.

“Sequencing DNA at a very cheap cost would enable scientists and doctors to better predict and diagnose disease, and also tailor a drug to an individual’s genetic code,” said Dr. Moon Kim, UT-Dallas professor of materials science and engineering.

(a–c) Shrinkage of a ∼3.3-nm-diameter nanopore, indicated by circles, and (d–f) enlargement of a ∼6-nm-diameter nanopore in a graphene sheet at 1200 °C.

(a–c) Shrinkage of a ∼3.3-nm-diameter nanopore, indicated by circles, and (d–f) enlargement of a ∼6-nm-diameter nanopore in a graphene sheet at 1200 °C. (c) University of Texas

The first complete human genome sequence was finally presented in 2003 by the international scientific research group known as the Human Genome Project after more than a decade of research and $2.3 billion. Now, various institutions and scientific groups are pushing the current technological limits to reach the $1000 DNA sequencing threshold cost for a person.

With fast and cheap DNA sequencing, physicians could easily prescribe medications keeping in mind your genetic tendencies, as well as avert various serious illnesses before they can evolve by tackling your genetic predispositions.  Graphene might become an essential components in such cheap DNA sequencing devices.

Because it’s so thin, but strong, the researchers saw it as a perfect candidate, and sought ways to control its pore size. The team of researchers manipulated the size of the nanopore by using an electron beam from an advanced electron microscope and in-situ heating up to 1200 degree Celsius temperature.  The nanopore shrinking process can be stopped by blocking the electron beam.

“This is the first time that the size of the graphene nanopore has been controlled, especially shrinking it,” said Kim. “We used high temperature heating and electron beam simultaneously, one technique without the other doesn’t work.”

As graphene pore size control has been proven, the next logical step is to implement it into a working device, something more of a challenge.

“If we could sequence DNA cheaply, the possibilities for disease prevention, diagnosis and treatment would be limitless,” Kim said. “Controlling graphene puts us one step closer to making this happen.”

Findings were published in the journal Carbon.

via KurzweilAI

MinION portable DNA sequencing device plugged to the USB port of a laptop

USB-powered DNA sequencer puts genetic analysis out of the lab to your laptop

Since the advent of modern DNA sequencing technology, biological research and discoveries has been dramatically accelerated. It’s absolutely instrumental to genetic research nowadays, which among other great achievements, has lead to the sequencing of the human genome. The methods and technologies involved in DNA sequencing are terribly complex, however, and usually require sophisticated research laboratories. What if you could simplify the process?

MinION portable DNA sequencing device plugged to the USB port of a laptop

Oxford Nanopore (ON) had this idea in mind for some time, and recently unveiled an extraordinary product the company has completed developing – a fast, portable, and disposable nucleotide sequencer the gets powered via USB and runs analysis on the same computer it gets plugged in. Extreme costs are promised to be alleviated once this products gets introduced on the market, eliminating the need for highly expensive facility usage for small projects and offering the possibility to perform genetic analysis on the go when needed.

The MinION, as it’s been dubbed by ON researchers, doesn’t need polymerase chain reaction (PCR) or other DNA amplification technique for optimum sensitivity, and can sequence up to 150 million base pairs within its six hour working life. The device accepts samples of  blood, plasma, and serum for an immediate analysis.

MinION’s centerpiece is its nanopore port. A nanopore is basically an organic molecule with a very narrow hole, just a few nanometers in width. This nanopore is embedded inside two molecule thick synthetic polymer membrane, which has a very high electrical resistance, such that the nanopore hole forms a path from one side of the membrane to the other. Through the nanopore hole electrophysiological fluid is inserted, which has its volume divided in half as a result of a specific geometry.

When passing through the variable geometry in the nanopore hole, the electrophysiological fluid is swept by an ionic current which causes a voltage difference. Each molecule, including DNA or RNA, has its own characteristic voltage, and thus using this technique the MinION can detect and identify the sample. Of course, the MinION’s main purpose is that of sequencing DNA, so the device is optimized to differentiate the four nucleobases (adenine, cytosine, guanine, and thymine) which encode genes in DNA. To analyze the DNA, the MiniON uses strand sequencing.

This diagram shows a protein nanopore set in an electrically resistant membrane bilayer.  An ionic current is passed through the nanopore by setting a voltage across this membrane. (c) Oxford Nanopore Technology

This diagram shows a protein nanopore set in an electrically resistant membrane bilayer. An ionic current is passed through the nanopore by setting a voltage across this membrane. (c) Oxford Nanopore Technology

The device’s sensing electronics has  512 nanopores embedded onto its sample chip, resulting in a total strand reading rate of about 7500 bases/second. During its limited 6 hours operation life time, the MinION can read 150 million bases; enough to read small chromosomes or bacteria genome. Check out this excellent video from Oxford Nanopore explain in great detail how the MinION works and how the DNA sequencing process unfolds.

Nanopore DNA sequencing from Oxford Nanopore on Vimeo.

The researchers working on the device have already tested the device successfully, after sequencing the genome of the lambda bacteriophage – 48500 base pairs in length. Clive Brown, the Chief Technology Officer of Oxford Nanopores, has been cited during the product’s announcement at AGBT 2012, that the MinION might be introduced on the market with a $900 price tag!

“The exquisite science behind nanopore sensing has taken nearly two decades to reach this point; a truly disruptive single molecule analysis technique, designed alongside new electronics to be a universal sequencing system.  GridION and MinION are poised to deliver a completely new range of benefits to researchers and clinicians,” said Dr Gordon Sanghera, CEO of Oxford Nanopore.  “Oxford Nanopore is as much an electronics company as a biotechnology company, and the development of a high-throughput electronics platform has been essential for us to design and screen a large number of new candidate nanopores and enzymes. Our toolbox is customer-ready and we will continue to develop improved nanopore devices over many years, including ongoing work in solid state devices.”

press release / via Gizmag

Data Center

IBM is building the largest data array in the world – 120 petabytes of storage

Data Center

IBM recently made public its intentions of developing what will be upon its completion the world’s largest data array, consisting of 200,000 conventional hard disk drives intertwined and working together, adding to 120 petabytes of available storage space. The contract for this massive data array, 10 times bigger than any other data center in the world at present date, has been ordered by an “unnamed client”, whose intentions has yet to be disclaimed. IBM claims that the huge storage space will be used for complex computations, like those used to model weather and climate.

To put things into perspective 120 petabytes, or 120 million gygabites would account for 24 billion typical five-megabyte MP3 files or 60 downloads of the entire internet, which currently spans across 150 billion web pages. And while 120 petabytes might sound outrageous by any sane standard today, in just a short time, at the rate technology is advancing, it might become fairly common to encounter a data center similarly sized in the future.

“This 120 petabyte system is on the lunatic fringe now, but in a few years it may be that all cloud computing systems are like it,” Hillsberg says. Just keeping track of the names, types, and other attributes of the files stored in the system will consume around two petabytes of its capacity.

I know some of you tech enthusiasts out there are already grinding your teeth a bit to this fairly dubious numbers. I know I have – 120 petabytes/200.000 equals 600 GB. Does this mean IBM is using only 600 GB hard drives? I’m willing to bet they’re not that cheap, it’s would be extremely counter-productive in the first place. Firstly, it’s worth pointing out that we’re not talking about your usual commercial hard drives. Most likely, the hard-drives used will be of the sort of 15K RPM Fibre Channel disks, at the very least – which beats the heck out of your SATA drive currently powering your computer storage. These kind of hard-drives are currently not that voluminous in storage as SATA ones, so this might be an explanation. There’s also the issue of redundancy which is encountered in data centers, which decreases the amount of available real storage spaces and increases as a data center is larger. So the hard-drives used could actually be somewhere between 1.5 and 3 TB, all running on cutting edge data transfer speed.

Steve Conway, a vice president of research with the analyst firm IDC who specializes in high-performance computing (HPC), says IBM’s repository is significantly bigger than previous storage systems. “A 120-petabye storage array would easily be the largest I’ve encountered,” he says.

To house these massively numbered hard-drives IBM located them horizontaly on drawers, like in any other data center, but made these spaces even wider, in order to accommodate more disks within smaller confines. Engineers also implemented a new data backup mechanism, whereby information from dying disks is slowly reproduced on a replacement drive, allowing the system to continue running without any slowdown. Also, a system called GPFS, meanwhile, spreads stored files over multiple disks, allowing the machine to read or write different parts of a given file at once, while indexing its entire collection at breakneck speeds.

Last month a team from IBM used GPFS to index 10 billion files in 43 minutes, effortlessly breaking the previous record of one billion files scanned in three hours. Now, that’s something!

Fast access to huge storage is of crucial necessity for supercomputers, who need humongous amounts of bytes to compute the various complicate model they’re assigned to, be it weather simulations or the decoding of the human genome. Of course, they can be used, and most likely are already in place, to store identities and human biometric data too. I’ll take this opportunity to remind you of a frightful fact we published a while ago – every six hours the NSA collects data the size of the Library of Congress.

As quantum computing takes ground and eventually the first quantum computer will be developed, these kind of data centers will become highly more common.

UPDATE: The facility has indeed opened in 2012. 

MIT Technology Review

The 100 Mb Ion 316 semiconductor sequencing chip released in July 2011

New DNA sequencing device could decode your genome for just $1000

The inventor Jonathan Rothberg with a semiconductor chip used in the Ion Torrent machine. (c) Christopher Capozziello , NY Times

The inventor Jonathan Rothberg with a semiconductor chip used in the Ion Torrent machine. (c) Christopher Capozziello , NY Times

News of a low-cost semiconductor-based gene sequencing machine has been reported this Wednesday in the journal Nature, by a team led by Jonathan Rothberg. The astonishing advancement might lead to a age of personal human genome sequence, where people will be able to decipher their own DNA for as low as $1000.

The human genome was first mapped in 2001 and cost roughly $1 billion to do. Now, ten years and other tens of billions of dollars later important advancements have led to further detailed research, like the sequencing of a complete neanderthal genome, as well as optimization of the process and technology employed so it might become cheaper and faster.

Inventor, Jonathan Rothberg of Ion Torrent Systems in Guilford, Conn., is one of several pursuing the goal of a $1,000 human genome, which he said he could reach by 2013 because his machine is rapidly being improved. To test their genome device, they chose to map the one of Intel’s co-founder, Gordon Moore, the man behind the famed “Moore’s Law” prediction of exponentially growing computer power.

“Gordon Moore worked out all the tricks that gave us modern semiconductors, so he should be the first person to be sequenced on a semiconductor,” Dr. Rothberg said.

The 100 Mb Ion 316 semiconductor sequencing chip released in July 2011

The 100 Mb Ion 316 semiconductor sequencing chip released in July 2011. (c) Ion Torrent

The technology employs semiconductor chip to sense DNA or genetic material by detecting a voltage change, instead of light. This eliminates the use of highly expensive equipment that would’ve been required otherwise. Using this tech, the evolution of which is compared by its researchers with that of the digital camera, scientists have been able to scan three bacterial strains and one human genome.

“When it [digital photography] first started out, the resolution was not good and the pictures were not as good as on film. But the technology improved, which made it more accessible and now more people can enjoy photography and become better photographers,” Dr. Maneesh Jain, vice president of marketing and business development at Ion Torrent said.

The human genome is that of Dr. Moore, as you’ve been given to find out earlier, and as for the bacterial strains, the first two genomes of the deadly E. coli bacteria that swept Europe in the spring were decoded on the company’s machines. The whole decoding process takes less than two hours to complete!

Applications, of course, are numerous especially for the common users. At $1000, a genome sequence might become as common as a medical check in the very close future. You’d then be confronted with your very own mapped genome, which when interpreted can describe various medical condition predispositions, leading to the so-called personalized medicine, which seeks to avoid trial-and-error by using genetic data found during a scan to better pair treatments with diseases.

Tell me what your genes are, so I can tell you who you are

Don’t expect everything you get back to be extremely accurate, though. Dr. Moore’s genome has a genetic variant that denotes a “56 percent chance of brown eyes,” one that indicates a “typical amount of freckling” and another that confers “moderately higher odds of smelling asparagus in one’s urine,” Dr. Rothberg and his colleagues reported. Also, Dr. Moore’s genome has two strains that seems to indicated towards an “increased risk of mental retardation” — which was obviously never the case.

Genetic hazards, however, come at a much lower stake than those caught up during one’s lifetime.

“Most of what genetics tell us is that there are a lot of fairly common variants that have a modest degree of risk for diseases,” Dr. Peter Gregersen, director of the Robert S. Boas Center for Genomics and Human Genetics at the Feinstein Institute for Medical Research in Manhasset, N.Y said. “This is important from a scientific point of view, but the data itself is not actionable.

“The risk of disease associated with high blood pressure, smoking and high cholesterol is far greater than most of the genetic risks coming out of whole genome scanning,” Gregersen added. For example, if your genome scan identified a mutation that put you at risk for macular degeneration, a leading cause of blindness, “you may see an ophthalmologist, and there are forms that are treatable, but knowing your genetics won’t impact this much,” he said.

More time, research and money is needed for a more useful information to be outputted by a genome sequencing machine, as the human DNA is decoded to a more precise degree. We might be headed towards Gattaca hell, a utopian/dystopian climate, depends on how you decide to favor it, where everything will be known about you before you’re even born – how you’ll look when you’re 25, how smart can you become, where you’d be best fitted for work, whether there’s a chance you’ll condone in criminal behavior, etc. It’s all in the genes my momma used to tell me…