Canadian scientists crack hidden DNA code

Last Updated: Wednesday, May 5, 2010 | 1:11 PM ET

Canadian researchers have unraveled a genetic “code within a code” that helps explain how the instructions for building complex organisms, like humans, can be found in a small number of genes.

University of Toronto scientists Brendan Frey and Benjamin Blencowe said they have found a hidden code in DNA that helps explain how a small number of genes can contain instructions for a larger number of proteins and structures.

When researchers fully sequenced the human genome in 2004, they were surprised at how few genes humans actually have.

“Human DNA has 22,000 genes. That might seem like a lot, but not when you consider that a poplar tree has 45,000,” said Frey, in a statement.

Frey said his team, including Blencowe and Yoseph Barash, found a second level of information that the cells of living organisms use to create a larger set of instructions.

“We discovered a hidden code within DNA that living cells use to turn 20,000 genes into hundreds of thousands of genetic messages, by rearranging their parts,” he said.

Barash and Frey, who is also a professor of computer science and engineering, created a computer program that analyzes DNA to find “code words” in the genome.

The code words together are called the “splicing code,” containing the biological information needed to splice together different parts of the genetic code in different orders to generate a greater number of messages.

“For example, three neurexin genes can generate over 3,000 genetic messages that help control the wiring of the brain,” said Frey.

Neurexin is a protein that glues together the connections between nerve cells in the brain.

Frey said their work is the result of a close collaboration between computer scientists and experimental biologists.

“Understanding a complex biological system is like understanding a complex electronic circuit. Our team ‘reverse-engineered’ the splicing code using large-scale experimental data generated by the group,” he said.

The research was the cover story in this week’s issue of the journal Nature.

DNAWellnessinfo.com Resource: http://www.cbc.ca/technology/story/2010/05/05/tech-dna-splicing-code.html#ixzz0n9Wn5yO0

Blood Tests May Reveal Tumor Size

Feb. 22, 2010 – cbsnews.com

(CBS) This article was written by Discover’sAndrew Moseman.

Doctors who are torn over how aggressively to treat a cancer patient, not knowing whether a tumor has fully regressed or is coming back, might someday be able to find out just by testing the patient’s blood. In a study forthcoming his week in Science Translational Medicine, John Hopkins researchers say they have tested a way to spot the “fingerprint” of cancer-the changes to the

Jeffery Schloss of the National Human Genome Research Institute, who wasn’t involved in the study, likened the approach to drawing a map. Sequencing the letters of the genetic code would be akin to plotting every house in a large neighborhood. The Hopkins team was looking only for neighborhoods-in particular, neighborhoods out of place compared with where they would be in normal tissue. The researchers in the study looked at tissue from people with breast or bowel cancer, and found multiple DNA rearrangements in each of the samples of cancerous tissue.

In each patient, the genetic changes in the cancerous cells amount to a unique marker of the patient’s tumor, the researchers say. Using blood samples from two of the colorectal cancer patients, they found the test was sensitive enough to detect this marker or “fingerprint” DNA that had been shed by tumors into the bloodstream.

The study’s approach could be invaluable for tracking the progress of a tumor. When a cancer is operated on or treated with radio – or chemotherapy, the levels of the fingerprint should fall, and vanish altogether if the tumor has been eradicated. Indeed, in one of their patients, the study authors saw the cancer biomarker drop after surgery but then rise again, suggesting to them that the cancer wasn’t fully eradicated.

Because the technique requires sequencing a person’s whole genome, it’s not coming to a hospital near you in the immediate future, says study author Bert Vogelstein: “This is really personalized medicine. This is not something off the shelf…. This is something that has to be designed for each individual patient”. But with the cost of genome sequencing rapidly coming down in price, this kind of approach might not be too far away, and doctors could use it to catch a recurring cancer before it’s large enough to be visible to other methods, like CT scans.


By Andrew Moseman
Reprinted with permission from Discover

DNAWellnessinfo.com Resource: http://www.cbsnews.com/stories/2010/02/22/tech/main6232081.shtml

Scientists develop universal DNA reader to advance faster, cheaper sequencing efforts

2/11/10 – physorg.com

Led by ASU Regents’ Professor Stuart Lindsay, director of the Biodesign Institute’s Center for Single Molecule Biophysics, the ASU team is one of a handful that has received stimulus funds for a National Human Genome Research Initiative, part of the National Institutes of Health, to make DNA genome sequencing as widespread as a routine medical checkup.

The broad goal of this “$1000 genome” initiative is to develop a next-generation DNA sequencing technology to usher in the age of personalized medicine, where knowledge of an individual’s complete, 3 billion-long code of DNA information, or genome, will allow for a more tailored approach to disease diagnosis and treatment. With current technologies taking almost a year to complete at a cost of several hundreds of thousands of dollars, less than 20 individuals on the planet have had their whole genomes sequenced to date.

To make their research dream a reality, Lindsay’s team has envisioned building a tiny, nanoscale DNA reader that could work like a supermarket checkout scanner, distinguishing between the four chemical letters of the DNA genetic code, abbreviated by A, G, C, and T, as they rapidly pass by the reader.

To do so, they needed to develop the nanotechnology equivalent of threading the eye of a needle. In this case, the DNA would be the thread that could be recognized as it moved past the reader ‘eye.’ During the past few years, Lindsay’s team has made steady progress, and first demonstrated the ability to read individual DNA sequences in 2008—but this approach was limited because they had to use four separate readers to recognize each of the DNA bases. More recently, they demonstrated the ability to thread DNA sequences through the narrow hole of a fundamental building block of nanotechnology, the carbon nanotube.

Lindsay’s team relies on the eyes of nanotechnology, scanning tunneling- (STM) and atomic force- (ATM) microscopes, to make their measurements. The microscopes have a delicate electrode tip that is held very close to the DNA sample.

In their latest innovation, Lindsay’s team made two electrodes, one on the end of microscope probe, and another on the surface, that had their tiny ends chemically modified to attract and catch the DNA between a gap like a pair of chemical tweezers. The gap between these functionalized electrodes had to be adjusted to find the chemical bonding sweet spot, so that when a single chemical base of DNA passed through a tiny, 2.5 nanometer gap between two gold electrodes, it momentarily sticks to the electrodes and a small increase in the current is detected. Any smaller, and the molecules would be able to bind in many configurations, confusing the readout, any bigger and smaller bases would not be detected.

“What we did was to narrow the number of types of bound configurations to just one per DNA base,” said Lindsay. “The beauty of the approach is that all the four bases just fit the 2.5 nanometer gap, so it is one size fits all, but only just so!”

At this scale, which is just a few atomic diameters wide, quantum phenomena are at play where the electrons can actually leak from one electrode to the other, tunneling through the DNA bases in the process.

Each of the chemical bases of the DNA genetic code, abbreviated A, C, T or G, gives a unique electrical signature as they pass between the gap in the electrodes. By trial and error, and a bit of serendipity, they discovered that just a single chemical modification to both electrodes could distinguish between all 4 DNA bases.

“We’ve now made a generic DNA sequence reader and are the first group to report the detection of all 4 DNA bases in one tunnel gap,” said Lindsay. “Also, the control experiments show that there is a certain (poor) level of discrimination with even bare electrodes (the control experiments) and this is in itself, a first too.”

“We were quite surprised about binding to bare electrodes because, like many physicists, we had always assumed that the bases would just tumble through. But actually, any surface chemist will tell you that the bases have weak chemical interactions with metal surfaces.”

Next, Lindsay’s group is hard at work trying to adapt the reader to work in water-based solutions, a critically practical step for DNA sequencing applications. Also, the team would like to combine the reader capabilities with the carbon nanotube technology to work on reading short stretches of DNA.

More information: The Nano Letters research article can be accessed online at URL: http://pubs.acs.org/doi/pdfplus/10.1021/nl1001185

Provided by Arizona State University (news : web)

DNAWellnessinfo.com Resource:  http://www.physorg.com/news185129971.html

Evolution faster than thought

2010-01-01 22:18 news24.com

Berlin – A team of German and US scientists has discovered that genetic mutation – the basic process of evolution – occurs much faster than previously thought, according to a study published on Friday.

The team of researchers from the Max Planck Institute for Molecular Biology in Tuebingen and the University of Indiana studied genome mutation in a species of cress (Arabidopsis thaliana), and found that each gene in the plant will mutate on average once in every 143 million generations.

Genomes are the complete set of genetic information for any organism, consisting of individual genes found in DNA.

“While the long-term effects of genome mutations are quite well understood, we did not know how often new mutations arise in the first place,” project leader Detlef Weigel of the Max Planck Institute said in a press statement.

Thousands of years

The discovery means that for many plant species, whose millions of individual members produce thousands of seeds with each generation, an entire genome mutation can occur within a relatively short space of time.

“Evolution reveals itself only after thousands, not millions of years,” Weigel said.

Such a rate of genetic change can explain how species adapt to changing circumstances quickly, and the study gives the example of weeds becoming resistant to specific herbicides within just a few generations.

60 new mutations in humans

The team used new methods to track all the genetic changes in five “lines” (plants with common ancestors) of Arabidopsis thaliana over 30 generations. In the final generation they searched for differences to the original plants.

“To ferret out where the genome had changed was only possible because of new methods that allowed us to screen the entire genome with high precision and in a very short time,” Weigel said.

The team said that the same speed of genetic change could in theory be expected in human DNA, meaning that with six billion people on earth each form of human gene would be permanently mutating somewhere on the planet.

“If you apply our findings to humans, then each of us will have in the order of 60 new mutations that were not present in our parents. Everything that is genetically possible is being tested in a very short period,” said Indiana University’s Michael Lynch. Max Planck Society:

- SAPA

DNAWellnessinfo.com Resource:  http://www.news24.com/Content/SciTech/News/1132/fde544679f8e47fb9d0155d6adc6171a/01-01-2010-10-18/Evolution_faster_than_thought

Faster, Cheaper DNA Sequencing Method Devised

ScienceDaily (Dec. 22, 2009) — Boston University biomedical engineers have devised a method for making future genome sequencing faster and cheaper by dramatically reducing the amount of DNA required, thus eliminating the expensive, time-consuming and error-prone step of DNA amplification.

A team of researchers led by Boston University biomedical engineer Amit Meller is using electrical fields to efficiently draw long strands of DNA through nanopore sensors, drastically reducing the number of DNA copies required for a high throughput analysis. (Credit: Figure copyright, Nature Nanotechnology, 2009)

In a study published in the Dec. 20 online edition of Nature Nanotechnology, a team led by Boston University Biomedical Engineering Associate Professor Amit Meller details pioneering work in detecting DNA molecules as they pass through silicon nanopores. The technique uses electrical fields to feed long strands of DNA through four-nanometer-wide pores, much like threading a needle. The method uses sensitive electrical current measurements to detect single DNA molecules as they pass through the nanopores.

“The current study shows that we can detect a much smaller amount of DNA sample than previously reported,” said Meller. “When people start to implement genome sequencing or genome profiling using nanopores, they could use our nanopore capture approach to greatly reduce the number of copies used in those measurements.”

Currently, genome sequencing utilizes DNA amplification to make billions of molecular copies in order to produce a sample large enough to be analyzed. In addition to the time and cost DNA amplification entails, some of the molecules — like photocopies of photocopies — come out less than perfect. Meller and his colleagues at BU, New York University and Bar-Ilan University in Israel have harnessed electrical fields surrounding the mouths of the nanopores to attract long, negatively charged strands of DNA and slide them through the nanopore where the DNA sequence can be detected. Since the DNA is drawn to the nanopores from a distance, far fewer copies of the molecule are needed.

Before creating this new method, the team had to develop an understanding of electro-physics at the nanoscale, where the rules that govern the larger world don’t necessarily apply. They made a counterintuitive discovery: the longer the DNA strand, the more quickly it found the pore opening.

“That’s really surprising,” Meller said. “You’d expect that if you have a longer ‘spaghetti,’ then finding the end would be much harder. At the same time this discovery means that the nanopore system is optimized for the detection of long DNA strands — tens of thousands basepairs, or even more. This could dramatically speed future genomic sequencing by allowing analysis of a long DNA strand in one swipe, rather than having to assemble results from many short snippets.

“DNA amplification technologies limit DNA molecule length to under a thousand basepairs,” Meller added. “Because our method avoids amplification, it not only reduces the cost, time and error rate of DNA replication techniques, but also enables the analysis of very long strands of DNA, much longer than current limitations.”

With this knowledge in hand, Meller and his team set out to optimize the effect. They used salt gradients to alter the electrical field around the pores, which increased the rate at which DNA molecules were captured and shortened the lag time between molecules, thus reducing the quantity of DNA needed for accurate measurements. Rather than floating around until they happened upon a nanopore, DNA strands were funneled into the openings.

By boosting capture rates by a few orders of magnitude, and reducing the volume of the sample chamber the researchers reduced the number of DNA molecules required by a factor of 10,000 — from about 1 billion sample molecules to 100,000.

The research was funded by the National Human Genome Research Institute of the Institutes of Health and by the National Science Foundation.

DNAWellnessinfo.com Resource:  http://www.sciencedaily.com/releases/2009/12/091220143923.htm

New DNA Test Could Speed Time to Sepsis Diagnosis

Method saves an average 18 hours over conventional blood culture, research shows

THURSDAY, Dec. 10 (HealthDay News) — A new DNA test for sepsis-causing bacteria provides results much sooner than the current gold-standard blood-culture method, a new study shows.

Sepsis is a potentially fatal condition caused by the immune system’s strong reaction to a serious infection. The sooner sepsis is diagnosed, the sooner infection-specific treatment can begin, leading to improved patient outcomes.

In this study, researchers found that the new Prove-it microarray platform — a series of microscopic spots of short DNA fragments whose sequences are specific for individual organisms — delivered results an average of 18 hours faster than the blood culture technique, which is based on detecting inhibition of growth of bacteria through antibiotics

.

The blood culture method typically takes one to three days to become positive. Another one or two days may be needed to identify the bacteria and their antibiotic sensitivity patterns, according to background information in the study.

“The Prove-it sepsis assay yielded a high sensitivity and specificity, and identified bacterial species about 18 hours before conventional culture methods did, providing practical and realistic delivery of same-day bacterial identification after the blood-culture positivity,” the researchers wrote.

“Our study was not designed to address health-care costs,” they added. “Although additional costs are associated with this assay, these costs need to be assessed in the context of the effect of early identification on total patient management, which might include savings relating to factors such as targeted investigation, length of stay in hospital, and outcomes for the patient.”

The study was released online Dec. 9 in advance of publication in an upcoming print issue of The Lancet.

DNAWellnessinfo.com Resource:  http://health.usnews.com/articles/health/healthday/2009/12/10/new-dna-test-could-speed-time-to-sepsis-diagnosis.html

DNA test could prevent blood disorder in infants

2009-12-09 22:11:17 CST

by Brendan Missett

Genetic testing in newborns can help identify T-cell lymphopenia, a blood disorder that disrupts the function of the immune system, according to new research.

As part of the study, which was published in the December 9 issue of the Journal of the American Medical Association, researchers screened all infants born in Wisconsin in 2008 for T-cell lymphopenia using a DNA test which measures the number of T-cell receptor excision circles (TREC) in a blood sample, HealthDay reports.

Of a the 71,000 infants screened, a total of 11 were found to have at least one abnormal TREC test result, eight of whom were diagnosed with T-cell lymphopenia after being evaluated by a clinical immunologist.

In many cases, the study notes, babies with the blood disorder, manifested by a low level of white blood cells, can appear to be healthy and have no family history of immunodeficiency.

“Consequently, many infants with severe T-cell deficiencies are not identified until life-threatening infections occur,” said Dr John Routes of the Medical College of Wisconsin.

He added that early diagnosis, which could be facilitated by the DNA testing, dramatically improves the prognosis of newborns with the condition.

The T-cell lymphopenia screen costs only $5.50 per test, according to Medscape.com.

DNAWellnessinfo.com Resource:  http://www.privatemdlabs.com/news/Blood_and_Blood_Diseases/DNA-test-could-prevent-blood-disorder-in-infants$19504807.php

Salivary DNA tests to support dentists’ fight against periodontal disease

New Dating Service Tests Your DNA for the Right Match

In Love & Sex by Jeffery , on Friday, November 13, 2009, 6:33 AM (PST)

Nothing says romance like deoxyribonucleic acid.

If you’ve been looking for love in all the wrong places, maybe you should look a little bit deeper… like in your DNA. In the latest trend in online matchmaking, genetic testing companies are saying your best bet for true romance could be in a quick cheek swab.

Through genetic testing, some companies are saying you can be provided with a better biological match, which theoretically could mean someone you’ll get along with better and possibly even create healthier children with.

According to Eric Holzle, founder of ScientificMatch.com, one of the first sites to offer the service, the idea of genetic testing could revolutionize matchmaking. “How many dating services can you think of where they can suggest you might have better children?” he said.

Folks who sign up for the service get a packet in the mail which includes a cheek swab for skin cells. They then mail it back and within two weeks an analysis is completed, and the swabee can post pictures and profile information to the site. The test, like the one soon to be launched by Swiss company GenePartner, will run the lovelorn around $100.

Still, not everyone is taken with the idea. Dr. Rocio Moran, medical director of the General Genetics Clinic at the Cleveland Clinic, calls the idea “ridiculous.”

“They are just trying to make a buck,” she said. “That if it’s genetic, it must be real science.”

So what do you think? Can love be found deep down in our chemical makeups, or is it more complicated than just having the right combination of amino acids?

DNAWellnessinfo.com Resource:  http://www.limelife.com/blog-entry/New-Dating-Service-Tests-Your-DNA-for-the-Right-Match/26323.html

Experts To Discuss DNA Barcodes And Their Uses

Article Date: 09 Nov 2009 – 2:00 PST – medical news today

World experts are gathering this week to discuss DNA barcodes and their uses, covering a wide range of areas from medicine to agriculture, health to fraud, from smuggling to exploring our planet’s prehistoric life.

About 350 experts from 50 countries are meeting for the third International Barcode of Life conference that is taking place from 9 to 11 November in Mexico City.

DNA barcoding is a new technique that uses a short DNA sequence from the genome of an organism, living or dead, as a molecular way of identifying the species it belongs to. DNA barcode sequences are very short compared to the entire genome and can be obtained quite quickly and cheaply.

The Consortium for the Barcode of Life (CBOL) is an international initiative devoted to developing DNA barcoding as a global standard for the identification of biological species.

Through the CBOL initiative, experts are agreeing a standard for DNA barcoding.

The challenge for the initiative is finding an area of DNA that does not vary much down generations, yet varies sufficiently between species to make identification reliable. A number of studies have shown that for higher animals, the variability of the “Folmer region” at the 5′ end of the cytochrome c oxidase subunit 1 mitochondrial region (COI) is very low (about 1 to 2 per cent) and even between closely related species it differs by several per cent, making this the ideal region on which to settle as the standard for DNA barcoding.

This section of DNA is 648 nucleotide pairs long for most groups and is surrounded by regions that are reasonably conserved, making it quite easy to isolate and analyze.

In some groups, COI is not an effective barcode region and a different standard region will have to be sought and agreed on. But the idea is that in all cases, DNA barcoding uses a short, standard region that enables cost-effective species identification.

As the standard is being thrashed out and discussed, all manner of professionals are starting to get interested in its application, from medical and agricultural researchers, to police and customs officers.

For instance, using DNA barcoding, palaeontologists hope to be able to sequence ancient plant and animal remains extracted from degraded DNA in northern permafrost cores to reveal Earth’s pre-historic life, and how life on Earth responded to global climate change.

And by analyzing the DNA of gut contents, scientists hope to discover secrets of what eats what in the animal world.

One such group is the The International Barcode of Life Project, headquartered in Guelph, Canada, where barcoding was pioneered. They will be telling meeting delegates about their discovery that eight species of bat feed on over 300 types of insect, one of the largest food webs ever found.

Conservationists are now getting very excited about the application of DNA barcoding to help unravel the complexity of the dynamics in the natural world.

Scott Miller, Acting Under Secretary for Science at the Smithsonian Institution and Chair of the Consortium for the Barcode of Life (CBOL), who are co-hosting the meeting with the Instituto Biologia, Universidad Nacional Autonoma de Mexico (UNAM), told the press that:

“DNA barcoding is opening a new window into the relations between hunter and prey in the wild and how diets may be changing due to climate change.”

He explained that like gut contents, soils contain a mixture of species that are hard to identify using convetional tools. Tiny soil organisms eat each other, they eat roots, and all sorts of animal and plant debris, so:

“Knowing what eats what is important to many studies, including investigations into how much carbon dioxide and other greenhouse gases are being released from soils into the atmosphere,” said Miller.

Another area of application would be producing evidence to prosecute smugglers of wild bushmeat and other products made from endangered species: a trade that last year netted 15 billion dollars worldwide.

When smoked or sundried, only DNA barcoding can differentiate bushmeat from domestic animal meat like beef, goat or pork, so law enforcement agencies are becoming increasingly interested in the DNA barcode library of endangered species that Dr George Amato of the American Museum of Natural History in New York is compiling.

The hope is that the Mexico meeting will bring about a global agreement on how to do the same with plants, which would for instance help to track down illegal timber trading and regulate herbal medicines, among others.

CBOL Executive Secretary David Schindel said:

“Biodiversity scientists are using DNA technology to unravel mysteries, much like detectives use it to solve crimes. It is having a profound impact on our understanding of organisms in nature and how they interact with the environment.”

Following increases in the number of puffer fish poisoning cases in the US due to fradulent food labelling, the US Food and Drug Administration (FDA) will be telling delegates about their interest in DNA barcoding and the challenge posed by trying to differentiate among different species in marketed seafood, an increasing proportion of which is now imported, and which is also processed to “a point where traditional morphologic species determination is not possible”.

An FDA representative told the press that:

“New methods that allow accurate and rapid species identifications are critical for both food borne illness investigations and for the prevention of deceptive practices, such as those where species are intentionally mislabeled to circumvent import restrictions or for resale as species of higher value.”

The FDA will also be presenting a study that showed DNA barcoding reliably distinguished the seedpods of Star Anise ( Illicium verum, a herb used in teas, herbal remedies and cooking) from otherwise identical seedpods of a sister species, Illicium anisatin, considered to contain neurotoxic compounds and therefore a health risk.

The delegates will also hear of a case from Canada, where students nationwide collected fish samples from stores and analyzed the resulting DNA data, revealing significant market “mislabelling” of seafood.

Another case that will be presented will be the successful apprehension of a Brazilian smuggler last year who was caught trying to smuggle parrot eggs which he said were quails’ eggs, but DNA barcoding revealed that they were the eggs of several species of parrots and macaws, many of which where either threatened or vulnerable.

A medical application of DNA barcoding will help to identify black flies in Brazil and other South American countries where they spread river blindness disease. So far 70 species of black flies have been barcoded to date, about 20 per cent of the number known to science, and including three previously unrecognized.

Other medical applications include identification of malaria mosquitoes in India, parasite bearing freshwater snails in the Cameroons, nematode parasites in Mexico that attack crops, humans and livestock.

Mexico is one of the countries that is moving ahead quickly in using DNA barcoding. Under the auspices of CONACYT, Mexico’s National Council on Science and Technology, they have established a national barcode network (MexBOL) involving 60 researchers from 15 institutions.

Mexico now has a number of new “barcode factories” at institutions in the north, center and south of the country, including CIBNOR (Centro de Investigaciones Biológicas del Noroeste), IBUNAM (Instituto de Biología, UNAM), and ECOSUR (El Colegio de la Frontera Sur).

Meeting co-host Patricia Escalante, chair of the Zoology Department, Institute of Biology, UNAM, said this work in Mexico and elsewhere was very important.

“Barcoding is a tool to identify species faster, more cheaply, and more precisely than traditional methods,” she explained.

MexBOL will produce barcodes for all important taxonomic groups including national campaigns, such as barcoding all trees (ArBOL), fungi, bees, aquatic insects, crayfishes, fishes, birds, mammals and more.

Escalante explained that:

“We need an accurate inventory of global biodiversity to recognize parasites of medical, economic or ecological importance.”

“This work will help develop biological control measures, monitor and control of human diseases and potential zoonoses, manage agricultural and aquaculture pathogens, and detect the presence of invasive species,” she added.

The largest barcode factory in the world is at the Biodiversity Institute of Ontario at the University of Guelph in Canada, where DNA barcoding was first proposed and developed.

Similar facilities are being set up at the French Museum National d’Histoire Naturelle, as well as in the Netherlands and Poland.

– 3rd International Barcode of Life Conference

Source: Consortium for the Barcode of Life (CBOL).

Written by: Catharine Paddock, PhD
Copyright: Medical News Today

DNAWellnessinfo.com Resource:  http://www.medicalnewstoday.com/articles/170276.php