Zombie DNA Can Cause Muscular Dystrophy is a post from: dnawellnessinfo.com

scienceblog.com

by bjs on August 10, 2010

PITTSBURGH, Aug. 10 — Single-molecule sequencing technology has detected and quantified novel small RNAs in human cells that represent entirely new classes of the gene-translating molecules, confirming a long-held but unproven hypothesis that mammalian cells are capable of synthesizing RNA by copying RNA molecules directly. The findings were reported in Nature by researchers from the University of Pittsburgh School of Medicine, Helicos Biosciences Corp., Integromics Inc., and the University of Geneva Medical School.

“For the first time, we have evidence to support the hypothesis that human cells have the widespread ability to copy RNA as well as DNA,” said co-author Bino John, Ph.D., assistant professor, Department of Computational and Systems Biology, Pitt School of Medicine. “These findings emphasize the complexity of human RNA populations and suggest the important role for single-molecule sequencing for accurate and comprehensive genetic profiling.”

Scientists had thought that all RNA in human cells was copied from the DNA template, Dr. John explained. The presence of mechanisms that copy RNA into RNA, typically associated with an enzyme called RNA-dependent RNA polymerase, has only been documented in plants and simple organisms, such as yeast, and implicated in regulation of crucial cellular processes. Since thousands of such RNAs have been detected in human cells and because these RNAs have never before been studied, further research could open up new fronts in therapeutics, particularly diagnostics, Dr. John said.

In the study, the researchers profiled small RNAs from human cells and tissues, uncovering several new classes of RNAs, including antisense termini-associated short RNAs, which are likely derived from messenger RNAs of protein-coding genes by yet uncharacterized, pervasive RNA-copying mechanisms in human cancer cell lines.

“This class of non-coding RNA molecules has been historically overlooked because available sequencing platforms often are unable to provide accurate detection and quantification,” said Patrice Milos, Ph.D., chief scientific officer at Helicos Biosciences. “Our technology provides the platform capability to identify and quantify these RNAs and reinforces the potential clinical advantages of our single molecule-sequencing platform.”

Co-authors include A. Paula Monaghan, Ph.D., and Sang Woo Kim, Ph.D., University of Pittsburgh School of Medicine; Sylvain Foissac, Ph.D., Integromics Inc.; Stylianos Antonarakis, M.D., Ph.D., and Christelle Borel, Ph.D., University of Geneva Medical School; and Philipp Kapranov, Ph.D., and others from Helicos BioSciences.

The research was funded by the American Cancer Society, the National Institutes of Health, the Swiss National Science Foundation, Integromics Inc., and Helicos BioSciences Corporation.

DNAWellnessinfo.com Resource:  http://scienceblog.com/37388/human-cells-can-copy-not-only-dna-but-also-rna-says-team-from-pitt-helicos-biosciences/

Human cells can copy not only DNA, but also RNA, says team from Pitt, Helicos BioSciences is a post from: dnawellnessinfo.com

thglobalherald.com

Australian researchers have uncovered a novel DNA mutation in the c-Myb gene that may be linked to the development of leukaemia, breast and colon cancer.

A team led by Dr Peter Papathanasiou from the John Curtin School of Medical Research at The Australian National University and Associate Professor Andrew Perkins from the Institute for Molecular Bioscience at The University of Queensland completed a three-year screening project to find the genes that control the development and turnover of stem cells.

“We’ve shown that blood stem cells with this genetic mutation behave the same way as those present in human bone marrow diseases, including diseases that can evolve into leukaemia,” said Dr Papathanasiou, who is also affiliated with the Australian Phenomics Facility at ANU.

“By understanding more about the genetic blueprint of these kinds of disorders, we can start to develop new ways of targeting diseases,” Dr Perkins said.

“Currently, there is no treatment for this group of blood diseases, but the discovery of this mutation provides new avenues for investigation.”

As a result of the screening project, the researchers have also identified five other abnormal blood stem cell profiles, adding to understanding of the genetic diversity of blood cells. The project has also led to a better understanding of how blood cells develop and how this process becomes corrupted.

“Given that the same genes that operate in stem cells also function in cancer cells – albeit with genetic mutation – this research also has potential implications for regenerative medicine, by understanding how to stimulate the growth of new blood cells,” Dr Papathanasiou said.

The project was the first in the world to mutate the mammalian genome in a specific search for novel genetic regulators of stem cells.

The following is taken from the research paper’s abstract:

Here we demonstrate that chemical mutagenesis of mice combined with advances in hematopoietic stem cell reagents and genome resources can efficiently recover recessive mutations and identify genes essential for generation and proliferation of definitive hematopoietic stem cells and/or their progeny.

We employed high-throughput FACS to analyze nine subsets of blood stem cells, progenitor cells, circulating red cells and platelets in >1,300 mouse embryos at embryonic day (E) 14.5. From 45 pedigrees we recovered six strains with defects in definitive hematopoiesis.

We demonstrate rapid identification of a novel mutation in the c-Myb transcription factor that results in thrombocythemia and myelofibrosis as proof-of-principal of the utility of our FACS-based screen.

The work was made possible by grants from the National Health & Medical Research Council, the Leukaemia Foundation, and by the Australian Government’s National Collaborative Research Infrastructure Strategy to establish the Australian Phenomics Network.

Get the full paper by visiting: http://bloodjournal.hematologylibrary.org/cgi/content/abstract/blood-2010-04-269951v1

DNAWellnessinfo.com Resource:  http://theglobalherald.com/science-dna-mutation-in-c-myb-gene-linked-to-leukaemia/5384/

DNA Mutation in c-Myb Gene linked to Leukaemia is a post from: dnawellnessinfo.com

NICHOLAS WADE
Published: August 9, 2010
nytimes.com

A new generation of DNA tests for colon cancer seems likely to improve the detection both of cancers and of the precancerous polyps that precede them. The tests, if validated, could reduce the burden of disease substantially by detecting tumors at an early stage, including those not picked up by a colonoscopy.

Colorectal cancers tend to grow slowly and are easily removed if caught early. But many people over 50 do not comply with the recommendation to have a colonoscopy — a time-consuming procedure in which a tube is threaded up the intestine — and even colonoscopies do not catch everything. Colorectal cancer has become the second most common cancer in the United States; each year it causes more than 50,000 deaths and costs about $14 billion to treat.

Colon tumors provide considerable evidence of their presence by shedding blood and cells that are detectable in the stool. Tests for blood have reduced deaths from colorectal cancer only modestly, because they are not very sensitive to precancerous polyps, the stage at which cancer is best prevented.

Researchers turned to measuring mutations in DNA after Dr. Bert Vogelstein of Johns Hopkins University discovered the series of mutations by which a colon polyp advances to full cancer. But no single mutation predicts a patient’s risk, and the mutation tests, though more accurate than the blood tests, have not been a decisive improvement.

By 2004 it was clear that looking for the Vogelstein mutations was “neat biology but not a home run,” said Dr. David Ransohoff, an expert on colon cancer screening at the University of North Carolina.

A new generation of tests being developed depends on a different process in cancer cells. All cells switch off the genes they do not need by attaching small chemicals called methyl groups to certain sites along their DNA. In cancer cells, there is generally less methylation than usual, except for certain regions of DNA where the methylation process is taken to excess, perhaps because the cells need to shut down tumor suppressor genes. These and other genes are highly methylated in colon tumors and other kinds of cancer.

Exact Sciences, a company based in Madison, Wis., is developing a colon cancer test based on highly methylated DNA. Its researchers reported last month that by testing for methylated DNA at four markers, pieces of DNA drawn from specific genes, they could detect colon tumors and polyps, distinguishing them from normal tissue with 100 percent sensitivity and with no false positives.

The tests of methylated DNA were performed directly on tumors and are expected to be less accurate in the real world, in which they would have to work in stool samples. Almost all of the DNA in stool is from bacteria, and the methylated DNA is a fraction of the 0.01 percent that is human DNA.

Still, Kevin T. Conroy, chief executive of Exact Sciences, said he expected that the four-marker test, when applied to stool samples, would detect at least half of all precancerous polyps and 85 percent of actual cancers. Results of a trial now under way in 1,600 patients will be reported in October, he said.

The test would cost less than $300, and samples could be collected at home. Patients would be advised to take the test every three years. People with a positive result would then have a colonoscopy to verify and remove any polyps, with the result that colonoscopies could be focused on high-risk patients instead of the population at large.

Exact Sciences’ test is based on work by Dr. Vogelstein, Dr. Sanford Markowitz at Case Western Reserve University and Dr. David A. Ahlquist of the Mayo Clinic. Dr. Ahlquist, who is a scientific adviser to the company, identified some of the highly methylated genes the company is testing as markers for colon cancer.

Dr. Ahlquist said that if the test worked as well as hoped on stool samples, “this will be the first noninvasive test that will reliably detect malignant lesions.” Cervical cancer has been virtually eliminated by the Pap test, he said, and “we feel that colon cancer could be eliminated to the same extent.”

The four-marker test can pick up a kind of precancerous tissue called a serrated polyp which is often missed by colonoscopies, Dr. Ahlquist said. It also ignores most innocuous small polyps.

Using different sets of four markers, other kinds of cancer can be detected. “We can detect all of the cancers above the colon — pancreas, esophagus, stomach, bile duct,” Dr. Ahlquist said. Thus in principle, all the cancers of the gastrointestinal tract, which account for nearly a quarter of all cancer deaths in the United States, should be detectable from stool samples.

Dr. Vogelstein said tests for DNA mutations would be better in theory than tests for DNA methylation because “mutations are entirely specific and they are what is driving the tumor”; the methylation is less causative and increases naturally with age.

But the DNA methylation tests are promising in principle, he said, and it seems feasible for Exact Sciences to get a sensitivity of better than 90 percent and a false positive rate of only 5 to 10 percent. “We can tolerate 5 to 10 percent false positives because those people will just get colonoscopies,” he said.

For cancers above the colon, there are many enzymes that digest DNA, so whether such cancers can be detected efficiently can be answered only with experiments, Dr. Vogelstein said. And false positives would be more of a problem, since for these cancers there is no easy verification method like colonoscopy. “That’s when these false positives really start to be the devil,” he said.

Dr. Ransohoff said the Exact Sciences test was still at a preliminary point. “This is neat and it’s promising,” he said. “But we’ve been down this road before and we need to be hopeful without being carried away.”

DNAWellnessinfo.com Resource:  http://www.nytimes.com/2010/08/10/health/10cancer.html?_r=1

DNA Test May Speed Colon Cancer Diagnosis is a post from: dnawellnessinfo.com

howstuffworks.com

by William Harris

How DNA Evidence Works is a post from: dnawellnessinfo.com

WSJ’s blog on health and the business of health – July 23, 2010, 11:30 AM ET

By Katherine Hobson

Direct-to-consumer genetic-testing companies were in the hot seat this week, with scrutiny from both the FDA and Congress. Fodder for some of the discussion was a new GAO report that focused on the scientific accuracy and marketing efforts of tests by companies including 23andMe, Pathway Genomics, deCODE genetics and Navigenics.

You can read about the GAO report in this story from today’s WSJ. And here’s the GAO report itself.

Investigators from the independent agency, which works on behalf of Congress, sent DNA samples for assessment of the risk of different diseases and conditions. The report found analyses of the same samples varied, in many cases wildly; the companies say they use different genetic markers, which means results won’t be uniform — though some agreed that there is a need for some common standards.

But for some Friday fun, listen to or read the transcripts of undercover calls to unnamed genetic-testing companies made by GAO investigators. (Undercover contact was made with 15 companies, including the four listed above.)

One fake customer asked a company rep, “So if I’m high risk, does that mean I’ll definitely get breast cancer?”

Rep: “You … you’d be in the high risk of, you know, pretty much getting it so …”

(The GAO notes these tests are not diagnostic and that this company didn’t even test for the BRCA gene variations that are linked to a higher chance — but by no means a certainty — of getting breast cancer. Experts consulted by the GAO called the rep’s response “horrifying.”)

Another marketing rep told a fake customer that “we can repair DNA damage.”

Fake customer: “You can, really?”

Rep: “Oh yeah, it’s called epigenetics and …”

Fake customer: “That’s repairing DNA?”

Rep: “Yeah … The genes are considered now not to be the source of our biology, they’re a symptom.”

(Experts told the GAO there was “no scientific basis for these claims.”)

The transcript also features company reps agreeing to process a DNA sample obtained surreptitiously, for a “surprise” analysis ordered by a woman for her fiancé (in most states, that’s an illegal breach of privacy); falsely claiming Lance Armstrong as a celebrity endorser, and claiming supplements can cure disease.

DNAWellnessinfo.com Resource: http://blogs.wsj.com/health/2010/07/23/listen-to-consumer-dna-test-company-sales-reps-behaving-badly/

Listen to Consumer DNA Test Company Sales Reps Behaving Badly! is a post from: dnawellnessinfo.com

foxnews.com
Thursday, July 22, 2010

Public swimming pools are more dangerous than you might think, a new study suggests. When sweat and urine, among other organics, mix with the disinfectants in pool water, the result can be hazardous to health.

The findings, announced this week, link the application of disinfectants in recreational pools to genetic cell damage that has been shown to be linked with adverse health outcomes such as asthma and bladder cancer.

Pool water represents extreme cases of disinfection that differ from the disinfection of drinking water as pools are continuously exposed to disinfectants. But with so many people cooling off and exercising in pools and water parks (339 million visits across the United States each year), the disinfectants are a must to prevent outbreaks of infectious disease.

Chlorine and Pee Don’t Mix

The problem occurs when the sanitizers mix with organic matter.

“All sources of water possess organic matter that comes from decaying leaves, microbes and other dead life forms,” said study researcher Michael Plewa, University of Illinois professor of genetics. “In addition to organic matter and disinfectants, pool waters contain sweat, hair, skin, urine and consumer products such as cosmetics and sunscreens from swimmers.”
These consumer products are often nitrogen-rich, and when mixed with disinfectants, these products may become chemically modified and converted into more toxic agents.

Long-term exposure to these disinfection byproducts can mutate genes, induce birth defects, accelerate the aging process, cause respiratory ailments, and even induce cancer, according to the researchers. While the new study did not examine actual effects on humans, it suggests such research might be warranted.

Pool Samples

In this study, researchers evaluated water samples from public pools and a control sample of tap water. They tested whether the byproduct chemicals in the samples could induce gene mutations using a so-called systematic mammalian cell genotoxicity analysis.

This sensitive DNA technology can detect genomic damage in mammalian cells, allowing researchers to investigate damage at the level of each nucleus within each cell.

Results proved that all disinfected pool samples had more genomic DNA damage than the source tap water, Plewa said.

The findings are published in the journal Environmental Science & Technology. The work was supported by grants from the National Science Foundation.
Cleaner Pools

All this doesn’t mean you need to ditch your pool plans. Plewa offers recommendations for pool operators and swimmers to reduce hazardous chemicals and make for safer pool water.

“Care should be taken in selecting disinfectants to treat recreational pool water,” Plewa advised.

“The data suggest that brominating agents should be avoided as disinfectants of recreational pool water. The best method
to treat pool waters is a combination of UV treatment with chlorine as compared to chlorination alone.”

In addition, organic carbon should be removed prior to disinfection when the pool water is being recycled, Plewa said.

Swimmers can also help by showering before entering the water, which would mean fewer organics and so reduce the genotoxicity of the pool water. One recommendation that may seem obvious: Don’t pee in the pool. Plewa suggests pool owners remind patrons about the potential harm caused by urinating in a pool.

DNAWellnessinfo.com Resource: http://www.foxnews.com/story/0,2933,597467,00.html

Urine in Public Pools Could Cause Cell Damage is a post from: dnawellnessinfo.com

English.news.cn 2010-07-06 05:51:08

By Xinhua writer Ren Haijun

WASHINGTON, July 5 (Xinhua) — A decade after the historic completion of the “book of life” — the first blueprint of human DNA, the benefits of the Human Genome Project still lie ahead. However, Francis Collins, director of the U.S. National Institute of Health (NIH), is “confident” the project will live up to its potential.

“The First Law of Technology states that a truly transformational discovery will always have its immediate consequences overestimated — and its long-term consequences, underestimated. That certainly is turning out to be true from what we are learning about the human genome sequence!” Collins told Xinhua in an interview.

“The greatest significance of the Human Genome Project is the door that it has opened into the vast and complex landscape of human biology,” Collins said. “Exploring this landscape in a way that benefits human health will require creative thinking and hard work by researchers in the United States, China, and everywhere else around the globe.”

Collins, noted for his leadership of the project, thought having the complete sequence of the human genome is similar to having all the pages of an instruction manual needed to make the human body.

“Thanks to the sequencing of the human genome, we have much more powerful tools to study the role that genetic factors play in more complex diseases, such as cancer, diabetes, and heart disease, and even in susceptibility to infectious diseases, such as acquired immunodeficiency syndrome (AIDS),” he said. “Genomic sequencing has facilitated the diagnosis of genetic conditions, ranging from very rare to quite common. It is shedding new light on the process of aging and providing tantalizing clues to the secrets of longevity. If we fully understand this instruction manual, it could become the most powerful textbook of medicine imaginable!”

The famous U.S. physician-geneticist thought cancer is one category of disease in which he expects genomic research to have a major impact in the near future.

Cancer is caused by changes in a cell’s genome. However, the pattern of these genomic changes varies among different types of cancer — and even among subsets of patients with the same cancer. So, it is important to produce genomic classification systems for many types and subtypes of cancer.

In the United States, the NIH is supporting an effort to build comprehensive catalogs of the key genomic changes in 20 major types and subtypes of cancer. This project, called The Cancer Genome Atlas, is working collaboratively with researchers in China and elsewhere around the world through the International Cancer Genome Consortium. The information generated by such research is already proving useful in developing new cancer therapies, as well as in matching individual cancer patients with the therapies most likely to work for them.

However, Collins warned that amid all the excitement over the promise of genomics research, we need to remember that genes do not operate in a vacuum. There are other important factors that influence people’s risk of developing most common diseases. These factors include smoking, diet, exercise, and exposure to pollution.

“Unless we as humans dramatically change our lifestyles and our environment, I do not see a future in which all common diseases are completely prevented or eradicated,” he said.
Collins, a supporter of free access to human genome sequencing data, thought human genetic information should be kept in the public domain to allow researchers to analyze it and to give members of the public fair access to medical treatments.

“From the outset, the Human Genome Project and the international endeavors that built upon its foundation, such as the International HapMap Project and 1,000 Genomes Project, have made all their data rapidly available to scientists around the globe,” he said. “In many ways, this is one of the most significant legacies of the Human Genome Project — and one that gives me hope that worldwide research community will come up with innovative ways to use this treasure trove of information to fight disease.”

Collins thought there are two major challenges associated with the application of sequencing technologies. The first is lowering the cost of DNA sequencing. “We’ve made dramatic progress in that area over the past 10 years. The cost of sequencing the first human genome was about 400 million dollars. Today, the cost of sequencing one genome is about 9,500 dollars, and we expect that cost to fall to 1,000 dollars or less within the next four or five years.”

The second, perhaps even bigger, challenge is figuring out how to analyze the tidal wave of data being generated by genomic sequencing and then translate those findings in ways that benefit patients in the clinic. However, “this is a challenge that can be met if we pull together the best minds in biology, medicine, statistics, and computer science.”

Collins also thought the completion of the human genome sequence was just the beginning of the effort to understand how all the parts of the genome work together to contribute to health and disease.

“Genomic research is not a sprint, it is a marathon that requires sustained commitment over a long period of time to yield maximum success,” he said.

DNAWellnessinfo.com Resource: http://news.xinhuanet.com/english2010/sci/2010-07/06/c_13384897.htm

Human Genome Project will live up to its potential: NIH director is a post from: dnawellnessinfo.com

CHANDIGARH, India, June 18 (UPI) — A researcher in India warns smokeless tobacco use may damage the body’s DNA and key enzymes.

Krishan Khanduja of the Postgraduate Institute of Medical Education and Research in Chandigarh, India, suggests smokeless tobacco not only may damage DNA, but may also affect the normal functioning of a key family of enzymes found in almost every organ.

Khanduja and colleagues found laboratory rats exposed to extracts of smokeless tobacco had altered DNA material in the liver, kidney and lungs — as well as changed function of the CYP-450 family of enzymes. This enzyme group affects many functions including the production of hormones such as estrogen and testosterone, the processing of cholesterol and vitamin D and the breaking down of prescription drugs and possibly toxic substances.

The study, published in Chemical Research in Toxicology, noted use of smokeless products is increasing not only among men but also among children, teenagers and women.

“These products are used around the world but are most common in Northern Africa, Southeast Asia, and the Mediterranean region,” the study authors said in a statement. “Most of the users seem to be unaware of the harmful health effects and, therefore, use smokeless tobacco to ‘treat’ toothaches, headaches, and stomachaches.”

DNAWellnessinfo.com Resource: http://www.upi.com/Health_News/2010/06/18/Smokeless-tobacco-may-hurt-DNA-enzymes/UPI-41481276902848/

Smokeless tobacco may hurt DNA, enzymes is a post from: dnawellnessinfo.com

By ACT court reporter Katherine Pohl

Updated Mon May 31, 2010 8:27am AEST

The use of DNA evidence in criminal court cases is under the spotlight with state and territory attorneys-general backing a review into collecting and testing procedures.

Questions have been raised about contamination and the risks of convicting someone on DNA evidence alone.

“Those two areas are of critical concern, not only to defence lawyers but to prosecutors as well,” New South Wales Deputy Senior Public Defender Andrew Haesler said.

Those issues have been recently examined by the High Court.

Benjamin Forbes was found guilty of sexually assaulting a Canberra teenager in 2005 as she walked home from work.

DNA was the only evidence linking him to the crime scene.

The High Court ruled that it was not a suitable test case on which to base a DNA challenge.

But Mr Haesler predicts it will not be long before such a case comes along.

“Judges and juries have to be very critical when evidence is presented that identifies an offender solely on the basis of DNA,” he said.

Contamination of DNA evidence is also a major issue.

Simon Walsh from the Australian Federal Police admits DNA evidence can be a double-edged sword.

“One of the advantages of the testing progress and technology is that it allows us to test very small amounts of DNA,” he said.

“The corollary of that is that it makes it potentially more susceptible to contamination.”

Contamination issues were at the centre of a case in Victoria earlier this month in which a man was wrongly convicted of rape because of tainted DNA evidence.

The case has prompted all state and territory attorneys-general to back a review of DNA collection and analysis.

ACT Attorney General Simon Corbell says there is a lot to learn from that particular case and he is encouraging prudent collection and testing procedures.

A working group is examining the issues.

DNAWellnessinfo.com Resource: http://www.abc.net.au/news/stories/2010/05/31/2913474.htm

DNA handling under the microscope is a post from: dnawellnessinfo.com