Article by Nicholas Wade – New York Times
Published: March 10, 2010

Two research teams have independently decoded the entire genome of patients to find the exact genetic cause of their diseases. The approach may offer a new start in the so far disappointing effort to identify the genetic roots of major killers like heart disease, diabetes and Alzheimer’s.

In the decade since the first full genetic code of a human was sequenced for some $500 million, less than a dozen genomes had been decoded, all of healthy people.

Geneticists said the new research showed it was now possible to sequence the entire genome of a patient at reasonable cost and with sufficient accuracy to be of practical use to medical researchers. One subject’s genome cost just $50,000 to decode.

“We are finally about to turn the corner, and I suspect that in the next few years human genetics will finally begin to systematically deliver clinically meaningful findings,” said David B. Goldstein, a Duke University geneticist who has criticized the current approach to identifying genetic causes of common diseases.

Besides identifying disease genes, one team, in Seattle, was able to make the first direct estimate of the number of mutations, or changes in DNA, that are passed on from parent to child. They calculate that of the three billion units in the human genome, 60 per generation are changed by random mutation — considerably less than previously thought.

The three diseases analyzed in the two reports, published online Wednesday, are caused by single, rare mutations in a gene.

In one case, Richard A. Gibbs of the Baylor College of Medicine sequenced the whole genome of his colleague Dr. James R. Lupski, a prominent medical geneticist who has a nerve disease, Charcot-Marie-Tooth neuropathy.

In the second, Leroy Hood and David J. Galas of the Institute for Systems Biology in Seattle have decoded the genomes of two children with two rare genetic diseases, and their parents.

More common diseases, like cancer, are thought to be caused by mutations in several genes, and finding the causes was the principal goal of the $3 billion human genome project. To that end, medical geneticists have invested heavily over the last eight years in an alluring shortcut.

But the shortcut was based on a premise that is turning out to be incorrect. Scientists thought the mutations that caused common diseases would themselves be common. So they first identified the common mutations in the human population in a $100 million project called the HapMap. Then they compared patients’ genomes with those of healthy genomes. The comparisons relied on ingenious devices called SNP chips, which scan just a tiny portion of the genome. (SNP, pronounced “snip,” stands for single nucleotide polymorphism.) These projects, called genome-wide association studies, each cost around $10 million or more.

The results of this costly international exercise have been disappointing. About 2,000 sites on the human genome have been statistically linked with various diseases, but in many cases the sites are not inside working genes, suggesting there may be some conceptual flaw in the statistics. And in most diseases the culprit DNA was linked to only a small portion of all the cases of the disease. It seemed that natural selection has weeded out any disease-causing mutation before it becomes common.

The finding implies that common diseases, surprisingly, are caused by rare, not common, mutations. In the last few months, researchers have begun to conclude that a new approach is needed, one based on decoding the entire genome of patients.

The new reports, though involving only single-gene diseases, suggest that the whole-genome approach can be developed into a way of exploring the roots of the common multigene diseases.

“We need a way of assessing rare variants better than the genomewide association studies can do, and whole-genome sequencing is the only way to do that,” Dr. Lupski said.

With 10 genomes of healthy humans sequenced, Dr. Gibbs, a specialist in DNA sequencing, decided it was time to decode the genome of someone with a genetic disease and asked his colleague Dr. Lupski to volunteer.

Mutations in any of 39 genes can cause Charcot-Marie-Tooth, a disease that impairs nerves to the hands and feet and causes muscle weakness.

Fifty thousand dollars later, Dr. Lupski turned out to have mutations in an obscure gene called SH3TC2. The copy of the gene he inherited from his father is mutated in one place, and the copy from his mother in a second.

Both his parents had one good copy of the gene in addition to the mutated one. A single good copy can generate enough, or nearly enough, of the gene’s product for the nerves to work properly. Dr. Lupski’s mother was free of the disease and his father had only mild symptoms.

In the genetic lottery that is human procreation, two of their eight children inherited good copies of SH3TC2 from each parent; two inherited the mother’s mutation but the father’s good copy and are free of the disease; and four siblings including Dr. Lupski inherited mutated copies from both parents. These four all have Charcot-Marie-Tooth disease. The results are reported in The New England Journal of Medicine.

In Seattle, Dr. Hood and Dr. Galas have also applied whole-genome sequencing to disease. They analyzed the genome of a family of four, in which the two children each have two single-gene diseases, called Miller syndrome and ciliary dyskinesia. With four related genomes available, the researchers could identify the causative genes. They also improved the accuracy of the sequencing because DNA changes that did not obey Mendel’s rules of inheritance could be classed as errors in the decoding process.

The Seattle team believes whole-genome sequencing can be applied to the study of the common multigene diseases and plans to sequence more than 100 genomes next year, starting with multigenerational families.

The family whose genomes they report in Science were sequenced by a company with a new DNA sequencing method, Complete Genomics of Mountain View, Calif., at a cost of $25,000 each. Clifford Reid, the chief executive, said that the company was scaling up to sequence 500 genomes a month and that for large projects the price per genome would soon drop below $10,000. “We are on our way to the $5,000 genome,” he said.

Dr. Reid said the HapMap and genomewide association studies were not a mistake but “the best we could do at the time.” But they have not yet revolutionized medicine, “which we are on the verge of doing,” he said.

Dr. Goldstein, of Duke University, said the whole-genome sequencing approach that was now possible should allow rapid progress. “I think we are finally headed where we have long wanted to go,” he said.

DNAWellnessinfo.com Resource:  http://www.nytimes.com/2010/03/11/health/research/11gene.html

Disease Cause Is Pinpointed With Genome is a post from: dnawellnessinfo.com

Naveen Kumar, TNN, Mar 6, 2010, 10.23pm IST

VARANASI: Now, the study of DNA repairing gene using single nucleotide polymorphism (SNP) marker would provide vital cue for cancer prevention, especially neck and head that comprises of as many as seven different types of cancer in the facial region. In addition, the study would also enable early prediction of much feared breast cancer in women.

While a team of scientists is studying the genomics in cancer, especially the squamous cell carcinoma in neck, head and breast region under the Hap Map project, the case studies in the last five years have revealed interesting contribution of DNA repairing genes including P53 associated genes, where SNP can be used as a marker for prompt diagnostic purpose.

Senior scientist Central Drug Research Institute Lucknow Dr SK Rath told TOI on Saturday, “The studies have shown that P53 associated genes play a vital role in DNA repair and act as tumour suppressor. It changes the DNA repair scene and plays pivotal role in protection against mutagenic and cytotoxic effects of DNA damage that also prevents cancer.” Similarly, SNP could also provide vital cue for DNA repairing in BRAC 1 and 2 genes that are believed to cause breast cancer in women, he added.

It is to be mentioned here that Dr Rath is a key member of the team that studied genotype of cancerous and non-cancerous cells under the project in the Xth five-year plan. Now, the team is researching on SNP of different people including smokers and non-smokers, drinkers and non-drinkers, where the cause of cancer

could not be ascertained.

Saying that million of SNPs exist in human genome that occur in gene within the regulatory region, Dr Rath emphasised that the method detects the most common type of variation in the genome, as it cater to small alteration, providing better scope for prediction. The SNP markers are preferred for population genomic disease association and are good indicators of squamous cell carcinoma in neck and head region that includes cancers of oral cavity, pharynx, nasopharynx, oropharynx, hypopharynx and tongue, he added.

Stressing that cancers of neck and head region are growing at alarming rate in states like UP, he said the case studies in Lucknow revealed that out of 100 cancer patients, the number of patients with cancer in the neck and head region increased from 30 to 49 (150 per cent increase) in the last five years. Worldwide, it is the fifth most common type of cancer affecting over one million population annually, he concluded.

DNAWellnessinfo.com Resource:  http://timesofindia.indiatimes.com/city/varanasi/-Vital-cues-for-cancer-prevention-through-DNA-repairing-gene/articleshow/5648729.cms

Vital cues for cancer prevention through DNA repairing gene is a post from: dnawellnessinfo.com

Matthew Herper, 02.25.10, 11:20 AM EST
Forbes Magazine dated March 15, 2010

Last year a five-month-old boy in Turkey stopped gaining weight and became dehydrated despite getting plenty of liquids. Specialists in Istanbul suspected Bartter’s syndrome, a potentially fatal kidney disorder that afflicts one in 100,000 babies, causing dangerously low levels of potassium and salt.

To confirm their hunch they sent a blood sample to Yale Medical School geneticist Richard Lifton. They asked him to determine whether the baby had the gene defect implicated in Bartter’s. But Lifton thought that Bartter’s might not be the culprit. So he did something that would have been prohibitively expensive a few years ago. He deciphered the DNA letters for all the baby’s genes. The gene scan revealed that the baby’s problem was not Bartter’s but something else called congenital chloride diarrhea, which also lowers salt levels. The result means that the baby, now doing better on a special diet, could be treated with drugs if his condition gets worse.

The case, published in the Proceedings of the National Academies of the Sciences in October, may be the first in which the results of DNA sequencing have altered treatment of a patient. Does this herald the beginning of a new kind of medicine in which patients with unexplained symptoms get their DNA sequenced? Yes, says Lifton: “This will be a court of last resort to try and identify causes of disease.”

Gene researchers have talked for years about how sequencing will transform medicine. Now that sequencing is cheap this transformation is under way. The cost of deciphering all 6 billion letters in the human genome has dropped from $1 million in 2007 to less than $20,000 today. Lifton used a two-step method to extract and sequence only the 1% of those letters that contain known genes, lowering the price to $2,500. New DNA sequencers just introduced by Illumina ( ILMN – news – people ) (whose model Lifton used) and Life Technologies ( LIFE – news – people ) could lower the cost of sequencing a whole genome to below $3,000 by year-end.

DNA sequencers haven’t been approved for use in medical testing, and insurers don’t pay for sequencing. But peering into DNA is becoming an option for wealthy patients with rare and scary diseases. Knome, a privately held company in Cambridge, Mass., started out in 2008 charging $350,000 to arrange sequencing and interpret the data for wealthy patrons as a vanity project. Now it offers the scans for as little as $25,000. Chief Executive Jorge Conde says several patients hoping to improve their care are among his customers.

The $600 million annual market for DNA sequencers is still all about research, with Illumina holding a 60% market share. But numerous companies are already jockeying for position in anticipation of a big future medical-test market.

Cancer patients may be among the first to benefit from DNA sequencing technology. In one early example of how this may work, Marco Marra, a researcher at the Michael Smith Genome Sciences Centre in Vancouver, last year sequenced the genes from a tumor that had spread from an 80-year-old patient’s tongue to his lungs. There is no standard therapy for this type of tumor. But the gene scan found the tumor was making large amounts of a growth-promoting protein called RET. When the patient’s medicine was switched to Pfizer ( PFE – news – people )’s Sutent, a drug that blocks this protein, the tumor shrank, according to a report in Nature.

A looming question is how the Food & Drug Administration will regulate sequencing technology. It could treat DNA sequencing like genetic tests and require separate approvals for each use. Some equipment makers hope for a faster path in which doctors practicing a new medical specialty emerge to evaluate and interpret gene scans, as radiologists do with X-rays. Clifford Reid, chief executive of Complete Genomics, which has finished 50 genomes, is skeptical that it will be that easy. “The FDA has been very quiet up until now,” he says. “We all have to expect the FDA to be intimately involved with these new tests.”

DNAWellnessinfo.com Resource:  http://www.forbes.com/forbes/2010/0315/health-illumina-genome-cancer-diagnosis-by-dna.html

A First: Diagnosis By DNA is a post from: dnawellnessinfo.com

ScienceDaily (Feb. 22, 2010) — Scientists from the U.S. Department of Energy’s Lawrence Berkeley National Laboratory have learned how an interval of DNA in an unexplored region of the human genome increases the risk for coronary artery disease, the leading cause of death worldwide.

Their research paints a fuller picture of a genetic risk for the disease that was discovered only three years ago and which lurks in one out of two people.

It also reinforces the tantalizing possibility that many more disease risks — and potential therapies — are hidden in the vast and uncharted part of the genome that doesn’t contain instructions for making proteins.

The research is reported in the February 21 advance online publication of the journal Nature.

The team focused on an interval of DNA in chromosome 9p21. People who carry variations of this interval have an increased chance of developing coronary artery disease, which is an accumulation of plaque in coronary arteries that restricts blood flow to the heart and causes heart attacks.

Determining how this DNA contributes to the disease is difficult because it’s in the poorly understood part of the genome that doesn’t code for proteins, the workhorses of cellular function.

In groundbreaking research, the Berkeley Lab scientists found that the DNA interval regulates a pair of genes that inhibit cell division, and that bad copies of the interval reduce the genes’ expression. Although more work is needed to understand how this mechanism contributes to coronary artery disease, the researchers speculate that the hobbled genes allow vascular cells to proliferate unchecked and narrow coronary arteries.

“We show that this non-coding interval affects the expression of two cell cycle inhibitor genes located almost 100,000 base pairs away. We believe that something goes awry in variants of this interval, causing vascular cells to divide and multiply more quickly than usual,” says Len Pennacchio, a geneticist with Berkeley Lab’s Genomics Division who conducted the research with Axel Visel and several other scientists from Berkeley Lab, as well as Jonathan Cohen of the University of Texas Southwestern Medical Center.

The link between an interval of DNA in chromosome 9p21 and a risk for coronary artery disease was established in several recent studies, one of which was published in the journal Science in 2007. In that study, led by Cohen and co-authored by several scientists including Pennacchio, the researchers scoured the human genome for differences in people who have coronary artery disease versus people who don’t.

This genome-wide association analysis alighted on a stretch of DNA in chromosome 9p21 that spans 58,000 base pairs of DNA. The study found that people with bad copies of this interval have a moderately higher risk of developing coronary artery disease. In addition, 50 percent of people have one bad copy and 25 percent have two bad copies.

“The risk of coronary artery disease isn’t very high in any give person with bad copies. But they are so common that population-wide the effect is significant,” says Pennacchio.

Remarkably, the study also found that the DNA interval isn’t associated with known risks for coronary artery disease such as diabetes, high blood pressure, and high cholesterol level. An unknown mechanism was at work.

“We landed on this risk interval and immediately said ‘wow!’ why doesn’t it link to problems that we know cause coronary artery disease?” says Pennacchio. “So the big question became: what is this DNA doing?”

Adding to the mystery, the DNA interval is among the 98 percent of our genome that doesn’t code for proteins. Most efforts to determine the function of the genome have focused on the two percent of our DNA that overlaps protein-coding genes. Scientists are just now beginning to explore the non-coding region, once referred to as “junk DNA.”

As part of this effort, the Berkeley Lab scientists set out to determine the function of the DNA interval in chromosome 9p21 that’s linked to coronary artery disease. They removed an analogous section of DNA from mice, then tracked what happened.

The expression level of two genes located far away, Cdkn2a and Cdkn2b, plummeted by about 90 percent in the “knock-out” mice compared to normal mice. These genes are important in controlling cell cycles and have been linked to cancer when mutated, but they had never been linked to coronary artery disease.

The scientists also studied heart tissue of the “knock-out” mice and found that the smooth muscle cells from their aortas had increased proliferation, a hallmark of coronary artery disease.

“Our research shows that the DNA interval plays a pivotal role in regulating the expression of two genes that control cell cycles. It also suggests that variants of the interval spur the progression of coronary artery disease by altering the dynamics of vascular cells,” says Pennacchio.

With this mechanism identified, scientists can develop therapies that fight coronary artery disease by targeting the two genes and jumpstarting them into action, says Pennacchio. He also believes that the genetic roots of many other diseases will be unearthed as scientists learn how to decipher the function of non-coding DNA.

“Non-coding DNA is a huge area of the genome, waiting to be explored, which could have huge dividends for understanding and treating disease,” says Pennacchio.

The research was funded by the National Institutes of Health.

Other Berkeley Lab scientists involved in the research include Yiwen Zhu, Dalit May, Veena Afzal, Elaine Gong, Cattia Attanasio, Matthew Blow, and Eddy Rubin.

DNAWellnessinfo.com Resource:  http://www.sciencedaily.com/releases/2010/02/100222094801.htm

From Uncharted Region of Human Genome, Clues Emerge About Origins of Coronary Artery Disease is a post from: dnawellnessinfo.com

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

Blood Tests May Reveal Tumor Size is a post from: dnawellnessinfo.com

BY Rosemary Black
DAILY NEWS STAFF WRITER

Wednesday, February 17th 2010, 5:04 PM

Here’s some new information about the science of attraction: Your body odor may provide your mate with subconscious clues about the strength of your immune system.

Researchers from the University of Western Australia, reporting in the journal “Animal Behavior,” say that whether or not the object of your desire finds you irresistible may depend on how sweet your sweat smells, according to a report in the Daily Mail. A woman’s sweat holds genetic information that signals to a potential hubby whether their offspring would possess the best chance of fighting off illness.

The more varied a woman’s histocompatibility, or MHC, genes are, the more attractive she appears to the opposite sex.

The researchers studied the DNA of nearly 150 college students, who filled out questionnaires about their love lives. They looked at the students’ DNA to find variation in genes that are known to have an influence on the immune system, and found that the more diverse these genes were, the more disease-resistant a person was.

The researchers then matched the results of the genetic tests with the survey answers and learned that the women with the most varied histocompatibility (MHC) genes also had the greatest number of sexual partners.

Previous research has shown that the more different a person’s perspiration is to yours, the more pleasant you’re likely to find him or her. It’s theorized that this phenomenon came about so people wouldn’t accidentally marry their relatives or anyone else who’s genetically similar.

Another theory is that women with varied MHC genes could be more outgoing.

“It is possible that MHC-diverse women have more sexual partners because they actively seek more partners, rather than because males prefer diverse partners,” wrote the researchers.

Relationship expert Laurent Mackler says parents may affect how successful a woman is at finding a boyfriend – but not necessarily because of genetics.

“We are invariably attracted to people based on how familiar that person is to us from childhood,” says Mackler, author of “SoleMate: Master the Art of Aloneness & Transform Your Life.”

“As human beings, we are always seeking homeostasis, or balance, and looking for the parts of us that got lost as we grew up and had to adapt to the family system. So we’re attracted unconsciously to the people who embody these traits. We are looking for our other half and may not always find him.”

DNAWellnessinfo.com Resource:  http://www.nydailynews.com/lifestyle/health/2010/02/17/2010-02-17_secrets_of_attraction_may_lie_in_immune_system_dna_thats_sensed_through_sweat_sc.html

Secrets of attraction may lie in immune system DNA is a post from: dnawellnessinfo.com

Scientists perfect quick, low-cost DNA test is a post from: dnawellnessinfo.com

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

Scientists develop universal DNA reader to advance faster, cheaper sequencing efforts is a post from: dnawellnessinfo.com

Feb 11, 2010 – usatoday.com

E.coli bacteria is seen under a microscope.

CAPTION

By Centers for Disease Control

Exposure to low levels of antibiotics increases mutations in E. coli and Staphylococcus bacteria hundreds of time more than normal, making the creation of drug-resistance strains more likely, says a paper in today’s edition of the journal Molecular Cell.

This finding adds to concerns about antibiotic resistance brought on by poor prescriptions practices among doctors, patients who don’t take all their medicine and even low doses of antibiotics given to help animals grow faster.

The researchers found that while low levels of antibiotics may not be enough to kill off the bacteria, they still stress them. That stress causes them to produce free radicals, says James Collins, a biomedical engineer at Boston University and one of the paper’s authors.

Those free radicals are produced by oxidation, a process that’s known to damage cells. In the case of bacteria, the free radicals damage the bacteria’s DNA, causing some of the affected bugs to mutate.

Two and a half years ago Collins’ group began looking at how bacteria respond to antibiotics. It was then that they discovered that antibiotics can stimulate the pathways that create free radicals in bacteria.

A year ago they started considering what other implications their discovery might have.

“We wondered whether sub-lethal levels still produce free radicals. We know the cells wouldn’t die, but we know that free radicals can damage DNA, and that increases mutenigenesis,” he says.

And that’s exactly what they found. Basically, if the antibiotic dose isn’t high enough to kill every bacteria in sight, “you could be creating a zoo with a wide range of mutations,” he says.

The  finding is important “within the context of our understanding — or lack of understanding — of how bacteria become resistant to antibiotics,” says Deborah Hung, a molecular biologist at Massachusetts General Hospital, who wrote an accompanying Perspective piece on the article.

The  truth is that no one really knows exactly how bacteria become resistant to antibiotics, says Hung. So knowing that low levels of antibiotics might potentially increase the random chance that bacteria might mutate into resistant forms could have important implications for medicine.

By Elizabeth Weise

DNAWellnessinfo.com Resource:  http://content.usatoday.com/communities/sciencefair/post/2010/02/a-new-theory-of-how-low-doses-of-antibioitics-create-antibiotic-resistance/1

A new theory of how low doses of antibioitics create antibiotic resistance is a post from: dnawellnessinfo.com

Thursday Feb 11 2010 Stanford News

By Krista Conger

The promise of stem cells sometimes seems no more than a distant glow on the horizon, particularly for patients afflicted with devastating conditions that could potentially benefit from stem-cell-based treatments.

One hurdle has been the difficulty of creating stem cells that match a patient’s genetic background–a must to avoid immune rejection or to study a person’s unique disease fingerprint. The most commonly used protocols to create so-called induced pluripotent stem cells (or iPS cells) have relied on viruses or bacterially based DNA circles called plasmids to introduce the genes necessary to transform a cell from an adult tissue like skin. Unfortunately, these methods work by either popping the genes willy nilly into a cell’s genome without regard to what they might muck up in the process, or they introduce foreign DNA that compromises the ability of the cell to express the necessary genes.

Now Stanford researchers Joseph Wu, MD, PhD; Michael Longaker, MD; and Mark Kay, MD, PhD, have devised a way to use tiny DNA minicircles–about one half the size of regular plasmids–to reprogram stem cells found in human fat. Their research was recently published in Nature Methods (subscription required). You can read our release about the work here.

DNAWellnessinfo.com Resource: http://scopeblog.stanford.edu/archives/2010/02/the-promise-of.html

Tiny DNA circles advance stem cell therapy prospects is a post from: dnawellnessinfo.com