/pollution/article/44404

Radiation exposure is not too good for one’s health and well being. But how much is enough and how much is deadly? A new study from MIT scientists suggests that the guidelines governments use to determine when to evacuate people following a nuclear accident may be too conservative. The study, led by Bevin Engelward and Jacquelyn Yanch and published in the journal Environmental Health Perspectives, found that when mice were exposed to radiation doses about 400 times greater than background levels for five weeks, no DNA damage could be detected.

Current U.S. regulations require that residents of any area that reaches radiation levels eight times higher than background should be evacuated. However, the financial and emotional cost of such relocation may not be worthwhile, the researchers say.

“There are no data that say thats a dangerous level,” says Yanch, a senior lecturer in MITs Department of Nuclear Science and Engineering. “This paper shows that you could go 400 times higher than average background levels and youre still not detecting genetic damage. It could potentially have a big impact on tens if not hundreds of thousands of people in the vicinity of a nuclear power plant accident or a nuclear bomb detonation, if we figure out just when we should evacuate and when its OK to stay where we are.”

Until now, very few studies have measured the effects of low doses of radiation delivered over a long period of time. This study is the first to measure the genetic damage seen at a level as low as 400 times background (0.0002 centigray per minute, or 105 cGy in a year).

The health hazards of low doses of ionizing radiation are unknown and controversial, because the effects, mainly cancer and genetic damage, take many years to appear, and the incidence due to radiation exposure can’t be statistically separated from the many other causes of these diseases. The average dose of background radiation, mostly from natural sources, that every human unavoidably receives during daily life. Background radiation level is widely used in radiological health fields as a standard for setting exposure limits. Presumably, a dose of radiation which is equivalent to what a person would receive in a few days of ordinary life will not increase his rate of disease measurably.

How much is too much?

Background radiation comes from cosmic radiation and natural radioactive isotopes in the environment. These sources add up to about 0.3 cGy per year per person, on average.

Exposure to low-dose-rate radiation is natural, and some people may even say essential for life. The question is, how high does the rate need to get before we need to worry about ill effects on our health? Yanch says.

Previous studies have shown that a radiation level of 10.5 cGy, the total dose used in this study, does produce DNA damage if given all at once. However, for this study, the researchers spread the dose out over five weeks, using radioactive iodine as a source. The radiation emitted by the radioactive iodine is similar to that emitted by the damaged Fukushima reactor in Japan.

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Radiation and DNA

(Phys.org) — By investigating the existence of an unusual four-stranded structure of DNA in human cells, scientists have opened the door to novel cancer therapeutics and a new era for personalised medicine.

When Watson and Crick discovered the double helix structure of DNA in 1953, they declared they had found the secret of life. However, as in all pursuits of science, the story did not end there. Less than 60 years later, a team led by chemist Professor Shankar Balasubramanian and cancer biologist Professor Steve Jackson has found that an unusual four-stranded configuration of DNA also forms at sites across the human genome in living cells.

Although known about by scientists for decades, the structure was considered to be something of a structural curiosity rather than a feature found in nature. It forms in regions of DNA that are rich in one of its building blocks, guanine (G), when a single strand of the double-stranded DNA loops out and doubles back on itself, forming a four-stranded handle in the genome.

G-quadruplexes have been known to occur at the ends of chromosomes in the regions known as telomeres, but it wasnt until a strong association had been noticed with genes responsible for cell proliferation that Balasubramanian and others began to suspect that G-quadruplexes might be a potential target for cancer therapy. If you synthesize a quadruplex-binding molecule and put it into cancer cells, it can impair the growth of these cells, he said. Weve come such a long way from thinking that we understand the genome and it appeared that this structure could tell us something new.

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Protecting the genetic code

At the heart of the new discovery is an innovative way of locating the structures in living cells and then capturing them for further examination. The scientists discovered that when pyridostatin binds to G-quadruplex DNA it causes a double-strand break in the double helix when the cell tries to replicate and copy its genes: Pyridostatin binding to G-quadruplexes is a major impediment to copying the genome so if a cell tries to replicate, this will generate breaks in the DNA, said Jackson.

Over the years, Jacksons lab has found that there are certain proteins in the cell that act as molecular policemen, patrolling the nucleus of the cell looking for damaged DNA. If they detect damage, they start making repairs, and at the same time set off alarm signals to alert the rest of the cell that theres a problem.

When there is no DNA damage, these molecular policemen are distributed evenly throughout each cells nucleus. But when cells are treated with pyridostatin, they congregate in specific locations on the DNA, indicating regions of damage, and showing up as dots under the microscope. The field really jumped on the idea that these dots represent telomeres that have G-rich sequences and in vitro have the potential to form G-quadruplexes, said Jackson. But we stained the dots for telomere proteins and found there was only a small amount of overlap. So clearly, this pyridostatin compound is inducing DNA damage in lots of other places, and we were faced with the issue: if they are not telomeres, what are they?

This confirmed an earlier finding in Balasubramanians lab by Julian Huppert, then a PhD student, who devised a computational search algorithm to map out every spot in the entire human genome that had potential to fold into a G-quadruplex. He found there were close to 350,000 of them.

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A new dimension to DNA and personalized medicine of the future

Posted on: 9:29 pm, May 15, 2012, by Natasha Chen, updated on: 11:13pm, May 15, 2012

(Memphis) Memphis Police Director Toney Armstrong said DNA evidence was the key in connecting six rape cases over a seven-year period.

On Tuesday, 41-year-old Anthony Alliano was indicted on 19 different counts, on top of existing charges for raping a 27-year-old woman.

He was indicted Tuesday on one count of rape of a child, two counts of aggravated rape, one count of aggravated robbery, five counts of aggravated sexual battery, five counts of aggravated burglary, and five counts of criminal attempt aggravated rape.

You have a community or a city that knows that the system has not failed them, Toney Armstrong said.

District Attorney General Amy Weirich said a joint effort across departments helped locate Anthony Alliano. The latest development where they released surveillance photos through the media triggered people to call with tips, which led to Allianos arrest.

Still, Armstrong said DNA was the key. DNA collected either from the scenes of the crimes or from rape kits were submitted to the Tennessee Bureau of Investigation, and at some point in time, the dots started to connect.

He said this type of case is particularly difficult because of the length of time that has passed.

But District Attorney General Amy Weirich said, Fortunately for the pursuit of justice, and unfortunately for that victim that lives with it every day, the details dont seem to be forgotten very quickly.

Armstrong could not say whether rape kits were tested in these cases, or if evidence from the scenes provided the DNA connection.

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DNA Evidence Helped Authorities Find Serial Rapist

STONY BROOK, NY–(Marketwire -05/15/12)- Applied DNA Sciences, Inc. (OTC.BB: APDN) announced its financial results for the second fiscal quarter ending March 31, 2012, generating revenues of $518,402. This represents the company’s highest recorded quarterly revenues, and is the second sequential quarter to set this record.

Second Quarter Highlights:

“The Company began FY ’12 with an exciting first quarter,” said Dr. James A. Hayward, President and CEO of Applied DNA Sciences. “Our developments in the cash-in-transit, semiconductor authentication and textile and apparel authentication markets have sustained that momentum and contributed to the increase in our revenues. We intend to pursue both domestic and international sales opportunities in each of these vertical markets. We continue to increase our customer base. In addition, the initial responses to our new product lines, smartDNA and digitalDNA, have been encouraging.”

Revenues in the quarter ending March 31, 2012 totaled $518,402, up (0.3%) from $516,904 for the quarter ending December 31, 2011. The revenue total for the second quarter 2012 compares to $140,443 for the second quarter ending March 31, 2011, an increase of 369%. The increase in revenues was substantially generated from sales of our SigNature DNA and BioMaterial GenoTyping, our principal anti-counterfeiting and product authentication solutions.

An aggregate of 67% of our revenues was earned from a single customer for the current quarter, while three customers accounted for 70% of the Company’s total revenues for the six months ending March 31, 2012.

Selling, general and administrative expenses increased from $1,619,355 for the three months ended March 31, 2011 to $1,824,646 for the three months ended March 31, 2012. The increase of $205,291 represents a 12.7% increase over the same quarter in the prior fiscal year.

Net loss dropped 36% for the quarter as compared to the quarter ending December 31, 2011. Loss in the three months ended March 31, 2012 decreased to $1,543,882 from a net loss of $2,409,905 for the three months ended December 31, 2011. Compared year over year for the quarter ending March 31, net loss decreased by $1,054,787 or 40%.

The Company incurred research and development expenses of $96,097 and $92,951 for the three-month periods ended March 31, 2012 and 2011, respectively, and $174,570 and $113,657 for the six month periods ended March 31, 2012 and 2011, respectively. The increase is attributable to additional research and development activity needed with current operations.

Total operating expenses decreased to $2,019,451 for the three months ended March 31, 2012 from $2,329,274 for the three months ended December 31, 2011, a decrease of $309,823 quarter over quarter, representing a 13% reduction. Compared year over year for the quarter ending March 31, total operating expenses increased by $215,252 or 12%.

Dr. Hayward commented further: “We are pleased to see revenues increase while we control our expenses closely. Our product shipments have expanded dramatically over the last twelve months. We expect production increases to continue.

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Applied DNA Sciences Reports Fiscal Second Quarter 2012 Results

Posted on: 3:44 pm, May 13, 2012, by Ben Handelman, updated on: 08:36pm, May 13, 2012

PEWAUKEE It is a journey that has put her in touch with doctors from around the world. On this Mothers Day, Mindy Brayman may be one step closer to solving the cause behind a disease that has crippled her two children, with the help of experts in her back yard.

Nine-year-old Jack and eight-year-old Todd suffer from a mysterious genetic disease, that has baffled doctors for years. But new breakthroughs, specifically DNA sequencing, may help finally discover what is causing the childrens brains to not communicate properly with the rest of their bodies. The two boys need 24/7 care.

Through a first-of-its-kind program at Childrens Hospital and The Medical College of Wisconsin, the boys gave DNA samples, that will be tested and researched, hoping to find the gene that caused the problems. With that information, their parents hope they can narrow in on treatment.

Low and behold Childrens Hospital in Wisconsin was the first in the world to have a clinical whole genome sequencing, where you can actually go to the clinic and see someone, and find out about it. There have been a lot of unknowns, so weve kind of had to learn how to deal with unexpected things coming along, Brayman said.

DNA samples were sent out to labs in January, and the family may get results back in the next few months.

In the meantime, the family is holding a fundraiser for the Medical College of Wisconsins DNA sequencing program. Money raised will go to help the boys and other families with medical mysteries.

The fundraiser is a golf outing and dinner on May 21st at the Legend of Brandybrook in Wales.

CLICK HERE for more information on the fundraiser, and to make a donation.

CLICK HERE for more information on the Medical College of Wisconsins DNA sequencing via the Human and Molecular Genetics Center.

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DNA sequencing the answer to boys’ mysterious disorder?

New Delhi: Senior politician and former Andhra Pradesh governor ND Tiwari has been ordered to either “gracefully appear” for a DNA test, or be forced to take the test by the Delhi Police.

The Delhi High Court warned Mr Tiwari to pick his option within two days. The court has also asked a Hyderabad lab to send kits to Delhi for the DNA test. Mr Tiwari has been ordered not to leave India.

Mr Tiwari has been fighting a paternity test for several years. Rohit Shekhar, in his 30s, claims to be his biological son. Last month, the High Court had said that Mr Tiwari must submit blood samples for a DNA test, or risk being subjected to it by force.

Mr Tiwari, who is 86 years old, was forced to resign as governor of Andhra Pradesh in 2009 after local channels broadcasted footage that allegedly showed him in a compromising position with three women.

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DNA test inevitable for ND Tiwari after court order

Mitotic spindle-chromosome attachments, marked in green, become unstable (on the right) compared to normal (on the left). Credit: Cook and Salmon labs, UNC School of Medicine

The foundation of biological inheritance is DNA replication a tightly coordinated process in which DNA is simultaneously copied at hundreds of thousands of different sites across the genome. If that copying mechanism doesn’t work as it should, the result could be cells with missing or extra genetic material, a hallmark of the genomic instability seen in most birth defects and cancers.

University of North Carolina School of Medicine scientists have discovered that a protein known as Cdt1, which is required for DNA replication, also plays an important role in a later step of the cell cycle, mitosis. The finding presents a possible explanation for why so many cancers possess not just genomic instability, but also more or less than the usual 46 DNA-containing chromosomes.

The new research, which was published online ahead of print by the journal Nature Cell Biology, is the first to definitively show such a dual role for a DNA replication protein.

“It was such a surprise, because we thought we knew what this protein’s job was to load proteins onto the DNA in preparation for replication,” said Jean Cook, PhD, associate professor of biochemistry and biophysics and pharmacology at the UNC School of Medicine and senior study author. “We had no idea it also had a night job, in a completely separate part of the cell cycle.”

The cell cycle is the series of events that take place in a cell leading to its growth, replication and division into two daughter cells. It consists of four distinct phases: G1 (Gap 1), S (DNA synthesis), M (mitosis) and G2 (Gap 2). Cook’s research focuses on G1, when Cdt1 places proteins onto the genetic material to get it ready to be copied.

In this study, Cook ran a molecular screen to identify other proteins that Cdt1 might be interacting with inside the cell. She expected to just find more entities that controlled replication, and was surprised to discover one that was involved in mitosis. That protein, called Hec1 for “highly expressed in cancer,” helps to ensure that the duplicated chromosomes are equally divided into daughter cells during mitosis, or cell division. Cook hypothesized that either Hec1 had a job in DNA replication that nobody knew about, or that Cdt1 was the one with the side business.

Cook partnered with Hec1 expert Edward (Ted) D. Salmon, PhD, professor of biology and co-senior author in this study, to explore these two possibilities. After letting Cdt1 do its replication job, the researchers interfered with the protein’s function to see if it adversely affected mitosis. Using a high-powered microscope that records images of live cells, they showed that cells where Cdt1 function had been blocked did not undergo mitosis properly.

Once the researchers knew that Cdt1 was involved in mitosis, they wanted to pinpoint its role in that critical process. They further combined their genetic, microscopy and computational methods to demonstrate that without Cdt1, Hec1 fails to adopt the conformation inside the cells necessary to connect the chromosomes with the structure that pulls them apart into their separate daughter cells.

Cook says cells that make aberrant amounts of Cdt1, like that seen in cancer, can therefore experience problems in both replication and mitosis. One current clinical trial is actually trying to ramp up the amount of Cdt1 in cancer cells, in the hopes of pushing them from an already precarious position into a fatal one.

See the original post:
DNA replication protein Cdt1 also has a role in mitosis, cancer

OKLAHOMA CITY –

A DNA match has linked an Oklahoma inmate with the rape and kidnapping of a 14-year-old Oklahoma City girl.

The case had grown cold for more than two years. The charges were just filed today against that 19-year-old prisoner. His DNA matched the sample taken from that young rape victim. And for now, he is the only one being linked to the disturbing crime.

The police report states it was back in November of 2009, that a 14-year-old girl was walking home from school when she was approached by two men.

It happened near N.W. 19th and Purdue. She says the men told her to get into their car, but she refused and kept walking. That’s when one of the men came up behind her, wrapped his gloved hand around her nose and mouth and grabbed her.

The police report states she thought there was some type of chemical on the glove and she passed out.

When she came to she says that’s when she discovered one of the men on top of her.

“She woke up being sexually assaulted inside the car, she was then forced out of the car and left,” MSgt. Gary Knight said.

Though she was not able to give police a good description of her attacker, police did conduct a rape exam and were able to get a DNA sample to run through CODIS, the national database.

“In order to get a CODIS hit we need a viable sample,” Knight said.

Read more:
DNA Links Inmate To Rape Of 14-Year-Old OKC Girl

May 14, 2012

Image Credit: Photos.com

The foundation of biological inheritance is DNA replication

This is a coordinated process in which DNA is copied at hundreds of thousands of different sites across the genome at the same time. If the copying mechanism doesnt work properly, the result may be cells with missing or extra genetic material, a hallmark of the genomic instability seen in most birth defects and cancers.

Scientists at the University of North Carolina School of Medicine have discovered a protein known as Cdt1. This is required for DNA replication and has an important role in a later step of the cell cycle, mitosis. This is a possible explanation why so many cancers possess not just genomic instability, but also more or less than the usual 46 DNA-containing chromosomes.

The new research was published online ahead of print by the journal Nature Cell Biology. It is the first to definitively show such a dual role for a DNA replication protein.

This was such a surprise. We thought this proteins job was to load proteins onto the DNA in preparation for replication, said Jean Cook, PhD, associate professor of biochemistry and biophysics and pharmacology at the UNC School of Medicine and senior study author. We had no idea it also had a night job, in a completely separate part of the cell cycle.

The cell cycle is the series of events that happen in a cell leading to its growth, replication and division into two daughter cells. It has four distinct phases: G1 (Gap 1), S (DNA synthesis), M (mitosis) and G2 (Gap 2). Cooks research focuses on G1, when Cdt1 places proteins onto the genetic material to get it ready to be copied.

Cook ran a molecular screen to find other proteins that Cdt1 could be interacting with inside the cell. She expected to only find more entities that controlled replication but was surprised to discover one that was involved in mitosis. That protein, called Hec1 for highly expressed in cancer, helps to ensure that the duplicated chromosomes are divided equally into daughter cells during mitosis. Cook hypothesized that either Hec1 had a job in DNA replication that nobody knew about, or that Cdt1 was the one with the side business.

To look at these two possibilities, Cook partnered with Edward (Ted) D. Salmon, PhD, professor of biology and co-senior author who is a Hec1 expert. After letting Cdt1 do its replication job, they interfered with the proteins function to see if it adversely affected mitosis. Using a high-powered microscope that records images of live cells, they showed that cells where Cdt1 function had been blocked did not undergo mitosis properly.

See original here:
DNA Replication Protein Plays Role In Cancer

ScienceDaily (May 13, 2012) The foundation of biological inheritance is DNA replication — a tightly coordinated process in which DNA is simultaneously copied at hundreds of thousands of different sites across the genome. If that copying mechanism doesn’t work as it should, the result could be cells with missing or extra genetic material, a hallmark of the genomic instability seen in most birth defects and cancers.

University of North Carolina School of Medicine scientists have discovered that a protein known as Cdt1, which is required for DNA replication, also plays an important role in a later step of the cell cycle, mitosis. The finding presents a possible explanation for why so many cancers possess not just genomic instability, but also more or less than the usual 46 DNA-containing chromosomes.

The new research, which was published online ahead of print by the journal Nature Cell Biology, is the first to definitively show such a dual role for a DNA replication protein.

“It was such a surprise, because we thought we knew what this protein’s job was — to load proteins onto the DNA in preparation for replication,” said Jean Cook, PhD, associate professor of biochemistry and biophysics and pharmacology at the UNC School of Medicine and senior study author. “We had no idea it also had a night job, in a completely separate part of the cell cycle.”

The cell cycle is the series of events that take place in a cell leading to its growth, replication and division into two daughter cells. It consists of four distinct phases: G1 (Gap 1), S (DNA synthesis), M (mitosis) and G2 (Gap 2). Cook’s research focuses on G1, when Cdt1 places proteins onto the genetic material to get it ready to be copied.

In this study, Cook ran a molecular screen to identify other proteins that Cdt1 might be interacting with inside the cell. She expected to just find more entities that controlled replication, and was surprised to discover one that was involved in mitosis. That protein, called Hec1 for “highly expressed in cancer,” helps to ensure that the duplicated chromosomes are equally divided into daughter cells during mitosis, or cell division. Cook hypothesized that either Hec1 had a job in DNA replication that nobody knew about, or that Cdt1 was the one with the side business.

Cook partnered with Hec1 expert Edward (Ted) D. Salmon, PhD, professor of biology and co-senior author in this study, to explore these two possibilities. After letting Cdt1 do its replication job, the researchers interfered with the protein’s function to see if it adversely affected mitosis. Using a high-powered microscope that records images of live cells, they showed that cells where Cdt1 function had been blocked did not undergo mitosis properly.

Once the researchers knew that Cdt1 was involved in mitosis, they wanted to pinpoint its role in that critical process. They further combined their genetic, microscopy and computational methods to demonstrate that without Cdt1, Hec1 fails to adopt the conformation inside the cells necessary to connect the chromosomes with the structure that pulls them apart into their separate daughter cells.

Cook says cells that make aberrant amounts of Cdt1, like that seen in cancer, can therefore experience problems in both replication and mitosis. One current clinical trial is actually trying to ramp up the amount of Cdt1 in cancer cells, in the hopes of pushing them from an already precarious position into a fatal one.

The research was funded by the National Institutes of Health. Study co-authors from UNC were Dileep Varma; Srikripa Chandrasekaran; Karen T. Reidy; and Xiaohu Wan.

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DNA replication protein also has a role in mitosis, cancer

Theres more to your DNA than your DNA. We are now becoming aware of the epigenome. While DNA controls you, your epigenome may help control your DNA, or rather, it can have an extensive impact on how your DNA is expressed. The epigenome consists of changes in the structure of your DNA, how it is packaged, what parts of it are available for expression into RNA and proteins. For example, adding methyls to DNA tends to decrease the gene expression of that DNA segment, while taking away methyl groups increases it. The cool thing about epigenetics is that the methylation can vary from tissue to tissue, controlling how different genes are expressed in say, liver vs spleen.

(I cant wait til Jonathan Coulton writes a song about the epigenome)

One of the most interesting things about the epigenome is that you can pass it along in the germline. To your kids. So in theory, if you had methylation in certain parts of your genome, your kids could as well. But were starting to realize that epigenetics is more malleable than that.

Take muscle tissue for instance. Gene expression in muscle tissue can change the efficiency of glucose metabolism by muscle. And glucose metabolism has a very large effect on many bodily processes, include weight gain and problems like cardiovascular disease and type II diabetes. Muscle itself is very plastic, and responds quickly to changes in the environment (which for a muscle, means increases and decreases in exercise or how many calories are getting in). We know that exercise can change gene expression in muscle, but can it also change the epigenome? While immediate changes in gene expression can be very short, changes to the epigenome indicate much longer-term changes. Could bouts of exercise influence the methylation of muscle, and thus have long-term effects?

Barres et al. Acute Exercise Remodels Promoter Methylation in Human Skeletal Muscle Cell Metabolism, 2012.

The cool thing is that the authors of this study were able to do large sections of this study in humans. Humans, at least, who did not object to getting muscle biopsies.

They took 14 sedentary humans and had them exercise to fatigue (a pretty difficult exercise bout). They biopsied the muscles before and after the exercise, and looked to see what the methylation in the muscle looked like.

What you can see here is that the acute bout of exercise decreased the methylation in the muscle tissue. When they looked a little closer, the authors found that the methylation was particularly decreased in the promotor regions of metabolically related genes. Many of these promotor regions, which directly control the expression of a gene, show changes in methylation during type II diabetes. After exercise the methylation in these promotor regions was decreased, which could result in more gene expression of those genes, and thus result in changes in metabolism.

Further studies showed that this change in methylation depended on exercise intensity. In a group of mice exposed to low or high intensity exercise, only the high intensity produced the gene methylation changes seen in humans.

Continue reading here:
Methylating Your Muscle DNA

Read more from the original source:
Suspect's spork helps crack robbery case

Doralee Freebairn sits in her Holladay, Utah home Friday May 11, 2012, looking at an old newspaper article about the search for her then 17-year-old brother, Alvin Nelson, who was swept away in a flash flood in Zion National Park in September 1961. This week, authorities used DNA to identify a skull fragment found by a man swimming in the Virgin River in 2006. It was Alvin Nelson.

Brian Skoloff, Associated Press

HOLLADAY A tragic 50-year-old mystery caused by a huge flood in Zion National Park has been solved with a chance find and a DNA match.

In September 1961, a Boy Scout troop from Salt Lake City was hiking along the Virgin River in an area of the park knows as “The Narrows.” When the surprise flood hit, a troop leader and four Scouts drowned.

Three of the bodies were recovered, but the remains of then 17-year-old Alvin Nelson and his best friend, Frank Johnson, were not.

“I always felt that something might turn up as these floods progressively came down the canyon,” Doralee Freebairn, Nelson’s sister said Friday.

With the severity of the flood, Freebairn said she wasn’t surprised that her brother didn’t make it out.

“When you’re trapped in a very small area, and there’s a wall of water that hits, you don’t have any chances of getting out of it,” Freebairn said.

The tragedy left Nelson’s family with a lot of questions.

“You have a lot of what ifs,’” said Tracy Myers, Freebairn’s daughter. “It could have changed the entire course of my mother’s life if he had lived. He would be near 70. What if I had cousins on that side?”

See more here:
DNA helps solve a mystery from 1961 flood in Zion National Park

Public release date: 10-May-2012 [ | E-mail | Share ]

Contact: Hannah Isom press.office@headoffice.mrc.ac.uk 44-207-395-2345 University of Edinburgh

Scientists from the Medical Research Council (MRC) Institute of Genetics and Molecular Medicine (IGMM) at the University of Edinburgh have discovered an enzyme that corrects the most common mistake in mammalian DNA.

The mistake is the inclusion of individual bits of RNA within the DNA sequence, which the researchers found occurs more than a million times in each cell as it divides. The findings, published in Cell, suggest the RNase H2 enzyme is central to an important DNA repair mechanism necessary to protect the human genome.

Each time a cell divides it must first make an identical copy of its entire genetic material, known as the genome. During this process, which is called DNA replication, the integrity of the genetic code is safeguarded by cellular ‘proofreading’ and error checking mechanisms.

But sometimes mistakes creep into the genetic code, which if not corrected could lead to genetic disease or cancer. Accidental incorporation of RNA is one such mistake. The individual building blocks of RNA (ribonucleotides) are very similar to those that make up DNA, however, they are much less stable and if they remain incorporated in DNA they cause harmful breaks in the double helix. Such breaks are common in cancer cells.

The researchers made the discovery while working on a rare childhood auto-immune disease known as Aicardi-Goutires syndrome, which is caused by mutations in the RNase H2 genes. It leads to inflammation of the brain soon after birth and can be fatal within the first few years of life.

To study this condition in more detail, the scientists knocked out one of the RNase H2 genes in mice. They found that without the enzyme, the developing mouse embryos accumulated more than 1,000,000 single embedded bits of RNA in the genome of every cell, resulting in instability of their DNA.

Dr Andrew Jackson from the MRC IGMM at the University of Edinburgh, who led the research, said:

“The most amazing thing is that by working to understand a rare genetic disease, we’ve uncovered the most common fault in DNA replication by far, which we didn’t even start out looking for! More surprising still is that a single enzyme is so crucial to repairing over a million faults in the DNA of each cell, to protect the integrity of our entire genetic code.

Excerpt from:
Enzyme corrects more than 1 million faults in DNA replication