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DNA proves Charles Darwin was right

By Aaron Findlay From: The Australian February 05, 2010

Ancestors left Africa 45,000 years ago
Darwin “would have been delighted”
Proves his “wild” theories

CHARLES Darwin may have been prone to the odd wild theory, but even he probably never imagined that DNA technology could help determine who his ancient ancestors were.

However, 200 years after his birth, the technology seems to have achieved just that, with an experiment involving his great-great-grandson apparently revealing that the family’s ancestors left Africa about 45,000 years ago, The Australian reported.

Chris Darwin, 48, took a cheek swab test analysing his Y chromosome, with the test revealing that he, and therefore his paternal great-great-grandfather Charles Darwin, are from the Haplogroup R1B, one of the most common European male lineages.

Mr Darwin, a tour guide from the Blue Mountains, west of Sydney, said his great-great-grandfather would have been both delighted and relieved, given he had gone “out on a limb” with his assertions that Africa was the “cradle of humankind”.

“When you look at it, he made some really wild statements – I mean, saying we’re all from Africa, he simply looked at the great apes around the world and considered that the similarities between the chimpanzees and the gorillas were greater with us than the similarities with the orangutans,” he said.

“And he then said we must be from Africa – but that is a pretty wild shot in the dark so he was really going out on a limb.”

Mr Darwin said the quest to find out what we are and where we come from was just as important as the work that went into the now acknowledged theory that Earth was not the centre of the universe.

” At some stage surely, don’t we need to decide what we are? Are we an image of a god or are we an ape from Africa?” he said.

The experiment, known as The Genographic Project, is a research partnership between National Geographic and IBM with field support from the Waitt Family Foundation.

The project’s test results show Mr Darwin’s paternal ancestors would have migrated from northeast Africa to the Middle East or North Africa about 45,000 years ago.

Men belonging to Haplogroup R1B are direct descendants of the Cro-Magnon people who, beginning 30,000 years ago, dominated the human expansion into Europe and heralded the demise of the Neanderthal species.

Read more at The Australian.

DNAWellnessinfo.com Resource: http://www.news.com.au/national/dna-proves-charles-darwin-was-right/story-e6frfkvr-1225827108398

Premature birth gene clue found

Friday, 5 February 2010 – bbc news

DNA differences which appear to affect the risk of giving birth early have been found by US scientists.

The US National Institutes of Health study found the variants in both babies and mothers, a US conference was told.

It is thought they may play a role in controlling immune responses which could theoretically trigger labour if they become too powerful.

Premature birth – which accounts for 7% of UK births – is one of the biggest threats to a baby’s future health.

The causes of premature birth are poorly understood, although infections and other medical complications are blamed in some cases.

The study looked at 700 DNA variants in 190 genes in women who delivered early, and those who carried their baby to term.

The cord blood of the babies was also tested for these variations.

They narrowed the search down to a handful of gene variations found more often in the women who gave birth prematurely, and their babies.

In particular, babies who carried the gene for the “Interleukin 6 receptor” were more likely to be born early.

This was a good candidate gene because Interleukin 6 is produced by cells in response to infection and is involved in inflammation.

High levels of Interleukin 6 in the amniotic fluid and foetal blood have been linked to the onset of premature labour.

Baby threat

Dr Roberto Romero, who led the study, said: “Our hypothesis is that the mother and/or the foetus signal the onset of preterm labour when the environment inside the uterus is unfavourable and threatens the survival of the maternal-foetal pair.

“When there is an infection in the uterus, the onset of premature labour appears to have survival value – it would allow the mother to rid herself of infected tissue and preserve her ability to have future pregnancies.”

The chief executive of charity Bliss, Andy Cole, welcomed the study results.

“In England alone, 54,000 babies are born prematurely each year, a third of these for no known reason,” he said.

“The development of a reliable test for identifying these mothers is vital in ensuring our most vulnerable babies have the best possible outcomes.”

DNAWellnessinfo.com Resource:  http://news.bbc.co.uk/2/hi/health/8498712.stm

Crash-Test Reveals DNA Traffic Control

1/29/10 – HHMI News

Enzymes that copy DNA don’t travel on a lonely highway, but instead ply their trade on crowded interstates. Now, Howard Hughes Medical Institute researchers have discovered that when those DNA-copying machines run head-on into oncoming traffic, they kick the obstacles out of their way.

DNAi_replication_354.mov

A detailed view of DNA replication showing both strands of the DNA double helix acting as templates for the new DNA strands.

Video: HHMI Biointeractive

“Losing an RNA transcript is no big deal. But the consequences would be dire if the replisome fell apart every time it met an RNA polymerase. ”
Michael E. O’Donnell

The finding, reported in the January 29, 2010, issue of Science, reveals new details about the “rules of the road” that help ensure that cells make accurate copies of their genetic material – essential for producing healthy new cells.

In preparation for cell division, cells rely on complex protein machines to pull apart and untwist opposing strands of DNA. Once the double helix is untwisted, both strands are copied to produce two complete sets of the genome. The replisome is a protein complex that moves at high speed for long distances on DNA, wrenching the helix apart as it goes. The replisome shares its tracks with other proteins that transcribe DNA into messenger RNA, which is then used to produce proteins. Sometimes these convoys move in opposite directions – and collisions are unavoidable. HHMI investigator Michael O’Donnell of Rockefeller University wondered what happens to the machines when they collide.

To find out, O’Donnell and his colleague Richard Pomerantz reconstructed a cellular traffic accident in a test tube. To do that, they first had to assemble the replisome on DNA in a test tube, an endeavor that required years of effort in O’Donnell’s lab. Once his group had successfully reconstructed a replisome from the relatively simple bacteria E. coli, they were ready to begin their experiments.

They set an RNA polymerase—the enzyme that transcribes DNA into RNA—in motion on a piece of DNA and then stalled it. Next, they assembled the components that make up the DNA replication machine at the opposite end of the DNA and nudged this complex into action. Then they analyzed the aftermath of the resulting collision.

They found that the DNA replication machine managed to copy the full length of the DNA molecule, indicating that it had traveled the full distance and somehow got past the RNA polymerase. Further analysis suggested that the DNA replication machine stops when it encounters the RNA polymerase, shoves the RNA polymerase off the DNA, and then proceeds.

Researchers knew that a protein called Mfd kicks RNA polymerase off DNA when it has stalled out because a section of DNA is damaged. In the current experiment, RNA polymerase was stalled by another means. But O’Donnell and Pomerantz wondered whether Mfd would help the DNA replication machinery move through RNA polymerase faster even in this case.

O’Donnell and Pomerantz repeated the crash test, this time including Mfd in the mix. With Mfd present, the replisome made even more full-length copies of the DNA than it did without Mfd, suggesting that Mfd helps give RNA polymerase the boot.

Scientists have reported conflicting observations about whether replisomes fall apart when they hit a road block, and O’Donnell’s results provide additional evidence that the replisome is hearty. “The replisome is very stable,” says O’Donnell. “It just sits there until it finally wins.”

It makes sense biologically to give the replisome priority, he adds. “Losing an RNA transcript is no big deal. But the consequences would be dire if the replisome fell apart every time it met an RNA polymerase. These collisions are probably common in the cell, so keeping the replisome moving ensures that DNA replication proceeds neatly and rapidly.”

O’Donnell is now searching for other factors that push the replisome through blocks. He’d also like to know whether the replisome in eukaryotic cells, such as yeast or mammalian cells, behaves similarly to the bacterial complex he and Pomerantz have studied. The replication machinery in those kinds of cells is much more complicated, and his group is still working on recreating the mammalian replisome in a test tube.

DNAWellnessinfo.com Resource:  http://www.hhmi.org/news/odonnell20100129.html

Missing DNA tied to obesity

Last Updated: Wednesday, February 3, 2010 | 6:02 PM ET
CBC News

Some severely obese people are missing a set of genes, a new study has found.

Researchers have found a small proportion of obese people are born without 30 or so of the estimated 30,000 genes in the human genome.

This deletion of genes was not found in any subjects of normal weight, the team from Imperial College London and their colleagues in Europe, the United States and Montreal reported in Wednesday’s issue of the journal Nature.

The missing genes may account for seven out of 1,000 cases of morbid obesity — people with a body mass index, or BMI, over 40, the study found. The body mass index is a tool used to determine the healthy weight range for a particular height. A BMI over 30 is considered obese and 25 to 29.9 is overweight.

The recent rise in obesity in the developed world has been attributed to an abundance of unhealthy food and too little exercise, but the way people respond to these environmental factors is often genetic, said Prof. Phillipe Froguel, lead author of the study at the School of Public Health at Imperial College London.

“It is becoming increasingly clear that for some morbidly obese people, their weight gain has an underlying genetic cause,” Froguel said in a news release.

“If we can identify these individuals through genetic testing, we can then offer them appropriate support and medical interventions, such as the option of weight-loss surgery, to improve their long-term health.”

Searched general population
In the first part of the study, researchers looked for the genes in obese teenagers and adults with learning difficulties or delayed development. They found 31 severely obese people with nearly identical deletions in one copy of their DNA.

The second part of the study looked at the genomes of 16,053 European people in the general population, reflecting a range of weights. Nineteen people in this group were missing the same set of genes, and all were morbidly obese.

Those lacking the genes tended to be normal weight as toddlers, overweight during childhood and severely obese as adults, the researchers said.

The study is the first to confirm that severe obesity in otherwise physically healthy individuals can be caused by a rare deletion of DNA, the authors said.

Until now, individual genes linked to weight gain have had a relatively modest effect of about two pounds.

“The genetic change identified in this study is much less common but leads to much more substantial changes in the body weight of the individuals that it affects,” study co-author Dr. Robert Sladek of McGill University in Montreal said in a release Wednesday.

Researchers have found a similar modest effect with genes influencing Type 2 diabetes. The approach the obesity researchers used — identifying the deletion in very obese people and then looking for the variant in a much broader population — could help to identify genetic influences on Type 2 diabetes and other diseases, the researchers said.

They now plan to study the function of the missing genes. Previous studies have suggested that deletions of these genes may be linked with delayed development, autism and schizophrenia.

DNAWellnessinfo.com Resource: http://www.cbc.ca/health/story/2010/02/03/obesity-dna-deletion.html

HIV Researchers Solve Key Puzzle After 20 Years of Trying

ScienceDaily (Jan. 31, 2010) — Researchers have made a breakthrough in HIV research that had eluded scientists for over 20 years, potentially leading to better treatments for HIV, in a study published January 30 in the journal Nature.

The researchers, from Imperial College London and Harvard University, have grown a crystal that reveals the structure of an enzyme called integrase, which is found in retroviruses like HIV. When HIV infects someone, it uses integrase to paste a copy of its genetic information into their DNA.

Prior to the new study, which was funded by the Medical Research Council and the US National Institutes of Health, many researchers had tried and failed to work out the three-dimensional structure of integrase bound to viral DNA. New antiretroviral drugs for HIV work by blocking integrase, but scientists did not understand exactly how these drugs were working or how to improve them.

Researchers can only determine the structure of this kind of molecular machinery by obtaining high quality crystals. For the new study, researchers grew a crystal using a version of integrase borrowed from a little-known retrovirus called Prototype Foamy Virus (PFV). Based on their knowledge of PFV integrase and its function, they were confident that it was very similar to its HIV counterpart.

Over the course of four years, the researchers carried out over 40,000 trials, out of which they were able to grow just seven kinds of crystals. Only one of these was of sufficient quality to allow determination of the three-dimensional structure.

Dr Peter Cherepanov, the lead author of the study from the Department of Medicine at Imperial College London, said: “It is a truly amazing story. When we started out, we knew that the project was very difficult, and that many tricks had already been tried and given up by others long ago. Therefore, we went back to square one and started by looking for a better model of HIV integrase, which could be more amenable for crystallization. Despite initially painstakingly slow progress and very many failed attempts, we did not give up and our effort was finally rewarded.”

After growing the crystals in the lab, the researchers used the giant synchrotron machine at the Diamond Light Source in South Oxfordshire to collect X-ray diffraction data from these crystals, which enabled them to determine the long-sought structure. The researchers then soaked the crystals in solutions of the integrase inhibiting drugs Raltegravir (also known as Isentress) and Elvitegravir and observed for the first time how these antiretroviral drugs bind to and inactivate integrase.

The new study shows that retroviral integrase has quite a different structure to that which had been predicted based on earlier research. Availability of the integrase structure means that researchers can begin to fully understand how existing drugs that inhibit integrase are working, how they might be improved, and how to stop HIV developing resistance to them.

DNAWellnessinfo.com Resouce:  http://www.sciencedaily.com/releases/2010/01/100131142438.htm

Researchers Find New Way To Study How Enzymes Repair DNA Damage

January 28, 2010

Researchers at Ohio State University have found a new way to study how enzymes move as they repair DNA sun damage — and that discovery could one day lead to new therapies for healing sunburned skin.

Ultraviolet (UV) light damages skin by causing chemical bonds to form in the wrong places along the DNA molecules in our cells. Normally, other, even smaller molecules called photolyases heal the damage. Sunburn happens when the DNA is too damaged to repair, and cells die.

Photolyases have always been hard to study, in part because they work in tiny fractions of a second. In this week’s online edition of the Proceedings of the National Academy of Sciences, Ohio State physicist and chemist Dongping Zhong and his colleagues describe how they used ultra-fast pulses of laser light to spy on a photolyase while it was healing a strand of DNA.

This is the first time that anyone has observed this enzyme motion without first attaching a fluorescent molecule to the photolyase, which disturbs its movements. They were able to see the enzyme’s motion to help the healing process as it happens in nature.

“Now that we have accurately mapped the motions of a photolyase at the site of DNA repair, we can much better understand DNA repair at the atomic scale, and we can reveal the entire repair process with unprecedented detail,” said Zhong, the Robert Smith Associate Professor of Physics, and associate professor in the departments of chemistry and biochemistry at Ohio State.

Such small motions are very hard to study. Typically, researchers deal with the problem by attaching tiny bits of fluorescent molecules to the enzymes they are trying to study. But adding an extra molecule to an enzyme such as photolyase could change how it moves.

“Once you tag it, you can’t be sure that the motions you detect are the true motions of the molecule as it would normally function,” Zhong explained.

So instead of using tags, he and his team took laser “snapshots” of a single photolyase in action in the laboratory. They mapped the shape and position of the photolyase molecule as it broke up the harmful chemical bonds in DNA caused by UV light. The whole reaction lasted only a few billionths of a second.

In nature, DNA avoids damage by converting UV rays into heat. Sunscreen lotions protect us by reflecting sunlight away from the skin, and also by dissipating UV as heat.

Sunburn happens when the DNA absorbs the UV energy instead of converting it to heat. This is due in part to the random position of the DNA molecule within our cells when the UV hits it. When the UV energy is absorbed, it triggers chemical reactions that form lesions — errant chemical bonds — along the DNA strand.

If photolyases are unable to completely repair the lesions, the DNA can’t replicate properly. Badly damaged cells simply die — that’s what gives sunburn its sting. Scientists also believe that chronic sun damage creates mutations that lead to diseases such as skin cancer.

More information: http://www.pnas.org/

Provided by The Ohio State University (news : web)

DNAWellnessinfo.com Resource:  http://www.physorg.com/news183913344.html

A New Way to Look for Diseases’ Genetic Roots

The hunt for the genetic roots of common diseases has hit a blank wall.

The genetic variants found so far account in most cases for a small fraction of the genetic risk of the major killers. So where is the missing heritability and why has it not showed up?

A Duke geneticist now suggests that the standard method of gene hunting had a theoretical flaw and should proceed on a different basis. The purpose of the $3 billion project to decode the human genome, completed in 2003, was to discover the genetic roots of common diseases like diabetes, cancer and Alzheimer’s. The diseases are called complex, meaning that several mutated genes are probably implicated in each.

A principal theory has long been that these variant genes have become common in the population because the diseases strike late in life, after a person has had children. Bad genes would not be eliminated by natural selection at that age, as they would if the diseases struck before the child-bearing years.

So to find disease genes, the thinking went, do not decode the entire genome of every patient — just look at the few sites where genetic variations are common, defined as being present in at least 1 percent of the population.

These sites of common variation are called SNPs (pronounced “snips”), and biotech companies have developed ingenious devices to recognize up to 500,000 SNPs at a time. The SNP chips made possible genomewide association studies in which the genomes of many patients are compared with those of healthy people to see which SNPs are correlated with the disease.

The SNP chips worked well, the studies were well designed, though enormously expensive, and some 2,000 disease-associated SNPs have been identified by university consortiums in the United States and Europe.

But this mountainous labor produced something of a mouse.

In each disease, with few exceptions, the SNPs accounted for small percentage of the genetic risk. A second puzzling feature was that many of the disease-linked SNPs did not occur in the DNA that codes for genes, but rather in the so-called junk regions of the genome. Biologists speculated that these SNPs must play an as-yet-undefined role in deranging the regulation of nearby genes.

In an article this week in the journal PLoS Biology, the Duke geneticist David B. Goldsteinph.d and his colleagues propose an explanation for both findings.

They argue that the common disease-common variant idea is largely incorrect: natural selection has in fact done far better than expected in eliminating disease-causing variants from the population. It follows that the major burden of disease is carried by a multitude of rare variants — ones too rare to have been programmed into the SNP chips.

So why have the genomewide association studies linked some SNPs to disease, if in fact it is the rare variants that cause it?

In Dr. Goldstein’s view, the SNPs could simply be acting as surrogate markers for the rare variants. Until now, geneticists have assumed a disease-linked SNP was either itself a cause or was a marker for a disease variant nearby. But Dr. Goldstein’s team calculated that the rare variants associated with a SNP can occur up to two million units of DNA away from it. This means that the disease-associated SNPs do not necessarily point to anything useful and that it is dangerous to assume the nearest gene is the cause of the disease.

If SNPs are indeed rather indirect markers of disease, that would explain why many have turned up in junk DNA.

But why do the SNPs get implicated in the genomewide association studies if in fact it is the rare variants that cause disease? Most of the SNPs are ancient, which is how they got to be common, whereas the disease-causing rare variants are mostly recent, because natural selection is always sweeping them away. After a SNP is created, some of the population has it and the rest continue to carry the standard DNA unit at that site in their genome.

When the rare disease-causing variants build up much later, Dr. Goldstein suggests, some will be on stretches of DNA containing the SNP and others on stretches of DNA with the standard unit. Since the allocation is random, more rare variants will be sometimes lie on the DNA with the SNP, and the SNP will appear as statistically associated with the disease even if it is not.

The association is not exactly spurious — Dr. Goldstein calls it “synthetic” — but it is indirect, so much so as to make many SNPs useless for identifying the genes that cause disease.

Geneticists have long been aware of this possibility, but Dr. Goldstein’s team has shown theoretically that this could happen more often than expected. He has also examined the question in reverse by doing a genomewide association study of sickle cell anemia.

Though the disease is known to be caused by a variant in a single gene, the Duke geneticists found a statistically significant association with 179 SNPs, spread across a stretch of DNA two and a half million units in length and containing dozens of genes. Most of these SNPs were clearly pointing at the wrong thing.

Genomewide association studies, conducted with hundreds of patients, can each cost in the range of $10 million or more. Though the studies may have led researchers up a blind alley in many cases, they were not a mistake, Dr. Goldstein believes.

“I think most people now view genomewide association studies as something we absolutely had to do and have now done,” he said. “It’s fair to say that for many common diseases nothing of very great importance was discovered, but those studies have told us what to do next.”

That next step, in his view, is to sequence, or decode, patients’ entire genomes and then to look for likely mutations in the genes themselves. The cost of sequencing a human genome has been plummeting in recent years, and it may now be possible to sequence large numbers of patients.

Finding even a few of the rare variants that cause disease could point to genes that make suitable targets for drug makers. The SNPs statistically linked to disease have mostly failed to identify the right genes, but the rare variants may, Dr. Goldstein said.

The Icelandic gene-hunting firm deCODE genetics, which emerged last week from bankruptcy, has long led in detecting SNPs associated with common disease. Dr. Kari Stefansson, the company’s founder and research director, agreed that whole genome sequencing would “give us a lot of extremely exciting data.” But he disputed Dr. Goldstein’s view that rare variants carried most of the missing heritability. Both deCODE genetics and scientists at the Broad Institute in Cambridge, Mass., have sequenced regions of the genome surrounding SNPs in search of rare variants, but have found very few, Dr. Stefansson said.

“We can speculate till we are blue in our faces,” he said, “but the fact of the matter is that there is no substitute for data.”

DNAWellnessinfo.com Resource:  http://www.nytimes.com/2010/01/26/science/26gene.html

Gene discovery may help guide breast cancer care

DNA Mapping Used To Track MRSA Transmission

Submitted by Barinder Khatra on Sat, 01/23/2010 – 18:50

In path breaking research, scientists from Britain’s Bath, Oxford and London and Portugal, Thailand and the United States came together at the University of Cambridge to discover a revolutionary method for precisely tracking the spread of MRSA from country to country, patient to patient. The technique involves the usage of DNA mapping technology in studying the genome of the bacteria.

HUMAN-DNA-MAPING

This study would now help scientists and medical practitioners to better understand the spread and of the super bug, whether the bacteria is being transmitted as a result of inner hospital infections or its coming in from the outside.

By comparing samples of patients from various parts of the world, the team appeared to have reached the conclusion that MRSA originated in Europe in the early 1960s as a result of the first large scale usage of anti-biotic.

According to Dr. Shannon Peacock of Cambridge University, “Our research should inform global surveillance strategies to track the spread of MRSA. The implications for public health are clear: this technology represents the potential to trace transmission pathways of MRSA more definitively so that interventions or treatments can be targeted with precision and according to need”.

DNAWellnessinfo.com Resource:  http://topnews.co.uk/22109-dna-mapping-used-track-mrsa-transmission

DNA testing should replace Pap smear as main way to screen for cervical cancer

Updated: 2010-01-20 18:21:04 CST

by Alex Schoenfeld

According to researchers from the Center for Cancer Prevention in Turin, Italy, DNA testing for human papillomavirus (HPV) should replace the Pap smear as the preeminent way to screen women for cervical cancer.

Authors of the study followed approximately 95,000 participants over a three-year period and found that the HPV test prevented more cases of cervical cancer than the traditional Pap smear.

Researchers discovered that HPV testing is more sensitive and picks up more pre-cancerous changes to cervical cells than the conventional exam, the BBC reports. Moreover, the data suggests that HPV tests would only be needed to be done every five years rather than the Pap smear, which needs to occur three times annually.

“This research suggests that by testing for HPV in women aged 35 and over we might be able to spot the warning signs even earlier,” said Lesley Walker, director of cancer information at Cancer Research UK, which funds one of the study’s authors.

Researchers have found that the HPV test would be unsuitable for women under 35 years of age because it is too sensitive and would create numerous false positives.

DNAWellnessinfo.com Resource:  http://www.privatemdlabs.com/news/DNA,_Paternity_and_Genetic_testing/DNA-testing-should-replace-Pap-smear-as-main-way-to-screen-for-cervical-can$19569114.php