Vital cues for cancer prevention through DNA repairing gene

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

Living fast? Scientists show lifespan is linked to DNA

Ian Sample, science correspondent
guardian.co.uk, Sunday 7 February 2010 19.55 GMT

Scientists have isolated a gene sequence that appears to determine how fast our bodies age, the first time a link between DNA and human lifespan has been found.

The discovery could have a profound impact on public health and raises the best hope yet for drugs that prevent the biological wear and tear behind common age-related conditions such as heart disease and certain cancers.

The work is expected to pave the way for screening programmes to spot people who are likely to age fast and be more susceptible to heart problems and other conditions early in life. People who test positive for the gene variant in their 20s could be put on cholesterol-lowering statin drugs and encouraged to exercise, eat healthily and avoid smoking.

The breakthrough is unlikely to lead to drugs that dramatically extend lifespan, but doctors say it may help prolong the lives of patients whose genes make them susceptible to dying young.

The research gives the kind of insight into the biology of ageing that has not emerged from work on other strategies that claim to extend lifespan, such as consuming vast quantities of antioxidants or pursuing a severely calorie-restricted diet.

“This may help us identify patients who are at a greater risk of developing common age-related diseases so we can focus more attention on them,” said Professor Nilesh Samani, a cardiologist at the University of Leicester, who led the research.

The research highlights the difference between chronological age and biological age, the latter of which is determined by our genetic makeup and lifestyle factors, such as diet and smoking. Two people of the same age can have biological ages that differ by more than 10 years.

A team led by Samani and Professor Tim Spector at King’s College, London found a common sequence of DNA was strongly linked to a person’s biological age. In a study of nearly 3,000 people, around 38% inherited one copy of the gene variant and were biologically three to four years older than those who did not carry the sequence.

A minority of 7% inherited two copies of the DNA sequence and were on average six to seven biological years older. The majority of the population, 55%, do not carry any copies of the variant.

The study, published in the journal Nature Genetics, was prompted by the huge variability in the age at which people develop medical problems that are often considered diseases of the elderly.

“I see patients in their 80s with high blood pressure who have healthy coronary arteries and I see people in their 40s who don’t seem to have any risk factors yet have advanced heart disease,” Samani said. “We think this kind of variability must have something to do with premature ageing.”

Most of the cells in our bodies contain long molecules of DNA called chromosomes that have protective caps at either end called telomeres. Every time a cell divides, the telomeres shorten, like plastic tips fraying on a shoelace. When the telomeres become very short, the cell starts to malfunction and show signs of ageing.

From blood samples, Samani and Spector found a particular gene sequence was more common in people who had unusually short telomeres for their age. The section of DNA was found on chromosome three, next to a gene called TERC, which makes an enzyme that repairs telomeres when they shorten.

People who carry one or two copies of the genetic sequence probably make less of the enzyme, called telomerase, when they are growing in the womb. This means they are born with shorter telomeres, and so are prone to ageing more quickly.

“The effect may be built in at a very early stage in life. If you’re born with shorter telomeres, there’s evidence you will be prone to heart disease and other age-related diseases,” Samani said.

Scientists are unlikely to reverse the ageing process by boosting telomerase in people’s bodies. Telomerase is almost completely deactivated after birth, but is switched back on in cancer cells so they can divide endlessly without dying. “Introducing telomerase might protect you from heart disease, but if you turn it on willy nilly you could cause cancer instead,” Samani said.

DNAWellnessinfo.com Resource:  http://www.guardian.co.uk/science/2010/feb/07/ageing-genetics

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

Gene discovery may help guide breast cancer care

Scientists turn DNA detectives to track spread of hospital superbugs

Mark Henderson, Science Editor

The genetic fingerprints of germs are to be mapped to open a new front in the battle against hospital superbugs.

Scientists have embarked on an ambitious project to read the complete genetic codes of pathogens taken from hundreds of people, so that DNA can be used to track the spread of infection and to identify the source of outbreaks of disease. Much as detectives use DNA to place suspects at crime scenes, the database will help doctors to determine the route by which patients with MRSA and Clostridium difficile have picked up these bacteria, and thus to control infection.

Clostridium difficile, one of the four pathogens that scientists are studying

When a patient falls ill with MRSA, the germ’s DNA will be sequenced, and compared with samples in the database. This should help to determine whether the infection was present when the patient was admitted to hospital or whether it was acquired on the ward. The information will help doctors to decide what must be done to stop the outbreak. This approach could even allow scientists to establish whether individual nurses or doctors are spreading disease through poor hygiene, by matching DNA from patients’ germs to samples from the skin or clothing of staff.

Large databases of genetic information about germs will also provide powerful insights into their biology, which promise to help the development of diagnosis and treatment.

Derrick Crook, a clinical microbiologist at the John Radcliffe Hospital in Oxford, who is leading the Modernising Medical Microbiology initative, said that it could transform infection control in hospitals and the community. “We want to forensically describe how germs are transmitted, and work out better ways of intervening and interrupting that transmission,” he said.

“This will help us to identify emerging threats, and may give us an understanding of which genetic changes in germs are harmful and which are not. We’ll be using the genomic sequence data as the equivalent of a barcode, which tells us what we’re dealing with and where it might have come from.”

Peter Donnelly, of the Wellcome Trust Centre for Human Genetics at the University of Oxford, said: “If someone gets a bug in hospital, you want to know whether they’ve brought it in with them or picked it up on the ward. Genomics should be able to tell us.”

The £6 million initiative is funded by the UK Clinical Research Collaboration. It also involves the Health Protection Agency and the Wellcome Trust Sanger Institute near Cambridge. It is concentrating on Staphylococcus aureus, the bacterial species that includes antibiotic-resistant MRSA strains; C. difficile; norovirus, which causes winter vomiting sickness; and tuberculosis.

Work has begun on sequencing 300 different samples of S. aureus and C. difficile, and the tuberculosis research will start this year. The norovirus project has been held up because there was not a significant outbreak in 2009.

The aim is to use the genetic mutations that each of these organisms acquire to construct their family trees. “The hope is that this will give us exquisitely detailed information with which to track infection and learn about patterns of transmission,” Professor Donnelly said. “In a sense, it is like genetic fingerprinting.

“When someone gets sick, you will sequence the bug and see whether it looks like something in the hospital or elsewhere. If you can determine enough about the pattern of spread — is it patient-to-patient, or via a worker on the ward — you can direct containment efforts much more effectively.”

Advances in DNA sequencing technology have made it practical to read the genetic code of hundreds of examples of the same germs at low cost. The differences between strains and lineages can then be mapped in a database, against which new samples can be compared to track their likely origins. Professor Donnelly added: “It could start to tell us the factors in the genome of a bug that influence virulence. It’s a huge opportunity to learn about the biology of these organisms, and why they make us sick.”

DNAWellnessinfo.com Resource:  http://www.timesonline.co.uk/tol/news/science/article6974765.ece

Evolution faster than thought

2010-01-01 22:18 news24.com

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

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

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

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

Thousands of years

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

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

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

60 new mutations in humans

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

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

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

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

- SAPA

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

Another ‘bad’ cholesterol linked to heart disease found

12/24/09 bbconline.com

Unlike the well-known LDL cholesterol, lipoprotein(a) or Lp(a) cannot be controlled by cutting down on dietary fats or taking a statin drug.

But researchers say high levels do not carry the same risk as LDL.

And other drugs might work to minimise its effects, they told the New England Journal of Medicine.

LDL is considered the aggressive tiger of the cholesterol world, furring the arteries and greatly increasing heart risk. Scientist believe Lp(a), which is inherited, is more of a pussycat, although it does appear to upset blood clotting.

Inherent risk

The researchers used gene-chip technology to scan DNA that they knew from previous studies were potential “hotspots” for heart disease risk. This analysis revealed the two genetic culprits.

Professor Martin Farrall, lead author of the study carried out at Oxford University, said one in six people carries one or more of the genes for Lp(a).

He said: “The increase in risk to people from high Lp(a) levels is significantly less severe than the risk from high LDL cholesterol levels.

“So Lp(a) doesn’t trump LDL, which has a larger impact and which we can already control pretty effectively.

“The hope now is that by targeting both we could get even better risk reduction.”

Some existing drugs, such as Niacin, and others coming on to the market, such as CETP-inhibitors, lower Lp(a) as well as LDL cholesterol.

Professor Peter Weissberg of the British Heart Foundation, which funded the study, said the findings were useful but urged people not to be alarmed by them.

“They highlight the importance of trying to lower Lp(a), which will spark new efforts to design a medicine to achieve this effectively.

“And they reveal clues that open a new avenue for research to decipher how heart disease develops.

“But LDL is still the type of cholesterol to be more concerned about.”

Fats from food are turned into cholesterol by the liver. There are different types but some, such as LDL, are known as “bad” cholesterol. They can lead to a build-up in the body’s cells.

Prof Weissberg said everyone could reduce their risk of heart disease by eating a healthy balanced diet, being physically active and avoiding smoking.

DNAWellnessinfo.com Resource:  http://news.bbc.co.uk/2/hi/health/8426591.stm

DNA Precision Launched

Wed Oct 14, 2009 3:54pm EDT  reuters.com

GAINESVILLE, Fla.–(Business Wire)– DNA Precision has begun offering services for genetic research and healthcare research. These include gene discovery, Agilent microarray processing and bioinformatics. DNA Precision is a division of EcoArray, Inc., a 7-year old environmental genomics firm in Gainesville, FL.

John Rogers, EcoArray`s President, said, “We started DNA Precision to provide the gene discovery and analysis services we have developed for our work in environmental testing to a broader base of customers in health care and personalized medicine research, as well as government and academic research.” DNA Precision offers complete gene discovery and analysis services, from library development to bioinformatics under both GLP (Good Laboratory Practices) and non-GLP standards.

DNA Precisions` services are directed at the new field of genetic research, which has led to better understanding of chronic diseases such as cancer and is opening the way to the exciting field of personalized medicine.

Barbara Carter, EcoArray`s Research Director, said, “We developed our processes with a focus on environmental testing. Since little work had been done in genomics in this area, we built the processes for our environmental business from the ground up. It now seems like a good idea to offer these services – gene libraries, contract sequencing, microarray development, microarray processing, PCR primer design and bioinformatics – to the broader research and healthcare research community.”

For details, see the DNA Precision website, www.dnaprecision.com. DNA Precision`s parent, EcoArray, has done gene discovery and related work in over two dozen species for researchers in the U.S., Canada and Europe. Working primarily in environmental toxicology, EcoArray has developed gene microarrays for the fathead minnow (a primary model species for fresh water in the U.S.), large- and small-mouth bass, Daphnia magna and the sheepshead minnow (in development).

For further information, contact DNA Precision at (352) 505-6896 or info@dnaprecision.com. DNA Precision, Gainesville John Rogers, 352-505-6896 info@dnaprecision.com Copyright Business Wire 2009

DNAWellnessinfo.com Resource:  http://www.reuters.com/article/pressRelease/idUS185715+14-Oct-2009+BW20091014

Gene Discovery May Advance Head and Neck Cancer Therapy

Expanded list of genetic links might improve diagnosis, treatment, researchers say

MONDAY, Oct. 5 (HealthDay News) — In a finding that could have a major impact on the diagnosis and treatment of one of the most deadly types of cancer, U.S. researchers have identified 231 potential new genes associated with head and neck cancer

Previously, only 33 genes were known to be linked to head and neck cancer, which includes cancers of the mouth, nose, sinuses, salivary glands, throat and lymph nodes in the neck.

“These new genes should advance selection of head- and neck-specific gene targets, opening the door to promising new molecular strategies for the early detection and treatment of head and neck cancer. It also may offer the opportunity to help monitor disease progression and a patient’s response to treatment,” study lead author Maria J. Worsham, director of research in the oncology department at Henry Ford Hospital, Detroit, said in a news release.

She and her colleagues examined DNA in five head and neck cancer tumor samples for 1,043 possible cancer-related genes. Of the 231 potential new genes associated with head and neck cancer, 50 percent were present in three or more of the DNA samples and 20 percent were present in all five samples.

The study was scheduled to be presented Oct. 4 at the annual meeting of the American Academy of Otolaryngology–Head and Neck Surgery Foundation in San Diego.

Head and neck cancer causes 2.1 percent of all cancer deaths in the United States. About 39,000 Americans develop head and neck cancer a year, according to the U.S. National Cancer Institute. Tobacco use is linked to 85 percent of head and neck cancers, according to the Cancer Institute.

More information

The American Society of Clinical Oncology has more about head and neck cancer.

DNAWellnessinfo.com Resource:  http://health.usnews.com/articles/health/healthday/2009/10/05/gene-discovery-may-advance-head-and-neck-cancer.html

Junk DNA may prove invaluable in quest for gene therapies

Date:9/21/2009 – bio-medicine.com

Scientists have identified how a protein enables sections of so-called junk DNA to be cut and pasted within genetic code a finding which could speed development of gene therapies.

The study by researchers at the University of Edinburgh sheds light on the process, known as DNA transposition, in which shifted genes have a significant effect on the behaviour of neighbouring genes. In the human genome, rearrangement of antibody genes can enable the immune system to target infection more effectively.

The research identifies how the enzyme is able to cut out a section of DNA and reinsert it elsewhere in the genome. The study, published in the journal Cell, was funded by the Wellcome Trust and the Medical Research Council.

The cut-and-paste property of shifted DNA is now being used to develop tools for scientific research and medical applications. Learning more about transposition could help scientists understand how to control the process and speed the development of gene therapies which introduce into cells genes with beneficial properties that, for example, can fight hereditary diseases or cancer.

Junk DNA, which accounts for almost half of the human genome, was originally believed to have no purpose. However, it is now emerging that movement of junk DNA, in a cut-and-paste mechanism, can lead to beneficial changes in cells.

Dr Julia Richardson of the University’s School of Biological Sciences, who led the study, said: “By forming a picture of the enzyme that causes DNA to shift, and discovering how this works, we understand more about how these proteins could be adapted and controlled. This may one day enable genes to be pasted into cells exactly where they are needed which could be of enormous benefit in developing gene therapies.”

DNAWellnessinfo.com Resource:  http://www.bio-medicine.org/medicine-news-1/Junk-DNA-may-prove-invaluable-in-quest-for-gene-therapies-57771-1/