Scientists reveal genetic root of prostate cancer

An international team of scientists have revealed the genetic root of prostate cancers in individual men, demonstrating that tumors share common gene faults which could potentially offer new targets for treatment.

Prostate cancer is the second most common cancer and second leading cause of cancer death in men.

The research, published in Nature, is part of the International Cancer Genome Consortium - a global project committed to revealing genetic changes driving prostate cancer, using the most up-to-date gene-sequencing technology available.

Tumor samples from 10 men with prostate cancer were analyzed, allowing the researchers to map a "family tree" of changes occurring at a genetic level as the cancer develops.

The researchers also learned more about how the disease spreads through the body and forms new tumors. They discovered that the first group of cells that spread from the prostate continues to travel throughout the body, developing new tumors as it goes.

"We gained a much broader view of prostate cancer by studying both the original cancer and the cells that had spread to other parts of the body in these men," says study author Prof. Ros Eeles from the Institute of Cancer Reseach in London, UK. "And we found that all of the cells that had broken free shared a common ancestor cell in the prostate."

Prostate cancer is the second most common cancer in American men behind skin cancer and the second most common cause of cancer death behind lung cancer. Around 1 in 7 men will be diagnosed with prostate cancer during their lifetime.

According to American Cancer Society (ACS) estimates, in 2015, around 220,800 new cases of prostate cancer will be diagnosed, and 27,540 deaths will occur attributable to the disease.

The researchers have already discovered that cancer cells taken from different sites within a man's prostate can be very diverse genetically. Despite this, the new study found that cancer cells moving away from the prostate share genetic faults that are unique to the man whose cancer it is.

"The common faults we found in each man could potentially offer new targets for treatment," states Prof. Eeles. "But we found that, once cancer cells have spread, they continue to evolve genetically, so choosing the most effective treatments will remain a key challenge."

Shared mutations represent 'a potential Achilles heel' for prostate cancer

Prof. Steven Bova from the University of Tampere in Finland believes that in order to find these shared genetic faults, multiple biopsies may be needed. "We must also study more patients to learn how to apply these findings to develop more personalized treatments for people with the disease," he adds.

Learning how cancer cells change and evolve as they metastasize (spread to other parts of the body) and thus become resistant to certain forms of treatment is crucial to developing future treatments for all forms of cancer.

Senior author Dr. Ultan McDermott says that while the shared tumor-causing genetic faults mapped by their "family tree" represent a potential Achilles heel for prostate cancer, "many of these shared mutations are in tumor suppressor genes and our approach to therapeutically targeting these needs to be prioritized."

"We have to zoom in on this crucial junction and gather more data on the impact different therapies have on prostate cancer's evolution and spread," he adds.

The study authors conclude that these findings "elucidate in detail the complex patterns of metastatic spread and further our understanding of the development of resistance to androgen-deprivation therapy in prostate cancer."

Recently, Medical News Today reported on new research suggesting that taking vitamin D supplements could slow or reverse the progression of low-grade prostate tumors, reducing the need for surgery or radiation therapy.

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Gene identified that drives aggressive form of breast cancer

A team of researchers have identified a gene that drives one of the most aggressive forms of breast cancer. They hope that by finding a way to block the gene they may be able to make the cancer less aggressive.

The authors believe the most aggressive form of triple-negative breast cancer originates from stem cells.

In their study, published in Nature Communications, the researchers found that the gene known as "inhibitor of differentiation 4" (ID4) not only indicates a highly aggressive form of triple-negative breast cancer but also appears to control it.

"We found that ID4 is produced at high levels in roughly half of all triple-negative breast cancers, and that these cancers have a particularly poor prognosis," says project leader Dr. Alex Swarbrick. "We also showed that if you block the ID4 gene in experimental models of triple negative breast cancer, the tumor cells stop dividing."

Triple negative breast cancers are breast cancers that lackestrogen, progesterone and HER2 receptors. Breast cancers that have these receptors can be targeted by drugs.

Around 15% of all breast cancer cases are triple-negative breast cancers. Patients that develop them typically have a higher risk of recurrence and shorter survival than patients with other forms of breast cancer.

There appears to be a division among patients with triple-negative breast cancer; some patients succumb to the disease within 3-5 years while others can survive disease-free for much longer than many non-triple-negative breast cancer patients.

The researchers discovered a likely explanation for this differentiation in survival prospects - there are two distinct forms of triple-negative breast cancer, appearing to originate from different cell types.

While the more benign form of triple-negative breast cancer appears to originate from specialized cells, the team found that the aggressive form of the disease seems to originate from stem cells.

Could blocking ID4 make aggressive forms of breast cancer respond to tamoxifen?

Stem cells have the capacity to develop into a variety of different cell types in the body, and in many bodily tissues they divide to replenish other cells, providing the body with a form of internal repair. The manner in which stem cells are flexible and can spread into other tissues is similar to the way that many cancers operate.

Previous research has shown that breast stem cells are a vital part of breast growth and development during both puberty and pregnancy. The new study has now demonstrated that ID4 is responsible for determining whether these stem cells develop into specialist cells or not.

When ID4 is blocked in a stem cell, other genes that drive cell specialization are activated. In addition, the estrogen receptor and a number of other genes expressed by forms of breast cancer with better prognoses are also activated.

"Estrogen receptor-positive breast cancers have a relatively good prognosis because the drug tamoxifen is very effective at blocking the estrogen receptor and hence their growth," explains Dr. Swarbrick.

"We speculate, therefore, that by blocking ID4 it might be possible to turn stem-cell-like breast cancers into less aggressive breast cancers that may even respond to tamoxifen. If we are correct, that would be remarkable."

Following their discovery, the team will now investigate ID4 in order to work out the best strategy for blocking it in humans. They are also planning a mouse study to assess whether blocking ID4 can make tumors vulnerable to tamoxifen.

"We don't know yet whether we are seeing a real estrogen-dependent cancer after ID4 is blocked - one with an effective estrogen receptor - or just a caricature of one," states Dr. Swarbrick.

The team will be working in collaboration with a world expert on estrogen receptor function and studying these biochemical processes on a genome-wide scale as they attempt to fully understand the role that ID4 could play in the development and treatment of breast cancer.

Earlier this month, Medical News Today reported on a study finding that the shape of breast cancer cells can influence a tumor's response to treatment. Changing the shape of these cells could be a way of making them more sensitive to treatment.

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Hayley Okines dies from rare premature aging disease aged 17

A courageous girl from the UK who raised awareness of a rare genetic disorder that causes premature aging - progeria - has died aged 17.

"Hayley was a pioneer - and one of the reasons that we now have the first treatment for progeria. Today we remember her tremendous courage and determination," said the Progeria Research Foundation.

Progeria, or Hutchinson-Gilford Progeria Syndrome (HGPS), affects around 1 in 4-8 million newborns worldwide. There are approximately 200-250 children living with the condition across the globe at any one time.

Progeria is caused by an abnormal protein in the LMNA gene, called progerin, which interferes with the production of lamin A - a protein that stabilizes a cell's nucleus. This disruption causes children with progeria to age up to 10 times faster than normal.

On Thursday evening, it was announced that 17-year-old progeria sufferer Hayley Okines - from Medical News Today's hometown Bexhill in East Sussex, England - had passed away.

Hayley's mother, Kerry Okines, posted the sad news on Facebook: "My baby girl has gone somewhere better. She took her last breath in my arms at 9.39 pm."

Hayley - who BBC News say had the "body of a 104-year-old" - was being treated in the hospital for pneumonia, but she returned home shortly before she died. "She came home for an hour and she saw her puppies, little brother Louie and her sister Ruby," Hayley's father, Mark Okines, told BBC News on Friday.

"I think she wanted to come home to say goodbye to everybody," he continued. "I think she knew that yesterday was going to be the time."

'We remember her tremendous courage and determination'

Children with progeria rarely live past the age of 14, often passing away from ailments that affect the elderly, such as heart disease and stroke.

Hayley was told she would not live past the age of 13, but in 2007, the teenager began undergoing pioneering treatment at Boston Children's Hospital, MA, as part of the first clinical trial for the condition.

In a statement following Hayley's death, the Progeria Research Foundation praised the teenager for her contribution to progeria research:

"The entire PRF community mourns the loss of one of our shining stars, Hayley Okines. Hayley was one of the first participants in the ongoing progeria clinical trials. Hayley was a pioneer - and one of the reasons that we now have the first treatment for progeria. Today we remember her tremendous courage and determination."

Hayley was an avid campaigner for progeria awareness, hailed locally and nationally as an inspiration for people with and without the condition. The teenager penned two books detailing her experiences of living with progeria - "Old Before My Time" and "Young at Heart" - and took part in numerous interviews.

As well as for her contribution to progeria awareness and research, Hayley was highly admired for her positive outlook on life, writing in "Young at Heart:"

"My life with progeria is full of happiness and good memories. Deep inside I am no different from anyone. We are all human."

Our thoughts and prayers are with Hayley's family and friends at this difficult time.

The news of Hayley's death comes just 15 months after it was announced Sam Burns, a boy from Foxborough, MA, had died from progeria aged 17.

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How far away is a cure for blindness?

Losing one of your senses is a frightening prospect for most people, but for many people, it is an unfortunate reality. Millions of people in the US face the prospect of irreversible changes to their ability to see the world around them.

Worldwide, there are an estimated 39 million people living with blindness. Around 82% are aged 50 and above.

As you read this passage, the fact that you have the ability to see and read might not even cross your mind. There are a lot of people who are not as fortunate. According to the World Health Organization (WHO), 285 million people are estimated to be visually impaired worldwide. Of these, 39 million are blind and 246 million have low vision.

A recent poll conducted by Research!America and the Alliance for Eye and Vision Research (AEVR) found that Americans regarded the loss of vision as potentially having the biggest impact on everyday life, ranking it alongside cancer, Alzheimer's disease and HIV as one of the top four "worst things that could happen to you."

Unfortunately, losing eyesight is a common problem, be it due to the process of aging or the development of a specific condition. The good news is that 80% of visual impairment can be prevented or cured, but what of the remaining 20%?

In this Spotlight article, we take a brief look at retinal degeneration disorders - a group of related conditions that are presently without a cure. What treatments are currently being developed? And can researchers envision a future where sight can be restored to all patients?

Curable and incurable disorders

Most frequently, visual impairment is caused by uncorrected refractive errors (43%) or cataracts (33%). Refractive errors include myopia (short-sightedness), hyperopia (far-sightedness) and astigmatism, whereby the cornea or lens does not have a perfectly curved shape.

When visual impairment is caused by these problems, often treatment is readily available. Refractive errors can be corrected with glasses, contact lenses or refractive surgery. Cataracts - the clouding of the lens - are commonly treated with a surgical procedure that is among the most frequently carried out in the US.

While 80% of visual impairment can be prevented or cured, there remains 20% of cases for which there is currently no way of curing. A range of conditions exists where those who develop them are faced with a gradual loss of vision until their impairment is so severe that they are effectively blind.

Retinal degeneration disorders have no cure. These diseases break down the retina, the layer of tissue found at the back of the eye containing cells that detect light entering the organ.

There are a number of these degenerative diseases, including retinitis pigmentosa, macular degeneration and Usher syndrome. In particular, age-related macular degeneration is the leading cause of blindness in the developed world.

Medical News Today asked Dr. Raymond Iezzi, an ophthalmology consultant with the Mayo Clinic, what the biggest obstacles were to finding a cure for retinal degeneration disorders. He told us that scientists and clinicians face many challenges in developing treatments as there are several hundred biochemical abnormalities underlying theses disorders.

"Further," he added, "while there are several patterns of retinal degeneration, each is treated differently depending on the cells affected as well as the stage and severity of their degeneration."

When retinal degeneration conditions were first diagnosed, they were all labeled as retinitis pigmentosa. As knowledge in this area has improved, scientists have become aware that there is a variety of different related conditions, each affecting different areas of the retina with their own specific mechanisms.

In patients whose vision is still good, therapeutic approaches can be directed at neuroprotection or gene therapy.

"By protecting cells within the retina from death associated with the underlying biochemical disorder, we may preserve sight among large populations of patients," explained Dr. Iezzi. "A robust neuroprotection strategy would prevent cell death and vision loss, regardless of the underlying biochemical abnormality."

Gene therapy focuses instead on correcting the biochemical abnormalities that lead to the death of retina cells. This approach is highly specific, and Dr. Iezzi told MNT that several hundred treatments would need to be developed in order to treat the full range of retinal degenerative diseases.

Restoring and protecting vision with stem cells

The eye lends itself to experimental treatments, being easy to operate on and often protected from inflammatory responses that could disrupt therapies. Due to its accessibility, surgeons can also easily observe and track how new treatments are progressing.

Dr. Iezzi stated that at Mayo Clinic they are currently working on new methods to grow stem cells from a patient's own tissue samples; a regenerative approach that could one day lead to the restoration of sight to people that have lost it.

Macular degeneration is a major cause of partial blindness among people aged over 50.

Embryonic stem cells could be used to build new retinal pigmented epithelial cells - cells that nourish retinal visual cells and absorb light - that could be transplanted into a patient.

Doing this could slow or prevent the loss of the visual cells, and while deriving new visual cells from embryonic stem cells could lead to even more pronounced results, researchers have found it more difficult to successfully derive these cells and transplant them into the retina.

Mouse studies have previously shown that this technique can work and that transplanted cells can integrate fully with the retina, restoring vision to the animals.

There are two types of photoreceptive cells in the retina - rod cells and cone cells. While rod cells are stimulated by light over a wide range of intensities, perceiving shape, size and brightness, it is the cone cells that perceive color and fine detail.

Researchers have managed to derive rod cells from embryonic stem cells and are currently working on deriving cone cells and transplanting them into animals. If these trials prove successful, the next step could be human trials.

Without adequate neuro protection, however, newly transplanted cells may be just as vulnerable to retinal degeneration disorders as the cells they replace. This problem underlies the importance of research into gene therapy aiming to correct the biochemical abnormalities that lead to cell death.

There is a form of treatment, however, that has led to the restoration of vision in patients with advanced forms of retinal degeneration disorders. Just as prosthetics can be used to restore function to individuals that have lost limbs, so too can individuals who have lost their vision use retinal prostheses.

The miracle of retinal prosthesis

"In patients who have already lost their sight, our therapeutic goal is to restore vision," said Dr. Iezzi. "This has been successfully accomplished via the Argus II retinal prosthesis in patients with advanced retinitis pigmentosa."

Last month, MNT reported on the story of Allen Zderad, a man who was effectively blind but is now able to make out the outlines of objects and people thanks to his new retinal prosthesis.

Dr. Iezzi was the ophthalmologist that put Mr. Zderad forward for the procedure, making him the 15th man in the US to receive the life-changing device. He is now able to navigate through crowded environments - such as shopping centers - without the use of a cane.

A camera connected to a pair of glasses transmits visual information to a small chip attached to the back of the eye via a small computer worn in a belt pack. The chip can send light signals directly to the optic nerve, bypassing the damaged retina and providing the patient with visual information in the form of flashes of light.

Dr. Iezzi describes what the retinal prosthesis provides as "artificial vision," unlike any form of vision that patients will have experienced before. While this form of vision could be considered basic compared with what normal-sighted people are used to, it is a marked improvement for many without sight.

As he used his retinal prosthesis for the first time, Mr. Zderad described the artificial vision as "crude, but significant."

"While this technology restores rudimentary vision, eventually as these devices improve, we may one day be able to treat patients with advanced macular disease such as Stargardt macular dystrophy or age-related macular degeneration," Dr. Iezzi suggested.

The future prospects of such treatment are truly exciting, but it is likely to be some time before the benefits of this technological breakthrough are widely experienced. Currently, the device costs $144,000, and the WHO estimate around 90% of the world's visually impaired live in low-income settings.

Keeping your eyes healthy

Many people will be fortunate enough not to develop a retinal degeneration disorder, but that does not mean that their eyes are invulnerable to harm. A large amount of visual impairment can be prevented, but what measures can be taken to ensure that this happens?

Regular comprehensive eye exams can detect eye disorders before any vision is lost.

The National Eye Institute (NEI) suggest a number of simple steps that can be taken to ensure your eyes are as healthy as they can be:

• Do not smoke. Smoking has been associated with increased risks of developing cataracts, optic nerve damage and age-related macular degeneration
• Eat a balanced diet and maintain a healthy weight
• Clean your hands and contact lenses properly to reduce the risk of eye infection
• Know you family's eye health history. Many serious eye disorders such as retinitis pigmentosa are hereditary and knowing your risk of developing such conditions can improve the level of treatment available
• Have a comprehensive eye exam. The only way to be completely sure of the health of the eyes is to visit an eye care professional.

WHO state that over the past 20 years there has been significant progress in preventing and curing visual impairment in many countries around the world. In 2013, the World Health Assembly approved the 2014-19 Action Plan for the universal access to eye health. The aim of this plan is to reduce avoidable visual impairments by 25% by 2019.

While many people believe that the loss of vision is one of the health problems that could have the biggest impact on everyday life, it is encouraging to think that visual impairment is no longer as absolute a prospect as it once was.

Thanks to prosthetics, people who have lost legs can walk around unaided, with most people unaware that they have any limbs missing. It is not too hard to now envisage a future world in which people could be cured of blindness, with any hints of their previous disability remaining invisible.

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Insight into why cancer incidence increases with age

The accumulation of age-associated changes in a biochemical process that helps control genes may be responsible for some of the increased risk of cancer seen in older people, according to a National Institutes of Health study.
Scientists have known for years that age is a leading risk factor for the development of many types of cancer, but why aging increases cancer risk remains unclear. Researchers suspect that DNA methylation, or the binding of chemical tags, called methyl groups, onto DNA, may be involved. Methyl groups activate or silence genes, by affecting interactions between DNA and the cell's protein-making machinery.
Zongli Xu, Ph.D., and Jack Taylor, M.D., Ph.D., researchers from the National Institute of Environmental Health Sciences (NIEHS), part of NIH, identified DNA methylation sites across the human genome that changed with age. They demonstrated that a subset of those sites - the ones that become increasingly methylated with advancing age - are also disproportionately methylated in a variety of human cancers. Their findings were published online in the journal Carcinogenesis.
"You can think of methylation as dust settling on an unused switch, which then prevents the cell from turning on certain genes," Taylor said. "If a cell can no longer turn on critical developmental programs, it might be easier for it to become a cancer cell."
Xu and Taylor made the discovery using blood samples from participants in the Sister Study, a nationwide research effort to find the environmental and genetic causes of breast cancer and other diseases. More than 50,000 sisters of women who have had breast cancer are participating in the study.
The researchers analyzed blood samples from 1,000 women, using a microarray that contained 27,000 specific methylation sites. Nearly one-third of the sites showed increased DNA methylation in association with age. They then looked at three additional data sets from smaller studies that used the same microarray and found 749 methylation sites that behaved consistently across all four data sets. As an additional check, they consulted methylation data from normal tissues and seven different types of cancerous tumors in The The Cancer Genome Atlas, a database funded by the National Cancer Institute and the National Human Genome Research Institute.
Taylor said that DNA methylation appears to be part of the normal aging process and occurs in genes involved in cell development. Cancer cells often have altered DNA methylation, but the researchers were surprised to find that 70-90 percent of the sites associated with age showed significantly increased methylation in all seven cancer types. Taylor suggests that age-related methylation may disable the expression of certain genes, making it easier for cells to transition to cancer.
The research also determined how fast these methylation events accumulate in cells. They occur at a rate of one per year, according to Xu.
"On your 50th birthday, you would have 50 of these sites [from the subset of 749] that have acquired methyl groups in each cell," Xu said. "The longer you live, the more methylation you will have."
For future work, Xu and Taylor want to examine more samples, using a newer microarray that will explore methylation at 450,000 genomic methylation sites. The additional samples and larger microarray, which will provide 16 times more genomic coverage, will allow them to address whether environmental exposures during adulthood or infancy affect methylation profiles. These additional studies will help scientists better understand why methylation happens as people march toward their retirement years.
DNA methylation is one of several epigenetic mechanisms that can control gene expression without changes in DNA sequence. This study is part of a broader research effort, funded by NIEHS, to understand how environmental and other factors affect epigenetic mechanisms in relation to health.

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Virus discovery: 'blast' mechanism used to infect host

Researchers have discovered the first "pressure-driven infection mechanism" in a human virus, which blasts infectious DNA into cells with pressure eight times higher than that of a typical car tire.
The study, published in the Journal of the American Chemical Society, suggests that this discovery could open the door to new treatments for viral infections.
Researchers from the US and Sweden analyzed the pressure inside the herpes simplex virus 1 (HSV-1), the infection that causes cold sores.
It was found that the HSV-1 virus enters human cells, settles on the nucleus and then blasts its way into DNA using high pressure built up from a "nanometer-scale protein shell" called the capsid, researchers explain. The capsid is the shell that contains the viral genome.
The researchers say that the viruses responsible for infections such as influenza and HIV are quickly becoming resistant to drugs that target viral proteins. The proteins can quickly disguise themselves and become resistant to ant-viral drugs as a result of genetic mutation.
For example, previous research published in PLoS Computational Biology has suggested that drug resistance to HIV, the virus that causes AIDS, can be caused by pre-existing mutations, which can actually progress even more once treatment is initiated.
Findings such as this one have led to a search for weaknesses in viruses that do not involve viral proteins, the researchers add, a reason why this study was conducted.
Previous research has also shown many viruses that infect bacteria, called bacteriophages, use the same pressure-driven mechanism in order to blast their DNA into bacteria nuclei.
They add that the same mechanism also exists in eight related viruses, including chickenpox in children, shingles in adults, and the virus responsible for mononucleosis.
The researchers believe that evolution has meant that this technique is now apparent in viral infection, paving the way for the development of treatments that can defeat particular viruses, such as HSV-1, in the same way.
They say:

"Despite billions of years of evolution separating eukaryotic viruses and bacteriophages, pressure-driven DNA ejection has been conserved. This suggests it is a key mechanism for viral infection and thus presents a new target for antiviral therapies."

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Three-Person IVF Gets UK Government Backing

The UK government has backed three-person IVF, i.e. creating babies using DNA from three people. The UK government said the procedure will probably be available in 2015 after draft regulations have been produced.

Current IVF techniques leave some babies open to potentially disabling and sometimes life-threatening mitochondrial diseases, which are inherited from the mother. Opponents question why couples who are concerned about inherited mitochondrial diseases do not use egg donors instead.

Mitochondria are the powerhouses of cells, organelles that act like a digestive system, taking in nutrients, breaking them down, and creating energy for the cell. Mitochondria are passed on through the egg, from mother to child.

Approximately 1 in every 6,500 babies inherits defective mitochondria from the mother. Without properly functioning mitochondria cells may starve, the baby can become blind, develop serious muscle weakness, become tired easily, there is a risk of heart disease, intestinal disorders, and in extreme cases premature death.

According to previous studies, using mitochondria from a donor egg could be one way of preventing mitochondrial diseases. In the UK alone, approximately ten couples each year would benefit from receiving mitochondria from a donor egg.

Baby would have DNA from three "parents"

Mitochondria have their own DNA, so if mitochondria from a donor egg were used, the baby would have DNA from the mother, father and the donor of the egg.

At the UK government's request, in September 2012 the Human Fertilisation and Embryology Authority launched a public consultation on the ethics of using DNA from three "parents" to prevent the passing on of serious mitochondrial diseases.

In the UK, carrying out mitochondrial replacement in the laboratory is legal, but embryos must not be used in treatment.

In March 2013, HFEA (Human Fertilisation and Embryology Authority) reported that there was no evidence that the three-person IVF procedure was unsafe and that there was "general support" for the idea.

On March 28th, HFEA sent the finalized public dialogue and scientific update reports from public consultation - "Medical frontiers: debating mitochondria replacement" - to the UK Government.

HFEA also gave the following advice regarding the ethics and science of new IVF-based techniques aimed at avoiding mitochondrial diseases:

• Only clinics licensed by HFEA should be allowed to offer mitochondria replacement


• Each mitochondria replacement proposal should be approved by HFEA. However, "Regulations should provide the flexibility to modify this in the future".


• IVF clinics must make sure that follow-up research is done on each child born.


• Mitochondria donors, like tissue donors have the right to anonymity. The resulting child should not have the right to track down the donor "although information exchange and contact could be arranged locally by mutual consent."


• "A further assessment of the safety and efficacy should be commissioned by the HFEA once a clinic has submitted an application to carry out one of the techniques. This follows advice from an expert scientific panel that there is no evidence to suggest that mitochondria replacement is unsafe, but that further specific experiments should be conducted."

England's Chief Medical Officer, Prof Dame Sally Davies said "Scientists have developed ground-breaking new procedures which could stop these diseases being passed on, bringing hope to many families seeking to prevent their future children inheriting them. It's only right that we look to introduce this life-saving treatment as soon as we can."

Mitchondrial Replacement in IVF Procedures

Scientists have developed mitochondrial replacement techniques that use mitochondria from donated eggs to prevent mothers passing on mitochondrial diseases to their offspring.

These techniques result in healthy embryos without mitochondrial diseases. They have the DNA of three different people - the father, mother and egg donor. 20,000 genes come from the mother and father and 37 mitochondrial genes from the donor.

Mitochondrial replacement in IVF procedures affects the "germ line" - the donor's mitochondrial DNA will be passed on to future generations of the "three-parent" child. This is a fundamental change to human genetic inheritance.

The BBC quotes Dr. David King, director of Human Genetics Alert, who said "These techniques are unnecessary and unsafe and were in fact rejected by the majority of consultation responses. It is a disaster that the decision to cross the line that will eventually lead to a eugenic designer baby market should be taken on the basis of an utterly biased and inadequate consultation."

HFEA responded to some of Professor King's allegations. With regard to King suggesting that the HFEA consultation process was flawed and the analysis of findings misrepresented in public opinion, HFEA wrote "We strongly refute Dr King's suggestions and think it is important to address his comments. The consultation was made up of many strands. One strand of the consultation showed a small majority against mitochondria replacement and those people tended to have broader concerns about IVF.

In all the other public engagement strands a majority of respondents and participants supported the use of mitochondria replacement. We used a range of methods to explore these complex issues. Our consultation was a more nuanced exercise than simply counting up votes for and against the techniques."

The IVF technique to eliminate mitochondrial disease was pioneered at Newcastle University, England, by Professor Doug Turnbull and Professor Mary Herbert at Newcastle University.

Professor Doug Turnbull said: "I am delighted that the Government is moving forward with publishing draft regulations this year and a final version for debate in Parliament next year. This is excellent news for families with mitochondrial disease. This will give women who carry these diseased genes more reproductive choice and the opportunity to have children free of mitochondrial disease. I am very grateful to all those who have supported this work."

Professor Mary Herbert said "Today's announcement is really encouraging news for families affected by mitochondrial DNA disease. The IVF-based techniques currently under development offer the possibility of greatly reducing the risk to children of affected women. We are in the fortunate position of having substantial Wellcome Trust funding to continue to refine the techniques and to optimise their safety and efficacy.

"We have made good progress in optimising the pronuclear transfer technique and will continue to need a supply of healthy eggs to perform further tests on the safety of the technique. Obviously, the timescale will depend on the outcome of those tests."

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Modern Diet Is Rotting Our Teeth

A study of the evolution of our teeth over the last 7,500 years shows that humans today have less diverse oral bacteria than historic populations, which scientists believe have contributed to chronic oral diseases in post-industrial lifestyles.

The researchers, from the University of Adelaide's Australian Centre for Ancient DNA (ACAD), the University of Aberdeen (Dept of Archeology), Scotland, and the Wellcome Trust Sanger Institute, Cambridge, England, published their study in Nature Genetics.

The authors say that analyzing the DNA of calcified bacteria on the teeth of humans throughout modern and ancient history "has shed light on the health consequences of the evolving diet and behavior from the Stone Age to modern day".

The scientists explained that there were negative changes in oral bacteria as our diets altered when we moved from being hunter-gatherers to farmers. Further changes were observed when humans started manufacturing food during the Industrial Revolution.

Study leader Professor Alan Cooper, ACAD Director, said, "This is the first record of how our evolution over the last 7500 years has impacted the bacteria we carry with us, and the important health consequences."

The introduction of processed sugar may have completely changed the composition of oral bacteria in humans.

"Oral bacteria in modern man are markedly less diverse than historic populations and this is thought to contribute to chronic oral and other disease in post-industrial lifestyles."

The scientists extracted DNA from calcified dental plaque (tartar) from 34 prehistoric human skeletons from northern Europe. They examined the changes in the nature of oral bacteria that were first present in prehistoric hunter-gatherers, through to the Bronze Age when farming became established, then to Medieval times and finally to the Industrial Revolution and later.

Dr Christina Adler, lead author, who was a PhD student at the University of Adelaide during the study, said "Genetic analysis of plaque can create a powerful new record of dietary impacts, health changes and oral pathogen genomic evolution, deep into the past." Dr. Adler now works at the University of Sydney.

The modern mouth exists in a permanent disease state

Professor Cooper said:

"The composition of oral bacteria changed markedly with the introduction of farming, and again around 150 years ago. With the introduction of processed sugar and flour in the Industrial Revolution, we can see a dramatically decreased diversity in our oral bacteria, allowing domination by caries-causing strains. The modern mouth basically exists in a permanent disease state."

Professor Cooper has been working with Professor Keith Dobney from the University of Aberdeen on this for the last 17 years. Professor Dobney said "I had shown tartar deposits commonly found on ancient teeth were dense masses of solid calcified bacteria and food, but couldn't identify the species of bacteria. Ancient DNA was the obvious answer."

Scientists examined tartar deposits found on ancient teeth in their study. (Photo: Alan Cooper/University of Adelaide)

Prof. Dobney explained that this study provides a completely new window on how human populations lived and died in the past. If we know the real genetic history of diseases humans still suffer from today, scientists might better understand them, and even treat them more effectively. "Being able to track them through time has huge implications for understanding the origins and history of human health - making the archaeological record extremely relevant and important to modern-day medics and geneticists," Dobney added.

In an Abstract in Nature Genetics, the authors wrote that "modern oral microbiotic ecosystems are markedly less diverse than historic populations, which might be contributing to chronic oral (and other) disease in postindustrial lifestyles."

It was not until 2007 that the team could control background levels of bacterial contamination properly. This became possible when ACAD's super-clean labs and stringent decontamination and authentications protocols became available.

The scientists are now expanding their studies geographically and chronologically, and including other species, such as Neanderthals.

There is some evidence that beeswax was used 6,500 ago in dentistry, scientists from Abdus Salam International Centre for Theoretical Physics, Italy, explained in the open access journal PLoS ONE on 19th September, 2012.

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24 Genes Responsible For Short-Sightedness Identified

The vision of a person with Myopia - everything looks blurred.

Researchers from King's College London have identified 24 new genes that are responsible for causing myopia, a very common eye disorder also known as short-sightedness.

The finding, published in Nature Genetics, finally reveals the genetic causes of the condition; this is very promising and could finally be the basis for future treatment of the disorder.

There is currently no cure for myopia, a condition which affects 30 percent of Westerners and up to 80 percent of Asians. Researchers from the Australian National University in Canberra reported in The Lancet that approximately 80% to 90% of 18-year-olds (school-leavers) in China, Taiwan, Japan, Singapore, Hong Kong and South Korea suffer from myopia.

Myopia occurs when light does not properly focus on the retina of the eye, a refractive error resulting in blurred vision.

Myopia begins to develop in childhood and adolescence when the eye grows too much in length, causing light to focus in front of the retina rather than directly on it. The only way that sight can be corrected is with glasses, contacts or undergoing surgery. In high degrees of myopia the retina becomes so thin it can lead to a series of health complications, such as glaucoma, macular degeneration or retinal detachment.

Myopia is heritable, however, little was known about the genetics behind it until now.

The researchers, who all belonged to the Consortium for Refraction and Myopia (CREAM), collected data from over 45,000 people across 32 different studies. They analyzed their genetic and refractive error data to identify any genes responsible for the disorder.

Genetic factors identified

They identified a total of 24 new genes linked to myopia and confirmed two previously reported genes. The genes they found were responsible for eye development, eye tissue signaling and the structure of the eye. They were associated with a high risk of myopia, potentially increasing a person's risk tenfold.

A combination of genetic predisposition and environmental factors significantly increases the likelihood of developing myopia. Environmental factors include reading, limited outdoor exposure, a higher level of education, and living in urban areas. However, how these factors actually cause the disorder remains a mystery. Further investigation by the consortium is necessary to fully understand these links.

Lead author of the paper, Professor Chris Hammond, from the Department of Twin Research and Genetic Epidemiology at King's College London, said:

"We already knew that myopia, or short-sightedness, tends to run in families, but until now we knew little about the genetic causes. This study reveals for the first time a group of new genes that are associated with myopia and that carriers of some of these genes have a 10-fold increased risk of developing the condition."

He added:

"Currently myopia is corrected with glasses or contact lenses, but now we understand more about the genetic triggers for the condition we can begin to explore other ways to correct it or prevent progression. It is an extremely exciting step forward which could potentially lead to better treatments or prevention in the future for millions around the world."

There aren't many treatment options to reduce the progression of myopia at the moment, the only drug developed so far, called atropine, has been reported to dilate the pupils and cause light sensitivity.

The findings from this study will hopefully help pave the way for future treatment options.

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Novel Protein Discovered That May Help Detect Lou Gehrig's Disease And Dementia

Researchers at Mayo Clinic have discovered an abnormal protein that accumulates in the brains of many patients affected with two common neurodegenerative disorders - amyotrophic lateral sclerosis, also known as ALS or Lou Gehrig's disease, and frontotemporal dementia. They say their findings have uncovered a potentially new therapeutic target and biomarker that would allow clinicians to confirm diagnosis of the diseases. The study is published online in the journal Neuron.

The Mayo research team, led by scientists at Mayo Clinic's campus in Florida, discovered the abnormal protein pathology that they call C9RANT. An error in the highly regulated cellular process through which proteins are generated causes the abnormal production of C9RANT. The team developed an antibody that can detect the specific, insoluble protein that clumps together and is present in patients with mutations in the C9ORF72 gene, which was previously identified by Mayo Clinic researchers as the most common genetic cause of ALS and frontotemporal dementia.

"This new finding sheds light on how the mutation causes these disorders, and it provides us with a marker that helps us track disease progression in patients with this disorder and potentially combat the disease," says senior author Leonard Petrucelli, Ph.D., a molecular neuroscientist and director of the Department of Neuroscience at Mayo Clinic in Florida.

If it is shown that, as suspected, these protein clumps are the cause of neuronal death and toxicity in these diseases, it may be possible to design therapies to break the clumps apart or to prevent the protein from accumulating in the first place, Dr. Petrucelli says.

Because the protein is found throughout the central nervous system in patients with ALS and frontotemporal dementia - but not in other neurodegenerative diseases - the researchers hope that in the future it can be tested through a spinal tap.

After Alzheimer's disease, frontotemporal dementia is the most common form of early onset neurodegenerative dementia. It is characterized by changes in personality, behavior and language due to loss of gray matter in the brain's frontal lobe. ALS destroys motor neuron cells that control essential muscle activity such as speaking, walking, breathing and swallowing.

This new discovery stems from a key finding, reported simultaneously in 2011 by Mayo researchers and scientists from the National Institutes of Health, that an unusual mutation - a short DNA sequence repeated hundreds to thousands of times - was found in almost 12 percent of familial frontotemporal dementia and more than 22 percent of familial ALS samples studied.

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Simple Blood Test Reveals DNA Marker That Predicts Breast Cancer Recurrence

Medical researchers at the University of Alberta tested the DNA of more than 300 women in Alberta and discovered a 'genetic marker' method to help accurately profile which women were more apt to have their breast cancer return years later.

Sambasivarao Damaraju, a professor with the Faculty of Medicine & Dentistry, and at the Cross Cancer Institute just published his team's findings in the peer-reviewed journal, PLoS One. Using a simple blood test, Damaraju and his team, which included his PhD student Yadav Sapkota, scanned the entire human genome of 369 women who had been diagnosed with breast cancer. Of those, 155 had their cancer come back and 214 did not.

"If we can accurately predict which women are at high risk of breast cancer recurrence, it gives the physicians and oncologists treating those women time to design a more aggressive therapy in hopes of preventing the cancer from coming back," says Damaraju, who works in the Department of Laboratory Medicine & Pathology. "Treatment strategies could be tailor made for these women based on their genetic make-up and how susceptible it makes them to breast cancer recurrence."

Damaraju and his team focused their research on good prognosis breast cancer - cancer that has a high success rate in terms of initial recovery and treatment. About 70% of all breast cancers fall into this category. Yet despite the high success rate with initial treatment for this type of breast cancer, the overall numbers of those who died or had their cancer spread in this 'good prognosis' group are substantial. The numbers are high simply because so many people have this common 'good prognosis' cancer.

Currently, treatment options for breast cancer patients are based on what doctors know about the tumour itself - its size, grade and the absence or presence of certain markers within the tumour. Damaraju noted there are patients who are given an excellent prognosis based on what doctors see within the tumour, yet the cancer comes back. And other women remain cancer free even though their doctors said they had a poor prognosis based on information gleaned from the tumour. Damaraju thinks the accuracy of prognosis could be improved by complementing tumor based markers with the DNA marker that can be found through a simple blood test.

Damaraju and his team are continuing their research in this area and would like to reconfirm their findings in a larger study, pending further funding. The results from that study could be published in about three years, and he suspects about two years after that, the DNA predictor test could be tested in prospective clinical studies prior to making them widely available for women.

The research was funded by the Canadian Breast Cancer Foundation - Prairies/NWT region, and the Alberta Cancer Foundation.

"The impact of Dr. Damaraju's significant discovery on personalized treatment for breast cancer patients is substantial," says Canadian Breast Cancer Foundation - Prairies/NWT Region CEO Trish Bronsch. "Knowing individual risks of breast cancer and reccurrence provides doctors and oncologists with a better picture in which they can create a treatment plan to fit personal needs. We are very excited to have been able to help fund Dr. Damaraju and his team to this discovery."

"We are pleased to see donor dollars having a direct impact on outcomes that are important to Albertans--in this case earlier detection and improved treatment options for breast cancer recurrence," says Myka Osinchuk, CEO of the Alberta Cancer Foundation. "We are excited to follow Dr. Damaraju and his team to ensure those women successfully treated for breast cancer continue to live cancer-free lives.

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Genetic Clue Discovered For Why Women Outlive Men

A new study of mitochondrial DNA in fruit flies offers a number of clues that might explain why females tend to outlive males across much of the animal kingdom, including humans.

Researchers from Monash University in Australia and Lancaster University in the UK, write about their work in the 2 August online issue of Current Biology.

They found male fruit flies appear to have mutations in their mitochondrial DNA that affect how fast they age and how long they live.

Scientists use fruit flies as models for studies in genes and aging because their biological processes are remarkably similar to that of other animals, such as humans, and with a lifespan of about a month, it doesn't take too long to investigate generational effects.

Senior author Damian Dowling, a research fellow in the Monash School of Biological Sciences, told the press:

"All animals possess mitochondria, and the tendency for females to outlive males is common to many different species. Our results therefore suggest that the mitochondrial mutations we have uncovered will generally cause faster male aging across the animal kingdom."

"Intriguingly, these same mutations have no effects on patterns of aging in females. They only affect males," he added.

Mitochondria are special subunits of cells, about the same size as bacteria, that provide the energy for life. They combine sugar and oxygen into adenosine triphosphate or ATP, molecular packets of energy that are usable by cells.

Mitochondria have their own DNA that is quite separate from the cellular DNA in the nucleus of the cell.

And, unlike cellular DNA, which is inherited from the sperm and egg that fuse to make the new individual, mitochondrial DNA comes only from the egg.

Thus, as mitochondrial DNA is passed down from generation to generation, the process of natural selection has no opportunity to "screen out" mutations in mitochondrial DNA that might be harmful to males. The researchers refer to this as a "sex-specific selective sieve".

For their study, Dowling and colleagues looked at differences in longevity and biological aging in male and female fruit flies whose mitochondria came from different origins.

They found genetic variations in both male and female mitochondrial DNA, but only the male ones could be linked to life expectancy. There weren't just a few mutations in one place, there were several, spread all over the mitochondrial genome:

"... our results indicate that the mitochondrial mutation loads affecting male aging generally comprise numerous mutations over multiple sites," they write.

The researchers suggest the mutations are entirely due to the way mitochondrial DNA is passed down through the female line.

"If a mitochondrial mutation occurs that harms fathers, but has no effect on mothers, this mutation will slip through the gaze of natural selection, unnoticed. Over thousands of generations, many such mutations have accumulated that harm only males, while leaving females unscathed," Dowling explained.

In an earlier study that looked at the effect of mitochondria being passed down the female line, the team had also discovered a link with male infertility.

Dowling said combining this latest study with their earlier work suggests mitochondria are "hotspots" for mutations that influece male health.

"What we seek to do now is investigate the genetic mechanisms that males might arm themselves with to nullify the effects of these harmful mutations and remain healthy," said Dowling.

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'Junk DNA' Plays Crucial Role In Human Diseases

A lot more of our genome is biologically active than previously thought - about 80% - an international team involving over 400 scientists revealed yesterday. The researchers explained that only approximately 1% of our genome has gene regions that code for proteins, which has made them wonder what is going on with the rest of the DNA. Now that we know that four-fifths of the genome is biochemically active, in a way that regulates the expression of nearby genes, geneticists realize that much less of our genome consists of junk DNA as once believed.

9 Experts believe these new findings will help us better understand how several diseases develop and behave, which may lead to more effective and targeted treatments.

The human genome has twice as many genes than previously thought. Many of the previously unknown genes play a role in cellular control, which may impact on the development of human diseases.

The international consortium of scientists analyzed and experimented on sequencing data from 140 different types of human cells and identified thousands of DNA regions that help direct our genes' activities.

Manolis Kellis, an associate professor of computer science at MIT, and co-author of a report that has appeared in several scientific journals, including Nature, said:

"Humans are 99.9 percent identical to each other, and you only have one difference in every 300 to 1,000 nucleotides. What ENCODE allows you to do is provide an annotation of what each nucleotide of the genome does, so that when it's mutated, we can make some predictions about the consequences of the mutation."

What is ENCODE?

ENCODE (Encyclopedia of DNA Elements) is a public research conglomerate launched by the NHGRI (National Human Genome Research Institute) in the USA, and the EMBL-European Bioinformatics Institute (EMBL-EBI) in the UK, in 2003. Its aim is to identify all the functional components of the human genome. The NHGRI and EMBL-EBI pledged to release all project data immediately into public databases.

What scientists initially thought was junk DNA is actually biochemically active.

One of the aims of ENCODE was to better understand the human genome beyond protein-coding genes. Scientists can do this by examining the chemical changes that occur in individual stretches of DNA - these stretches control when specific genetic regions become active. The chemical modifications vary by cell type, and can change the DNA directly, or just the histone proteins that DNA surrounds.

A pilot project was published in 2007, which had looked at 1% of the human genome.

To map these epigenomes (modifications), the researchers gathered data from various cell types. While some laboratories measured DNA histone modifications, others gauged the accessibility of various DNA stretches by cutting them into fragments with enzymes.

ENCODE is a collaboration of 442 scientists from 32 laboratories in Japan, Singapore, Spain, the USA and UK. Together, they generated and examined over 15 terabytes of raw data - all this data is now publicly available. They have used approximately 300 years' worth of computer time, focusing on 147 tissue types to find out what turns certain genes on and off, and the specific characteristics of switches in different cell types.

The ENCODE scientists found that about 80% of the human genome is involved in some type of biochemical event, such as protein binding, specifically binding to proteins that impact on how neighboring genes are used. They also found that the very same regulatory regions have different roles to play, depending on what kind of cell they are acting in.

The scientists analyzed the conservation of the A, T, C and G nucleotides in the new regulatory regions they had identified. Nucleotides are conserved if they stay the same over long periods during our evolution. This can be examined by either comparing how variations occur between different species, or among individuals of the same species.

In an online communiqué, the European Bioinformatics Institute, wrote:

"On 5 September, an international team of researchers reveal that much of what has been called 'junk DNA' in the human genome is actually a massive control panel with millions of switches regulating the activity of our genes. Without these switches, genes would not work - and mutations in these regions might lead to human disease."

Three Billion Pairs of Genetic Code

So far, all three billion pairs of genetic code that make up human DNA have been analyzed by ENCODE. Scientists at the European Bioinformatics Institute explained that they have identified the genome function of 4 million gene switches, which will help researchers hone-in on specific areas of human disease, and hopefully find ways to better treat or cure them. They added that the switches are frequently a long way along the genome from the gene they regulate.

Ewan Birney of the European Bioinformatics Institute, lead analysis coordinator for ENCODE, said: "Our genome is simply alive with switches: millions of places that determine whether a gene is switched on or off. The Human Genome Project showed that only 2% of the genome contains genes, the instructions to make proteins. With ENCODE, we can see that around 80% of the genome is actively doing something. We found that a much bigger part of the genome - a surprising amount, in fact - is involved in controlling when and where proteins are produced, than in simply manufacturing the building blocks."

Ian Dunham, also of European Bioinformatics Institute, said that ENCODE is a useful research tool for any researcher looking into human diseases. Scientists investigating diseases often have a good idea about which genes are involved, but need data on which switches play a role. In some cases the locations of these switches are not where they expected them to be. Dunham said "ENCODE gives us a set of very valuable leads to follow to discover key mechanisms at play in health and disease. Those can be exploited to create entirely new medicines, or to repurpose existing treatments."

A principal investigator on ENCODE, Dr Michael Snyder, professor and chair at Stanford University, explained that ENCODE provides us with the knowledge required so that we can look beyond the genome's linear structure to how the whole network is connected. Genome-wide association studies are helping us understand where certain genes are located, as well as which sequences control them. Snyder said "Because of the complex, three-dimensional shape of our genome, those controls are sometimes far from the gene they regulate and looping around to make contact. Were it not for ENCODE, we might never have looked in those regions. This is a major step toward understanding the wiring diagram of a human being. ENCODE helps us look deeply into the regulatory circuit that tells us how all of the parts come together to make a complex being."

Before, generating and storing enormous volumes of data was a problem in biomedical research. However, as productivity of genome sequencing has improved and become more economical, the focus has moved to analysis, i.e. interpreting data generated from genome-wide association studies. Cambridge University scientists said "ENCODE partners have been working systematically through the human genome, using the same computational and wet-lab methods and reagents in laboratories distributed throughout the world."

Ewan Birney said:

"Getting the best people with the best expertise together is what this is all about. ENCODE has really shown that leading life scientists are very good at collaborating closely on a large scale to produce excellent foundational resources that the whole community can use."

The scientists emphasized that it will be several years before doctors and patients see any tangible benefits from ENCODE.

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