New Era for Human Genetics Begins

1000 Genomes Project focuses on genetic differences which could lead to greater understanding of disease, evolution

Art Chimes | St. Louis, Missouri 27 October 2010

An international effort to build a detailed map of human genetic variation has completed its pilot phase and could shape a new understanding of human evolution and may help in fighting disease.

The 1000 Genomes Project aims to sequence the genetic code of 2,500 people.

A decade ago, scientists made worldwide headlines when they announced they had sequenced the human genome - made a kind of map, in other words, of DNA, the inherited molecule that makes us human. But that was only one genome. Everyone on Earth has a unique genetic makeup, and researchers have now sequenced thousands of individuals' DNA.

The first effort to sequence the human genome came in under budget and ahead of schedule, and the process has gotten progressively cheaper and faster.

"In the last 10 years," said Richard Durbin, co-chair of the 1000 Genomes Project. "DNA sequencing technology has advanced dramatically so it has become feasible to systematically sequence many people to find genetic variants, and build a catalog which we can use as a basis for investigations into disease, genetics, and which variants may be functional."

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Genetic variations are the way your genes differ from other people's. Some variations relate to differences we can see, like eye color. Others may put us at greater risk for disease. Some variations are inherited. Others can be caused by toxic chemicals or radiation or simply by mistakes in copying DNA.

Most genetic variations are found in lots of unrelated people. Scientists have started to investigate possible links between disease and some of these variations, called single nucleotide polymorphisms, or SNPs. The researchers aim to probe deeper.

"The 1000 Genomes Project makes this approach much more complete and much more powerful," said David Altschuler, 1000 Genomes co-chair, "by going down to much lower frequencies, and also broader range of populations and more complete data in each frequency range and each population."

At the University of Washington in Seattle, meanwhile, Evan Eichler and his colleagues have been using a technique to identify pieces of the genome that duplicate other parts of the DNA code. Writing in the journal Science, the researchers describe how they identified more than four million places where they found these duplicates, called copy-number variants.

Eichler says these variants could help identify genes that may be associated with disease that are what he called "inaccessible" using other techniques. He also said it can help improve the understanding of human evolution.

"We think the veil has been lifted for us in terms of a whole new level of genetic diversity. And when we compare these roughly 159 humans that we've analyzed to date, and compared variations they've found in their genomes to that of the great apes, we have the ability, I think pretty clearly, to identify the genes and the gene families which have expanded specifically in our lineage of evolution since we separated from that of chimpanzee and gorilla," Eichler said.

Back at the 1000 Genomes project, co-chair David Altshuler says the organization's work will provide data so scientists can answer questions about the role genes play in health based on facts, not guesswork. "And so rather than speculate," he said, "I think we'd say we are helping to create the foundation to answer that question, and anyone who does speculate, I think is speculating."

By the way, the goal of the 1000 Genomes project isn't to sequence the genetic code of exactly 1,000 people. Instead, the aim is to identify genetic variations that occur in at least one out of every 100 people or one percent. In particular, that will require using genetic material from many thousands of people from all over the world. And it will need to include a lot more geographic diversity. Only a handful of genomes from Latin America and Africa have been sequenced so far.

Researchers May Some Day Treat Depression with Gene Therapy

Jessica Berman 21 October 2010

Doctors may some day treat patients suffering from major depression with gene therapy. So say scientists who report they are encouraged by human and animal research.

Scientists have identified a protein called p11 in a small region of the brain that plays a role in major depression. The brain region, known as the nucleus accumbens, is responsible for feelings of pleasure and reward.

Researcher Michael Kaplitt of the department of neurological surgery at Presbyterian / Weill Cornell Medical Center in New York, says mice bred without the p11 gene showed signs of severe depression, including passivity when dangled by their tails instead of trying to get away and a disinterest in sugar water, which he says is like candy to mice who normally drink a lot of it.

Kaplitt also says autopsy studies of tissue taken from the brains of people with severe depression showed extremely low levels of p11 in the nucleus accumbens compared to the brains of individuals without depression.

"So if human beings have lower levels of p11 in this area of the brain, if they have depression, and if animals when they have low p11 levels in this area show depression-like behaviors, then that suggests that this might be a very important component of depression; not the only component but it may be a very important component," said Kaplitt.

Using so-called knock-out mice that completely lacked the p11, Kaplitt says researchers inserted a normal copy of the protein into a harmless virus and infused it into the nucleus accumbens of the depressed rodents.

"Now when we restored it to these adult mice, it completely normalized their behaviors; it reversed these depression-like behaviors so that they were back to normal," he said. "So that suggested that if you have low p11 levels in that area, and if that is a cause of depression, that we could potentially reverse it with gene therapy."

Kaplitt and colleagues have also been conducting promising therapy trials with Parkinson's disease patients.

The researchers hope to soon begin gene therapy experiments in patients with major depression who do not respond to anti-depressant medications.

An article on gene therapy for major depression is published in the journal Science Translational Medicine.

Scientists Discover Pain Genes

Jessica Berman | Washington 11 November 2010

Scientists have discovered hundreds of genes that appear to play a role in determining pain sensitivity. Researchers say slight variations in one pain gene in particular seem to affect how intensely pain is felt.

Under normal circumstances, scientists say pain serves an important biological function; a sharp poke with a needle or knifepoint, or slight burn, causes most people to recoil, protecting them from further harm.

Then there is another type of pain, according to Clifford Woolf a neurobiologist at Children's Hospital in Boston, Massachusetts.

"The other kind of pain is when the fire alarm system is on all the time, and these would be patients who have chronic persistent pain," Woolf explained. "And that is a situation where pain has become a disease in its own right. It's no longer warning of damage; the fire alarm is on all the time and there's no fire."

Scientists say studies of twins show that the degree to which an individual feels pain is largely inherited.

In an effort to identify genes involved in pain, an international team of researchers led by Woolf identified some 600 potential genes in fruit flies which are similar in humans.

Scientists focused on one gene in particular called "Alpha 2 Delta 3."

In a study of 189 healthy volunteers, researchers found reduced sensitivity to heat among participants who had slight alphabet variations to the DNA code within or close to the location of the Alpha 2 Delta 3 gene.

Researchers also found in another study that back pain patients who had the rarer genetic variants were less likely to experience persisting pain after surgery.

By learning the genetic underpinnings of pain, Woolf says it will someday be possible to develop medications to treat a variety of pain syndromes.

"There's pain associated with damage to the nervous system. Pain associated with the inflammatory diseases," neurobiologist Woolf noted. "There's post-operative pain. And each of them operates in slightly different ways, and so there will be different targets and different analgesics required for these different kinds of pain."

Researchers say it may one day be possible to develop genetic risk profiles to determine who is at greatest risk of chronic pain following surgery. Such information could be useful in helping patients decide whether to go forward with an operation.

An article describing the pain genes is published in the journal Cell.

Stem Cell Therapy Gaining Ground in Asia

Heda Bayron | Hong Kong 25 November 2010

Asians are beginning to warm up to the idea of using their own stem cells to treat a host of illnesses such as heart disease, cystic fibrosis or leukemia. Some parents are preserving their babies' umbilical cords, hoping that as technology advances their children can use the umbilical blood to cure future illnesses.

It is a nightmare for parents to hear their child has developed a disease that requires a bone marrow transplant. For instance, patients with leukemia, a type of blood cancer, sometimes have a hard time finding a bone marrow match.

Scientists say the umbilical cord that attaches a baby to its mother is a rich source of stem cells, which can treat diseases like leukemia. They can be collected immediately after birth and stored in freezers by companies such as Cordlife, which operates cord blood banks in Hong Kong, Singapore, Indonesia, India and the Philippines. If a child needs it, doctors can retrieve cord blood for treatment.

"We're seeing an explosion umbilical cord blood banking as a source of biological insurance for parents in Asia and their children," said Andrew Wu, Cordlife's technical and laboratory director.

Scientists around the world are finding new ways to use cord blood stem cells to treat problems such as spinal cord damage, diabetes, cerebral palsy and heart disease.

At Cordlife, parents pay about $4,000 to keep their children's cord blood for 18 years.

"I'm most excited to see the use of stem cell in therapy becoming a standard of care, where clinicians when they look at a disease would ask, 'What's my stem cell option in terms of therapy? How I can look to stem cells to treat this disease or regenerate this organ or to combat this tumor?'" Wu said.

Asia appears striding toward the use of stem cells for treatment.

Dr. Supachai Chaithiraphan, a professor emeritus of Thailand's Mahidol University and director of the cardiac center at Chao Phya hospital in Bangkok, conducted a clinical trial in 2004 that injected stem cells derived from human blood to treat people with end-stage heart disease.

"Eighty percent showed improvement in terms of New York Heart Association classification and also the Canadian [Cardiac Society] angina classification. So we feel that this group of patients can derive benefit from their own stem cell therapy," Supachai said.

In Asia, there are fewer regulations regarding the use of stem cells than in the United States, which encourages research and clinical uses.

In the U.S., the use of stem cells has been controversial because of ethical concerns over the use of embryonic stem cells - derived from early-stage embryos that develop from human eggs fertilized in a laboratory. Under President Bush, the government limited funding to a few batches of stem cell lines. But the Obama administration has since relaxed those rules.

However, cord blood storage appears to be increasing in the U.S. A new national cord blood bank has been established at Duke University in the state of North Carolina.

Some practitioners, such as Wu worry that Asia's lax regulations may lead to inflated expectations and false promises.

"A lot still needs to go into building this understanding and building appropriate regulations around the use of these stem cells so that the industry as a whole can develop within a legal framework that not only benefits the companies but most importantly benefits the clinicians and the patients at the end of the day," Wu said.

Poor medical facilities in some developing Asian nations also hold back use of stem cells.

But Supachai says in time, stem cell therapy will be more accessible.

"I would foresee that in the near future more doctors would come to realize that this cell therapy is really of help to certain number of patients with certain diseases, in particular heart disease," Supachai said.

The World Health Organization estimates that about 20 million people worldwide will die from cardiovascular disease annually by 2015. The number of people in developing nations suffering from heart disease is expected to rise as incomes increase.

Scientists say DNA provides 'historical archive'

Edinburgh scientists say they have developed a genetic test that can tell if people's ancestors were from a large populated area or a rural village.

The team found that a person's DNA records provide a "historical archive" of where they are from.

The test can also detect if a person's ancestors were related, such as if they are from a community where marriage between cousins was commonplace.

It could help identify people who are more prone to genetic illnesses.

Gene pool

A team at Edinburgh University analysed the DNA of more than 1,000 people across 51 different ethnic groups, ranging from Europeans to Amazonian tribes, during the study.

They identified those who had inherited the same genetic material from both parents The study found that native South Americans had the highest amount of shared DNA, suggesting that those communities were small and isolated over many generations.

By contrast, African communities had the lowest degree of genetic similarity, indicating a more diverse population over time.

The team believe this could be explained by the fact that humans originated in Africa and so have had the most time to develop a diverse gene pool.

Dr Jim Wilson, Royal Society research fellow at Edinburgh University, said: "The exciting thing about these results is that it shows our genes are recording the history of movements in our population.

"It's like an archive being written in genetic code, so that we can understand the way our populations have developed from the distant past.

"The findings are also important because it highlights those areas of the world where genetic similarity is common and this can be a risk factor for some diseases like cystic fibrosis, which can be caused when you inherit a faulty gene from both parents."

The scientists said DNA records provided a "historical archive" of where people are from

(source: BBC)