Jumping genes may tell why people have varied looks, disease risks

Washington, Feb 5: A Johns Hopkins study has identified ''jumping genes'' in humans that may one day explain why people have such varied physical traits and disease risks.

Using bioinformatics to compare the standard assembly of genetic elements, the team revealed 1,016 new insertions of RIPs, or retrotransposon insertion polymorphisms, thereby expanding the catalog of insertions that are present in some individuals and absent in others.

Retrotransposons are travelling bits of DNA that replicate by copying and pasting themselves at new locations in the genome. Having duplicated themselves and accumulated over evolutionary history, transposable elements now make up about half of the human genome.

"In any individual, only between 80 to 100 retrotransposons are actively copying and inserting into new sites. We''re not only discovering where they are and who has which ones, but also finding out that they insert with a remarkable frequency: On the order of one in every 50 individuals has a brand-new insertion that wasn''t in their parents," said Haig Kazazian of the Johns Hopkins University School of Medicine.

The researchers recognized L1 retrotransposons because these actively jumping genes are human specific and almost exactly the same in sequence from one person to another.

The results appeared in the journal Genome Research. (ANI)

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Greediness gene dooms dieting

London, Nov 15 - Your dieting resolve can be doomed if you are carrying a 'greediness' gene, a study shows.

Researchers have shown that a rogue gene linked to obesity makes us fat by boosting appetite.

This deep-seated drive to eat could also explain why so many of us succumb to temptation, no matter how strong our initial resolve to lose weight, according to the journal Nature Genetics.

The breakthrough opens the door for drugs that take the edge off appetite, melting away 'muffin tops' and pruning pot bellies, reports the Daily Mail.

Oxford University and the Medical Research Council researchers studied a gene called FTO, which when discovered in 2007, was the first gene to be linked with obesity.

Up to 14 percent of Britons carry two rogue copies of FTO, increasing their risk of obesity by 70 percent and diabetes by 50 percent. These people are, on average, almost half a stone heavier.

The 49 percent who have inherited just one flawed FTO gene are 30 percent more likely to be obese than those with two normal copies of the gene and 25 percent more likely to develop diabetes.

Scientists found that mice bred to have extra copies of the rogue gene were healthy, but ate more and became heavier than normal rodents.

Researcher Chris Church said: "For the first time, we have provided convincing proof that the FTO gene causes obesity."

Prof Frances Ashcroft, one of the research leaders, said: "Too much activity of this gene canlead to putting on weight by overeating." (IANS)

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Targeting malaria’s ‘sticky’ proteins could put an end to the disease

Washington, July 10 : A team of Australian researchers have identified a key mechanism that enables malaria-infected red blood cells to stick to the walls of blood vessels and avoid being destroyed by the body''''s immune system.

The discovery highlights an important potential new target for anti-malarial drugs.

Malaria is caused by the malaria parasite, which is injected into the bloodstream from the salivary glands of infected mosquitoes.

There are a number of different species of parasite, but the deadliest is the Plasmodiumfalciparum parasite.

The malaria parasite infects healthy red blood cells, where it reproduces, producing up to thirty-two new daughter parasites.

The parasite secretes a ‘glue’, known as PfEMP1, which travels to the surface of the infected red blood cells, leading to the formation of the knobs on the surface of the cells.

The cells become sticky and adhere to the walls of the blood vessels.

This prevents the cells being flushed through the spleen, where the parasites would be destroyed by the body''''s immune system, but also restricts blood supply to vital organs.

Now, researchers, led by Professor Alan Cowman from the Walter and Eliza Hall Institute of Medical Research in Melbourne, Australia, have identified eight new proteins that transport the P. falciparum parasite''''s ‘glue’ to the surface of the infected red blood cells.

They have shown that removing just one of these proteins prevents the infected red blood cells from sticking to the walls of the blood vessels.

"These findings greatly enhance our understanding of how the malaria parasite commandeers the red blood cell for its own survival and avoids our immune defences," Cowman said.

"They also suggest that a drug that targets the ''''stickiness'''' proteins could be an effective treatment for malaria," he added.

The study is published in the journal Cell. (ANI)

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Rare genetic disease mutation protects against malaria

London, Apr 17: The mutation that causes the raregenetic disease pyruvate kinase deficiency protects against malaria, states a new study.

Approximately 1 in 20,000 people have two copies of a genetic mutation that prevents red blood cells from producing energy and causes anaemia.

And patients with the condition often die young.

But, according to Philippe Gros, a geneticist at McGill University in Montreal who led the new study, people with one mutated pyruvate kinase (PK) gene might be spared from the malaria parasite Plasmodium falciparum.

"These guys are absolutely normal; they don't know that they have one copy of the mutation," New Scientist quoted him, as saying.

The research team is currently collecting blood samples in areas rife with malaria to determine whether the mutation offers some resistance in people with one mutation.

"In one or two years max we'll have the answer," Gros said.

Another disease, sickle cell anaemia, protects against malaria in a similar way. Patients with a single mutation in a gene for the blood protein haemoglobin have partial resistance to malaria, while two copies spell disease.

For this, the research team tracked down several patients and collected blood from them.

When the researchers tried infecting the red blood cells with P. falciparum, the sickly cells were virtually impervious to the parasite.

Some parasites managed to invade, but those cells proved easier targets for the immunesystem. White blood cells destroyed the infected cells in a Petri dish.

Gros' team performed the same tests in cells of people who had only one mutation in the PK gene.

Their red blood cells easily succumbed to the malaria parasite. However, white blood cells made easy work of the infected cells. This suggests that people with PK mutations – but no disease – might get some protection from malaria, Gros said.

The study is published in The New England Journal of Medicine.

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Curing Human Genetic Disease at the Salk Institute

Modernist architect Louis I. Kahn designed the twin-structured building in 1965. The landscape includes a courtyard area with the “Stream of Life,” a foot-wide water display inspired by architect Luis Barragán that flows through the marble courtyard between the buildings.

This inspiring place is the Salk Institute for Biological Studies — located on wind-worn bluffs overlooking the rolling surf at La Jolla, California — and it’s one of the world’s preeminent research institutions. You can almost hear Jonas Salk wandering the labs and research facilities of his famous namesake.

These days Salk scientists make cross-disciplinary contributions to the study of cancer, aging, Alzheimer’s, diabetes, and cardiovascular disorders. Areas of research include neuroscience, genetics, cell and plant biology, and related disciplines.

Until 1955, when the Salk vaccine was introduced, polio was one of the most frightening public health problems of the post-World War II period. Jonas Salk changed all that — we no longer worry much about crippling polio. He went on to found his biological research institute in 1960. Among the founding consultants were Jacob Bronowski and Francis Crick.

A nearby street is known as Nobel Drive, as five scientists trained at the Institute have won Nobel Prizes, and four current resident faculty members are Nobel Laureates. Juan Carlos Izpisúa Belmonte, a professor at Salk’s Gene Expression Laboratory, continues to walk the halls and offices of the Institute — in the footsteps of Jonas Salk.

In a stunning article in Nature, his research team has proven, in principle, that a human genetic disease can be cured using a combination of gene therapy and induced pluripotent stem (iPS) cell technology. Salk’s director of communications Mauricio Minotta told h+, “It’s a pretty remarkable discovery that hasn’t been extensively covered in the mainstream press. It’s a major step in getting regenerative medicine from the laboratory to the clinic.”

A pluripotent cell can create all cell types, with the exception of extra embryonic tissue. Using iPS technology, Belmonte’s team corrected a defective gene in cells taken from patients with Fanconi anemia, a disease that can lead to bone marrow failure, leukemia and other cancers.

Working with Inder Verma, Ph.D., a professor at Salk’s Laboratory of Genetics, and colleagues at the CMRB, and the CIEMAT in Madrid, Spain, Belmonte selected Fanconi anemia — a characteristic and debilitating genetic disease — for experimentation. Fanconi anemia is responsible for a series of hematological abnormalities that impair the body’s ability to fight infection, deliver oxygen, and clot blood. Even after receiving bone marrow transplants to correct the hematological problems, patients remain at high risk of developing cancer and other serious health conditions.

Using hair and skin cells from patients with Fanconi anemia, the research team corrected the defective gene in the patients’ cells using gene therapy techniques pioneered in Verma’s laboratory. They then successfully reprogrammed the repaired cells into induced pluripotent stem (iPS) cells using a combination of transcription factors (proteins) to transfer the genetic information from DNA to RNA. The resulting cells were “disease free” and indistinguishable from human embryonic stem cells or iPS cells generated from healthy donors. Nature reported: “Corrected Fanconi-anaemia-specific iPS cells can give rise to haematopoietic progenitors of the myeloid and erythroid lineages that are phenotypically normal, that is, disease-free.”

“We haven’t cured a human being, but we have cured a cell,” says Belmonte. “In theory we could transplant it into a human and cure the disease.”

Stem cells are seen by many researchers as having virtually unlimited application in the treatment and cure of many human diseases and disorders including Alzheimer’s, diabetes, cancer, and strokes.

There are three general types of stem cells:

Embryonic. A primitive type of cell that can be coaxed into developing into all of the 220 types of cells found in the human body — this includes blood cells, heart cells, brain cells, nerve cells, and so forth. In the past, they have always been derived from human embryos in a controversial process that destroys embryos.

Adult. Similar to embryonic stem cells, adult stem cell research is 20 years ahead of embryonic stem cell research. Some therapies have advanced to human trial stage. Unfortunately, adult cells are limited in flexibility, and are only capable of developing into a few of the cell types.

Induced purpotent (iPS). Used in Belmonte’s research, these are specially treated ordinary cells — such as skin and hair cells — that are specially processed to emulate embryonic stem cells.

As reported in h+ Magazine’s interview with Sean Hu, the founder of China’s Beike Biotechnology, the U.S. is a bit late to the global stem cell research game. (See the “See Also” box included on this page.) Japan’s Dr. Shinya Yamanaka demonstrated the ability to reprogram adult cells to behave as embryonic stem cells as early as 2007. Beike Biotechnology has made almost miraculous strides in actually using stem cells to treat and cure diseases such as blindness, cerebral palsy, and spinal cord injuries. Beike’s therapies involve stem cells harvested from umbilical cord blood, not the more controversial procedure of removing stem cells from human fetuses.

The recent Salk Institute announcement now confirms both U.S. leadership in stem cell research and the potential of stem cells to cure human genetic disease. Dr. Belmonte: “The hope in the field has always been that we’ll be able to correct a disease genetically and then make iPS cells that differentiate into the type of tissue where the disease is manifested and bring it to clinic.”

While obstacles remain — Belmonte and Verma must prevent the reprogrammed cells from inducing tumors — in coming months they will be exploring ways to overcome this and other impediments. And in April 2009, they received $6.6 million from the California Institute Regenerative Medicine (CIRM) to pursue research aimed at translating basic science into clinical cures.

Dr. Verma says, “If we can demonstrate that a combined iPS-gene therapy approach works in humans, then there is no limit to what we can do.” (Gene therapy is the insertion of genes into an individual’s cells and tissues to treat a disease like Fanconi anemia.) Viruses such as the adenovirus vector can be used as vehicles to carry “good” genes into a human cell. All viruses bind to their hosts and introduce their genetic material into the host cell as part of their replication cycle. This genetic material contains basic instructions on how to produce more copies of these viruses, commandeering the body’s normal machinery to serve the needs of the virus.

For example, a new gene is inserted into an adenovirus vector. It is then used to introduce the modified DNA into a human cell. If the treatment is successful, the new gene will make a functional protein. This is also done using retroviruses, a family of viruses that can insert themselves into a cell’s genome as the vector, or delivery vehicle.

When Dr. Verma and his team conducted the first successful study to use viruses to deliver therapeutic genes into cells in 1983, the news made the front page of the New York Times. The research demonstrated that a genetic disease, in this case, Lesch-Nyhans syndrome, could be corrected in a Petri dish using retroviruses.

Verma’s team went on to use viral vectors to introduce genes into animals, correcting such genetic diseases as hemophilia and severe combined immunodeficiency syndrome (SCID), or “bubble boy disease.” Currently, more than 60 percent of all gene therapy trials worldwide rely on viruses to transport their genetic payload into cells.

If Jonas Salk were alive today, he’d be amazed by the breadth, depth, and scope of the world-class research being conducted at his institute, and the quality and dedication of researchers like Belmonte and Verma who have proven in principle that a human genetic disease can be cured using a combination of gene therapy and induced pluripotent stem (iPS) cell technology.

Knowledge acquired in Salk laboratories provides new understanding and potential new therapies and treatments for diseases ranging from cancer to AIDS; from Alzheimer’s disease to cardiovascular disorders; from anomalies of the brain to birth defects.

Walking along the Stream of Life in the marble courtyard of the Salk Institute is like entering an ancient Greek temple. It’s a reminder of Heraclitus’ famous and enigmatic maxim, “No man ever steps in the same river twice, for it’s not the same river and he’s not the same man.” And stepping into the stream of life at Salk may just mean a permanently changed man — one without human genetic disease.

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