Awesome X
Chromosome responsible for many diseases is laid bare
PARIS
In international team of gene scientists has unveiled the first complete analysis of the X chromosome, the secretive coil of DNA that shapes human sex and whose malfunctions are to blame for nearly 10 percent of inherited diseases.
Their landmark work, published in March in Nature, suggests that men and women owe their sex partly to chromosomes that evolved from a sexless organism less than 300 million years ago. The study also opens up new paths for understanding sources of mental retardation and diagnosing-and later possibly curing--testicular cancer, immune-system disorders, and many other inherited ailments.
"The human X chromosome has a unique biology that was shaped by its evolution... [and] holds a unique place in the history of medical genetics," says the paper.
In the study, a team led by the Wellcome Trust Sanger Institute in Cambridge, England, sequenced and analyzed more than 99 percent of the X chromosome, identifying a whopping tally of 1,098 genes on it, about four percent of the total on the entire genome.
Seeking to understand this remarkable difference between X and Y, the team believes the two chromosomes evolved from humble beginnings as an "ordinary" pair of identical chromosomes in a sexless organism.
Changes to a gene on one of the pairs triggered the molecular cascade that led to male development, and set in train the degeneration of that chromosome to its present rump-like state. X, though, has remained largely preserved over millions of years. The theory is that it serves to maintain a fuller panoply of genes to offset the shrinking of the Y.
Out of 3,199 identified inherited diseases, 307 can be attributed to mutations, or flaws, on the X chromosome that disrupt vital protein-making machinery, the study says.
Many of these diseases, including hemophilia and Duchenne muscular dystrophy, have already been traced to the X because they only occur among men. The reason for this is that men have only one copy of the X, whereas women have a backup copy, which means they are less exposed to that particular mutation risk.
But there are also many other rarer diseases common to both genders that can be attributed to X, the study says.
Already, thanks to the new sequence, 43 more genes have been named as the suspected culprits for conditions ranging from cleft palate and blindness to testicular cancer, a disregulation of the immune system called X-linked lymphoproliferative disease (XLP) and NS-LXMR, a form of mental retardation.
"From studying such genes, we can get remarkable insight into disease processes," said Mark Ross, project leader at the Wellcome Trust Sanger Institute. "From our study of one gene involved in an X-linked disease, a genetic test was developed and a new pathway that controls the workings of the immune system was discovered."
The study found that nearly a third of the entire X chromosome is taken up by a repetitive DNA sequence. The theory is that this is a mechanism to "silence" genes, something that is especially important for females, for it ensures that unneeded genes on their backup copy of the X remain deactivated.
Richard Ingham, AFP
Adult stem cells offer similar therapeutic possibilities as embryonic cells
SYDNEY
Australian research showing that adult stem cells can offer the same therapeutic possibilities as cells drawn from human embryos has been hailed as an ethical breakthrough by the Catholic Church and "right to life" advocates.
A team of scientists led by Alan Mackay-Sim of Brisbane's Griffith University said adult stem cells harvested from olfactory mucosa, the organ of smell in the human nose, had been successfully grown into a wide variety of other cells.
Mackay-Sim said the olfactory stem cells showed the same generative ability of embryonic stem cells, which can transform themselves into nerve, heart, liver, kidney, or muscle cells for use in treatment of spinal injuries and degenerative illnesses like Parkinson's disease and cardiac ailments.
If successful, olfactory stem cells would provide an alternative to stem cells derived from human embryos left over from in vitro fertilization procedures--a practice staunchly opposed by the Catholic Church and right-to-life advocates who believe that life begins at the moment of conception.
Mackay-Sim said the adult stem cells also had the advantage of offering patients the possibility of using their own cells for therapy, lessening the chance of the body rejecting the transplanted cells. He said the stem cells could be obtained from all individuals and were relatively easy to grow in the lab. "These attributes make them good candidates for stem-cell-transplantation therapies and tissue reconstruction," he said.
The discovery was the result of a four-year research program funded in part by the Australian Catholic Church under the patronage of Archbishop George Pell, who has lobbied hard for a national ban on embryonic-stem-cell research. Cardinal Pell said he would send the results of Mackay-Sim's research to the Vatican. "I would be happy to communicate it to the Pontifical Academy of Science to expedite the scientific examination and also to spread the word about the success," he said.
Health minister Tony Abbott, a devout Catholic and leading opponent of embryonic-stem-cell research, also hailed the new study.
AFP
Fixin' a broken heart
Gene-transfer technology could make pacemakers obsolete
SYDNEY
Pacemakers could be obsolete within a decade after Australian researchers managed to revive heart tissue withered by cardiac arrests. The Sydney-based Children's Medical Research Institute (CMRI) said the breakthrough involved injecting a virus containing two of the patients' own genes into the scar tissue caused by heart attacks known as fibroblasts.
Ian Alexander, CMRI head of gene therapy, said the process revived electrical pathways in the fibroblasts, allowing the scar tissue to once again "twitch" like normal heart muscle cells in response to the cardiac system's natural electrical pulses. "It means we can take two genes and we can say to these scar tissue cells 'we want you to take on the properties of heart muscle cell that is capable of being excited electrically,'" he said.
While the gene-transfer technology has so far only been used to repair heart cells in the laboratory, Alexander said he hoped trials on animals, and eventually humans, would begin soon.
"What we would envisage is you might have a patient with damage to those electrical pathways caused by scarring from a heart attack, an operation or even in childhood with a congenital heart problem--we could go in and genetically reprogram them to be a useful cell type that restores the function of the heart," he said.
Alexander said the technology had the potential to replace pacemakers, which are currently implanted for a variety of cardiac complications including in heart attack victims to pass on the electrical pulses. It meant patients could potentially avoid having pacemaker hardware installed in their bodies, avoiding problems with battery life and parts wearing out.
The therapy involves injecting two genes contained in a virus into the fibroblasts. The first reprograms the cells to act like muscle cells and the second allows the cells to communicate with each other so they can pass on electrical pulses.
Alexander said a single injection had the potential to repair thousands of scarred heart cells.
The breakthrough, published in the journal Circulation, was developed by a CMRI cardiologist Eddy Kizana during his PhD studies. Kizana is now carrying out studies with US experts to develop his discovery.
AFP
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