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RxPG News : Genetics
Medical News and Information
- History, geography also seem to shape our genome
( from http://www.rxpgnews.com ) History and geography shape our genome, according to a new study.
The movements of humans within and among continents, expansions and contractions of populations and vagaries of genetic chance, have influenced the distribution of genetic variations.
In recent years, geneticists have identified a handful of genes that have helped human populations adapt to new environments within just a few thousand years - a strikingly short time scale in evolutionary terms.
However, a team from the Universities of Chicago, California and Stanford, which jointly conducted the study, found that for most genes, it can take at least 50,000-100,000 years for natural selection to spread favourable traits through a human population.
They found that gene variants tend to be distributed throughout the world in patterns that reflect ancient population movements and other aspects of population history.
'We don't think that selection has been strong enough to completely fine-tune the adaptation of individual human populations to their local environments,' says study co-author Jonathan Pritchard, professor in human genetics and Howard Hughes Medical Institute investigator.
'In addition to selection, demographic history -- how populations have moved around -- has exerted a strong effect on the distribution of variants,' he added.
Selection may still be occurring in many regions of the genome, said Pritchard. But if so, it is exerting a moderate effect on many genes that together influence a biological characteristic, according to a Howard Hughes release.
'We don't know enough yet about the genetics of most human traits to be able to pick out all of the relevant variation,' said Pritchard.
'As functional studies go forward, people will start figuring out the phenotypes - associated with selective signals,' said lead study author Graham Coop.
'That will be very important, because then we can figure out what selection pressures underlie these episodes of natural selection.'
The study was published in the Friday edition of the open-access journal PLoS Genetics. - Induced pluripotent stem cell lines from pigs
( from http://www.rxpgnews.com ) The discovery that adult skin cells can be 'reprogrammed' to behave like stem cells has been a major scientific boon, providing a way to tap the potential of embryonic stem cells without the associated ethical quandaries. Now, in a study appearing online in JBC, researchers have created a line of such reprogrammed stem cells from adult pigs. As pigs are large animals with a physiology very similar to humans, this work provides a valuable model to study the therapeutic potential of this new "induced pluripotent stem cell" (iPS) technology. iPS cells have already been developed from both mice and humans. Both systems will help researchers answer many biological and genetic questions about these cells, but still leave a gap before clinical applications can begin. These iPS cells cannot be tested on humans before thorough safety and efficacy trials in animal models, but the size, physiology and short lifespan of mice makes them less than ideal for these trials. Duanqing Pei and colleagues turned to a better pre-clinical model: pigs. These large animals share a remarkably similar biology to humans, as evidenced by their already extensive contributions to medicine, such as using pig insulin to treat diabetes or pig heart valves in transplant surgery. The research group modified the current iPS protocols to successfully generate a line of stem cells from a miniature Tibetan pig (whose smaller size would make breeding and maintenance easier). A biochemical analysis revealed these cells expressed the key proteins that would classify them as 'stem cells' and had the ability to differentiate into many other types of cells. Importantly, these pig iPS cells more closely resembled human stem cells than other animals, confirming their value in pre-clinical studies. The researchers believe porcine iPS technology is an emerging and exciting field that should progress quickly and lead to many applications - Egg cells help extend life of sperms
( from http://www.rxpgnews.com ) In contrast to women, men are fertile throughout life, but research at the Sahlgrenska Academy, University of Gothenburg, Sweden, has now shown that a fertilising sperm can get help from the egg to rejuvenate. The result is an important step towards future stem cell therapy. The risk of chromosomal abnormalities in the foetus is highly correlated to the age of the mother, but is nearly independent of the age of the father. One possible explanation is that egg cells have a unique ability to reset the age of a sperm."We are the first to show that egg cells have the ability to rejuvenate other cells, and this is an important result for future stem cell research", says Associate Professor Tomas Simonsson, who leads the research group at the Sahlgrenska Academy that has made this discovery. Each time a cell divides, the genetic material at the ends of the chromosomes becomes shorter. The ends of the chromosomes, known as "telomeres", are important for the genetic stability of the cell and they act as a DNA clock that measures the age of the cell. The cell stops dividing and dies when the telomeres become too short. The discovery that the egg cell can extend the telomeres of a fertilising sperm cell is important in the development of stem cell therapy. Stem cell therapy involves replacing the cell nucleus in unfertilised egg with a nucleus from a somatic cell that has come from a patient who needs a stem cell transplantation. As soon as the cell has divided a few times, it is possible to harvest stem cells that are then allowed to mature to the cell type that the recipient needs. "The genetic stability of the transplanted cells has been a serious concern up until now, and it was feared that the lifetime of these cells would depend on the age of the cell nucleus that was transferred. Our results suggest that this is not the case", says Tomas Simonsson. - Family of genes known as KRAB-ZFP regulate genes dealing with stress
( from http://www.rxpgnews.com ) Research conducted by a team in Switzerland suggests that a family of genes involved in regulating the expression of other genes in the brain is responsible for helping us deal with external inputs such as stress. Their results, appearing in the December 11 advance online version of the journal Neuron, may also give a clue to why some people are more susceptible to anxiety or depression than others. The researchers from EPFL and the National Competence Center "Frontiers in Genetics" studied the role of a family of genes known as KRAB-ZFP, which acts like a group of genetic censors, selectively silencing the expression of other genes. These repressors make up about 2% of our genetic material, but little is known about how this "epigenetic" silencing process works, what the long-term consequences are, and even which genes are targeted. (Epigenetics refers to a change in gene expression that is caused by something other than a change in the underlying DNA sequence.) The researchers bred a strain of mice that lacked in the hippocampus, a part of the forebrain involved in short-term memory and inhibition, a key cofactor used by the KRAB family. The genetically altered mice appeared completely normal until they were placed in a stressful situation. Then they became extremely anxious. Although the normal mice quickly adapted, the altered mice never managed to overcome their stress, and remained anxious and unable to complete simple cognitive tasks. The disruption of the KRAB-mediated regulatory process thus altered the mice's normal behavioral response to stress."The KRAB regulators appeared fairly recently on an evolutionary scale," notes EPFL professor Didier Trono, lead author on the study, " and it's very likely that there is a fair degree of polymorphism between individuals. We postulate that variability in these genes is one factor that may participate in predisposing people to anxiety syndromes or depression. " Because epigenetic alterations are often long-lasting and sometimes permanent, one could also interpret them as a way in which an individual's personal history can have a lasting impact on his or her genetic expression. "It's a way for a cell to have a sort of memory," explains Trono. This work opens promising leads for further exploration, because evidence of epigenetic modification has been observed in animal models of depression, addiction, schizophrenia and neuro-developmental disorders. Some psychoactive drugs like cocaine or anti-psychotics also cause changes in some of the co-factors involved in this genetic regulatory system. With an understanding of the molecular mechanisms involved in epigenetic modulation, it might be possible to develop targeted therapies for those individuals in whom it malfunctions. - New screening strategy increases Down's syndrome