Investigadores de Scripps Research descubren nuevo gen ligado al Síndrome de X frágilContributed by: Anonymous · Views: 1,166
Contributed by: Anonymous · January 24, 2008 @ 02:00 PM MST · Views: 1,166
Scripps Research Scientists Discover New Gene Linked to Fragile X Syndrome
Discovery Suggests Potential Targets for Autism and Other Neurological Disorders
The study on the new gene-which the Scripps Research scientists have dubbed FMR4-was published January 23 in the journal PLoS ONE.
"FMR4 is a novel gene that is located in the same chromosomal neighborhood as FMR1, a well established causative gene in fragile X syndrome," said Claes Wahlestedt, a professor at the Scripps Research campus in Jupiter, Florida. "Like FMR1, FMR4 is silenced in fragile X patients and up-regulated in FXTAS (fragile X-associated tremor/ataxia syndrome), a disease that resembles Parkinson's disease. Our discovery could lead to the development of new diagnostic tests or even to novel therapies for these defects."
Fragile X syndrome affects thousands of patients worldwide with severe learning disabilities, often accompanied by anxiety disorders, obsessive-compulsive behavior, and attention deficit hyperactivity disorder. There are currently no therapeutic treatments available for fragile X syndrome. Approximately one-third of all children diagnosed with fragile X syndrome also have some degree of autism, according to The National Fragile X Foundation, including such behaviors as social anxiety, poor eye contact, and hand biting.
More than 16 years ago, scientists linked fragile X syndrome to inactivation of FMR1 gene expression, leading to the lack of a protein known as the fragile X mental retardation protein, now considered to be critical for neuronal function. Until the current study, no other functional gene other than FMR1 had been shown to be inactivated in the disorder.
However, Wahlestedt knew the FMR1 gene locus-a specific point on a chromosome-was not well mapped. Wahlestedt and his colleagues hypothesized that unknown regulatory genes might be transcribed from the region.
The new study shows at least one other functional gene-FMR4-from this genetic region is linked to fragile X syndrome, although the gene's exact role in the intact brain remains uncharacterized..
"FMR4 is the new neighbor on the block and should not be ignored," Wahlestedt said. "While there is no direct relationship between these two genes [FMR1 and FMR4] that we know of, our study shows that FMR4 is not a conventional gene-it's a non-coding RNA transcript. It's not a dead piece of the genome, it has a pronounced functional effect in human cultured cells.."
The Role of Non-coding RNA
Non-coding RNA (ncRNA) transcripts or genes produce functional RNA molecules (ncRNAs) rather than encoding proteins. These ncRNAs are active in a number of different processes, including RNA modification, chromosome replication, and protein degradation.
A number of studies have suggested that at least 40 to 50 percent of the mammalian genome becomes transcribed, Wahlestedt pointed out, but only one to two percent of these transcripts are translated into proteins. "Several studies suggest that some ncRNA genes can be involved in various human diseases," he said. "FMR4 certainly falls into that category."
According to the study, FMR4 directly affects human cell proliferation in vitro-when the gene is silenced, changes in the cell cycle and a rise in apoptosis or programmed cell death occur. Overexpression, on the other hand, leads to increased cell proliferation.
The full meaning of this anti-apoptosis function is still unclear. "It could be critical for some cells to live or die at a certain stage in development, but we don't know what cells those might be," Wahlestedt added. "The fact that FMR4 is widely expressed in the human brain in both embryos and adults may possibly indicate a broad function."
The new study underscores the growing awareness among scientists of the complexity and unpredictability of the human genome.
"We know now that our genome is very busy and very complicated," Wahlestedt said "A great deal of this newly found complexity is about the regulation of other genes. As evolution has progressed, particularly in the higher organisms, there has been a corresponding increase in the need for regulatory mechanisms-to maintain more control over genome. Non-coding RNAs are at the center of these regulatory mechanisms."
The FMR4 discovery also highlights the mission of The Translational Research Institute at Scripps Florida, which is focused on translating basic research like the discovery of FMR4 into potential new therapeutics. The Translational Research Institute has a structure similar to a drug discovery company, and many of the researchers have pharmaceutical experience.
In addition to Wahlestedt, other authors of the study include Ahmad M. Khalil, Mohammad Ali Faghihi, Farzaneh Modarresi, and Shaun P. Brothers of The Scripps Research Institute in Jupiter, Florida.
The study, A Novel RNA Transcript with Antiapoptotic Function is Silenced in Fragile X Syndrome, was supported by Conquer Fragile X Foundation (now part of National Fragile X Foundation) and The Scripps Research Institute Florida. Upon publication, the study will be available at http://www.plosone.org/doi/pone.0001486.
About The Scripps Research Institute
The Scripps Research Institute is one of the world's largest independent, non-profit biomedical research organizations, at the forefront of basic biomedical science that seeks to comprehend the most fundamental processes of life. Scripps Research is internationally recognized for its discoveries in immunology, molecular and cellular biology, chemistry, neurosciences, autoimmune, cardiovascular, and infectious diseases, and synthetic vaccine development. Established in its current configuration in 1961, it employs approximately 3,000 scientists, postdoctoral fellows, scientific and other technicians, doctoral degree graduate students, and administrative and technical support personnel. Scripps Research is headquartered in La Jolla, California. It also includes Scripps Florida, whose researchers focus on basic biomedical science, drug discovery, and technology development. Currently operating from temporary facilities in Jupiter, Scripps Florida will move to its permanent campus in 2009.
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