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http://www.cdc.gov/

New microRNA mechanism for regulating brain function

Non-coding regions of the genome - those that don't code for proteins - are now known to include important elements that regulate gene activity. Among those elements are microRNAs, tiny, recently discovered RNA molecules that suppress gene expression.

Increasing evidence indicates a role for microRNAs in the developing nervous system, and researchers from Children's Hospital Boston now demonstrate that one microRNA affects the development of synapses - the points of communication between brain cells that underlie learning and memory. The findings appear in the January 19th issue of Nature.

"This paper provides the first evidence that microRNAs have a role at the synapse, allowing for a new level of regulation of gene expression," says senior author Michael Greenberg, PhD, Director of Neuroscience at Children's Hospital Boston. "What we've found is a new mechanism for regulating brain function."
The brain's ability to form and refine synapses allows organisms to learn and respond to their environment, strengthening important synaptic connections, forming new ones, and allowing unimportant ones to weaken. Experiments in Greenberg's lab, done in rats, showed that a microRNA called miR-134 regulates the size of dendritic spines, the protrusions from a neuron's dendrites where synapses form. When neurons were exposed to miR-134, spine volume significantly decreased, weakening the synapse. When miR-134 was inhibited, spines increased in size, strengthening the synapse.
Further experiments showed that miR-134 acts by inhibiting expression of a gene called Limk1, which causes dendritic spines to grow. When neurons were exposed to a growth factor known as brain-derived neurotrophic factor (BDNF), this inhibition was overcome and Limk1 became active again, enhancing spine growth.

Greenberg believes that miR-134 - and other microRNAs his lab is studying - may play a role in fine-tuning cognitive function by selectively controlling synapse development in response to environmental stimuli. "A single neuron can form a thousand synapses," says Greenberg, also a professor of neurology and neuroscience at Harvard Medical School. "If you could selectively control what's happening at one synapse without affecting another, you greatly increase the information storage and computational capacity of the brain."
Greenberg also speculates that miR-134 may be relevant to disorders such as mental retardation and autism. He notes that loss of Limk1 due to a chromosomal deletion is associated with Williams syndrome, and that the BDNF pathway that activates Limk1 includes proteins that are disabled in tuberous sclerosis and Fragile X syndrome. All three genetic disorders can cause cognitive impairment and autistic-like behaviors.

http://www.childrenshospital.org

Utah researchers confirm chromosome may harbor autism gene

Data strikingly similar to Finnish studies

Using technology that allows DNA from thousands of genes to be collected and surveyed on a 3 x 1½-inch chip, University of Utah medical researchers have confirmed that a region on a single chromosome probably harbors a gene that causes autism. The researchers at the U School of Medicine made the finding by tracing variations in the DNA of an extended Utah family that has a high occurrence of the disorder and whose members are descended from one couple.

As part of the study, the researchers also ruled out one gene that appeared to be a good candidate for being linked to autism. They're now looking at other genes for a connection to the disorder.
Published in Human Heredity online, the study is part of the Utah Autism Research Project. The researchers are interested in finding more families with a history of autism to join the study.
The just-published research confirms Finnish studies of families that linked autism to the same region on chromosome 3, according to principal author Hilary Coon, Ph.D., research associate professor of psychiatry. In fact, the results of the U of U research were surprisingly similar to the Finnish studies, Coon said.
"It was remarkable to confirm the Finnish studies," she said. "Our results were so close to their evidence, we thought it was important."

Autism is a behavioral disorder that strikes before age 3 and is characterized by impaired ability in social interactions and communication. Those with autism also display repetitive behaviors and interests.
The study involved 31 members of a family of Northern European ancestry, seven of whom have autism or an autism-related disorder. The family members are part of the Utah Population Database, a computerized set of the genealogies of 170,000 Utah families comprising 1.6 million people. Information on some families goes back to the state's pioneer founders.

The researchers used a gene chip similar to a microarray to search for genetic markers of autism.
They used a coated glass chip from Affymetrix, Inc. This chip has 10,000 short segments of DNA with known gene sequence variations, called single nucleotide polymorphisms (SNPs), attached to 3/8 by 3/8-inch area. The DNA strands of the family members were broken up and then bonded to the DNA on the chip, allowing researchers to compare the variations in the SNPs of the different DNA on an extremely fine scale.
The chance of the same variants of SNPs in a particular region on a chromosome being passed through several generations from a founding couple to multiple affected family members is slight. When such identical blocks of SNPs are found, the chromosomal region often is a good candidate for being linked to a disease.
Other studies, including the Finnish ones, have found a high degree of evidence linking chromosome 3 to autism, so Coon and the other U researchers began their search on that chromosome. The first region of the chromosome they looked at contained 106 SNPs, 70 of which strongly indicated a gene in that region being linked to autism.

One gene, FXR1, appeared to be a likely candidate for a link to autism. FXR1 is similar to the X-chromosome Fragile X gene, FMR1. Mutations in FMR1 cause Fragile X Syndrome, an inherited condition that can cause mental impairments ranging from learning disabilities to severe cognitive problems. Fragile X syndrome has been shown to overlap with autism, and because FXR1 is similar to the gene that causes the syndrome, U researchers suspected FXR1 might be linked to autism. But after analyzing the entire coding sequence of FXR1, the researchers found no alterations in the gene likely to contribute to autism.
Based on statistical evidence, they're now looking at other genes. But evidence that a gene on a particular region of chromosome 3 is linked to the disorder doesn't preclude other genes from being a cause of autism, according to Coon. All in all, the researchers have a daunting search ahead of them.
"We're just looking for the needle in the haystack," Coon said.

Along with the original family, the U researchers are studying two more families with autism in some members, and they'd like to find others in which the disorder occurs. Large and small families with individual or multiple cases of autism are welcome to join. Those interested can call (801) 585-9098.
Other authors of the study are: Nori Matsunami, Jeff Stevens, Judith S. Miller, Ph.D, assistant professor of psychiatry, and Carmen Pingree, all with the Neurodevelopmental Genetics Project in the Department of Psychiatry; Nicola J. Camp, Ph.D., assistant professor of medical informatics; Alun Thomas, Ph.D., professor of medical informatics; Janet E. Lainhart, M.D., associate professor of psychiatry; Mark F. Leppert, professor and chair of Human Genetics; and William M. McMahon, M.D., professor of psychiatry and principal investigator of the Utah Autism Research Project.

Genetic Testing

Approximately 600 genetic tests are currently available for clinical testing and most are used for diagnosis of rare single-gene disorders or chromosome abnormalities, with a few being used for newborn screening. However, a growing number of genetic tests may have population-based applications, which includes determining the risk of developing a disease or condition in the future (e.g., predictive testing for breast cancer or cardiovascular disease), and recognizing genetic variations that can influence response to medicines (pharmacogenomics).

Genomics - Description

The goal of Genomics is to promote the understanding of the structure, function, and evolution of genomes in all kingdoms of life and the application of genome sciences and technologies to challenging problems in biology and medicine. The scope of the journal is broad and we welcome original, full-length, and timely papers in all of the following areas:
• Comparative genomics analysis that yields valuable insights into conserved and divergent aspects of function, regulation, and evolution • Bioinformatics and computational biology with particular emphasis on data mining and improvements in data annotation and integration
• Functional genomics approaches involving the use of large-scale and/or high-throughput methods to understand genome-scale function and regulation of transcriptomes and proteomes
• Identification of genes involved in disease and complex traits, including responses to drugs and other xenobiotics
• Significant advances in genetic and genomics technologies and their applications, including chemical genomics

What is Genomics?

The study of genes and their function. Recent advances in genomics are bringing about a revolution in our understanding of the molecular mechanisms of disease, including the complex interplay of genetic and environmental factors. Genomics is also stimulating the discovery of breakthrough healthcare products by revealing thousands of new biological targets for the development of drugs, and by giving scientists innovative ways to design new drugs, vaccines and DNA diagnostics.

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