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Archive - Aug 25, 2013


Discovery of New Brain Circuit May Aid Treatment of “Lazy Eye”

A study in mice reveals an elegant circuit within the developing visual system that helps dictate how the eyes connect to the brain. The research, funded by the National Institutes of Health, has implications for treating amblyopia (also known as “lazy eye”), a vision disorder that occurs when the brain ignores one eye in favor of the other. Amblyopia is the most common cause of visual impairment in childhood, and can occur whenever there is a misalignment between what the two eyes see—for example, if one eye is clouded by a cataract or if the eyes are positioned at different angles. The brain at first has a slight preference for the more functional eye, and over time—as that eye continues to send the brain useful information—the brain's preference for that eye gets stronger at the expense of the other eye. Patching the strong eye can help correct amblyopia. But if the condition isn't caught and corrected during childhood, visual impairment in the weaker eye is likely to persist into adulthood. "Our study identifies a mechanism for visual development in the young brain and shows that it's possible to turn on the same mechanism in the adult brain, thus offering hope for treating older children and adults with amblyopia," said Joshua Trachtenberg, Ph.D., an associate professor of neurobiology at the David Geffen School of Medicine, University of California, Los Angeles (UCLA). The study was published online on August 25, 2013 in Nature. Within the brain, cells in a limited region called the binocular zone can receive input from both eyes. During brain development, the eyes compete to connect within this zone, and sometimes one eye prevails—a process known as ocular dominance. Ocular dominance is a normal process and is an example of the brain's ability to adapt based on experience—called plasticity. But it can also set the stage for amblyopia.

New Software Tool Enhances Search for Genetic Mutations

Concealed within the vastness of the human genome, (comprised of some 3 billion base pairs), mutations are commonplace. While the majority of these appear to have a neutral effect on human health, many others are associated with diseases and disease susceptibility. Dr. Reed Cartwright, a researcher at Arizona State University's Biodesign Institute, along with colleagues at ASU, Washington University, and the Wellcome Trust Sanger Institute, Cambridge, UK, report on a new software tool known as DeNovoGear, which uses statistical probabilities to help identify mutations and more accurately pinpoint their source and their possible significance for health. Improvements in the accuracy of mutation identification and validation could have a profound impact on the diagnosis and treatment of mutation-related diseases. "These techniques are being considered in two different realms," Dr. Cartwright says. "The first is for pediatric diseases." Here, a child with an unusual genetic disease may undergo genomic sequencing to see if the mutations observed have been acquired from the parents or are instead, unique to the child. "We can identify these mutations and try to detect which gene may be broken," he says. The second application is for cancer research, where tumor tissues are genetically compared with normal tissue. Many now believe that the identification of a specific cancer mutation may eventually permit clinicians to customize a treatment for that tissue type. "We are developing methods to allow researchers to make those types of analyses, using advanced, probabilistic methods," Dr. Cartwright says. "We actually model the whole process." Indeed, the method described provides the first model-based approach for ferreting out certain types of mutations. The group's research results were published online on August 25, 2013 in Nature Methods.

New Genetic Clues Implicate Two Different Pathways in Origin of Schizophrenia

A new genome-wide association study (GWAS) estimates the number of different places in the human genome that are involved in schizophrenia. In particular, the study identifies 22 locations, including 13 that are newly discovered, that are believed to play a role in causing schizophrenia. "If finding the causes of schizophrenia is like solving a jigsaw puzzle, then these new results give us the corners and some of the pieces on the edges," said study lead author Patrick F. Sullivan, M.D. "We've debated this for a century, and we are now zeroing in on answers. This study gives us the clearest picture to date of two different pathways that might be going wrong in people with schizophrenia. Now we need to concentrate our research very urgently on these two pathways in our quest to understand what causes this disabling mental illness." Dr. Sullivan is a professor in the departments of Genetics and Psychiatry and director of the Center for Psychiatric Genomics at the University of North Carolina School of Medicine. The new study was published online on August 25, 2013 in Nature Genetics. The results are based on a multi-stage analysis that began with a Swedish national sample of 5,001 schizophrenia cases and 6,243 controls, followed by a meta analysis of previous GWAS studies, and finally by replication of single nucleotide polymorphisms (SNPs) in 168 genomic regions in independent samples. The total number of people in the study was more than 59,000. One of the two pathways identified by the study, Dr. Sullivan said, is a calcium channel pathway. This pathway includes the genes CACNA1C and CACNB2, whose proteins touch each other as part of an important process in nerve cells. The other pathway is the "micro-RNA 137" pathway.