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Widening the Genetic Net to RNA Snags Schizophrenia Risk Gene Candidates

11 May 2016

News Story: 

May 12, 2016. A new study in Nature Medicine published May 9 has identified likely risk genes for schizophrenia on chromosome 10. Led by Daniel Weinberger of the Lieber Institute for Brain Development in Baltimore, Maryland, the study examined brain RNA transcripts—the intermediate step of producing proteins from gene blueprints—to locate the genes, one called BORCS7, and a never-before-detected form of the AS3MT gene.

The researchers' approach picks up where strictly genetic studies have left off. For example, comparing DNA between those with schizophrenia and controls have pinpointed regions on chromosomes that harbor genetic variants associated with schizophrenia, but stop short of identifying the operative genes. That's because a genetic variant associated with schizophrenia does not usually occur in a single gene, but rather stands in the expanses between genes.

One notable example has been a region in chromosome 10: A genetic signal in the region has been found for schizophrenia, but it casts suspicion on 10 to 20 nearby genes.

To decipher the true culprits, the new study turned to the brain to see whether changes in how much a gene was turned on or off changed with a genetic variant. Using RNA sequencing technology, the researchers found that only two genes varied with the genetic signal found in previous studies, both increasing their production of RNA. This suggests that higher-than-normal generation of RNA and, subsequently, protein from BORCS7 and the new form of AS3MT gene somehow predispose the brain to schizophrenia. (For more details, see the related news story.)—Michele Solis.