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Exome Sequencing Highlights Chromatin Remodeling in Schizophrenia

May 20, 2014. A new study published online April 29 in Molecular Psychiatry, led by Dick McCombie of Cold Spring Harbor Laboratory, New York, and Aiden Corvin of Trinity College Dublin, Ireland, highlights a role in causing schizophrenia for molecules that oversee how proteins are made.

Normally, special molecular machinery attaches itself to the DNA instructions of a gene and churns out a new protein. This process is complicated by the fact that the very long DNA molecules of our genome are tightly wrapped around spool-like proteins, so that the genome is compact enough to fit inside a cell’s nucleus. When it’s time to make a protein, the DNA must be loosened from the spool so that it may be “read” by the protein-making machines.

The new study suggests there may be problems with this loosening process in schizophrenia. Scanning the genes of 57 people with schizophrenia, the researchers found mutations in three genes that have a role in making DNA available to the protein-making machines. Called “chromatin modifiers,” some of these genes have also been implicated in autism and intellectual disability, which suggests some genetic overlap between these disorders. Together, the results suggest that, in some cases of schizophrenia, there are problems with the process of making proteins from genes. (For more details, see the related news story.)—Michele Solis.

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