

The team, the product of an ongoing collaboration between Professors W. Richard McCombie of Cold Spring Harbor Laboratory (CSHL) and Aiden Corvin of Trinity College, Dublin, studied a type of gene aberration called de novo mutation, in a sample of 42 “trio” families in which the child, but neither parent, was diagnosed with schizophrenia and/or psychosis and 15 trio families with a history of psychosis.




This makes the discovery particularly interesting, because “there’s a growing awareness of the importance of epigenetic regulation during brain development, as well as in cognition in the mature brain,” McCarthy points out. It is possible, the team speculates, that the genes found to affect the same biological function in multiple disorders are examples of those upon which normal brain development depends.

“Research made possible by the CSHL-Trinity College collaboration is leading us toward a much better understanding of how complex sets of genes are involved in complex illnesses,” says McCombie, who is director of the Stanley Institute for Cognitive Genomics at CSHL. “Our work and that of other researchers, when taken together, is beginning to clarify our view of causation in these very complex, but also very common illnesses.”

The Stanley Institute is dedicated to discovering the genetic causes of bipolar disorder, schizophrenia, depression and other cognitive disorders. The Institute’s collaboration with Trinity College Dublin has the broader goal of integrating genetics, neurobiology and clinical application in order to impact current and future treatment of mental illness.

Professor McCombie notes that many genes can contribute to complex disorders such as schizophrenia. The challenge for scientists, he explains, is that “the number of differences between even healthy individuals is so great that finding which specific variant might contribute to a specific disorder such as schizophrenia from among those that don’t cause problems, is difficult.”

The team’s newly published study narrows down the search to a portion of the human genome called the exome. This is the small fraction—some 3%-4% of the total human genome sequence—that contains protein-encoding genes. This strategy is especially useful in comparing children with their parents, because children have very few genetic variants—de novo mutations, by definition -- that are not in one or the other parent. “Finding de novo variants in a child compared to their parents is technically relatively simple,” says McCombie, and presents scientists with a particularly strong “signal” of potentially significant genetic variation in children who have an illness like schizophrenia that is not evident in either parent.


Source: Cold Spring Harbor Laboratory