Dr. Vitkup looked at large mutations called copy number variants (CNVs) that can lead to either schizophrenia or autism. CNVs involve long stretches of the genome containing several genes that have been either duplicated or deleted. Duplication of a region increases the "dosage" of its genes; deletion of a region decreases the dosage.
In CNVs involved in the growth of dendrites, or dendritic spines, at the ends of neurons, he found decrease in growth to be more common in schizophrenia and increase in growth more common in autism. "That's consistent with what's been found by postmortem brain studies," he said.
"Evidence of functional convergence among risk genes is consistent with the notion that schizophrenia and autism are both primarily diseases of neuronal communication. However, they have distinct clinical features and the challenge remains to identify the critical neural circuits and mechanisms that differentiate them," said Dr. Joseph A. Gogos. "This is a step in that direction."
Dr. Vitkup predicts that many more genes involved in schizophrenia and autism will eventually be foundpossibly up to 1000 genes for each disorderbut a significant fraction of them will likely fall into the networks and pathways identified in the current study.
"Until a few years ago, people were looking for just a handful of genes responsible for autism and schizophrenia, so the idea that many hundreds of genes are involved is a big change in thinking," Dr. Vitkup said. "Our study and the studies of our collaborators suggest that in the search for the causes of complex genetic disorders, it will be more productive to look for common pathways and gene circuits than for a handful of causal genes. This type of network analysis gives us a way to begin to make sense of what's happening."
Study points way to future approaches to gene discovery
|Contact: Karin Eskenazi|
Columbia University Medical Center