To discover potential connections among genes mutated in schizophrenia, Dr. Vitkup and colleagues developed a computational approach, called NETBAG+, to identify networks of genes likely to be responsible for the same genetic phenotype. They then gathered the strongest mutations that had been observed in schizophrenia by other researchersincluding a set of de novo mutations recently described by a team of Columbia researchers led by Maria Karayiorgou, MD, and Joseph A. Gogos, MD, PhDand fed them into the program.
The program uncovered two genetic networks. Genes in the first network are involved primarily in axon guidance, synapse function, and cell migration. Genes in the second network are involved in chromosomal organization and remodeling.
Parts of both networks are highly active during prenatal development, suggesting that changes in the brain that cause schizophrenia later in life are laid down very early in life.
Connection to autism
Dr. Vitkup also compared his schizophrenia networks with networks found in neurodevelopmental disorders such as autism. One schizophrenia network is strongly related to an autism network he described in a study published last year. Both networks contain genes involved in axon guidance, synapse function, and cell migration.
"Our recent mutational analysis showed that this overlap includes primarily genes that are important for early fetal development. This is not surprising, because some cases of schizophrenia and likely many cases of autism have neurodevelopmental origin," said Dr. Karayiorgou.
The close relationship between genetic networks involved in autism and schizophrenia raises an intriguing question: How can mutations in the same or related genes cause two different disorders?
"I like to use the analogy of car brakes," said Dr. Vitkup. "Different mechanical malfunctions of the brake mechanism can have very d
|Contact: Karin Eskenazi|
Columbia University Medical Center