Project Summary

Maja Bucan, Ph.D. (Distinguished Investigator 2006) of the University of Pennsylvania, notes that there is a tremendous need for novel integrated analysis that will extend the interpretation and utility of genomic data to the biology of psychiatric disorders. She notes that while the Human Genome Project provided the sequence of the human genome and the genomes of several important model organisms, comparison of genome sequence between different organisms revealed striking conservation of sequence in parts of the genome that do not encode proteins. Since current evidence suggests that these elements may be critical for our understanding of the genetic basis of mental illness, Dr. Bucan will gather genomics information on all genes in schizophrenia candidate regions and, using state-of-the-art computational tools, will select and characterize these highly conserved nonprotein coding sequences. Specifically, she will perform bioinformatics analysis of hundreds of genes in seven schizophrenia candidate regions (6p24-22, 1q21-22, 1q42, 13q32-34, 8p21-22, 6q16-25, 22q11-12), and will undertake large-scale comparative analysis of genomic sequence for 5-7 positional candidate genes (DTNBP1, NRG1, DISC1, DAO, DAOA, RGS4) and a set of ~ 50 synaptic genes that map to confirmed schizophrenia candidate regions. Ultimately, this project may help elucidate the regulatory mechanisms that underlie the function and plasticity of the neuronal synapse, which are a fundamental biological problem and a key to understanding the basis of neurodevelopmental, neurological, and psychiatric disorders.

Program Area: SCHIZOPHRENIA/PSYCHOTIC DISORDERS\Schizophrenia

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