Project Summary

Sherman Weissman, M.D. (Distinguished Investigator 2004) of Yale University, will apply an emerging technology called Genomic Tiling Microarrays (GTMs) to research 22q11 deletion syndrome (22q11DS)-associated schizophrenia. Approximately 25 – 30% of patients with this syndrome (also known as velo-cardio-facial syndrome or DiGeorge syndrome) also develop schizophrenia. Therefore, detailed analysis of this region is likely to reveal important clues about genetic mechanisms underlying schizophrenia. Using the new GTMs will improve over the current technology (Fluorescent In Situ Hybridization or FISH) at least 100-fold in the detection of microdeletions on 22q11. Using GTMs will permit several lines of investigation not previously possible, including: precise mapping of deletion breakpoints and possible duplications using high resolution genomic hybridizations; screening for small deletions in the indicated areas; chromosome-wide high resolution determination of DNA methylation patterns; and precise mapping of protein-DNA interactions within 22q11 and 22q11-encoded factors elsewhere on the chromosome. Dr. Weissman believes this project may provide insights into the genetics and epigenetics of schizophrenia at multiple levels of analysis, and may lead to new methods for clinically applicable large-scale/low cost screening of psychotic populations for 22q11 abnormalities (undetectable by current methods). Diagnosis of such abnormalities early in the course of the illness (or even before onset in high-risk children and adolescents) would improve both medical and behavioral healthcare of patients with, or at-risk for, schizophrenia.

Program Area: SCHIZOPHRENIA/PSYCHOTIC DISORDERS\Schizophrenia

Search Again