Project Summary

Rosanna Weksberg, M.D., Ph.D., FRCP(C), FCCMG (Distinguished Investigator 2005) of University of Toronto, will study individuals with the 22q11 deletion syndrome (22qDS) phenotype, as individuals born with deletions of chromosome region 22q11 have, in addition to multiple congenital malformations, a 25% risk of developing schizophrenia (SZ). Dr. Weksberg hypothesizes that the genomic determinants associated with this syndrome could include a variety of mechanisms associated with the unusual genomic architecture of this region. She notes that 22q11 deletions may be associated with as yet unidentified duplications or loss of heterozygosity, and further states that in relation to haploinsufficiency, functional polymorphic variation affecting copy number and gene expression in this region may be critical in determining the phenotype of 22qDS individuals, and could account for significant variation in phenotype, such as whether SZ is or is not clinically expressed. Using descriptions of a cohort of individuals with the 22qDS phenotype that she has obtained over the last 10 years, in conjunction with a multidisciplinary group, Dr. Weksberg hopes to define genomic parameters for each patient in the study, and to analyze differences among patients with the 22qDS phenotype with and without SZ using various methodologies. This award will allow Dr. Weksberg to analyze, from a genomic point of view, a well-characterized population subtype at high risk of developing SZ. She hopes to identify genomic or transcriptional alterations associated with the development of SZ in this population. Screening for such alterations could also represent the basis for susceptibility to SZ in the general population. Testing for such alterations in the general population could facilitate risk assessment for SZ and allow early identification and treatment of individuals at high risk of developing this illness.

Program Area: SCHIZOPHRENIA/PSYCHOTIC DISORDERS\Schizophrenia

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