Rutgers University School of Arts and Sciences Division of Life Sciences
 

Schizophrenia

Molecular Genetics of Schizophrenia Susceptibility

In collaboration with Dr. Anne Bassett, at the University of Toronto, we have conducted multiple studies on a sample of moderately large, extended families from eastern Canada.  We initially identified a strong linkage peak on chromosome 1q21-22 in these families (Brzustowicz et al, Science, 2000), subsequently narrowing the linkage peak and identifying significant evidence of linkage disequilibrium to markers within the gene NOS1AP (Brzustowicz et al, American Journal of Human Genetics, 2004). We have also demonstrated altered expression of NOS1AP in post mortem brain samples of individuals with schizophrenia and bipolar disorder (Xu et al, PLoS Medicine, 2005) and have identified a specific functional polymorphism within NOS1AP that can alter gene expression (Wratten et al, American Journal of Psychiatry, 2009).  Further work on the genetics of NOS1AP and interacting genes is ongoing.

 

Schizophrenia Risk in 22q Deletion Syndrome

22q Deletion Syndrome (22qDS; also known as velocardiofacial syndrome) is a deletion syndrome of chromosome 22q11.2 characterized by cleft palate, cardiac anomalies, mild dysmorphic features, hypernasal speech, and learning disabilities. The extent of the deletion is somewhat variable, with most individuals deleted for a common 3 Mb region. The commonly deleted region includes the gene DGCR8, important in the biogenesis of microRNAs.  Approximately 25% of adults with 22qDS have schizophrenia. In collaboration with Dr. Anne Bassett, at the University of Toronto, we are analyzing DNA from individuals with 22qDS with and without schizophrenia to determine changes that increase risk of psychotic illness.  We are exploring how alterations in the microRNA system interact with other genetic polymorphisms to increase risk of schizophrenia in individuals with 22qDS.