Diane Dickel

Joined Program: 2005
Previous Degree: B.A. Biological Sciences, University of Chicago
King Lab
dedickel [ a t ] u.washington.edu

Research:
Schizophrenia is a common psychiatric disorder, many cases of which are likely caused by rare, highly penetrant mutations. Repeat expansions are of special interest to schizophrenia considering the disorder’s neurological phenotype, paternal age bias, and possible evidence for anticipation. The purpose of this project is to identify pathogenic repeat expansions that contribute to the etiology of schizophrenia. We have undertaken a bioinformatics search using the UCSC Genome Browser and identified 327 tri-, tetra-, or pentanucleotide repeats that are in transcribed regions of the genome and are likely to be polymorphic. These repeats are being genotyped in a case population to identify loci that have an excess of homozygosity, which may result from the presence of expanded alleles that do not amplify well with PCR. The subject population currently includes 133 unrelated individuals diagnosed with schizophrenia or a closely related spectrum disorder, and more subjects are likely to become available during the course of this project. Using this PCR-based screen, we have found an excess of homozygosity at several of the repeat loci. These loci will be further examined using Southern blots and appropriate cell line experiments to determine if any repeat expansions exist and, if so, what their biological significance is to schizophrenia. Genes containing pathogenic repeats can then be sequenced in all affected individuals to identify other mutations that contribute to the disorder.