SPRING GREETINGS FOR WED 4/26/00:

City College of CUNY
Department of Chemistry
Biochemistry Seminar
Wednesday, April 26, 2000
Room J1027 at 11:15 AM
Cassandra Smith
Professor of Biology and Biomedical Engineering
Boston University

Specificity Genomes, Twins, and Schizophrenia: New Insights
The genomic DNA blueprin= t directs human development and is passed from parent to child mostly unchanged. This is apparent from the large number of observed characteristics that are conserved in different generations within the same family and especially between twins. However, a low level of DNA instability in the germ-line cells, eggs and sperm, is required for evolution. Meanwhile changes to DNA in somatic cells that make up rest of the body is not under the same constraints. Somatic cell DNA is disposed of after each generation. Thus, it is important to realized that the function of the heritable and disposable genomes is different and that the number and types of changes that occur to these genomes can be quite different. For instance, irreversible changes to the disposable genomes may be a normal part of development and aging. Changes to both genomes have the potential to influence phenotype. The challenge is to identify DNA changes and relate them to phenotypic characteristics. Twins studies form the basis of our studies on genomic stability in the heritable a disposable genomes during normal development, aging, and disease. This approach is especially useful for understanding complex phenotypes such as behavioral and cognitive behaviors. Targeted genomic differential display (TGDD) was developed to allow us to compare selected regions of the human genomes in closely matched samples, like DNA from monozygotic twins or cells from the same individual. This method allows us to quantitate and isolate DNA differences in pairs of samples. TGDD compares the composition of genomic restriction fragments pools containing a selected interspersed repeated sequence. The target sequence can be a simple repeated sequence like (CAG)n characteristic of gene sequences expressed in the nervous system and associated with an increasing number of neurodegenerative diseases, or a consensus s sequence defining a complex repeating sequence element, e. g. Al u or defining a protein motif or cis-acting regulatory element. Monozygotic twins begin live s with identical genomes that diverge during development and aging.   Our results show that genome similarity in true monozygotic twins may not be as great as believe. Hence, somatic and/or epigenetic DNA changes may account for discordant phenotypes in MZ twins far beyond what was previously believed. Such changes may also account for age dependent phenotypes. The application of TDGG to twins affected by Schizophrenia and presented to us as monozygotic revealed that misclassification and misunderstanding of genomic stability calls into question the results and conclusions of many studies on twins.