GENOTYPE-PHENOTYPE CORRELATIONS IN WILLIAMS-BEUREN SYNDROME INDIVIDUALS THROUGH THE ANALYSIS OF GLOBAL GENE EXPRESSION CHANGES BY MICROARRAY TOOLS

Williams-Beuren Syndrome (WBS) is a rare, non-hereditary developmental disorder. The patients have mental retardation and numerous physical abnormalities as, for example, short stature, heart, dental and kidney abnormalities. The affected individuals show a peculiar cognitive profile characterized by good verbal abilities but very deficient visual-spatial faculties. Interesting features observed in WBS individuals include musical creativity and high sociability. The molecular basis of the disorder is defined by the deletion of a large DNA segment in chromosome 7 (microdeletion) that involves at least 25 genes. To date a genotype-phenotype correlation has only been established between the elastin gene (ELN) and the cardiovascular problems seen in WBS patients. As a consequence, it is a great challenge to understand the role and contribution of each gene to the disease. In this study, we propose to monitor the changes in global gene expression caused by the WBS microdeletion by using powerful and sensitive methods such as the microarray and Quantitative PCR (qPCR) analysis. These two methods allow to accurately calculate the expression level of each single gene in the study population. The identification of global gene expression changes will contribute to our understanding of the WBS pathology by A. helping to assess the contribution of specific genes to WBS traits and phenotypes B. Identifying genes or pathways dysregulated in this disorder that might relate to the specific phenotypes, and thus provide novel therapeutic targets for treating this disorder.