A NETWORK ANALYSIS STRATEGY TO IDENTIFY GENES IMPLICATED IN NOONAN AND LEOPARD SYNDROMES

Noonan syndrome is a relatively common congenital genetic condition affecting approximately 1/1000 newborn children worldwide. The principal clinical features include congenital heart malformation, short stature and learning problems. The principal genetic defect responsible for more than 50% of the cases has been identified in the product of a gene, known as PTPN11, that encodes a protein (SHP-2) whose function is that of removing phosphate groups from proteins. Why a defect in such a function results in severe developmental problems is not fully understood because the details of the molecular processes that amplify this defect are not known. In our project we propose to apply a strategy to integrate experimental results with computer analysis to produce a list of genes whose function is likely to modify the expression of PTPN11, the disease gene. The success of this approach might open new therapeutic avenues by offering to the pharmacologist new candidate drug targets whose inhibition or stimulation may control the disease phenotype.