Prader-Willi syndrome (PWS) is a complex genetic condition due to imprinting or the differential expression of genetic information depending on the parent of origin. The majority of subjects with PWS have a deletion of chromosome 15q11-q13 region received from the father while others have maternal disomy 15 (both 15s from the mother) or a mutation or defect of the imprinting center controlling the activity or expression of the genes in the region. Genes in the 15q11-q13 region are implicated in metabolism, energy expenditure and behavior including obsessive uncontrolled eating. Obesity resulting from overeating is the leading cause of death in PWS. Recently studies have shown differences in plasma ghrelin (and peptide YY) levels in PWS subjects compared with obese controls. Ghrelin and peptide YY are produced by the gastrointestinal system and involved with controlling appetite. These findings suggest that obesity in PWS may have a different underlying mechanism than simple obesity. In order to develop an effective treatment to control appetite and eating behavior in individuals with PWS, a clearer understanding of the abnormal pathways and genetic regulation is needed. Appetite is controlled by several interconnected pathways in a highly specialized center in the brain influenced by neuropeptides made in the gastrointestinal system under genetic control. A thorough genetic study for the cause of the obsessive eating behavior in PWS is lacking. In this study, we will investigate abnormalities in the appetite-regulating pathways in PWS by evaluating plasma levels of proteins and expression activity of genes involved in controlling appetite and behavior. We will measure the activity of selected genes involved with eating behavior and a genome wide search of genes simultaneously with microarray technology at the blood and brain levels to yield valuable information for a better understanding of the causes of uncontrolled eating and obesity in PWS.