This second year of funding expands Dr. Bochukova's work to understand how genetic variants outside the PWS region influence the frequency and severity of symptoms associated with PWS.
Dr. Theresa Strong, Director of Research Programs, shares details on this project in this short video clip.
Prader-Willi syndrome is a complex genetic disease associated with the loss or lack of expression of multiple genes (some present in multiple copies) in the Prader-Willi critical region on chromosome 15q11-13. Despite all (or nearly all) PWS patients having lost the same genes, the characteristics of the disease are highly variable from patient to patient. To a great extent, this variability it is due to variation in genes outside of the PWS critical region which make up more than 99.9% of the genome. In order to understand these genetic contributions to the severity and complexity of the disease, it was critical to first assemble a large population of PWS patients and for each to extensively measure and assess the clinical features of the disease and to generate extensive genetic data. We have assembled a population of nearly 160 PWS patients, and for each accurately measured 39 biochemical, metabolic, behavioral, physical characteristics and also identified their genetic makeup at more than 4 million positions across all their chromosomes. The research proposed here involves conducting some very complicated genetic analysis in which we will evaluate how variation at each of these >4 million chromosomal positions is related to variation in the measured biochemical, metabolic, behavioral and physical characteristics of these patients. We will extend this analysis to additional 50 patients from the PWS Registry and the PWS Genome Pilot Project, which will increase the power to detect strong genetic signals, and potentially refine the regions of interest. The goals of this analysis include: increasing understanding of genetic contributions to the severity and complexity of PWS from genes outside the Prader-Willi critical region but, importantly, the potential to identify new targets for therapeutic intervention in PWS.