Differences in PWS symptoms across individuals may be due to variation in genes outside of the PWS critical region. To understand how genetic variants contribute to the severity and complexity of the disease, Dr. Bochukova will analyze variations in the genetic makeup of 160 PWS participants. With support from Soleno Therapeutics, biochemical, metabolic, behavioral and physical characteristics of participants have been assessed, and DNA variants have been determined. The goal of this analysis is to examine the association of DNA variants with these parameters, to potentially identify DNA variants that influence symptom severity.
This project has been made possible in part by the generous support of FPWR-UK.
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 more than 100 biochemical, metabolic, behavioral, physical characteristics and also identified their genetic makeup at more than 4 million positions across all their chromosomes. This funded research involves conducting some very complicated 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. The goals of this analysis include: to deepen our understanding of genetic contributions to the severity and complexity of PWS from genes outside the Prader-Willi critical region. This analysis has the potential to identify new targets for therapeutic intervention in PWS and potentially other forms of hyperphagic obesity.
Elena Bochukova, DPhil
University of London
Elena Bochukova, DPhil