RAMSAY 2018: MEET DR. LIZ WORTHEYOctober 9, 2018

“Whole genome sequencing and analysis of ME/CFS”

A project summary as written by Dr. Liz Worthey, PhD:

We propose to utilize whole genome sequencing (WGS) combined with cutting edge informatics approaches in patients afflicted with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in order to elucidate the genetic and molecular mechanisms behind the complex presentation and progression of this disease. Despite an increase in research projects over the last several years, the pathophysiology of ME/CFS still remains unknown. We hypothesize that ME/CFS is the result of an intrinsic genetic defect(s) that alters cellular metabolic homeostasis towards an unstable state. This unstable state is tipped into an irreversible deficiency by an external stimuli such as a viral or bacterial illness or physical or emotional trauma. We believe that the course of illness is based on the type of variant or where in a metabolic pathway an individual’s defect lies. This approach has the potential to molecularly define the several subtypes clinically observed in this disease, such as mild, moderate, and severe dysfunction. We will perform WGS and will analyze the data using various algorithmic approaches, including our custom network analysis algorithms, which support the identification of single nucleotide substitutions and other classes of small variants, structural variants (including more complex types of rearrangements), fusion products, expanded tandem repeats, and variants in regulatory regions that alter expression. We will be testing the following hypothesis; ME/CFS is caused by a genetic alteration(s) in one or more metabolic pathways that leads to an unstable cellular energetic state. The course of illness is based on the type of variant or where in a metabolic pathway an individual’s defect lies.