Regulation of the metabolic changes in Chronic Fatigue Syndrome: role of CNV

Grant Winners

Dean

Abstract

Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) is a complex illness affecting 4 million Americans. Costs of CFS/ME were estimated at $33 billion in lost productivity and health care annually. Causes of CFS/ME remain unclear. Symptoms of CFS/ME include malaise, muscle pain, and impaired cognition. CFS/ME symptoms are triggered by stressful events, such as exercise. Our laboratory has developed a systematic and quantitative way to analyze changes in gene expressions between CFS/ME patients and healthy controls (HC) by triggering symptoms via exercise challenge. Measurements of gene expression were assessed by blood samples taken before, during and after exercise challenge using peripheral blood mononuclear cells (PBMC), Our preliminary data using gene expression Affymetrix U133 plus 2 microarrays showed that genes mapped to 132 metabolic pathways, including energy metabolism and immune system signaling genes, are differentially expressed in CFS/ME patients. We extended the gene expression project involving a larger number of patients and more comprehensive Affymetrix Gene microarraysas well as Nanostring assays of miRNAs. Here, we hypothesize that a reason for the change in the metabolism in CFS/ME may be a change in the number of genes at the genomic DNA level, known as Copy Number Variation (CNV). CNV may be inherited (parent to child) or caused by the environment (epigenetics). Our long term aim is to understand the mechanisms of CFS/ME and to develop new therapeutic treatments. In order to test our hypotheses, we will perform:

Specific Aim I: To determine genomic targets for Nanostring CNV assays.
Specific Aim II: Design specific Nanostring probes for determination of CNVs for identified genomic regions based on gene expression analysis of PBMCs.

Our state-of-the art innovative approach will focus on the root causes of CFS/ME and on development of therapeutics for direct patient treatment as well as prevention of symptom relapse.