Delineating Expressional Difference in the Blood Mononuclear Cells
between Healthy and Turner Syndrome Individuals
Abstract
Turner Syndrome (TS) is a rare disorder associated either with complete
or partial loss of one X chromosome in women. Comparing the healthy and
individuals with Turner Syndrome may help elucidate the mechanisms
involved in TS pathophysiology. Gene expression differences between
healthy and individuals with Turner Syndrome were characterized using
the systems-biology approach of weighted gene coexpression network
analysis (WGCNA) on 182 microarray peripheral mononuclear blood samples
(PBMC). The co-expression networks of healthy and TS had scale-free
topology that ensures network robustness. In the process, five modules
were preserved between healthy and TS, which carry several genes common
in each module. Previously reported genes of TS, specifically,
PTPN22, RPS4X, CSF2RA, and TIMP1 were
missing in their respective modules. Dysfunction, differential
expression, or absence of these genes could lead to a progressive
disruption of molecular pathways leading to the pathophysiology of TS.
Indeed, we observed a significant difference in the functions of these
modules when compared within and across the healthy and TS samples. We
identified 4 clusters in the PPI network constructed from the top 15 K
ME enriched in significant functions. Overall, our work
highlights the potential molecular functions, pathways, and molecular
targets of TS that can be exploited therapeutically in the human health
care system.