Human 45,X Fibroblast Transcriptome Reveals Distinct Differentially Expressed Genes Including Long Noncoding RNAs Potentially Associated with the Pathophysiology of Turner Syndrome

Abstract

Turner syndrome is a chromosomal abnormality characterized by the absence of whole or part of the X chromosome in females. This X aneuploidy condition is associated with a diverse set of clinical phenotypes such as gonadal dysfunction, short stature, osteoporosis and Type II diabetes mellitus, among others. These phenotypes differ in their severity and penetrance among the affected individuals. Haploinsufficiency for a few X linked genes has been associated with some of these disease phenotypes. RNA sequencing can provide valuable insights to understand molecular mechanism of disease process. In the current study, we have analysed the transcriptome profiles of human untransformed 45,X and 46,XX fibroblast cells and identified differential expression of genes in these two karyotypes. Functional analysis revealed that these differentially expressing genes are associated with bone differentiation, glucose metabolism and gonadal development pathways. We also report differential expression of lincRNAs in X monosomic cells. Our observations provide a basis for evaluation of cellular and molecular mechanism(s) in the establishment of Turner syndrome phenotypes.

Recognition and management of adults with Turner syndrome: From the transition of adolescence through the senior years

“…Therefore, the frequency of heart and lymphatic problems in Turner syndrome may be best explained by a combination of copy number variation of X chromosome genes and altered expression of autosomal genes that also contribute to congenital defects in the general population. Recent studies identified autosomal gene mutations or epigenetic changes in women with Turner syndrome who have cardiac abnormalities, providing the first evidence to support this hypothesis (Corbitt et al, ; Prakash et al, ; Rajpathak, Vellarikkal, Patowary, Sivasubbu, & Deobagkar, ; Trolle et al, ).…”

Neighboring Gene Regulation by Antisense Long Non-Coding RNAs

“…Dysregulation of lncRNAs has also been associated with a broad range of physiological defects. Silver–Russell, Turner, Prader–Willi and HELLP (hemolysis, elevated liver enzymes, and low platelets in the mother) syndromes are some representative examples [ 33 , 34 , 35 , 36 ]. Additionally, cardiac diseases, myopathies, neurodegenerative disorders and cancers have also been linked with lncRNAs [ 31 , 37 , 38 , 39 , 40 ].…”

DNA methylation signature in peripheral blood reveals distinct characteristics of human X chromosome numerical aberrations

“…Several other studies analyzed single loci in order to develop a molecular diagnosis method for detection [ 15 , 16 ]. Regarding Turner syndrome, here, too, only few studies exist which performed genome-wide expression analysis, i.e., in fibroblast [ 17 ] and in cell free DNA derived form amniotic fluid [ 18 ]. In other studies, single loci were analyzed mainly for diagnostic purposes [ 19 ].…”