Altered Expression of Immune-Related Genes in Children with Down Syndrome

Abstract

Individuals with Down syndrome (DS) have a high incidence of immunological alterations with increased susceptibility to bacterial and viral infections and high frequency of different types of hematologic malignancies and autoimmune disorders. In the current study, we profiled the expression pattern of 92 immune-related genes in peripheral blood mononuclear cells (PBMCs) of two different groups, children with DS and control children, to identify differentially expressed genes that might be of pathogenetic importance for the development and phenotype of the immunological alterations observed in individuals with DS. PBMCs samples were obtained from six DS individuals with karyotypically confirmed full trisomy 21 and six healthy control individuals (ages 2–6 years). Gene expression was profiled in duplicate according to the manufacturer's instructions provided by commercially available TaqMan Human Immune Array representing 92 immune function genes and four reference genes on a 96-plex gene card. A set of 17 differentially expressed genes, not located on chromosome 21 (HSA21), involved in immune and inflammatory pathways was identified including 13 genes (BCL2, CCL3, CCR7, CD19, CD28, CD40, CD40LG, CD80, EDN1, IKBKB, IL6, NOS2 and SKI) significantly down-regulated and four genes (BCL2L1, CCR2, CCR5 and IL10) significantly up-regulated in children with DS. These findings highlight a list of candidate genes for further investigation into the molecular mechanism underlying DS pathology and reinforce the secondary effects of the presence of a third copy of HSA21.

Down Syndrome Developmental Brain Transcriptome Reveals Defective Oligodendrocyte Differentiation and Myelination

“…We then carried out gene ontology enrichment analysis of each module to gain insight into the biological significance of these clusters of co-expressed genes ( Table S6 ). This analysis confirmed a number of cellular and molecular processes previously found to be altered in DS or mouse model brains, including cell morphogenesis (Module [M] 24; Figure S5A ), RNA processing (M31), gene transcription (M52), immune responses (M54; Figure S5B ), neuronal differentiation (M4 and M45; Figure S6A,D ), synaptic transmission and regulation (M10 and M34; Figure S6B,C ) and electron transport (M14) ( Table S6 ) (Bahn et al, 2002; Lockstone et al, 2007; Sahun et al, 2014; Yoshida et al, 2013; Zampieri et al, 2014). …”

Vulnerability to Disease as a Predictor of Faster Life History Strategies

“…Because the activity of one's immune system involves many distinctly separate yet cooperative facets of immune function, each of which converge to impact one's risk of extrinsic mortality, even those growing up in safe, benign environments with few external mortality threats are predicted to adopt faster life history strategies if they lack immune competence. Indeed, it has long been known that various genetic problems -from genetic anomalies writ large, such as the presence of extra chromosomes [e.g., trisomy 21 (Heston 1977;Zampieri et al 2013)] to more subtle single-gene / single nucleotide mutations -factor significantly into a large number of immunological problems. As is true for the genetics of height (Allen et al 2010;Wood et al 2014), but to an much greater extent given the tremendously multifaceted nature of immune function, a large number of small variations in numerous relevant alleles may impact outcome when it comes to immune competence, sometimes with suboptimal outcomes.…”

Revealing localization and regulation of GTPase PmRab7 in lymphoid cells of Penaeus monodon after WSSV infection

“…PmRab7 gene with housekeeping elongation factor 1-alpha gene [26] has shown significantly up-regulated with certain fold changes in the lymphoid tissues with the post WSSV infection till 72 h of post infection. Interestingly, it has reported no significant fold changes found in the PmRab7 expression after WSSV challenge in the earlier study, while it has also been reported that significant upregulation of all GTPase family of gene after WSSV internalization by subtractive hybridization in Penaeus japonicus [27].…”