Genome-wide gene expression analysis in the placenta from fetus with trisomy 21

Abstract

BackgroundWe performed whole human genome expression analysis in placenta tissue (normal and T21) samples in order to investigate gene expression into the pathogenesis of trisomy 21 (T21) placenta. We profiled the whole human genome expression of placental samples from normal and T21 fetuses using the GeneChip Human Genome U133 plus 2.0 array. Based on these data, we predicted the functions of differentially expressed genes using bioinformatics tools.ResultsA total of 110 genes had different expression patterns in the T21 placentas than they did in the normal placentas. Among them, 77 genes were up-regulated in the T21 placenta and 33 genes were down-regulated compared to their respective levels in normal placentas. Over half of the up-regulated genes (59.7%, n = 46) were located on HSA21. Up-regulated genes in the T21 placentas were significantly associated with T21 and its complications including mental retardation and neurobehavioral manifestations, whereas down-regulated genes were significantly associated with diseases, such as cystitis, metaplasia, pathologic neovascularization, airway obstruction, and diabetes mellitus. The interactive signaling network showed that 53 genes (40 up-regulated genes and 13 down-regulated genes) were an essential component of the dynamic complex of signaling (P < 1.39e-08).ConclusionsOur findings provide a broad overview of whole human genome expression in the placentas of fetuses with T21 and a possibility that these genes regulate biological pathways that have been involved in T21 and T21 complications. Therefore, these results could contribute to future research efforts concerning gene involvement in the disease’s pathogenesis.

Integrative analyses of genes and microRNA expressions in human trisomy 21 placentas

“…The miRNAs and genes differentially expressed between the placentas of normal and T21 fetuses were found in our previous data [ 20 , 21 ], and in this study we could identify genes showing a negative correlation with miRNAs, and explored the biological function and molecular pathways of the identified genes using various bioinformatics tools.…”

“…Study subjects were constructed with 10 women with euploid fetuses and seven women with T21 fetuses. The CVS from five euploid and three T21 placentas were used for expression profiling of genome-wide whole genes [ 20 ], and those from the other five euploid and four T21 placentas were used for miRNA expression analysis [ 21 ]. Table 1 shows the clinical characteristics of the subjects.…”

“…Expression of genes and miRNAs in the whole genomes was analyzed based on our previous studies [ 20 , 21 ]. In brief, total RNA was extracted from normal and T21 fetal placentas.…”

“…An RNA quantity, quality, and integrity number were measured by an Agilent 2100 Bioanalyzer (Agilent Technologies, CA, USA) and a NanoVue Plus spectrophotometer (GE Healthcare, London, UK). Expression profiles of whole genes were determined using the Affymetrix GeneChip Human Genome U133 Plus 2.0 Array (Affymetrix Inc., Santa Clara, CA, USA) [ 21 ]. The miRNAs expressions were profiled using Human miRNA Microarray kit, 8 × 60 K (based on miRBase release 16.0, Agilent Technologies) [ 20 ].…”

“…In our previous studies, we profiled expression levels of genome-wide miRNAs and genes in placental samples from normal and T21 fetuses using microarray analyses [ 20 , 21 ]. Our results demonstrated that 34 miRNAs (16 up-regulated and 18 down-regulated) and 110 genes (77 up-regulated and 33 down-regulated) were significantly differentially expressed in the T21 placenta compared with that in normal placentas.…”