Global transcriptome dysregulation in second trimester fetuses with FMR1 expansions.

Objective: We tested the hypothesis that FMR1 expansions would result in global gene dysregulation as early as the second trimester of human fetal development.

Method: Using cell-free fetal RNA obtained from amniotic fluid supernatant and expression microarrays, we compared RNA levels in samples from fetuses with premutation or full mutation allele expansions with control samples.

Results: We found clear signals of differential gene expression relating to a variety of cellular functions, including ubiquitination, mitochondrial function, and neuronal/synaptic architecture.

Chromatin Signature Identifies Monoallelic Gene Expression Across Mammalian Cell Types.

Monoallelic expression of autosomal genes (MAE) is a widespread epigenetic phenomenon which is poorly understood, due in part to current limitations of genome-wide approaches for assessing it. Recently, we reported that a specific histone modification signature is strongly associated with MAE and demonstrated that it can serve as a proxy of MAE in human lymphoblastoid cells. Here, we use murine cells to establish that this chromatin signature is conserved between mouse and human and is associated with MAE in multiple cell types.

The amniotic fluid transcriptome as a guide to understanding fetal disease.

Numerous recent studies have shown the power of cell-free fetal RNA, obtained from amniotic fluid supernatant, to report on the development of the living fetus in real time. Examination of these transcripts on a genome-wide basis has led to new insights into the prenatal pathophysiology of multiple genetic, developmental, and environmental diseases. Each studied condition presents a unique, characteristic fetal transcriptome, which points to specific disrupted molecular pathways.

RNA-Seq and expression microarray highlight different aspects of the fetal amniotic fluid transcriptome.

Objective: The aim of this study was to compare the complexity of the amniotic fluid supernatant cell-free fetal transcriptome as described by RNA Sequencing (RNA-Seq) and gene expression microarrays.

Methods: Cell-free fetal RNA from the amniotic fluid supernatant of five euploid mid-trimester samples was divided and prepared in tandem for analysis by either the Affymetrix HG-U133 Plus 2.0 Gene Chip microarray or Illumina HiSeq.

Autosomal monoallelic expression in the mouse.

Background: Random monoallelic expression defines an unusual class of genes displaying random choice for expression between the maternal and paternal alleles. Once established, the allele-specific expression pattern is stably maintained and mitotically inherited. Examples of random monoallelic genes include those found on the X-chromosome and a subset of autosomal genes, which have been most extensively studied in humans.