Placental transcriptomes in the common aneuploidies reveal critical regions on the trisomic chromosomes and genome-wide effects

ObjectiveChromosomal aberrations are frequently associated with birth defects and pregnancy losses. Trisomy 13, Trisomy 18 and Trisomy 21 are the most common, clinically relevant fetal aneusomies. This study used a transcriptomics approach to identify the molecular signatures at the maternal-fetal interface in each aneuploidy. MethodsWe profiled placental gene expression (13-22weeks) in T13 (n=4), T18 (n=4) and T21 (n=8), and in euploid pregnancies (n=4). ResultsWe found differentially expressed transcripts (2-fold) in T21 (n=160), T18 (n=80) and T13 (n=125). The majority were upregulated and most of the misexpressed genes were not located on the relevant trisomic chromosome, suggesting genome-wide dysregulation. A smaller number of the differentially expressed transcripts were encoded on the trisomic chromosome, suggesting gene dosage. In T21, <10% of the genes were transcribed from the Down syndrome critical region (21q21-22), which contributes to the clinical phenotype. In T13, 15% of the upregulated genes were on the affected chromosome (13q11-14), and in T18, the percentage increased to 24% (18q11-22 region). ConclusionThe trisomic placental (and possibly fetal) phenotypes are driven by the combined effects of genome-wide phenomena and increased gene dosage from the trisomic chromosome. (c) 2016 John Wiley & Sons, Ltd.