Placental transcriptomes in the common aneuploidies reveal critical regions on the trisomic chromosomes and genome‐wide effects. (25th July 2016)

• Record Type: Journal Article
• Authors: Bianco, Katherine; Gormley, Matthew; Farrell, Jason; Zhou, Yan; Oliverio, Oliver; Tilden, Hannah; McMaster, Michael; Fisher, Susan J.
• Is Part Of: Prenatal diagnosis. Volume 36:Number 9(2016)
• Page Start: 812
• Page End: 822
• Publication Date: 2016-07-25
• Subjects: Prenatal diagnosis -- Periodicals; Fetus -- Diseases -- Diagnosis -- Periodicals; Electronic journals; 618.32075
• DOI: 10.1002/pd.4862
• Languages: English
• ISSNs: 0197-3851

Abstract

Abstract: Objective: Chromosomal 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. Methods: We profiled placental gene expression (13–22 weeks) in T13 ( n = 4), T18 ( n = 4) and T21 ( n = 8), and in euploid pregnancies ( n = 4). Results: We 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). Conclusion: The trisomic placental (and possibly fetal) phenotypes are driven by the combined effects of genome‐wide phenomena and increased gene dosage from the trisomic chromosome. © 2016 John Wiley & Sons, Ltd. Abstract : What's Already Known About This Topic? There are limited data about trisomy 13, trisomy 18 and trisomy 21 molecular signatures in terms of placental gene expression. What Does This Study Add? Our data suggested that the trisomic placental (and possibly fetal) phenotypes are driven by the combined effects of genome‐wide phenomena and critical region gene dosage from the trisomic chromosome.