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Placental transcriptomes in the common aneuploidies reveal critical regions on the trisomic chromosomes and genome‐wide effects
Author(s) -
Bianco Katherine,
Gormley Matthew,
Farrell Jason,
Zhou Yan,
Oliverio Oliver,
Tilden Hannah,
McMaster Michael,
Fisher Susan J.
Publication year - 2016
Publication title -
prenatal diagnosis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.956
H-Index - 97
eISSN - 1097-0223
pISSN - 0197-3851
DOI - 10.1002/pd.4862
Subject(s) - trisomy , aneuploidy , biology , chromosome 21 , gene dosage , down syndrome , chromosome , transcriptome , gene , genetics , phenotype , genome , fetus , andrology , gene expression , pregnancy , medicine
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.