Abstract
BACKGROUND: Genomic imprinting, mediated by parent-of-origin-specific epigenetic silencing, adjusts the gene expression dosage in mammals. We aimed to clarify parental allelic expression in the human placenta for 396 claimed candidate imprinted genes and to assess the evidence for the proposed enrichment of imprinted expression in the placenta. The study utilized RNA-Seq-based transcriptome and genotyping data from 54 parental-placental samples representing the three trimesters of gestation, and term cases of preeclampsia, gestational diabetes, and fetal growth disturbances. RESULTS: Almost half of the targeted genes (n = 179; 45%) were either not transcribed or showed limited expression in the human placenta. After filtering for the presence of common exonic SNPs, adequacy of sequencing reads and informative families, 91 genes were retained (43 loci form Geneimprint database; 48 recently proposed genes). Only 11/91 genes (12.1%) showed confident signals of imprinting (binomial test, Bonferroni corrected P < 0.05; > 90% transcripts originating from one parental allele). The confirmed imprinted genes exhibit enriched placental expression (PHLDA2, H19, IGF2, MEST, ZFAT, PLAGL1, AIM1) or are transcribed additionally only in the adrenal gland (MEG3, RTL1, PEG10, DLK1). Parental monoallelic expression showed extreme stability across gestation and in term pregnancy complications. A distinct group of additional 14 genes exhibited a statistically significant bias in parental allelic proportions defined as having 65-90% of reads from one parental allele (e.g., KLHDC10, NLRP2, RHOBTB3, DNMT1). Molecular mechanisms behind biased parental expression are still to be clarified. However, 66 of 91 (72.5%) analyzed candidate imprinted genes showed no signals of deviation from biallelic expression. CONCLUSIONS: As placental tissue is not included in The Genotype-Tissue Expression (GTEx) project, the study contributed to fill the gap in the knowledge concerning parental allelic expression. A catalog of parental allelic proportions and gene expression of analyzed loci across human gestation and in term pregnancy complications is provided as additional files. The study outcome suggested that true imprinting in the human placenta is restricted to well-characterized loci. High expression of imprinted genes during mid-pregnancy supports their critical role in developmental programming. Consistent with the data on other GTEx tissues, the number of human imprinted genes appears to be overestimated.