Effect of the Placental Transcriptome on Stunting in a Longitudinal African Cohort

Mammals with placentas and flowering plants evolved genomic imprinting in nutritive tissues, the placenta and endosperm, respectively. In these tissues, the genomes inherited from the mother and father are in conflict over resource allocation to offspring. In imprinted genes, transcription is repressed on the paternal or the maternal allele, resulting in allele specific expression (ASE). We investigated the variation in ASE of imprinted genes in term human placentas in order to detect loss of imprinting (LOI), which leads to partial expression of the repressed allele. We collected the placental tissue from birth to women in our multigenerational, prospective cohort study in Mali, West Africa. We followed the women from their own infancies, early childhood to adulthood (age 18+ years). Contingent on prior informed consent, we collected placental tissue and umbilical cord tissue.

We conducted RNA-Seq of the fetal compartment of the placentas and targeted DNA-Seq of the umbilical cord tissue, which is fetal, and of saliva samples from parents. Our sequencing effort produced two datasets. The first dataset is the whole transcriptome RNA-Seq dataset of 111 biopsies (59 placentas) and genotyping of 96 genes. Birth length, weight, and placental weight for the children associated with this dataset are listed in the phenotype file (DOI: 10.1093/molbev/msz226). The second dataset includes targeted RNA-Seq of 262 samples (251 placentas) and targeted DNA-Seq for 766 genes. The genes were selected because they met any one of the following criteria: (1) imprinted and reported in some studies, (2) highly expressed in placenta, or (3) relevant to diseases of interest in this cohort (https://doi.org/10.1093/g3journal/jkab176).

This study provides the first systematic analysis of variation in LOI across genes and individuals in a human population, and should shed light on the hypothesis that the modulation of imprinting is an epigenetic mechanism and plays a role in the regulation of offspring growth.

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Inclusion Criteria: Placentas must be associated with a birth of an F1 generation member in the prospective cohort study which was initiated by the principal investigator in 1998. The F1 individuals were exclusively born between April 15, 1993 and July 5, 2000 in a set of villages which belong to one clan on the Bandiagara Escarpment in central Mali. The F2 progenies associated with the placentas were enrolled at their birth time. Occasionally, both parents were members of the F1 cohort, but usually only one of the parents was the F1 cohort member. The non-F1 cohort parent was enrolled around the time of the F2 birth. Only persons who gave informed consent/assent were enrolled. ]]>
1998 - 2000: F1 subjects enrollment. 2013 - 2019: Collection of placentas and umbilical cord tissue/blood which were associated with F2 birth. ]]>