Loss of Imprinting in Human Placentas Is Widespread, Coordinated, and Predicts Birth Phenotypes
| Autor: | Weisheng Wu, Beverly I. Strassmann, Kerby Shedden, Claudius Vincenz, Jennie L Lovett |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Adolescent
placenta loss of imprinting Offspring allele-specific expression Biology Mali Young Adult 03 medical and health sciences Exon 0302 clinical medicine Pregnancy Genetics Birth Weight Humans Prospective Studies Allele Imprinting (psychology) Promoter Regions Genetic Molecular Biology Gene Discoveries Ecology Evolution Behavior and Systematics 030304 developmental biology 0303 health sciences Sequence Analysis RNA Gene Expression Profiling Infant Newborn Maternal effect Phenotype Body Height genomic imprinting Linear Models Female Maternal Inheritance RNA-seq Genomic imprinting 030217 neurology & neurosurgery |
| Zdroj: | Molecular Biology and Evolution |
| ISSN: | 1537-1719 0737-4038 |
| DOI: | 10.1093/molbev/msz226 |
| Popis: | Genomic imprinting leads to mono-allelic expression of genes based on parent of origin. Therian mammals and angiosperms evolved this mechanism in nutritive tissues, the placenta, and endosperm, where maternal and paternal genomes are in conflict with respect to resource allocation. We used RNA-seq to analyze allelic bias in the expression of 91 known imprinted genes in term human placentas from a prospective cohort study in Mali. A large fraction of the imprinted exons (39%) deviated from mono-allelic expression. Loss of imprinting (LOI) occurred in genes with either maternal or paternal expression bias, albeit more frequently in the former. We characterized LOI using binomial generalized linear mixed models. Variation in LOI was predominantly at the gene as opposed to the exon level, consistent with a single promoter driving the expression of most exons in a gene. Some genes were less prone to LOI than others, particularly lncRNA genes were rarely expressed from the repressed allele. Further, some individuals had more LOI than others and, within a person, the expression bias of maternally and paternally imprinted genes was correlated. We hypothesize that trans-acting maternal effect genes mediate correlated LOI and provide the mother with an additional lever to control fetal growth by extending her influence to LOI of the paternally imprinted genes. Limited evidence exists to support associations between LOI and offspring phenotypes. We show that birth length and placental weight were associated with allelic bias, making this the first comprehensive report of an association between LOI and a birth phenotype. |
| Databáze: | OpenAIRE |
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