Imprinting in Human Placentas: The Intergenerational Transmission of Health

Low birth weight is a global health problem in the Life Sciences–one of the Templeton Foundation?s Core Areas. Stunted mothers tend to give birth to low birth weight infants, but the epigenetic mechanisms that underlie this inter-generational transmission are poorly understood. We will investigate 30 imprinted genes in placentas from 400 primiparous mothers to test the hypothesis that genetic imprinting plays a crucial role. We will use our prospective cohort study of a rural African population in which we followed 600 girls and 600 boys from infancy, and measured them annually during childhood and adolescence up to age ~24 years. We are uniquely poised to combine our longitudinal data, spanning 3 generations, with the analysis of allele-specific expression of placental genes. Based on the conflict hypothesis, we hypothesize that maternal stunting is associated with higher levels of placental imprinting in growth promoting genes such as IGF2, and lower levels of placental imprinting in growth inhibiting genes such as PHLDA2. We address the Big Question: How do environmental conditions modify the human genome? The answer will be reported in scientific articles, presentations, and a web page, and will lead to the identification of targets for epigenetic interventions.