SRA

The discovery of genomic imprinting through studies of manipulated mouse embryos indicated that the paternal genome has a major influence on placental development. However, previous research has not demonstrated paternal bias in imprinted genes. We applied RNA sequencing to trophoblast tissue from reciprocal hybrids of horse and donkey, where genotypic differences allowed parent-of-origin identification of most expressed genes. Using this approach, we identified a core group of 15 ancient imprinted genes of which 10 were paternally expressed. An additional 78 candidate novel imprinted genes identified by RNA-seq also showed paternal bias. Pyrosequencing was used to confirm the imprinting status of six of the novel genes, including the insulin receptor (INSR), which may play a role in growth regulation with its reciprocally imprinted ligand, histone acetyltransferase (HAT1), the first example of an imprinted gene involved in chromatin modification, and LY6G6C, the first imprinted gene to be identified in the major histocompatibility complex. The 78 novel candidate imprinted genes displayed parent-of-origin expression bias in placenta but not fetus, and most showed less than 100% silencing of the imprinted allele. Some displayed variability in imprinting status among individuals. This results in a unique epigenetic signature for each placenta that contributes to variation in the intrauterine environment and thus presents the opportunity for natural selection to operate on parent-of-origin differential regulation. Taken together, these features highlight the plasticity of imprinting in mammals and the central importance of the placenta as a target tissue for genomic imprinting. Overall design: Examine allelic expression from four individual samples of invasive trophoblast tissue of the chorionic girdle from gestation day 33 conceptuses of horse, donkey, mule and hinny.