Genomic Imprinting in the Brain: the persistent influences from Mom and Dad

Abstract

Most mammalian genes are equally expressed from the two inherited parental alleles. However, a puzzling subgroup known as imprinted genes are preferentially expressed from either the maternally- or paternally-inherited copy. Interestingly, many imprinted genes identified so far are expressed in the brain and mutations cause striking defects in brain development and function, in some cases leading to mental disorders such as autism-spectrum disorders. To better understand the extent of genomic imprinting in the brain and gain insights into its potential roles, I have investigated genomic imprinting in the Cerebellum. The Cerebellum provides several experimental advantages and has interesting functions, some of them recently associated with autism. Using RNA-Seq I have profiled the maternal and paternal transcriptomes in the developing and adult mouse Cerebellum, and uncovered 124 genes under imprinting regulation, 40 of which had not been described as imprinted before. Interestingly, the parental bias of 50% of detected genes are regulated according to age. Furthermore, parental biases appear to substantially vary across adult brain regions and are often not observed in non-brain tissues. Finally, I observed an overrepresentation of genes involved in programed cell death among imprinted genes, suggesting that the phenomenon of imprinting may target this pathway with interesting functional implications.