SU63 - GENETIC EFFECTS ON MICRORNA EXPRESSION IN THE DEVELOPING HUMAN BRAIN

Abstract

Background MicroRNAs (miRNAs) are small (18–22 nucleotide) RNAs that regulate the expression of other genes in the developing and adult brain by binding to their mRNA and causing translational repression and / or mRNA destabilization. Altered miRNA expression has been reported in the post-mortem brains of individuals with various psychiatric disorders, including schizophrenia, bipolar disorder and autism. Moreover, genes encoding miRNA / molecules involved in miRNA biogenesis are located at several high confidence genomic risk loci for psychiatric disorders, consistent with an etiological role in these conditions. However, despite the known importance of miRNA in brain development, effects of genetic variation on miRNA expression in the prenatal human brain have yet to be investigated. Methods We are performing small RNA sequencing on a large collection (>120) of human brain samples from the second trimester of gestation. We will combine these data with genome-wide genotype information from the same samples with the aim of identifying eQTL for miRNA in the developing brain. We will test for association between identified miRNA eQTL and risk variants for neuropsychiatric disorders. Results Details of miRNA and genetic variants influencing their expression in the human fetal brain will be presented. Discussion Our data will provide important information on miRNA expression and its genetic regulation in the developing human brain.