36 - TRANSCRIPTOMIC STUDIES OF THE HUMAN PRENATAL BRAIN.

Several neuropsychiatric disorders are thought to have an early developmental component, which could be partly conferred by individual differences in gene expression. In order to explore sex and genotypic effects on gene expression in the human prenatal brain, we have performed whole transcriptome sequencing and genome-wide genotyping on a large collection (N > 120) of human fetal brain samples from the second trimester of gestation. Strand-specific whole transcriptome RNA-seq libraries were prepared from total RNA following ribosomal RNA depletion and deeply sequenced on an Illumina HiSeq. Genomic DNA from each sample was genotyped using Illumina arrays followed by SNP and indel imputation. Sex effects on gene expression were assessed by likelihood ratio tests. Expression quantitative trait loci (eQTL) in the human fetal brain will be identified using measures of total and allele-specific gene expression. We have identified hundreds of autosomal as well sex-linked genes exhibiting sex differences in expression or splicing in the prenatal human brain. Details of fetal brain eQTL and their association with neuropsychiatric disorders will also be presented. Our findings of sex differences in gene expression highlight an early stage of sexual differentiation of the human brain, which could have relevance to sex-biased neurodevelopmental disorders. Identification of fetal brain eQTL associated with neuropsychiatric disorders will help elucidate neurodevelopmental mechanisms contributing to these conditions. [ABSTRACT FROM AUTHOR]