Gene expression is one of the marks of cellular state and function. The relative abundance of transcripts defines and is a result of the differentiation status of a cell. Interrogation of gene expression levels and patterns in the human and other genomes can be informative about perturbations from the average pattern due to external stimuli or internal factors such as genetic variants. Gene expression profiles have been extensively used to assess developmental processes, pathways contributing to cell differentiation, and predicting the outcome of disease status.Understanding the effects of genetic variation in basic cellular processes such as gene expression is key to the dissection of the genetic contributions to whole organism phenotypes.We propose to interrogate the transcriptome of primary fibroblasts, primary T-cells and EBV-transformed B-cell (lymphoblastoid cell lines or LCLs) from umbilical cords of 200 individuals of European descent using next generation sequencing (mRNAseq). A subset will also be interrogated for transcriptionally engaged RNA polymerases (GROseq) and protein abundance. These data will be analyzed for the detection of eQTLs and other genetic effects associated with variation in alternative splicing and other properties of the transcripts and dissection of the genetic effects from primary transcription to protein and their tissue specific effects. These data will be integrated with genome-wide association studies and other efforts to dissect the genetic basis of complex traits and diseases in humans. In addition, we will develop bioinformatic models to understand the fine scale regulatory signals that are responsible for the regulatory patterns observed and how sequence variants have an effect on them.