PROJECT ABSTRACT We propose to establish the Laboratory, Data Analysis, and Coordinating Center (LDACC) for the Developmental Genotype-Tissue Expression (dGTEx) Project to generate, analyze, and integrate multimodal genomic data from various tissues, with emphasis on multiple brain regions, across 4 age groups: infancy, early childhood, late childhood and adolescence. We will develop an atlas that integrates genotyping data and functional genomic data to help predict functional impact of noncoding genomic variants, both common and rare on gene expression. Our project will address two key knowledge gaps. First, large-scale efforts by GTEx and other consortia have focused on adult or prenatal ages and only to a limited extent, on the postnatal developmental ages from birth to adolescence, critical periods because humans have prolonged postnatal development, particularly prominent in the brain. Second, resolution at the level of specific cell types in lacking in many studies. Studying postnatal development at the level of specific cell types is critical because the effects of genetic variants on gene regulation are often cell-type specific. To address these critical knowledge gaps, we propose to 1) create an atlas of pediatric tissue gene expression in bulk tissues and single cell populations, 2) analyze differences in gene expression, regulation, and known expression QTLs and splicing QTLs across postnatal human development, and 3) create and make available a biobank of as many tissues as possible (up to 50 tissues per donor), and associated data for further characterization. 4) develop a data portal for data dissemination as well as integration of our data with Genotype Tissue Expression (GTEx), Brain Initiative Cell Census Network (BICCN) and other consortia. By so doing, we will radically expand upon earlier efforts by GTEx and create a comprehensive and broadly available community resource on human developmental tissues, to help drive research forward in multiple research fields, and generally any disease.

PROJECT NARRATIVE Little is known about how genomic variants affect human postnatal development, function, and lead to disorders. To address this, we propose a large-scale study to identify DNA variants and their effects on gene expression and regulation in many tissues and cell types across human brain development. This will provide unprecedented functional insights into human development.