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.
