The human and non-human primate developmental GTEx projects

Abstract

Many human diseases are the result of early developmental defects. As most paediatric diseases and disorders are rare, children are critically underrepresented in research. Functional genomics studies primarily rely on adult tissues and lack critical cell states in specific developmental windows. In parallel, little is known about the conservation of developmental programmes across non-human primate (NHP) species, with implications for human evolution. Here we introduce the developmental Genotype-Tissue Expression (dGTEx) projects, which span humans and NHPs and aim to integrate gene expression, regulation and genetics data across development and species. The dGTEx cohort will consist of 74 tissue sites across 120 human donors from birth to adulthood, and developmentally matched NHP age groups, with additional prenatal and adult animals, with 126 rhesus macaques (Macaca mulatta) and 72 common marmosets (Callithrix jacchus). The data will comprise whole-genome sequencing, extensive bulk, single-cell and spatial gene expression profiles, and chromatin accessibility data across tissues and development. Through community engagement and donor diversity, the human dGTEx study seeks to address disparities in genomic research. Thus, dGTEx will provide a reference human and NHP dataset and tissue bank, enabling research into developmental changes in expression and gene regulation, childhood disorders and the effect of genetic variation on development.

Figure 1:. Sampling across development and species

Schematic representation of the sampling timepoints across the developmental timeline of rhesus macaques (upper), marmosets (middle) and humans (lower). G=gestational day, d=day, mo=month, yr=year. n= number of donors per group. The typical age in gestational days, meaning days post-conception, at birth is G165 for macaques, G145 for marmosets and G265 for humans.

Figure 2:. Overview of the workflow

Schematic detailing the workflow for human (left) and NHP (right) donors, tissues, and aliquots with the collection sites, processing locations and methods, and the data analysis and biorepository centers.

Figure 3:. Sampling strategy for the heart across age ranges and species

Heart weights for humans^,, macaques and marmosets across age groups sampled in dGTEx. Solid line indicates a locally estimated scatterplot smoothing (LOESS) regression, black solid arrowheads signify the transition to a more detailed sampling strategy, as indicated in the overview below the graph.