PROJECT SUMMARY: DEVELOPMENTAL GENOMICS/EPIGENETICS CORE (DGC) The primary objective of the Developmental Genomics/Epigenetics core (DGC) is to support innovative and cutting-edge genome-scale research of intellectual and developmental disabilities (IDDs) across the lifespan— from conception to adulthood, tailored to a rural population. Under the leadership of co-directors Dr. Richard Smith and Dr. Jake Michaelson, who together have substantial, NIH-backed experience in experimental (Smith) and computational (Michaelson) genomics, the DGC will provide broad expertise that encompasses model system development, high-throughput sequencing technologies (e.g., genome and exome sequencing, RNA sequencing, chromatin immunoprecipitation sequencing, methylation sequencing, and ribosome sequencing), and bioinformatics and computational analysis of the results. Each of these foundational services is housed within its own organizational unit: 1) the Genomics Division provides high-throughput sequencing and array services including exome and genome sequencing, RNA-sequencing (including 10X Chromium single-cell sequencing), and array-based genotyping and methylation services under the direction of Dr. Richard Smith, an accomplished genomics investigator; and 2) the Bioinformatics Division provides services for quality control, basic processing (e.g., alignment, variant calling, and expression quantification), and pipelines for calculating polygenic risk scores from data produced by array or sequencing services generated by the genomics division, and is led by Dr. Jake Michaelson, an experienced computational genomics investigator. The DGC will utilize existing resources within the Iowa Institute for Human Genetics (led by co- director Dr. Richard Smith), which has a strong track record in education and dissemination, with regularly occurring workshops, tutorials, videos, and online certification opportunities. Since its inception, the DGC has been calibrated to the overall theme of the Hawk-IDDRC: IDD research across the lifespan. In particular, epigenetic signatures specific to development and aging are accessible through the Core's epigenetic array- and sequencing-based assays. The DGC also interrogates intrinsic and extrinsic sources of risk by offering genomic (intrinsic) and epigenetic (extrinsic) assay options. Finally, a focus on rural populations is achieved through the extensive experience of both Drs. Smith and Michaelson in collecting samples from sparsely populated areas, both in person and through mail recruitment campaigns (e.g., using saliva collection kits or Guthrie cards). Services from the DGC will complement and synergize with those of the other Cores in the Center, such as with the Clinical Translational Core in recruitment efforts to obtain biosamples, and will support 17 federally funded projects ($4.8 million per year). Collectively, the available expertise and cutting- edge services provided by the DGC will catalyze IDD research by min...