Core C: Developmental Genomics-Epigenetics Core

项目概要：药物基因组学/表观遗传学核心（DGC） 发育基因组学/表观遗传学核心（DGC）的主要目标是支持创新和 尖端的基因组规模的研究智力和发育障碍（IDDs）在整个生命周期- 从受孕到成年，专为农村人口量身定制。在联合主任理查德博士的领导下， 史密斯和杰克迈克尔森博士，谁一起有大量的，NIH支持的实验经验， （史密斯）和计算（迈克尔森）基因组学，DGC将提供广泛的专业知识，包括 模型系统开发，高通量测序技术（例如，基因组和外显子组测序， RNA测序、染色质免疫沉淀测序、甲基化测序和核糖体 测序），以及结果的生物信息学和计算分析。这些基础服务 位于其自己的组织单位内：1）基因组学部门提供高通量测序 和阵列服务，包括外显子组和基因组测序、RNA测序（包括10 X Chromium 单细胞测序），以及基于阵列的基因分型和甲基化服务的指导下，博士。 理查德·史密斯，一位有成就的基因组学研究者; 2）生物信息学部门提供服务 对于质量控制，基本处理（例如，比对、变体识别和表达定量），以及 用于根据由阵列或测序服务产生的数据计算多基因风险评分的管道 由基因组学部门，并由杰克迈克尔森博士，一个经验丰富的计算基因组学 调查员DGC将利用爱荷华州人类遗传学研究所的现有资源（由共同领导）， 主任理查德·史密斯博士），该组织在教育和传播方面有着良好的记录， 举办研讨会、教程、视频和在线认证机会。自成立以来，DGC 该项目已根据Hawk-IDDRC的总体主题进行了校准：整个生命周期的IDD研究。特别是， 通过内核的表观遗传阵列，可以获得发育和衰老的表观遗传特征- 和基于测序的测定。DGC还询问内在和外在的风险来源， 基因组（内在）和表观遗传（外在）测定选项。最后，实现了对农村人口的关注 通过史密斯博士和迈克尔森博士在收集稀疏样本方面的丰富经验， 人口稠密地区，无论是在人和通过邮件招募活动（例如，使用唾液收集试剂盒或 古特里牌）。该署的服务将与 中心，如与临床翻译核心在招聘工作中获得生物样本，并将 支持17个联邦资助的项目（每年480万美元）。总的来说，现有的专业知识和切割- DGC提供的边缘服务将通过最小化进入基因组的障碍来促进IDD研究， 神经发育和认知功能的规模研究。

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 minimizing barriers for entry into genome- scale studies of neurodevelopment and cognitive function.