DNA sequencing and Bioinformatics

摘要 建议用于支持SickleGenAfrica项目的共享生物信息学核心解决了 努力对镰状细胞病器官损伤的发病机制产生新见解的关键问题 非洲人口：即获得高通量和高质量的基因组扫描和分析 该中心具有丰富的全球基础设施建设经验。这个核心的领导者已经处理和分析了数十个 数以千计的基因分型阵列，以U54机制的形式领导大财团(作为NIH主席 神经科学微阵列联盟)，并提供了对病理生物学的新见解，这些见解已经发表 发表在《细胞》、《自然遗传学》、《新英格兰医学杂志》和《科学》等期刊上。核心解决的关键关键障碍是 获得关于基因组扫描和分析的深入经验。当此共享核心的目标是 实现后，我们将生成一组训练数据，用于识别 古老的单倍型小块和几个SCD相关表型。更广泛地说，这些数据将用于 改进原因变体的位置，并形成协作数据集的一个组件，该数据集通知 来自整个非洲大陆的基因组结构。这些对易感等位基因的新见解将 使项目重点关注的器官功能障碍的发病机制有了更深入的了解 然后，可以将其用于风险筛查或靶向治疗开发。成功者 完成这一核心的目标将利用新技术，H3Africa阵列，这是最新的创新 在特定于非洲人口的阵列设计中，来自公共和私人测序数据集。这 从这个核心的工作中获得的对古代非洲基因组的新的和最全面的看法将使 美国将史无前例地解决与某些病毒相关并提高风险的变种 SCD最常见的并发症，这可能构成新的诊断和治疗的基础 发展。重要的是，核心领导者在翻译和商业化这种新的 以向公众提供解决方案的产品/公司(如Navigenics)的形式提供见解， 将纳税人资助的基础研究中的点连接起来，是这一核心的差异化之处。

Summary The Shared Bioinformatics Core that is proposed to support the Projects of SickleGenAfrica addresses a critical problem in the effort to generate new insights into pathogenesis of organ damage in sickle cell disease populations in Africa: namely access to a high throughput and high quality genome scanning and analysis center that is deeply experienced in GWAS. The leader of this Core has processed and analyzed tens of thousands of genotyping arrays, led large consortia in the form of the U54 mechanism (as Chairman of the NIH Neuroscience Microarray Consortium), and provided new insights into pathobiology that have been published in journals such as Cell, Nature Genetics, NEJM, and Science. The key critical barrier that the Core solves is access to deep experience with genome scanning and analysis. When the aims of this Shared Core are achieved, we will have generated a training set of data that will be used to identify novel correlations between small ancient haplotype blocks and several SCD-related phenotypes. More generally, this data will be used to refine locations of causative variants, and also form a component of a collaborative data set that informs genomic architecture from across the African continent. These new insights into predisposition alleles will enable a more refined understanding of the pathogenesis of organ dysfunction that the Projects are focused on, which can then be parlayed into risk screening or targeted therapeutic development. The successful completion of the aims of this Core will utilize new technology, the H3Africa array, which is the latest innovation in array design specific to African populations, derived from both public and private sequencing data sets. This new and most comprehensive view of the ancient African genomes derived from the work in this Core will allow us to get unprecedented resolution into the variants that are correlated to, and enhance risk for, some of the most prevalent complications of SCD, which may form the basis for new diagnostic and therapeutic development. Importantly, the Core leader has led the field in translation and commercialization of such new insights in the form of products/companies (such as Navigenics) that deliver solutions to the population, connecting the dots from taxpayer funded basic research, and is a differentiator of this Core.