DNA sequencing and Bioinformatics

总结 建议支持SickleGenAfrica项目的共享生物信息学核心解决了以下问题： 在镰状细胞病器官损伤的发病机制中产生新见解的努力中的一个关键问题 非洲人口：即获得高通量和高质量的基因组扫描和分析 在GWAS中经验丰富的中心。这个核心的领导者已经处理和分析了数十个 成千上万的基因分型阵列，以U 54机制的形式领导大型财团（作为NIH的主席 神经科学微阵列联盟），并提供了新的见解，病理生物学已发表 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 获得基因组扫描和分析的丰富经验。当这个共享核心的目标是 实现，我们将生成一组训练数据，这些数据将用于识别 小的古老单倍型块和几个SCD相关表型。一般来说，这些数据将用于 细化致病变异的位置，并形成协作数据集的一个组成部分， 非洲大陆的基因组结构。这些对易感等位基因的新见解将 使我们能够更精确地了解项目所关注的器官功能障碍的发病机制 然后可以将其用于风险筛查或靶向治疗开发。成功 为了实现这一核心目标，将利用新技术，即H3非洲阵列，这是最新的创新 在特定于非洲人群的阵列设计中，来自公共和私人测序数据集。这 从本核心的工作中获得的关于古代非洲基因组的新的和最全面的观点将允许 我们要得到前所未有的决议，以变异相关，并提高风险，一些 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类新的领域中处于领先地位。 以产品/公司（如Navigenics）的形式为人们提供解决方案的见解， 将纳税人资助的基础研究的点连接起来，是这个核心的区别。

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.