DNA sequencing and Bioinformatics

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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.