AWI-Gen Phase 2: Genomic and environmental risk factors for cardiometabolic disease in Africans

项目摘要 根据H3非洲联盟和母公司赠款(AWI-GEN)的目标，这项研究 旨在增强来自不同人群的非洲基因组数据，以确保非洲不会被留在 在基因组革命中落后。我们将专门针对以前未研究过的人群 发现更多的非洲遗传多样性，并进行种群遗传研究， 阐明了导致当前人口分布的移民和混杂事件 大陆。这项研究分三个阶段进行，每个阶段提供更多信息和 将向全球研究界提供的数据集。这第一阶段将包括 来自8个以前未被研究的非洲种群(每个50个个体)的短阅读序列。 第二阶段将把每个群体的样本量增加到100个，以更好地估计等位基因 频率，还将包括长读测序，以建立非洲的参考图 以提高变种叫声的准确性。第三阶段将评估转录本 300名个体的甲基化特征，以深入了解基因的功能 全基因组关联研究中发现的新变种和变种。为以下项目开发数据 更好地代表跨越四大民族语言分区的非洲遗传多样性 (尼日尔-刚果、尼罗-撒哈拉、非洲-亚洲和北非)我们将从 研究不足的地理区域(图1)。WGS数据将集成到一个开放的和 易于获取的资源，例如由 H3ABioNet。我们将进行深入的种群遗传分析，以更好地了解 关于非洲大陆的基因组多样性、迁徙、混合和人口历史的研究。这将会 包括测试班图移民的各种替代模式，并将提供更好的 古代基因组数据的语境化。为了更好地集合短文阅读 我们计划使用长时间的测序来对这些基因组的一个子集进行测序 技术(PacBio)。这一数据集将有助于旨在生成 参考基因组。转录和甲基化数据集将在 推断新发现的变异的可能作用及其在健康和疾病中的相关性。 通过这一目标，我们将开始为非洲人口建立功能基因组资源 为了加强全球努力，重点放在eQTL识别、交替剪接和meQTL上。 1

Project Summary In line with the objectives of the H3Africa Consortium and the parent grant (AWI-Gen) this study aims to augment African genomic data from diverse populations to ensure that Africa is not left behind in the genomic revolution. We will specifically target previously unstudied populations to discover additional African genetic diversity and to perform population genetic studies that will shed light on migration and admixture events that led to the current population distribution on the continent. The research is proposed in three phases, each providing more information and datasets that will become available to the global research community. This first phase will involve short-read sequences from eight previously unstudied African populations (50 individuals each). The second phase will increase the sample size per population to 100, to better estimate allele frequencies, and will also include long-read sequencing to build reference graphs for African populations to improve variant calling accuracy. The third phase will assess the transcriptomic and methylation profiles in 300 individuals to provide insight into the functional interpretation of novel variants and variants identified in genome-wide association studies. To develop data for better representation of African genetic diversity spanning the four major ethnolinguistic divisions (Niger-Congo, Nilo-Saharan and Afro-Asiatic and North African) we will focus on WGS from understudied geographic regions (Figure 1). The WGS data will be integrated into an open and easily accessible resource such as the African Genome Variation database being developed by H3ABioNet. We will perform in depth population genetic analyses aimed at a better understanding of genomic diversity, migration, admixture and demographic history on the continent. This would include testing various alternative models for the Bantu-migration and will provide a better contextualization of data from ancient genomes. To enable a better assembly of short-read sequences we plan to sequence a subset of these genomes using a long-read sequencing technique (PacBio). This dataset would contribute to other global efforts aimed at generating reference genomes. The transcriptomic and methylation datasets will be of immense value in inferring the possible roles of newly discovered variants and their relevance in health and disease. Through this objective we will start building a functional genome resource for African populations to augment global efforts focused on eQTL identification, alternate splicing and meQTLs. 1