Core 3: Genomic Sequencing and Population Genetics Core

摘要-基因组测序与群体遗传学核心-核心3 基因组测序和种群遗传学核心(核心3)支持该计划的两个项目 评估和理解CCMV基因变异、传播和免疫之间的关系 回应。核心是对理解疱疹病毒和人类巨细胞病毒做出反应 尤其是大型DNA病毒，其序列多样性程度令人惊讶： 患者样本通常在共识和人群水平上都有1,000‘S多态。这 长期遗传变异的水平在生物学上是重要的，因为它已经被证明在 一系列临床传染病的挑战。例如，在巨细胞病毒中，遗传多样性对时间的影响 以及先天性胎儿感染的等位基因频率的区间性变化。支持调查 在我们的RhCMV模型中，基因组测序核心将对RhCMV的种群进行排序 项目1-2(目标1)提供的动物、接种物和培养病毒样本的基因组。数列 READ将通过参考介导的比对的迭代过程被映射为RhCMV序列 然后构建新的重叠群。RhCMV序列数据集将用于定义带注释的共识(即 最常见的)每个样本的序列，并提供病毒种群的汇总统计。摘要 统计数据包括序列读取总数、映射读取/效率、平均覆盖率、多态 在关于亲本病毒和种群多样性的共识上。结果将提供给 项目。此外，Core将通过对RhCMV饱和度数据集进行编目来改进工作流程，改进 处理协议，并将与病毒病原体和分析资源(ViPR)合作提供 RhCMV序列数据及其简单、可搜索格式的体内相关数据(目标2)。散体序列 数据将提交给公开可用的NCBI序列读取档案。最后，核心将采用 群体遗传学策略研究先天性RhCMV模型中的RhCMV进化模式 询问病毒载量和病毒种群序列空间以确定多样性和分化机制 在产妇和婴儿中传播病毒(目标3)。影响感染、传播的其他参数 和包括病毒基因缺失株(项目2)和免疫状态改变(项目1)在内的疾病将 被分析其对病毒种群多样性的影响，创始人规模和隔间效应的关系 传播和疾病。综上所述，核心将提供对体内如何 进化过程，如瓶颈和选择压力，影响病毒传播和胎儿 疾病。

ABSTRACT – Genomic Sequencing and Population Genetics Core – Core 3 The Genomic Sequencing and Population Genetics Core (Core 3) supports the Program’s two projects in evaluating and understanding the relationship between cCMV genetic variation, transmission, and immune response. The Core is responsive to the understanding that herpes viruses, and human cytomegalovirus (HCMV) in particular, are large DNA viruses that exhibit surprising levels of sequence diversity: HCMV samples from patients often have 1,000’s polymorphisms at both the consensus and population levels. This level of standing genetic variation is biologically important, as it has been shown to play a significant role in a range of clinical infectious disease challenges. For example, in HCMV, genetic diversity contributes to temporal and compartmental changes in allele frequencies in congenital fetal infections. To support investigations of such dynamics in our RhCMV model, the Genomic Sequencing Core will sequence populations of RhCMV genomes from animals, inoculum, and cultured virus samples provided by Projects 1-2 (Aim 1). Sequence reads will be mapped as RhCMV sequences through an iterative process of reference mediated alignments and de novo contig builds. RhCMV sequence datasets will be used to define an annotated consensus (i.e., the most common) sequence of each sample and provide summary statistics of viral populations. Summary statistics include total number of sequences reads, mapped reads/efficiency, mean coverage, polymorphisms in the consensus relative to the parental virus and population diversity. Results will be made available to the Projects. In addition, the Core will improve workflow by cataloguing an RhCMV saturation dataset, improve processing protocols, and will collaborate with the Viral Pathogen and Analysis Resource (ViPR) to provide RhCMV sequence data and related in vivo data for their simple, searchable format (Aim 2). Bulk sequence data will be submitted to the publicly available NCBI Sequence Read Archive. Finally, the Core will employ population genetics strategies to investigate the patterns of RhCMV evolution in congenital RhCMV models by interrogating viral loads and viral population sequence space to define diversity and mechanisms of divergence amongst maternal and infant viral populations (Aim 3). Other parameters that influence infection, transmission and disease including viral gene deletion strains (Project 2) and altered immunological states (Project 1) will be analyzed for their influence on viral population diversity, founder size and compartmental effects in relation to transmission and disease. Taken together, the Core will provide important understanding of how in vivo evolutionary processes, such as bottlenecks and selective pressure, influence viral transmission and fetal disease.