Host Genetics Core

宿主遗传学核心

• 批准号: 8294660
• 负责人: NORMAN L LETVIN
• 金额: $ 134.08万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8294660
• 关键词: AIDS/HIV problem; Acute; Affect; Area; Biometry; Candidate Disease Gene; Characteristics; Chronic; Clinical; Computational Biology; Containment; Core Facility; Data; Data Set; Databases; Disease Progression; Genes; Genetic; Genomics; Genotype; Goals; HIV-1; Human; Immunology; Individual; Infection; Leadership; Length; Macaca mulatta; Molecular Biology; Patients; Predisposition; Research Personnel; Sequence Analysis; Services; Strategic Planning; System; Translating; Vaccine Design; Vaccines; Variant; Viral; Virus; computerized data processing; data management; env Genes; genetic association; tool; transmission process; virus genetics

The overall goal of this CHAVI application is to elucidate viral and host determinants of HIV-1 transmission, persistence, and partial containment in primary human infection, and to translate these findings into rational vaccine design. Core A will support this effort by providing expertise and service in the areas of host genomics and HIV-1 genetics. The Core is comprised of three sections: 1. The Host Genomics Section (under the leadership of Dr. David Goldstein) will elucidate host genetic differences affecting susceptibility to HIV-1 infection and disease progression in early HIV-1 infection. Specific tasks include to (i) identify, validate, and genotype a robust set of tagging SNPs (tSNPs) for 500 high priority human genes to facilitate indirect genetic association studies, (ii) identify putative functional variants among the candidate genes for direct association studies; (iii) develop uniform experimental genotyping approaches; (ivj optimize sequencing primers for direct association studies in the rhesus monkey; (v) investigate all associations at the genetic and functional level; and (vi) establish a robust data management system for clinical as well as host and viral genetic data. 2. The HIV-1 Molecular Biology and Sequencing Section (under the leadership of Dr. Beatrice Hahn), will generate functional HIV-1 env clones and full-length HIV-1 sequences from acutely and chronically infected individuals to elucidate the genetic, biologic, antigenic, and structural characteristics of sexually transmitted virus and the mechanisms underlying this transmission. Specific tasks include to (i) amplify, clone and sequence functional env genes from acute HIV-1 infections; (ii) examine envelopes from acute and chronic HIV-1 infections for phenotypic differences, and (iii) derive full-length HIV-1 sequences from patients with acute HIV-1 infection. 3. The HIV-1 Computational Biology and Biostatistics Section (under the leadership of Bette Korber), will provide interactive automated HIV-1 sequence entry and analysis tools, and establish and maintain an Acute HIV-1 Sequence Database. Specific tasks include to (i) provide an interactive automated HIV-1 sequence data entry system that enables users to identify sequencing errors and contamination as part of their initial data processing; (ii) provide interactive automated tools for baseline analysis/of CHAVI HIV-1 sequences, (iii) make CHAVI HIV-1 sequences publicly available, (iv) build CHAVI investigator interfaces for data entry of immunological data, (v) analyze HIV-1 sequence datasets for acute infection sequence signatures and (vi) provide statistical support for the CHAVI effort. In Year 02, each of these sections will become an independent core facility (see Strategic Plan), commensurate with the anticipated increase of both host and HIV-1 sequence analysis.

此CHAVI应用的总体目标是阐明HIV-1的病毒和宿主决定因素 原发性人类感染中的传播，持久性和部分遏制，并将这些发现转化为理性疫苗设计。核心A将通过在宿主基因组学和HIV-1遗传学领域提供专业知识和服务来支持这一工作。核心由三个部分组成： 1。宿主基因组学部分（在戴维·戈德斯坦博士的领导下）将阐明宿主遗传差异，影响HIV-1早期感染中HIV-1感染和疾病进展的易感性。特定任务包括（i）识别，验证和基因型的一组可靠的标记SNP（TSNP），用于500个高优先级人类基因，以促进间接遗传关联研究，（ii）在候选基因中识别直接关联研究的候选功能变体； （iii）发展统一的实验基因分型方法； （IVJ优化恒河猴直接关联研究的测序引物；（v）研究遗传和功能水平上的所有关联；并且（vi）（vi）建立了临床以及宿主和病毒遗传数据的强大数据管理系统。 2。HIV-1分子生物学和测序部分（在Beatrice Hahn博士的领导下）将产生功能性HIV-1 ENV克隆和全长的HIV-1序列，从急性和长期感染的个体中阐明了这种传播病毒和这种传播机制的遗传，生物学，抗原和结构特征，以阐明遗传，生物学，抗原和结构性特征。特定的任务包括（i）从急性HIV-1感染中放大，克隆和序列功能性ENV基因； （ii）检查表型差异的急性和慢性HIV-1感染的信封，以及（iii）从急性HIV-1感染患者中得出全长HIV-1序列。 3。HIV-1计算生物学和生物统计学部分（在Bette Korber的领导下）将提供交互式自动化的HIV-1序列输入和分析工具，并建立和维护急性HIV-1序列数据库。特定任务包括（i）提供交互式自动化的HIV-1序列数据输入系统，该系统使用户能够识别排序错误和污染作为其初始数据处理的一部分； （ii）提供用于基线分析/CHAVI HIV-1序列的交互式自动化工具，（iii）使CHAVI HIV-1序列公开可用，（iv）构建CHAVI研究者的界面，用于免疫数据的数据输入，（V）分析HIV-1序列数据集用于急性感染序列序列序列数据集 签名和（vi）为Chavi努力提供统计支持。在第02年，这些部分中的每一个都将成为独立的核心设施（请参阅战略计划），与宿主和HIV-1序列分析的预期增加相称。