NON-HUMAN PRIMATE MAJOR HISTOCOMPATIBILITY COMPLEX ALLELE DISCOVERY AND TYPING TECHNOLOGY AND DEVELOPMENT - HIV/AIDS

非人类灵长类主要组织相容性复合体等位基因的发现和分型技术与开发 - HIV/AIDS

• 批准号: 9574543
• 负责人: RACHEL KULOW
• 金额: $ 60.61万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-06-01 至 2018-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9574543
• 关键词: AIDS/HIV problem; Alleles; Communities; Development; Frequencies; Genes; Genetic; Genome; Genomics; Genotype; Goals; HIV; HIV/SIV vaccine; Haplotypes; Immune; Immunoglobulins; Killer Cells; Macaca; Major Histocompatibility Complex; Major Histocompatibility Complex Gene; Methods; Program Development; Proteins; Receptor Gene; Reproducibility; Research; Technology; Variant; exome sequencing; gene discovery; genomic profiles; improved; killer immunoglobulin-like receptor; knowledge base; nonhuman primate; receptor; reference genome; technology development; vaccine trial

“The goals of the NHP MHC Gene Discovery and Typing Development Program are to advance the detailed knowledge base of nonhuman primate (NHP) major histocompatibility complex (MHC) genetic loci, alleles, and haplotypes, and their frequencies; expand discovery and characterization of NHP killer-cell immunoglobulin-like receptors (KIRs) genes, alleles, haplotypes, and frequencies; and develop robust, high-throughput genotyping and haplotyping methods.” Host genomics, and particularly major histocompatibility complex (MHC) class I genetics, are extremely important for maximizing the reproducibility and experimental robustness of nonhuman primate HIV/SIV vaccine studies. Because HIV cure strategies under development have different mechanisms of action, a targeted approach akin to MHC genotyping macaques in vaccine trials will likely be insufficient. Instead, genotyping of the MHC and other immune loci will need to be married with studies of high impact variation throughout the genome. The overarching goal of this research is to develop technologies that will enable simultaneous immunogenotyping and identification of protein-truncating variants in non-immune genes to support HIV cure studies in macaques. This project will develop and improve target-capture arrays that enable simultaneous exome sequencing and immunogenotyping (genomic profiling) of MHC class I and class II and killer immunoglobulin-like receptor (KIR) loci from NHP used in HIV cure research; stimulate community enthusiasm for utilizing macaque genomics in HIV cure studies; and improve macaque reference genomes by defining alternate sequence representations of MHC and KIR regions.

“NHP MHC基因发现和分型开发计划的目标是推进非人灵长类动物（NHP）主要组织相容性复合体（MHC）遗传基因座、等位基因和单倍型及其频率的详细知识基础;扩大NHP免疫细胞免疫球蛋白样受体（KIR）基因、等位基因、单倍型和频率的发现和表征;并开发出强大的、高通量的基因分型和单体型分型方法。” 宿主基因组学，特别是主要组织相容性复合体（MHC）I类遗传学，对于最大限度地提高非人灵长类HIV/SIV疫苗研究的重现性和实验稳健性至关重要。 由于正在开发的HIV治疗策略具有不同的作用机制，因此类似于疫苗试验中MHC基因分型猕猴的靶向方法可能是不够的。相反，MHC和其他免疫位点的基因分型需要与整个基因组的高影响变异研究相结合。这项研究的总体目标是开发能够同时进行免疫基因分型和识别非免疫基因中蛋白质截短变体的技术，以支持猕猴中的HIV治愈研究。 该项目将开发和改进目标捕获阵列，使同时外显子组测序和免疫基因分型（基因组分析）的MHC I类和II类和杀手免疫球蛋白样受体（KIR）基因座从NHP用于艾滋病毒治疗研究;刺激社区的热情，利用猕猴基因组学在艾滋病毒治疗研究;和改善猕猴参考基因组，通过定义替代序列表示的MHC和KIR区域。