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

NHP MHC基因发现和分型开发计划的目标是推进关于非人灵长类主要组织相容性复合体(NHP)主要组织相容性复合体(MHC)遗传位点、等位基因和单倍型及其频率的详细知识库；扩大NHP杀伤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；开发可靠、高通量的基因分型和单倍型分析方法。 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，对于最大化非人类灵长类HIV/SIV疫苗研究的重复性和实验稳定性是极其重要的。由于正在开发的艾滋病毒治疗策略有不同的作用机制，类似于疫苗试验中MHC基因分型猕猴的有针对性的方法可能是不够的。相反，MHC和其他免疫位点的基因分型将需要与在整个基因组中进行高影响变异的研究结合起来。这项研究的首要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断变体的技术，以支持猕猴的艾滋病毒治愈研究。该项目将开发和改进靶标捕获阵列，以实现用于艾滋病毒治愈研究的NHP的MHC I类和II类和杀伤免疫球蛋白样受体(KIR)基因座的同步外显子组测序和免疫基因分型(基因组图谱)；激发社区对在艾滋病毒治愈研究中利用猕猴基因组学的热情；并通过定义MHC和KIR区的替代序列表示来改进猕猴参考基因组。

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.