SEQUENCE AND POLYMORPHISM OF RHESUS MACAQUE MHC

恒河猴动物模型在HIV疫苗开发和发病机制研究中的应用 这就需要为该物种发展坚实的遗传学和免疫遗传学数据基础设施。相对于人类 数据，关于猕猴MHC更大范围的基因含量的信息很少，而且很少有多态性 来自猕猴I类和I1类基因的外部数据。作为一个尖锐的例子，存在间接证据表明可能存在AS 在某些猕猴单倍型上，多达3个I类B基因座和2个I A类基因座，但这尚未得到直接证实 基因组分析。因此，在单个实验猕猴中活跃表达的I类基因的数量可能是 未知。一些I1类基因座背后有一个本质上相似的故事，关于数百个I1基因座的结构数据非常少 猕猴MHC中还存在其他基因，其中超过三分之一的基因也直接参与了免疫反应。这些 基因缺陷为更好地了解恒河猴的遗传学和免疫遗传学提供了直接的动力 在猴免疫缺陷(SIV)艾滋病疫苗实验的设计和实施中可能有用的猕猴 以及使用这种非人类灵长类物种的嵌合SIV-HIV(SIV-HIV)动物模型。为此，我们建议制定 完成的高质量数据的猕猴主要组织相容性复合体(MHC)的DNA序列。我们进一步建议 使用扩展多态数据(SNP)和更大范围的单倍型变化来注释该数据字符串，并相对于 该区域的完整基因内容。一个基本的优先事项是有效地组织和传播这些数据给 感兴趣的科学界。为了开发这一资源，我们建议实现以下具体目标：1)派生 猕猴主要组织相容性复合体(MHC)的完整和高质量的基因组序列。2)至 开发和定义一组SNPs和更大规模的单倍型结构，作为与MHC- 连锁表型。3)鉴定和注释猕猴MHC中的基因和多态，并将这一资源 以一种对科学界有用和令人愉快的形式提供。我们将在一定程度上通过联合 来自三个成熟实验室的猕猴遗传学、基因组学和功能方面的资源和专业知识。

The increased utility of the rhesus macaque animal model in both HIV vaccine development and pathogenesis studies necessitates the development of a solid genetics and immunogeneticsdata infrastructure for this species. Relative to human data, there is a paucity of information about the larger-scale gene content of the macaqueMHC and very littlepolymorphism data from outsideof the macaque class I and I1 genes. As a pointed example, indirect evidence exists that there may be as many as 3 class I B loci and 2 class I A loci on certain macaque haplotypes, but this has not been confirmed through direct genomic analysis. Thus the number of actively expressed class I genes in an individual experimental macaque may be unknown. An essentially similar story underlies some class I1 loci, and very little structural data exists about the hundreds of other genes present in the macaque MHC, more than a third of which are also directly involved in the immuneresponse. These deficiencies provide substantial immediate motivation to better understand the genetics and immunogenetics of rhesus macaques that could be useful in the design and conduct of AIDS vaccine experiments in the simian immunodeficiency(SIV) and chimeric SIV-HIV(SHIV) animal models using this nonhuman primate species. Towards this end, we propose to develop a DNA sequenceof a macaque major histocompatibility complex (MHC)of finished high quality data. We further propose to annotatethis data string with extensivepolymorphism data (SNP) and larger-scale haplotypic variation, and with respect to the complete gene content of the region. One fundamental priority will be to effectively organize and disseminate this data to the interested scientific community. Todevelop this resource, we propose to accomplish the following specific aims: 1) To derive a complete and high quality genomic sequence of a major histocompatibility complex (MHC)from the rhesus macaque. 2) To develop and define a set of SNPs and larger scale haplotype structures useful as mapping tools in the association with MHC- linked phenotypes. 3) To identify and annotate genes and polymorphims in the macaque MHC and make this resource available in a useful and palatable form tothe scientific community. We will accomplish these aims in part by combining resources and expertise in macaque genetics,genomics, and function from three accomplished laboratories.