Gene-Targeted SNP discovery in rhesus macaques

描述(申请人提供)：这项提案的总体目标是在恒河猴(猕猴)中发现与基因相关的SNPs，并使非人类灵长类研究社区容易获得这些SNPs。我们将专注于识别与感兴趣的基因相关的SNPs，期望这些SNPs将对NHP研究人员进行候选基因关联研究大有裨益。这项工作将在10,000个猕猴基因中确定标记基因，并将是在非人类灵长类动物中识别基于基因的标记的第一次大规模努力。将有两个具体目标。在特定的目标1中，我们将在恒河猴基因的3‘端区域发现SNPs。在具体目标2中，我们将创建一个可公开访问的恒河猴SNP数据库。SNPs可能存在于基因组的许多区域。然而，基因间隔区的SNP在候选基因方法中的应用有限。如果发现编码区的SNP，可以立即使用，但相对较少。基因3‘端的SNP在恒河猴中的频率很高，或在其附近。此外，其中一些SNP已被发现具有功能意义。因此，我们的方法具有以下优点：1.高效地发现许多SNPs；2.识别基因中的SNPs；3.发现功能性SNPs。我们已经确定了6,000多对用于扩增恒河猴基因3‘端区域的引物，并将在最初的提案结束时确定10,000多对这样的引物。我们将开发和部署一个网络可访问的数据门户，允许访问NCBI数据库中的所有恒河猴SNP。这个门户和配套的工具集将有助于获取恒河猴SNP信息，包括SNP身份、位置、种群特异性和等位基因频率。它还将为用户提供基本工具，以分析印度和中国恒河猴群体之间和群体内的SNP基因型别。这种有针对性地获得基因中包含的SNPs的方法，将为恒河猴研究界提供一套与特定基因相关联的全面的SNPs，以推进复杂特征的遗传分析。我们发现的基于基因的SNPs将促进以下领域的翻译研究：SIV/HIV生物学、酒精中毒、压力/焦虑、神经退行性疾病、黄斑变性、干细胞生物学、生殖功能障碍和糖尿病。

DESCRIPTION (provided by applicant): The overall goal of this proposal is to discover gene-linked SNPs in rhesus macaques (Macaca mulatta) and to make these SNPs easily accessible to the non-human primate research community. We will focus on identifying SNPs associated with genes of research interest anticipating that these SNPs will be of great use to NHP investigators pursuing candidate gene association studies. This work will result in marker loci being identified in 10,000 rhesus macaque genes, and will be the first large-scale effort to identify gene-based makers in non-human primates. There will be two specific aims. In Specific Aim 1, we will discover SNPs in the 3' end region of rhesus macaque genes. In Specific Aim 2, we will create a publicly accessible rhesus macaque SNP database. SNPs may be found in many regions of the genome. However, SNPs in intergenic regions are of limited utility for candidate gene approaches. SNPs in coding regions are of immediate use, if found, but are relatively rare. SNPs in, or in close proximity to, the 3' end of genes can be found in rhesus macaques at high frequency. In addition, some of these SNPs have been found to have functional significance. Thus, our approach has the following advantages: 1. Efficient discovery of many SNPs; 2. Identifying SNPs in genes; 3. The potential to discover functional SNPs. We have identified over 6,000 primer pairs that have been used to amplify the 3' region of rhesus macaque genes and will have identified over 10,000 such primer pairs by the end of the original proposal. We will develop and deploy a Web accessible data portal allowing access to all rhesus macaque SNPs in the NCBI dbSNP database. This portal and accompanying tool set will facilitate access to rhesus macaque SNP information, including SNP identity, position, population specificity and allele frequency. It will also provide users with basic tools to analyze SNP genotypes between and within Indian and Chinese rhesus populations. The targeted approach to obtaining SNPs contained within genes, will provide the rhesus macaque research community with a comprehensive set of SNPs linked to specific genes to advance the genetic analysis of complex traits. The gene-based SNPs we discover will advance translational research the areas of: SIV/HIV biology, alcoholism, stress/anxiety, neurodegenerative diseases, macular degeneration, stem cell biology, reproductive dysfunction and diabetes.