Gene-Targeted SNP discovery in rhesus macaques

描述（由申请人提供）：本提案的总体目标是发现恒河猴（Macaca mulatta）的基因连锁snp，并使这些snp容易被非人类灵长类动物研究界获取。我们将专注于识别与研究兴趣基因相关的snp，预计这些snp将对NHP研究者进行候选基因关联研究有很大的帮助。这项工作将导致在1万个恒河猴基因中发现标记位点，这将是在非人类灵长类动物中首次大规模发现基于基因的制造者。有两个具体目标。在Specific Aim 1中，我们将发现恒河猴基因3'端区域的snp。在Specific Aim 2中，我们将创建一个可公开访问的恒河猴SNP数据库。snp可能存在于基因组的许多区域。然而，基因间区域的snp对候选基因方法的效用有限。编码区的snp如果被发现，可以立即使用，但相对较少。在恒河猴中，基因3‘端或接近3’端的snp出现的频率很高。此外，其中一些snp已被发现具有功能意义。因此，我们的方法有以下优点：1。有效地发现许多snp；2. 鉴定基因中的snp；3. 发现功能性snp的潜力。我们已经确定了超过6000对引物，用于扩增恒河猴基因的3'区，到最初的提案结束时，我们将确定超过10,000对这样的引物。我们将开发和部署一个Web可访问的数据门户，允许访问NCBI dbSNP数据库中的所有恒河猴snp。该门户网站及其配套工具集将有助于获取恒河猴SNP信息，包括SNP身份、位置、群体特异性和等位基因频率。它还将为用户提供分析印度和中国恒河猴种群之间和内部SNP基因型的基本工具。这种靶向获取基因内snp的方法，将为恒河猴研究界提供一整套与特定基因相关的snp，从而推进复杂性状的遗传分析。我们发现的基于基因的snp将推进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等领域的转化研究。

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.