Gene-Targeted SNP discovery in rhesus macaques

恒河猴中基因靶向 SNP 的发现

• 批准号: 7909837
• 负责人: ROBERT B. NORGREN
• 金额: $ 53.89万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-09 至 2011-09-08
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7909837
• 关键词: Gene; Targeted; SNP; discovery; rhesus

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.

描述（由申请人提供）：本提案的总体目标是在恒河猴 (Macaca mulatta) 中发现基因相关的 SNP，并使非人类灵长类研究界能够轻松获取这些 SNP。我们将专注于识别与研究兴趣基因相关的 SNP，预计这些 SNP 对 NHP 研究人员进行候选基因关联研究将非常有用。这项工作将在 10,000 个恒河猴基因中鉴定出标记基因座，并且将是在非人类灵长类动物中鉴定基于基因的标记物的首次大规模努力。将有两个具体目标。在具体目标 1 中，我们将在恒河猴基因的 3' 端区域发现 SNP。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。 SNP 可能存在于基因组的许多区域。然而，基因间区域的 SNP 对于候选基因方法的实用性有限。编码区的单核苷酸多态性（SNP）如果被发现的话可以立即使用，但相对较少。在恒河猴中，基因 3' 端或附近的 SNP 频率很高。此外，其中一些 SNP 已被发现具有功能意义。因此，我们的方法具有以下优点：1.高效发现许多SNP； 2. 识别基因中的SNP； 3. 发现功能性SNP的潜力。我们已经鉴定出超过 6,000 个引物对，用于扩增恒河猴基因的 3' 区域，并且到原始提案结束时将鉴定出超过 10,000 个这样的引物对。我们将开发和部署一个可通过网络访问的数据门户，允许访问 NCBI dbSNP 数据库中的所有恒河猴 SNP。该门户网站和随附的工具集将有助于访问恒河猴 SNP 信息，包括 SNP 身份、位置、群体特异性和等位基因频率。它还将为用户提供基本工具来分析印度和中国恒河猴种群之间和内部的 SNP 基因型。获得基因中包含的 SNP 的有针对性的方法将为恒河猴研究界提供与特定基因相关的一套全面的 SNP，以推进复杂性状的遗传分析。我们发现的基于基因的 SNP 将推进以下领域的转化研究：SIV/HIV 生物学、酗酒、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。