Gene-Targeted SNP discovery in rhesus macaques

恒河猴中基因靶向 SNP 的发现

• 批准号: 8069199
• 负责人: ROBERT B. NORGREN
• 金额: $ 58.29万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-06-18 至 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8069199
• 关键词: Alcoholism; Animal Model; Animals; Anxiety; Area; Biology; Candidate Disease Gene; Cell Aging; Chinese People; Chromosomes; Code; Communities; Complex; Data; Databases; Deposition; Diabetes Mellitus; Disease; Environment; Environmental Risk Factor; Frequencies; Functional disorder; Gene Frequency; Gene Targeting; Genes; Genetic; Genetic Markers; Genome; Genomics; Genotype; Goals; HIV; Haplotypes; Hereditary Disease; Human; Human Genetics; Immune system; Individual; Intercistronic Region; Link; Location; Macaca mulatta; Macular degeneration; Minor; Monkeys; Neurodegenerative Disorders; Neurosciences; Phenotype; Population; Positioning Attribute; Process; Reproductive Biology; Research; Research Personnel; Resources; Role; SIV; Single Nucleotide Polymorphism; Site; Solutions; Source; Specificity; Stress; Testing; Translational Research; Work; base; cell age; data portal; gene discovery; genetic analysis; human disease; interest; nonhuman primate; reproductive; stem cell biology; tool; trait; web site; web-accessible

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发现恒河猴（Macaca mulatta）中的基因连锁SNP，并使这些SNP易于为非人灵长类动物研究界所用。我们将专注于识别与研究兴趣基因相关的SNP，预计这些SNP将对进行候选基因关联研究的NHP研究人员有很大用处。这项工作将导致在10，000个恒河猴基因中识别标记位点，并将是第一次大规模识别非人类灵长类动物中基于基因的标记的努力。将有两个具体目标。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可以在基因组的许多区域中发现。然而，基因间区域的SNP对于候选基因方法的效用有限。编码区中的SNPs如果被发现，可以立即使用，但相对罕见。在恒河猴中可以以高频率发现基因的3'端中或紧邻3'端的SNP。此外，已经发现这些SNP中的一些具有功能意义。因此，我们的方法具有以下优点：1。有效发现许多SNP; 2.识别基因中的SNP; 3.发现功能性SNPs的潜力。我们已经鉴定了超过6，000对用于扩增恒河猴基因3'区域的引物对，并且在原始提案结束时将鉴定超过10，000对这样的引物对。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。该门户网站和配套工具集将有助于获得恒河猴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。有针对性的方法来获得包含在基因内的SNP，将提供恒河猴研究社区与特定基因的SNP链接的一套全面的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。

项目成果

Leveraging human genomic information to identify nonhuman primate sequences for expression array development.

• DOI: 10.1186/1471-2164-6-160
• 发表时间: 2005-11-15
• 期刊: BMC genomics
• 影响因子: 4.4
• 作者: Spindel ER;Pauley MA;Jia Y;Gravett C;Thompson SL;Boyle NF;Ojeda SR;Norgren RB Jr
• 通讯作者: Norgren RB Jr

Limitations of the rhesus macaque draft genome assembly and annotation.

• DOI: 10.1186/1471-2164-13-206
• 发表时间: 2012-05-30
• 期刊: BMC genomics
• 影响因子: 4.4
• 作者: Zhang X;Goodsell J;Norgren RB Jr
• 通讯作者: Norgren RB Jr

Advantages of an Improved Rhesus Macaque Genome for Evolutionary Analyses.

• DOI: 10.1371/journal.pone.0167376
• 发表时间: 2016
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Gradnigo JS;Majumdar A;Norgren RB Jr;Moriyama EN
• 通讯作者: Moriyama EN

Type I interferon responses in rhesus macaques prevent SIV infection and slow disease progression.

• DOI: 10.1038/nature13554
• 发表时间: 2014-07-31
• 期刊: NATURE
• 影响因子: 64.8
• 作者: Sandler, Netanya G.;Bosinger, Steven E.;Estes, Jacob D.;Zhu, Richard T. R.;Tharp, Gregory K.;Boritz, Eli;Levin, Doron;Wijeyesinghe, Sathi;Makamdop, Krystelle Nganou;del Prete, Gregory Q.;Hill, Brenna J.;Timmer, J. Katherina;Reiss, Emma;Yarden, Ganit;Darko, Samuel;Contijoch, Eduardo;Todd, John Paul;Silvestri, Guido;Nason, Martha;Norgren, Robert B., Jr.;Keele, Brandon F.;Rao, Srinivas;Langer, Jerome A.;Lifson, Jeffrey D.;Schreiber, Gideon;Douek, Daniel C.
• 通讯作者: Douek, Daniel C.