Large-scale Discovery of Functional Genetic Variation in Rhesus Macaques

大规模发现恒河猴功能遗传变异

基本信息

批准号：
8932205
负责人：
JEFFREY A. ROGERS
金额：
$ 54.51万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-01 至 2018-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8932205
关键词：
Acquired Immunodeficiency Syndrome Affect Alcoholism Animal Model Animals Anxiety Disorders Back Behavioral Bioinformatics Biological Process Biomedical Research Communicable Diseases Communities Copy Number Polymorphism DNA DNA Sequence Data Databases Development Diabetes Mellitus Disease Disease Progression Disease susceptibility Endocrine Functional disorder Funding Funding Agency Gastrointestinal Diseases Genes Genetic Genetic Polymorphism Genetic Variation Genetic study Genome Genomics Goals HIV HIV Infections Health Human Individual Introns Investigation Investments Knowledge Laboratories Laboratory Organism Lead Macaca Macaca mulatta Medicine Mental Depression Mental disorders Metabolic Diseases Modeling Neurobiology Nucleotides Osteoporosis Pathogenesis Pharmacologic Substance Phase Phenotype Polycystic Ovary Syndrome Population Population Research Prevention Primates Reproductive Biology Request for Applications Research Research Personnel Risk Risk Factors SIV Sampling Sequence Analysis Staging Study Subject Surveys United States National Institutes of Health Vaccines Variant addiction analytical tool base clinical risk college combat genetic information genetic variant genome sequencing genomic variation human disease human genome sequencing improved innovation nonhuman primate novel novel vaccines programs public health relevance response tool trait

项目摘要

DESCRIPTION (provided by applicant): Rhesus macaques (Macaca mulatta) are the most widely used nonhuman primates in biomedical research. This species is critically important in efforts to understand the causes and potential new treatments for many human diseases. Rhesus macaques are a premier model organism for the study of the pathogenesis of HIV-AIDS, and for development of novel treatments and new vaccines against HIV infection. In addition, rhesus macaques are commonly used in studies of basic neurobiology, risk factors for psychiatric illnesses such as anxiety disorders and depression, metabolic diseases such as diabetes and osteoporosis, and reproductive biology. This project will dramatically increase the value and impact of this laboratory primate species for all types of biomedical research by generating a substantial amount of new information about genetic variation within the species. It is well established that genetic differences among people influence their risk of developing many, probably most, diseases including those listed above. Genetic variation can also influence the progression of disease and the responses of different people to a specific treatment. We will facilitate research concerning the genetic basis of disease susceptibility and response to treatment by identifying large numbers of new DNA sequence variants in functional genes and intervening sequences within the rhesus genome. To accomplish this, we will produce high-quality whole genome DNA sequence data for 433 rhesus macaques. The sequence data will be used to identify currently unknown DNA sequence variation present in this species, including single nucleotide variants, small indels, CNVs and other variants. The study subjects will be animals already characterized for one or more disease-related phenotypes, such as vaccine protection against SIV-AIDS, neurobiological traits, behavioral traits, metabolic disorders such as diabetes or polycystic ovary syndrome, and gastrointestinal diseases. By sequencing these animals, we will generate BOTH general information about variation across the macaque genome and specific information beneficial to the investigators who have phenotypically characterized these animals and contributed these DNA samples. All the data generated will be made publicly available through appropriate NIH and NPRC databases.

描述（由申请人提供）：恒河猴（Macaca mulatta）是生物医学研究中使用最广泛的非人类灵长类动物，该物种对于了解许多人类疾病的原因和潜在的新疗法至关重要。恒河猴通常用于研究艾滋病毒/艾滋病的发病机制，以及开发针对艾滋病毒感染的新疗法和新疫苗。该项目将在神经生物学、焦虑症和抑郁症等精神疾病的危险因素、糖尿病和骨质疏松症等代谢疾病以及生殖生物学方面产生大量成果，从而极大地提高该实验室灵长类动物对所有类型生物医学研究的价值和影响。关于物种内遗传变异的大量新信息已经明确，人与人之间的遗传差异会影响他们患上许多（可能是大多数）疾病的风险，遗传变异也会影响疾病的进展和不同疾病的反应。我们将促进有关特定治疗的研究。通过识别恒河猴基因组中功能基因和干预序列中的大量新 DNA 序列变异，为疾病易感性和治疗反应奠定基础。为了实现这一目标，我们将为 433 只恒河猴生成高质量的全基因组遗传 DNA 序列数据。序列数据将用于识别该物种中目前未知的 DNA 序列变异，包括单核苷酸变异、小插入缺失、CNV 和其他变异，研究对象将是已经具有一种或多种疾病相关特征的动物。表型，例如针对 SIV-AIDS 的疫苗保护、神经生物学特征、行为特征、糖尿病或多囊卵巢综合症等代谢紊乱以及胃肠道疾病。通过对这些动物进行测序，我们将生成有关猕猴基因组变异的一般信息和特定信息。对研究这些动物的表型特征并贡献这些 DNA 样本的研究人员有利的信息将通过适当的 NIH 和 NPRC 数据库公开。