Large-scale Discovery of Functional Genetic Variation in Rhesus Macaques

大规模发现恒河猴功能遗传变异

• 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
• 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

 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（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灵长类动物。这个物种在理解许多人类疾病的原因和潜在的新治疗方法方面至关重要。恒河猴是研究HIV-AIDS发病机制和开发抗HIV感染的新疗法和新疫苗的首要模式生物。此外，恒河猴通常用于基础神经生物学、焦虑症和抑郁症等精神疾病的风险因素、糖尿病和骨质疏松症等代谢疾病以及生殖生物学的研究。该项目将通过产生大量关于物种内遗传变异的新信息，大大增加这种实验室灵长类物种对所有类型生物医学研究的价值和影响。众所周知，人与人之间的遗传差异会影响他们患上包括上述疾病在内的许多疾病（可能是大多数疾病）的风险。遗传变异也可以影响疾病的进展和不同人对特定治疗的反应。我们将通过鉴定恒河猴基因组中功能基因和间插序列中大量新的DNA序列变异，促进有关疾病易感性和治疗反应的遗传基础的研究。为了实现这一目标，我们将为433只恒河猴提供高质量的全基因组DNA序列数据。序列数据将用于鉴定该物种中目前未知的DNA序列变异，包括单核苷酸变异、小indel、CNV和其他变异。研究受试者将是已经表征了一种或多种疾病相关表型的动物，如针对SIV-AIDS的疫苗保护、神经生物学性状、行为性状、代谢紊乱如糖尿病或多囊卵巢综合征和胃肠道疾病。通过对这些动物进行测序，我们将产生关于猕猴基因组变异的一般信息和有利于研究人员的特定信息，这些研究人员对这些动物进行了表型表征并贡献了这些DNA样本。所有生成的数据将通过适当的NIH和NPRC数据库公开提供。