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（由适用提供）：恒河猕猴（Macaca mulatta）是生物医学研究中使用最广泛的非人类私人私人。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。恒河猕猴是研究HIV-AID发病机理的主要模型生物，以及开发新的治疗方法和针对HIV感染的新疫苗。此外，猕猴通常用于基本神经生物学的研究，焦虑症和抑郁症等精神病的危险因素，糖尿病和骨质疏松症等代谢疾病以及生殖生物学。该项目将通过产生有关该物种内部遗传变异的大量新信息来大大增加该实验室灵长类动物对所有类型的生物医学研究的价值和影响。众所周知，人们之间的遗传差异会影响他们患有许多疾病（包括上述疾病）的风险。遗传变异也会影响疾病的进展以及不同人对特定治疗的反应。我们将通过鉴定功能基因中的大量新DNA序列变体和恒河猴基因组中的介入序列来促进有关疾病敏感性和对治疗反应的遗传基础的研究。为此，我们将使用序列数据来识别该物种中存在的当前未知的DNA序列变化，包括单个核丁基变体，小实例，CNV和其他变体。该研究受试者将是已经针对一种或多种与疾病相关的表型进行特征的动物，例如针对SIV-AID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征和胃肠道疾病等代谢性疾病。通过对这些动物进行测序，我们将同时生成有关猕猴基因组变异的一般信息，也将对具有表型表征这些动物并贡献这些DNA样品的研究人员有益于研究人员。生成的所有数据将通过适当的NIH和NPRC数据库公开提供。