Genomic Sequencing to Establish a Macaque Genotype and Phenotype Research Resource

基因组测序建立猕猴基因型和表型研究资源

• 批准号: 9149897
• 负责人: BETSY M FERGUSON
• 金额: $ 87.92万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9149897
• 关键词: Address; Adenocarcinoma; Age related macular degeneration; Age-associated memory impairment; Alcohol consumption; Animal Experimentation; Animal Model; Animals; Anxiety; Arthritis; Behavior Disorders; Behavioral; Behavioral inhibition; Biomedical Research; Breeding; Cardiovascular Diseases; Chromosome Positioning; Clinic; Clinical; Clinical Data; Colitis; Communicable Diseases; Computer software; Data; Data Set; Databases; Development; Disease; Disease model; Disease susceptibility; Electronic Health Record; Ensure; Foundations; Funding; Future Generations; Generations; Genes; Genetic; Genetic Variation; Genome; Genomic medicine; Genomics; Genotype; Goals; HIV; Hereditary Disease; Home environment; Human; Human Genetics; Impaired cognition; Individual; Institution; Investments; Life; Lung diseases; Macaca; Macaca mulatta; Macular degeneration; Malaria; Maps; Measures; Methods; Modeling; Monoclonal Antibody R24; Nucleotides; Obesity; Oregon; Phenotype; Physiological; Plants; Population; Pre-Clinical Model; Primates; Recording of previous events; Research; Research Personnel; Resources; Risk; Study Subject; Technology; Time; Translations; United States; Update; Variant; West Nile virus; Work; age related; base; chikungunya; clinical phenotype; comparative; cost; disease phenotype; endometriosis; frontier; genetic association; genetic pedigree; genetic variant; genome sequencing; genome-wide; genomic data; human disease; insight; interest; member; nervous system disorder; nonhuman primate; novel; open source; personalized medicine; phenotypic data; pre-clinical; preclinical trial; research study; tool; trait; whole genome; Address; Adenocarcinoma; Age related macular degeneration; Age-associated memory impairment; Alcohol consumption; Animal Experimentation; Animal Model; Animals; Anxiety; Arthritis; Behavior Disorders; Behavioral; Behavioral inhibition; Biomedical Research; Breeding; Cardiovascular Diseases; Chromosome Positioning; Clinic; Clinical; Clinical Data; Colitis; Communicable Diseases; Computer software; Data; Data Set; Databases; Development; Disease; Disease model; Disease susceptibility; Electronic Health Record; Ensure; Foundations; Funding; Future Generations; Generations; Genes; Genetic; Genetic Variation; Genome; Genomic medicine; Genomics; Genotype; Goals; HIV; Hereditary Disease; Home environment; Human; Human Genetics; Impaired cognition; Individual; Institution; Investments; Life; Lung diseases; Macaca; Macaca mulatta; Macular degeneration; Malaria; Maps; Measures; Methods; Modeling; Monoclonal Antibody R24; Nucleotides; Obesity; Oregon; Phenotype; Physiological; Plants; Population; Pre-Clinical Model; Primates; Recording of previous events; Research; Research Personnel; Resources; Risk; Study Subject; Technology; Time; Translations; United States; Update; Variant; West Nile virus; Work; age related; base; chikungunya; clinical phenotype; comparative; cost; disease phenotype; endometriosis; frontier; genetic association; genetic pedigree; genetic variant; genome sequencing; genome-wide; genomic data; human disease; insight; interest; member; nervous system disorder; nonhuman primate; novel; open source; personalized medicine; phenotypic data; pre-clinical; preclinical trial; research study; tool; trait; whole genome

SUMMARY Rhesus macaques are the most commonly studied non-human primate (NHP) in academic biomedical research. Due to their high level of genomic, physiological, anatomical and behavioral similarity to humans, macaques often serve as an indispensable preclinical model. The close evolutionary history of macaques and humans is evident in their similar disease susceptibilities and genetic associations (e.g., S/HIV, macular degeneration, obesity, cardiovascular disease, age-associated cognitive decline, etc.). The Oregon National Primate Research Center (ONPRC) is home to more than 4,000 Indian-origin rhesus macaques, the current members of a pedigreed breeding colony that spans 10 generations. This colony supports 38 federally funded research studies at the ONPRC, an additional 60+ studies at other research institutions, and several collaborative, large scale phenotyping studies. However given the absence of genome-wide genotyping tools for macaques, genomic data on the ONPRC rhesus macaque colony remain extremely sparse. This R24 will develop a novel and efficient approach for the large-scale genomic characterization of this heavily studied colony. We will obtain 30X whole genome sequence data on at least 200 selected individuals to generate a dense genomic map of the colony. We will then utilize genotype-by-sequencing (GBS), an approach commonly used in genomic studies of plants but still rarely used in biomedical research, in concert with genome-wide imputation to obtain complete genomic data in an additional 1,000 subjects. By leveraging the dense pedigree structure for the accurate imputation of genome-wide genotypes, we will establish a very low- cost method for the continued characterization of future generations, ensuring a lasting resource for biomedical research. To facilitate widespread use of the data we generate, we will develop a database that enables public access in near real-time to the genotype data produced. The database will also include clinical data on the same animals, making it the first publically accessible resource to provide both NHP genotype and phenotype data. The clinical/phenotypic data can be analyzed for disease associations, for the identification of animals of interest, or to download with genomic data for comparative analyses. Finally, because the characterized subjects include living animals, researchers can also identify potential study subjects based upon the presence or absence of particular genomic variants, clinical data or both. The latter option will provide opportunity to identify rare animals of research interest, an important goal for NHP model disease development. We expect that this resource will attract new investigators who wish to leverage the genotype or clinical/phenotype data as an entree to NHP research, be it at the ONPRC or elsewhere. As a result of this work, we will establish the first genomically characterized, pedigreed rhesus macaque research colony, develop a sustainable approach for the continued characterization of future generations, and establish the tools, resources and methods to support genome imputation in other rhesus macaque breeding colonies.

概括 恒河猕猴是学术生物医学中最常见的非人类灵长类动物（NHP） 研究。由于它们的基因组，生理，解剖学和行为相似， 猕猴通常是必不可少的临床前模型。猕猴和 人类在类似的疾病敏感性和遗传关联中很明显（例如，S/HIV，黄斑 退化，肥胖，心血管疾病，与年龄相关的认知下降等）。俄勒冈国民 灵长类动物研究中心（ONPRC）拥有4,000多个印度 - 原始恒河猕猴，当前 跨越10代的血统繁殖菌落的成员。这个殖民地支持38个联邦资助 ONPRC的研究，其他研究机构的另外60多项研究，几个研究 协作，大规模表型研究。但是，鉴于缺乏全基因组基因分型工具 对于猕猴，有关ONPRC恒河猕猴菌落的基因组数据仍然非常稀疏。这个R24会 开发一种新颖有效的方法，用于对此深入研究的大规模基因组表征 殖民地。我们将在至少200个选定个体上获得30倍的整个基因组序列数据，以生成A 菌落的密集基因组图。然后，我们将利用基因型逐序（GBS），一种方法 通常用于植物的基因组研究，但仍然很少在生物医学研究中使用 全基因组插补以在另外1,000名受试者中获得完整的基因组数据。通过利用 致密的血统结构，为全基因组基因型的准确插定，我们将建立一个非常低的 持续表征子孙后代的成本方法，确保生物医学的持久资源 研究。为了促进广泛使用我们生成的数据，我们将开发一个数据库，使公众 几乎实时访问所产生的基因型数据。该数据库还将包括有关 相同的动物，使其成为第一个提供NHP基因型和表型的公开访问资源 数据。可以分析疾病关联的临床/表型数据，以鉴定 兴趣，或使用基因组数据下载进行比较分析。最后，因为特征是 受试者包括活体动物，研究人员还可以根据存在来识别潜在的研究对象 或缺乏特定的基因组变体，临床数据或两者。后者的选项将为 识别研究兴趣的稀有动物，这是NHP模型疾病发展的重要目标。我们期望 该资源将吸引希望利用基因型或临床/表型数据的新调查员 NHP研究的参与，无论是在ONPRC还是其他地方。由于这项工作，我们将建立 首先以基因组为特征的，建，恒河猕猴研究殖民地开发了一种可持续的方法 为了继续表征子孙后代，并建立工具，资源和方法 在其他恒河猕猴繁殖菌落中支持基因组归因。