Genetic Linkage Mapping in Rhesus Monkeys

恒河猴的遗传连锁图谱

• 批准号: 7983791
• 负责人: JEFFREY A. ROGERS
• 金额: $ 24.75万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7983791
• 关键词: AIDS vaccine development; Acquired Immunodeficiency Syndrome; Alcoholism; Animal Model; Animals; Area; Arts; Biology; Biomedical Research; Budgets; Chromosome Mapping; Collaborations; Communities; DNA Sequence; Data; Data Linkages; Databases; Development; Diabetes Mellitus; Disease; Generations; Genes; Genetic; Genetic Markers; Genetic Polymorphism; Genome; Genomics; Genotype; Goals; HIV Infections; Health; Human; Immunology; Informatics; Investigation; Laboratories; Leadership; Location; Macaca; Macaca mulatta; Maps; Methods; Microsatellite Repeats; Monoclonal Antibody R24; Neurobiology; Neurosciences; Obesity; Pathogenesis; Pharmacology; Physical Map of the Human Genome; Positioning Attribute; Primates; Psychology, Other; Quantitative Trait Loci; Range; Reproductive Biology; Request for Applications; Research; Research Personnel; Research Project Grants; Resources; Science; Screening procedure; United States National Institutes of Health; autosome; base; bone; density; design; developmental psychology; genetic analysis; genetic linkage analysis; genetic pedigree; genome sequencing; human disease; improved; nonhuman primate; novel; novel strategies; physical mapping; programs; tool; trait

The goal of this competitive renewal is to increase the value of rhesus macaques (Macaca mulatto) for genetic and genomic research by continuing development of a highly informative genetic linkage map for this species. Rhesus monkeys are the most widely used nonhuman primate in biomedical research. This species is already an important model organism for studies of neurobiology, immunology, HIV infection and AIDS, pharmacology, diabetes and obesity, bone biology, alcoholism, developmental psychology and other significant human health problems. Improved research tools and information related to genetics and genomics will make this species even more valuable for analyses of the genetic basis of various human diseases. During the first four years of this project, an initial genetic linkage map was produced that consists of 241 human microsatellite loci genotyped and analyzed in more than 800 pedigreed rhesus monkeys. This initial map covers all 20 rhesus autosomes, and the average spacing between markers is approximately 9.3 centiMorgans. However, the value of this map is limited by the lack of genetic markers in some chromo- somal regions, and the low heterozygosity of loci in others. In this renewal application, support is requested to add 300 additional microsatellite polymorphisms to this initial rhesus linkage map. This will improve the density, coverage and scientific value of the rhesus linkage map. Support is also requested to establish a collaboration with the Baylor Human Genome Sequencing Center in order to integrate the growing genetic linkage map with the whole genome DNA sequence that BHGSC is generating for this species. Integration of genetic linkage data with physical mapping and sequence data will benefit both projects and make these resources and this species more useful for many different genetic analyses. Finally, this project will establish a website designed to give the research community easy access to up-to-date rhesus linkage mapping data, including detailed information about the microsatellite polymorphisms discovered through this study. A more informative linkage map for this species will significantly increase the opportunity for and statistical power of whole genome linkage screens (i.e. QTL mapping analyses) intended to locate functional genes that influence significant traits related to human health and disease.

这次竞争性更新的目标是增加猕猴(Macaca Mulatto)的价值。 通过继续开发信息丰富的遗传连锁图谱来进行遗传和基因组研究 这个物种。恒河猴是生物医学研究中使用最广泛的非人类灵长类动物。这 物种已经是研究神经生物学、免疫学、艾滋病毒感染和 艾滋病、药理学、糖尿病和肥胖症、骨生物学、酗酒、发展心理学等 严重的人类健康问题。改进的研究工具和与遗传学和 基因组学将使这个物种在分析不同人类的遗传基础方面更加有价值 疾病。在这个项目的头四年里，制作了一个初步的遗传连锁图谱，它包括 对800多只恒河猴的241个人类微卫星基因座进行了基因分型和分析。这 初始图谱涵盖了所有20个恒河猴常染色体，标记之间的平均间距约为9.3 厘米摩根。然而，由于一些显性遗传标记的缺乏，该图谱的应用价值受到限制。 其他基因座杂合度较低。在此续订申请中，请求支持 在这个最初的恒河猴连锁图谱中增加300个额外的微卫星多态。这将改善 恒河猴连锁图谱的密度、覆盖率和科学价值。还要求提供支持以建立一个 与贝勒人类基因组测序中心合作，以整合不断增长的基因 与BHGSC为该物种生成的全基因组DNA序列的连锁图谱。整合 将遗传连锁数据与物理作图和序列数据结合起来将使这两个项目受益，并使这些 资源和这一物种对许多不同的遗传分析更有用。最后，这个项目将建立 一个网站，旨在让研究界轻松获取最新的恒河猴连锁图谱数据， 包括通过这项研究发现的微卫星多态的详细信息。一个 该物种的信息更丰富的连锁图谱将显著增加获得和统计的机会 全基因组连锁筛选(即QTL作图分析)的能力，旨在定位 影响与人类健康和疾病相关的重要性状。