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Component: MHC Genetic Core

成分：MHC 遗传核心

基本信息

批准号：
10457477
负责人：
Amanda Vinson
金额：
$ 7.45万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-08-01 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10457477
关键词：
Acquired Immunodeficiency Syndrome Address Adult Age Algorithms Alleles Animal Husbandry Animal Model Animals Award Base Sequence Biological Assay Biomedical Research Breeding Caring Development Disease Disease Progression Ensure Female Gene Frequency Genetic Genetic Variation Genome Genomics Genotype Goals HIV Health Immigrant Individual Infant Informatics Knowledge Lead MHC Class I Genes Macaca Macaca mulatta Maintenance Morbidity - disease rate Practice Management Primates Protocols documentation Reporting Research Research Support SNP genotyping Technology Time Uncertainty Work animal breeding animal colony cost experience feasibility testing genetic pedigree genetic testing genome-wide human disease improved male member mortality novel offspring preservation recruit simian human immunodeficiency virus success trait working group

项目摘要

PROJECT SUMMARY, Core C: MHC Genetic Typing Core Genetically well-characterized animal models are critical for the success of HIV/SHIV research, including characterization for MHC genotype, known ancestry, and pedigree relationships. In particular, informative and accurate MHC genotyping is essential, due to the complexity of the MHC class I loci in macaques, and the influence of allele type on disease progression. The need for genetically well-characterized animal models for research must also be balanced against the need to preserve genetic diversity in animal colonies dedicated to supporting biomedical research. This is a requirement not only to ensure long-term colony health, but to ensure the relevance of experimental findings to human disease. The ONPRC is a leader in the development in many of the current recommended approaches and technologies used in genetic typing and management of NHP colonies. The aims of the Genetics Core for this project are to 1) use state-of-the-art genetic testing to produce colony offspring of known parentage, ancestry, and MHC genotype and 2) to maintain the genetic diversity of this extended SPF colony while producing sufficient numbers of offspring to meet research needs. We will continue to use the Fluidigm 96-SNP parentage array to assign parentage. All new colony offspring will be typed for MHC Class I alleles using a sequence-based expressed allele assay. We will also conduct genetic management using new protocols developed to assign genetic value for each animal, and to propose breeding groups that will minimize the loss of genetic diversity in the colony. Lastly, we will develop new informatics protocols to support these efforts, including the consideration of MHC type in the maintenance of genetic diversity.

项目总结，核心C：MHC基因分型核心基因特征良好的动物模型对艾滋病毒/希沃克病毒研究的成功至关重要，包括 MHC基因、已知血统和系谱关系的特征。尤其是，信息量大，由于猕猴MHC I类基因座的复杂性，准确的MHC基因分型是至关重要的，而且等位基因类型对疾病进展的影响。对基因特征良好的动物模型的需求研究还必须与保护动物群体中的遗传多样性的需要相平衡支持生物医学研究。这不仅是为了确保殖民地的长期健康，也是为了确保实验结果与人类疾病的相关性。ONPRC在许多领域的发展中处于领先地位目前推荐用于NHP基因分型和管理的方法和技术殖民地。这个项目的遗传学核心的目标是1)使用最先进的基因测试来生产已知亲缘关系、血统和MHC基因的群体后代和2)保持这种扩展的SPF菌落同时产生了足够数量的后代来满足研究需要。我们会继续使用Fluidigm 96-SNP父子关系数组来指定父子关系。所有新的殖民地后代都将是使用基于序列的表达等位基因分析对MHC I类等位基因进行分型。我们还将进行基因改造使用新开发的协议进行管理，为每种动物分配遗传值，并建议进行繁殖这些群体将最大限度地减少群体中遗传多样性的损失。最后，我们将发展新的信息学支持这些努力的议定书，包括考虑MHC类型在维持遗传多样性。