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MHC Genetic Typing Core

MHC 基因分型核心

基本信息

批准号：
9271698
负责人：
Amanda Vinson
金额：
$ 18.15万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/9271698
关键词：
Acquired Immunodeficiency Syndrome Adult Age Algorithms Alleles Animal Genetics Animal Husbandry Animal Model Animal Testing Animals Base Sequence Biological Assay Biomedical Research Breeding Caring Computer software Consult Data Development Disease Disease Progression Ensure Female Gene Frequency Genetic Genetic Variation Genetic screening method Genomics Genotype Goals HIV Health Immigrant Individual Infant Informatics Knowledge Letters MHC Class I Genes Macaca Macaca mulatta Maintenance Morbidity - disease rate Primates Protocols documentation Recruitment Activity Research Research Support SNP array Source Technology Time Uncertainty Wisconsin animal breeding animal colony base cost genetic pedigree human disease innovation male member mortality nonhuman primate novel offspring 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 of many of the current recommended approaches and technologies used in genetic typing and management of NHP colonies. Thus, 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 U42 colony while producing sufficient numbers of offspring to meet research needs. To do this, we will transition parentage analysis in this colony to a new SNP assay based on the Fluidigm platform. We will continue to genotype all new colony offspring for MHC Class I alleles using sequence-based typing, and expand MHC Class I genotyping efforts to include P51 females. 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于HIV/SHIV研究的成功至关重要，包括 MHC基因型、已知祖先和系谱关系的表征。特别是，准确的MHC基因分型是必不可少的，因为猕猴中MHC I类基因座的复杂性，等位基因类型对疾病进展影响。需要遗传上良好表征的动物模型，研究还必须与保护动物群体遗传多样性的需要相平衡，支持生物医学研究。这不仅是为了确保长期的菌落健康，实验结果与人类疾病的相关性。ONPRC是许多发展中国家的领导者。现时建议采用哪些方法和技术进行非爱滋病病毒的基因分型和管理殖民地因此，该项目的遗传学核心的目标是：1）使用最先进的基因检测，产生具有已知亲子关系、血统和MHC基因型的群体后代; 2）维持遗传这一U42群体的多样性，同时产生足够数量的后代，以满足研究需要。要执行此操作，我们将在该群体中将亲子关系分析转换为基于Fluidigm平台的新SNP测定。我们将继续使用基于序列的分型对所有新的群体后代进行MHC I类等位基因的基因分型，并扩大 MHC I类基因分型努力包括P51女性。我们还将使用新的制定协议，为每只动物分配遗传价值，并提出育种群体，殖民地遗传多样性的丧失。最后，我们将开发新的信息学协议来支持这些努力，包括考虑MHC类型在维持遗传多样性。