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.

项目摘要，核心 C：MHC 基因分型核心遗传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、已知血统和谱系关系的表征。特别是信息丰富且由于猕猴中 MHC I 类基因座的复杂性，准确的 MHC 基因分型至关重要等位基因类型对疾病进展的影响。需要具有良好遗传特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。这不仅是为了确保蜂群的长期健康，也是为了确保实验结果与人类疾病的相关性。 ONPRC 是许多领域发展的领导者目前推荐用于 NHP 基因分型和管理的方法和技术殖民地。因此，该项目遗传学核心的目标是，1）使用最先进的基因测试来产生已知亲子关系、祖先和 MHC 基因型的群体后代，2) 维持遗传该 U42 群体的多样性，同时产生足够数量的后代以满足研究需求。为此，我们将把这个群体中的亲子关系分析转变为基于 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菌落后代进行 MHC I 类等位基因的基因分型，并扩展 MHC I 类基因分型工作包括 P51 女性。我们还将利用新的方法进行基因管理制定协议来分配每只动物的遗传价值，并提出育种群体，以最大限度地减少群体遗传多样性的丧失。最后，我们将开发新的信息学协议来支持这些努力，包括在维持遗传多样性方面考虑 MHC 类型。