The MHC of wild chimpanzees: genetic variation, disease and reproductive success

野生黑猩猩的 MHC：遗传变异、疾病和繁殖成功

• 批准号: 7999464
• 负责人: Emily Elizabeth Wroblewski
• 金额: $ 5.14万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7999464
• 关键词: Affect; Alleles; Antigens; Biological Models; Code; Couples; DNA; Disease; Disease Resistance; Disease susceptibility; Environment; Feces; Gene Cluster; Genes; Genetic Polymorphism; Genetic Variation; Genome; Genotype; Goals; Graft Rejection; Health; Human; Immune response; Immune system; Immunocompetence; Immunogenetics; Individual; Infertility; Life; Link; Major Histocompatibility Complex; Measures; Pan Genus; Pan troglodytes; Parasite resistance; Parasites; Partner in relationship; Pattern; Play; Population; Pregnancy; Proteins; Recording of previous events; Relative (related person); Reproduction; Role; Tanzania; Testing; Tissues; Vertebrates; Wild Animals; fighting; pressure; public health relevance; reproductive success; social; socioeconomics

DESCRIPTION (provided by applicant): The major histocompatibility complex (MHC) is a cluster of genes critical to the immune response since it codes for antigen-presenting proteins in all vertebrates. It maintains a high level of polymorphism and has been linked to disease and parasite resistance and reproductive success. Studies of the MHC in wild animal populations in their natural environment are essential to understanding MHC function, selective pressures and evolutionary history. The long-term goal is to understand how the MHC influences health and reproduction in humans. The objective of this proposal is to examine the genetic variation and function of the MHC in the first study of wild chimpanzees. They are a valuable model system for humans because they are our closest living relative and have over 98% identical genomes and similar social patterns but less socioeconomic confounds. The study will 1) Characterize the MHC genetic variation in the chimpanzee population (Pan troglodytes schweinfurthii) at Gombe National Park, Tanzania; 2) Examine the correlation between MHC genotype and health measures, including parasite load and disease susceptibility; 3) Investigate the relationship between MHC genotype and reproductive success. Chimpanzees will be genotyped at MHC class I (A, B, C) and class II (DR, DQ, DP) classical loci using DNA isolated non-invasively from feces. Genetic variation will be characterized within chimpanzees and will also be compared to that of comparable human populations. Measures of health and reproductive success will be correlated with the presence or absence of particular alleles as well as the degree of heterozygosity of individuals. MHC-matched mating pairs will also be tested for evidence of decreased reproductive success compared to MHC-unmatched pairs. Immunogenetic study of MHC polymorphism and function is essential because MHC polymorphism, and its role in self and non-self recognition, is a key factor causing tissue transplant rejection. This study will also further the understanding of disease resistance as studies suggest MHC allelic composition and diversity are directly related to immunocompetence. Furthermore, it will contribute to the understanding of infertility and failed pregnancy due to particular deleterious alleles and the degree of heterozygosity of individuals, as well as parental MHC matching. PUBLIC HEALTH RELEVANCE: Study of the genes that code for the core components of the immune system is essential to several aspects of human health. These genes determine the body's recognition of self versus non-self, and therefore play a key role in tissue transplant rejection. Additionally, differences in these genes affect the body's ability to fight disease as well as the ability of individuals and couples to successfully reproduce.

描述（由申请人提供）：主要组织相容性复合体（MHC）是一组对免疫反应至关重要的基因，因为它编码所有脊椎动物的抗原呈递蛋白。它保持高水平的多态性，并与疾病和寄生虫抗性以及繁殖成功有关。研究自然环境下野生动物种群的MHC对理解MHC的功能、选择压力和进化史至关重要。长期目标是了解MHC如何影响人类的健康和生殖。这项提议的目的是在野生黑猩猩的第一次研究中检查MHC的遗传变异和功能。对于人类来说，它们是一个有价值的模型系统，因为它们是我们最亲近的亲戚，拥有98%以上相同的基因组和相似的社会模式，但社会经济混乱较少。本研究将1)对坦桑尼亚贡贝国家公园黑猩猩种群（Pan troglodytes schweinfurthii）的MHC遗传变异进行表征；2)检查MHC基因型与健康指标的相关性，包括寄生虫载量和疾病易感性；3)探讨MHC基因型与生殖成功的关系。黑猩猩将使用从粪便中非侵入性分离的DNA对MHC I类（A、B、C）和II类（DR、DQ、DP）经典位点进行基因分型。遗传变异将在黑猩猩中被描述，并将与可比较的人类群体进行比较。健康和生殖成功的衡量标准将与特定等位基因的存在与否以及个体的杂合程度相关。与mhc不匹配的配对相比，mhc匹配的配对也将被测试生殖成功率降低的证据。MHC多态性及其在自我和非自我识别中的作用是引起组织移植排斥反应的关键因素，因此对MHC多态性及其功能的免疫遗传学研究是必要的。这项研究还将进一步了解疾病抗性，因为研究表明MHC等位基因的组成和多样性与免疫能力直接相关。此外，它将有助于理解由于特定有害等位基因和个体杂合程度以及亲本MHC匹配而导致的不孕和妊娠失败。