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: 8099683
• 负责人: Emily Elizabeth Wroblewski
• 金额: $ 4.84万
• 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/8099683
• 关键词: Affect; Africa; Alleles; Antigens; Biological Models; Code; Complement; Couples; DNA; Data; Disease; Disease Resistance; Disease susceptibility; Economics; Environment; Equilibrium; Evolution; Feces; Gene Cluster; Genes; Genetic; Genetic Polymorphism; Genetic Variation; Genome; Genotype; Goals; Graft Rejection; HIV; Health; Human; Immune response; Immune system; Immunocompetence; Immunogenetics; Individual; Infertility; Life; Link; Major Histocompatibility Complex; Major Histocompatibility Complex Gene; Measures; Modeling; Pan Genus; Pan troglodytes; Parasite resistance; Parasites; Partner in relationship; Pattern; Phylogenetic Analysis; Play; Population; Pregnancy; Proteins; Recording of previous events; Relative (related person); Reporting; Reproduction; Research; Role; SIV; Tanzania; Testing; Tissues; Variant; Vertebrates; Wild Animals; fighting; fitness; insight; interest; pandemic disease; pathogen; 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）是对免疫反应至关重要的一组基因，因为它编码所有脊椎动物中的抗原呈递蛋白。它保持高水平的多态性，并与疾病和寄生虫抵抗力以及繁殖成功有关。对自然环境中野生动物种群 MHC 的研究对于了解 MHC 功能、选择压力和进化历史至关重要。长期目标是了解 MHC 如何影响人类的健康和生殖。该提案的目的是在首次对野生黑猩猩的研究中检查 MHC 的遗传变异和功能。它们对于人类来说是一个有价值的模型系统，因为它们是我们现存的最近亲，具有超过 98% 的相同基因组和相似的社会模式，但社会经济混乱较少。该研究将 1) 描述坦桑尼亚贡贝国家公园黑猩猩种群 (Pan troglodytes schweinfurthii) 的 MHC 遗传变异特征； 2）检查MHC基因型与健康指标之间的相关性，包括寄生虫载量和疾病易感性； 3）研究MHC基因型与生殖成功之间的关系。将使用从粪便中非侵入性分离的 DNA 对黑猩猩进行 MHC I 类（A、B、C）和 II 类（DR、DQ、DP）经典位点的基因分型。黑猩猩的遗传变异将得到表征，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或不存在以及个体的杂合性程度相关。 MHC 匹配的交配对也将接受测试，以寻找与 MHC 不匹配的配对相比繁殖成功率下降的证据。 MHC 多态性和功能的免疫遗传学研究至关重要，因为 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的关键因素。这项研究还将进一步加深对疾病抵抗力的理解，因为研究表明 MHC 等位基因组成和多样性与免疫能力直接相关。此外，它将有助于了解由于特定有害等位基因和个体杂合性程度以及父母 MHC 匹配而导致的不孕和妊娠失败。 公共卫生相关性：对编码免疫系统核心成分的基因的研究对于人类健康的多个方面至关重要。这些基因决定了身体对自我和非自我的识别，因此在组织移植排斥中发挥着关键作用。此外，这些基因的差异会影响身体抵抗疾病的能力以及个人和夫妇成功繁殖的能力。