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）：主要的组织相容性复合物（MHC）是对免疫反应至关重要的基因簇，因为它代码在所有脊椎动物中代码抗原呈递蛋白。它保持了高水平的多态性，并且与疾病和寄生虫的抗性和生殖成功有关。对自然环境中MHC的研究对于了解MHC功能，选择性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繁殖。该提案的目的是检查MHC在野生黑猩猩的首次研究中的遗传变异和功能。它们是人类的宝贵模型系统，因为它们是我们最亲密的亲戚，具有超过98％的相同基因组和相似的社会模式，但社会经济的混淆较少。该研究将为1）表征坦桑尼亚Gombe国家公园的黑猩猩种群（Pan Troglodytes Schweinfurthii）的MHC遗传变异； 2）检查MHC基因型与健康措施（包括寄生虫负荷和疾病易感性）之间的相关性； 3）研究MHC基因型与生殖成功之间的关系。黑猩猩将在MHC I类（A，B，C）和II类（DR，DQ，DP）经典基因座进行基因分型，并使用从粪便中非侵袭性的DNA进行基因分型。遗传变异将在黑猩猩内表征，也将与可比的人类种群进行比较。健康和生殖成功的度量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有关。与MHC Unmatched Pairs相比，还将测试MHC匹配的配对对生殖成功的证据。 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身识别中的作用是导致组织移植排斥反应的关键因素。这项研究还将进一步了解疾病抗性，因为研究表明MHC等位基因组成和多样性与免疫能力直接相关。此外，由于特殊的有害等位基因以及个体的杂合性程度以及父母的MHC匹配，这将有助于理解不孕症和怀孕失败。 公共卫生相关性：研究为免疫系统的核心组成部分编码的基因对人类健康的几个方面至关重要。这些基因决定了人体对自我和非自我的认识，因此在组织移植排斥中起着关键作用。另外，这些基因的差异会影响人体对抗疾病的能力以及个人和夫妻成功繁殖的能力。