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

描述（由申请人提供）：主要组织相容性复合体（MHC）是一组对免疫应答至关重要的基因，因为它编码所有脊椎动物中的抗原呈递蛋白。它保持了高水平的多态性，并与疾病和寄生虫抗性和繁殖成功有关。研究野生动物群体在自然环境中的MHC对于理解MHC的功能、选择压力和进化历史是必不可少的。长期目标是了解MHC如何影响人类的健康和生殖。这项计划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。它们是人类的一个有价值的模型系统，因为它们是我们最近的亲戚，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（包括寄生虫负荷和疾病易感性）之间的相关性; 3）调查MHC基因型与生殖成功之间的关系。使用从粪便中非侵入性分离的DNA，在MHC I类（A、B、C）和II类（DR、DQ、DP）经典基因座对黑猩猩进行基因分型。遗传变异将在黑猩猩中进行表征，并与可比较的人类种群进行比较。健康和繁殖成功的措施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。还将对MHC匹配的交配对进行检测，以确定与MHC不匹配的配对相比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导致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。这项研究也将进一步了解抗病性，因为研究表明MHC等位基因的组成和多样性与免疫活性直接相关。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匹配而导致的不孕症和妊娠失败。 公共卫生相关性：研究编码免疫系统核心成分的基因对人类健康的几个方面至关重要。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反应中起着关键作用。此外，这些基因的差异影响身体对抗疾病的能力以及个人和夫妇成功繁殖的能力。

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.