GENOME VARIATION IN COCCIDIOIDES IMMITIS ANTIGEN LOCI

粗球孢子菌将用于询问发病机制是否与 基因型变异，如果抗原基因产物产生的变异， 病原体避免宿主免疫，如果进化选择发生在 病原体产生的抗原，如果不同的分离物 毒力可以比较，以确定必要的基因引起的疾病？ 与真菌发病机制相关的遗传变异非常明显， 物种到物种，例如，C.伊米蒂斯相比，其关闭 良性相对Uncinocarpus reesii，但它可以在一个更神秘的 物种 C.历史研究伊米提人在以下方面有已知的差异 临床表现、小鼠疾病和丰富的形态学特征 变异，但表型和 基因型 我们正在利用核酸序列变异， 鉴定临床分离的C.免疫球蛋白 为了找到多态位点， 基因组的匿名区域从所有分离株中扩增， 筛选变异 通过以下方式证实了该变化 核苷酸测序，基因座和等位基因是精确和明确的， 越好. 正在进行的工作表明，序列变异是丰富的 并且容易在C.遗传性 变异与地理位置相关，并从一个地点分离 是可变的，并显示出一定的相关性。 为了支持疫苗生产计划，C。犬肺炎分离株 将在小鼠中测试基因型的范围以确定 致病性 为了排除非普遍表达的抗原， C.将检测犬肺炎分离株的抗原转录 基因. 为确保在所有国家和地区实现保护， 病原体多样性，免疫小鼠将由代表性的 一组隔离物。 病原体进化和致病性遗传基础分析 将从小鼠试验和抗原研究中得出 生产 对病原体基因产物的选择要强 被主持人认出来了。 我们可以比较基因中的核苷酸变异 C. immitis和C. immitis和U. reesii来检测这个选择。 如果我们发现 致病性（由新的环境分离物从土壤和小 哺乳动物）。我们可以利用基因组或其转录本的差异来搜索 致病性的决定因素。

Coccidioides immitis will be used to ask if pathogenesis is related to genotypic variation, if variation in antigenic gene products produced by a pathogen avoids host immunity, if evolutionary selection is occurring in the antigens produced by the pathogen, and if isolates of different virulence can be compared to identify genes necessary to cause disease? Genetic variation related to fungal pathogenesis is blazingly obvious from species to species, e.g., the virulence of C. immitis compared to its close benign relative Uncinocarpus reesii, but it can be more cryptic within a species. Historical studies of C. immitis have known differences in clinical presentation, disease in mice, and abundant morphological variation, but there has been little connection between phenotype and genotype. We are using nucleic acid sequence variation to genetically characterize clinical isolates of C. immitis. To find polymorphic loci, anonymous regions of the genome are amplified from all isolates, and are screened for variation electrophoretically. The variation is confirmed by nucleotide sequencing, and loci and alleles are as precise and unambiguous as possible. Work in progress shows that sequence variation is abundant and easily found within and among populations of C. immitis; genetic variation correlates with geographic location and isolates from one site are variable and show a range of relatedness. To support the program of vaccine production, the C. immitis isolates of the range of genotypes will be tested in mice to determine variation in pathogenicity. To rule out antigens that are not universally expressed, the set of C. immitis isolates will be tested for transcription of antigen genes. To ensure that protection is achieved throughout the range of pathogen diversity, immunized mice will be challenged by a representative set of isolates. Analysis of pathogen evolution and of the genetic basis of pathogenicity will follow from the tests in mice and from the study of antigen production. Selection should be strong on pathogen gene products recognized by the host. We can compare the nucleotide variation in genes for antigenic proteins within C. immitis and between C. immitis and U. reesii to detect this selection. If we find strong variation in pathogenicity (aided by new environmental isolates from soil and small mammals). we can use differences in the genome or its transcripts to search for the determinants of pathogenicity.