IMMUNOGENETICS OF SEX DETERMINATION

性别决定的免疫遗传学

• 批准号: 3135637
• 负责人: STEPHEN S WACHTEL
• 金额: $ 10.92万
• 依托单位: CENTER FOR REPRODUCTIVE BIOLOGY
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-01 至 1988-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3135637
• 关键词: HY antigen; gene expression; genetic mapping; glycopeptides; human population genetics; human subject; immunogenetics; monoclonal antibody; sex linked trait

Studies under this grant have been concerned with elucidation of the mechanisms of sex determination in the vertebrates, and with evaluation of the hypothesis that the molecule bearing serologically-defined H-Y antigen is the determinant of the heterogametic (XY) gonad. H-Y genes have been located on the Y chromosome and on the X; evidence has been provided that development of the XY gonad is secondary to reaction of H-Y and a gonadal receptor; and H-Y minus and H-Y plus classes have been discovered among clinical cases of XY gonadal dysgenesis, of which the latter may be at risk for gonadal tumors. Current research is moving toward evaluation of further theory: that testis-determining structural loci of the mammal are autosomal and regulated by the sex chromosomes; that structural H-Y loci comprise a system of genes of which some are absent in XX males; and that H-Y phenotype is predictive for heterogamety among the vertebrates in general, and for malignancy in cases of XY gonadal dysgenesis in the human. Technical advances are likely to be central to this work. We have devised a sensitive ELISA for detection of H-Y at the cell surface or in solution. The ELISA is based on reaction of biotin-conjugated monoclonal H-Y antibody and a plated antigen source followed by addition of avidinbiotin-enzyme complex and substrate. The result is scored for optical density in an ELISA plate reader. By use of this method, free H-Y has been demonstrated in the supernatant fluids of cultured Sertoli cells and cultured Daudi cells, and cell-surface H-Y has been measured by quantitative absorption in the chicken and mouse. The method will be applied to the study of H-Y in normal populations, and the data obtained will be used as a statistical foundation for the study of H-Y in clinical cases of abnormal sex differentiation and in subjects with aberrant sex chromosome constitutions. Our phylogenetic survey has revealed H-Y antigens in 32 new species and has provided evidence that male and female heterogamety and sex-specific expression of H-Y have evolved several times -- independently in the different species. It is proposed to further extend that survey with emphasis on temperature-controlled sex determination and on systems characterizing transition from male to female heterogamety, the latter evidently governed by a single mutation. The expectation is that analysis of sex determining systems in the different vertebrate classes will provide a comprehensive base for further elucidation of the evolution, genetics and function of the putative inducer molecule.

根据这项赠款进行的研究涉及阐明 脊椎动物性别决定的机制， 假设携带血清学定义的H-Y抗原的分子 是异配子生殖腺（XY）的决定因素。 H-Y基因已经被 位于Y染色体和X染色体上;证据表明， XY性腺的发育次要于H-Y和性腺的反应 受体;和H-Y减和H-Y加类已被发现之间 XY性腺发育不全的临床病例，后者可能处于风险中 治疗性腺肿瘤 目前的研究正朝着评估 进一步的理论：哺乳动物的睾丸决定结构基因座是 常染色体和性染色体调控;结构H-Y基因座 包含某些基因在XX男性中缺失的基因系统;并且 H-Y表型是脊椎动物异配子体的预测， 一般，以及XY性腺发育不全病例中的恶性肿瘤， 人类 技术进步可能是这项工作的核心。 我们有 设计了一种灵敏的ELISA检测H-Y在细胞表面或 溶液 ELISA基于生物素缀合的单克隆抗体的反应， H-Y抗体和平板抗原源，然后加入 抗生物素蛋白-酶复合物和底物。 结果被评分为 ELISA酶标仪中的光密度。 利用这种方法， 已在培养的支持细胞的上清液中得到证实 和培养的Daudi细胞，细胞表面H-Y已经通过 鸡和小鼠中的定量吸收。 该办法将 应用于正常人群的H-Y研究， 将作为H-Y临床研究的统计学基础 性别分化异常和性别异常受试者中的病例 染色体结构 我们的系统发育调查显示 在32个新物种的抗原，并提供了证据，男性和女性， 异型配子和H-Y性别特异性表达已经进化了几次 在不同的物种中是独立的。 拟进一步 把重点放在温度控制的性行为上 决定和从男性到女性的过渡特征系统 异配子体，后者显然是由一个单一的突变。 的 期望的是，分析性别决定系统在不同的 脊椎动物类将提供一个全面的基础， 阐明推定诱导物的进化、遗传学和功能 分子。