IMMUNOGENETICS OF SEX DETERMINATION

性别决定的免疫遗传学

• 批准号: 3135638
• 负责人: STEPHEN S WACHTEL
• 金额: $ 18.95万
• 依托单位: UNIVERSITY OF TENNESSEE HEALTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-03-01 至 1990-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3135638
• 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.

此项资助下的研究涉及阐明 脊椎动物性别决定机制，并评估 假设该分子带有血清学定义的 H-Y 抗原 是异配（XY）性腺的决定因素。 H-Y基因已 位于 Y 染色体和 X 染色体上；已提供证据表明 XY 性腺的发育继发于 H-Y 和性腺的反应 受体；和 H-Y minus 和 H-Y plus 类已被发现 XY 性腺发育不全的临床病例，其中后者可能面临风险 用于性腺肿瘤。 目前的研究正转向评估 进一步的理论：哺乳动物的睾丸决定结构基因座是 常染色体并受性染色体调节；该结构 H-Y 基因座 包含一个基因系统，其中一些基因在 XX 男性中不存在；还有那个 H-Y表型可预测脊椎动物之间的异配性 一般情况下，以及 XY 性腺发育不全的恶性肿瘤 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，用于检测细胞表面或细胞内的 H-Y 解决方案。 ELISA 基于生物素结合的单克隆抗体的反应 H-Y 抗体和平板抗原源，然后添加 亲和素生物素-酶复合物和底物。 结果得分为 ELISA 酶标仪中的光密度。 通过使用这种方法，免费的H-Y 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，并通过以下方法测量了细胞表面 H-Y 鸡和小鼠的定量吸收。 该方法将是 应用于正常人群H-Y的研究，得到的数据 将作为临床H-Y研究的统计基础 性别分化异常的病例和性别异常的受试者 染色体构成。 我们的系统发育调查揭示了 H-Y 32 个新物种中的抗原，并提供了雄性和雌性的证据 H-Y 的异配性和性别特异性表达已经进化了好几次 ——在不同物种中独立存在。 建议进一步 扩大调查范围，重点关注控制温度的性行为 决定和表征从男性到女性转变的系统 异配性，后者显然由单一突变控制。 这 期望的是对不同性别决定系统的分析 脊椎动物类将为进一步的研究提供全面的基础 阐明假定诱导物的进化、遗传学和功能 分子。