GENETIC ANALYSIS: PEPTIDE HORMONE AND COLLAGEN DISORDER

遗传分析：肽激素和胶原蛋白紊乱

• 批准号: 3233892
• 负责人: John Atlas Phillips III
• 金额: $ 18.76万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-08-01 至 1989-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3233892
• 关键词: Marfan syndrome; alleles; autosomal dominant trait; autosomal recessive trait; autosome; azacitidine; biological polymorphism; chromosome disorders; cytogenetics; developmental genetics; family; gene expression; gene mutation; genetic disorder diagnosis; genetic mapping; genetic models; human population genetics; insulin; linkage mapping; messenger RNA; nucleic acid sequence; osteogenesis; parathyroid hormones; peptide hormone; somatomammotropin

My overall objective is to contribute to the understanding of why expression of specific genes is deranged in different human genetic diseases. Using restriction mapping, cloning and nucleotide suquencing, I will study the mutations, rearrangements, and altered modification states of polypeptide hormone or collagen genes that are associated with clinical symptoms. Specific objectives of these studies include determining (1) the molecular basis of growth hormone (GH) gene deletions and familial types of GH deficiency; (2) the origin of a spcific GH gene polymorphism; (3) the contributions of alterations in the parathyroid hormone (PTH) gene, its copy number or methylation state to different types of hyperparathyroidism; (4) the contribution of pro Alpha1(1) or pro Alpha2(1) collagen gene alterations to osteogenesis imperfecta (OI), OI associated with GH deficiency, or the Marfan syndrome; (5) the chromosomal assignment of the arginine vasopressin (AVP) gene, its copy number, and allelic forms seen in individuals with familial diabetes insipidus due to AVP deficiency and (6) the contribution of insulin gene alterations in certain mandelian types of diabetes mellitus. Alterations found in the polypeptide hormone or collagen genes which are associated with familial disorders affecting the expression of these genes should have similarities to defects in other inborn errors of metabolism and should provide insight into the functional relationship between normal gene structure and expression.

我的总体目标是为理解为什么 特定基因的表达在不同的人遗传中被危险 疾病。 使用限制映射，克隆和核苷酸急诊，I 将研究突变，重排和改变的修饰状态 与临床相关的多肽激素或胶原蛋白基因的 症状。 这些研究的具体目标包括确定（1） 生长激素（GH）基因缺失和家族类型的分子基础 GH缺乏症； （2）Spcific GH基因多态性的起源； （3） 甲状旁腺激素（PTH）基因改变的贡献，其 拷贝数或甲基化状态至不同类型的甲状旁腺功能亢进症； （4）Pro alpha1（1）或Pro alpha2（1）胶原蛋白基因的贡献 与GH相关的成骨剂（OI）（OI）的改变 缺乏症或Marfan综合征； （5） 精氨酸加压素（AVP）基因，其拷贝数和等位基因形式 由于AVP缺乏症而引起的家族性糖尿病的患者，（6） 胰岛素基因改变在某些曼德尔类型中的贡献 糖尿病。 在多肽激素或 胶原基因与影响的家族性疾病有关 这些基因的表达应与其他缺陷有相似之处 天生的新陈代谢错误，应提供对功能的见解 正常基因结构与表达之间的关系。