GENETIC ANALYSIS: PEPTIDE HORMONE AND COLLAGEN DISORDER

我的总体目标是帮助理解为什么 特定基因的表达在不同的人类遗传基因中是混乱的。 疾病 利用限制性酶切图谱、克隆和核苷酸测序， 将研究突变、重排和改变的修饰状态， 多肽激素或胶原蛋白基因，与临床 症状 这些研究的具体目标包括：（1）确定 生长激素（GH）基因缺失的分子基础和家族型 GH缺乏症;（2）特定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与不同类型甲状旁腺功能亢进的关系; (4)前α 1（1）或前α 2（1）胶原基因贡献 成骨细胞（OI）改变，OI与GH相关 （5）马凡氏综合征（Marfan syndrome）; 精氨酸加压素（AVP）基因，它的拷贝数，和等位基因形式， 由于AVP缺乏而患有家族性尿崩症的个体和（6） 胰岛素基因改变在某些孟德尔遗传型中的作用 糖尿病的 在多肽激素中发现的改变或 胶原基因与家族性疾病有关， 这些基因的表达应该与其他基因的缺陷有相似之处。 先天性代谢缺陷，并应提供洞察功能 正常基因结构和表达之间的关系。

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.