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基因中错乱 疾病。利用限制图谱、克隆和核苷酸测序，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基因 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及其家系类型 GH缺乏症；(2)特定GH基因多态的起源；(3) 甲状旁腺激素(PTH)基因突变的作用 甲状旁腺功能亢进症不同类型的拷贝数或甲基化状态； (4)前α1(1)或前α2(1)胶原基因的贡献 与生长激素相关的成骨不全(OI)、OI改变 缺乏，或马凡综合征；(5)染色体分配 精氨酸加压素(AVP)基因、其拷贝数和等位基因形式 AVP缺乏所致的家族性尿崩症患者和(6) 胰岛素基因改变在某些扁桃体型糖尿病中的作用 糖尿病。多肽荷尔蒙或 与家族性疾病相关的胶原基因影响 这些基因的表达应该与其他基因缺陷有相似之处 新陈代谢的先天错误，应该提供对功能性 正常基因结构与表达的关系。

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.