CLEFT LIP/PALATE & OSTEOGENESIS IMPERFECTA

唇裂/腭裂

• 批准号: 3775608
• 负责人: REBECCA L SLAYTON
• 金额: --
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3775608
• 关键词: cleft lip; cleft palate; collagen; dental research; fibroblasts; gel electrophoresis; gene expression; gene mutation; genetic polymorphism; glycoprotein biosynthesis; molecular cloning; nucleic acid sequence; osteogenesis imperfecta; polymerase chain reaction; retinoids

Rotation #1: Association studies with candidate genes for non-syndromic cle palate. Malformations resulting in cleft lip with or without cleft palate are caused combination of environmental and genetic factors. Genes chosen were Osteopo Aspartylglucosaminidase and Retinoic Acid Receptor-alpha. Polymorphism dete unsuccessful in the Osteopontin and Aspartylglucosaminidase genes. For the receptor-alpha gene, seven pairs of oligonucleotide primers were synthesize different segments within the 3' untranslated region of the RAR-alpha gene. Reaction (PCR) was used to amplify DNA from 100 Philippines cleft subjects, controls, 20 Iowa controls and 20 Iowa cleft subjects. Amplified DNA was th SSCP gel to detect polymorphisms among these populations. A polymorphism wa among 15% of the Philippines cleft subjects but was not detected in any of t populations. Further research is needed to screen additional subjects from population and to characterize this polymorphism to determine whether it is with clefting. Rotation #2: Characterization of mutations in COLA1 gene of type I collagen with osteogenesis imperfecta type I. Osteogenesis imperfecta (OI) type I is the mildest form of inherited brittle bone disease. Fibroblasts from affected individuals produce about half the expected amount of structurally normal type I collagen as a result of decrea synthesis of pro`1, one of its constituent chains. Preliminary data indicat that OI type I results from mutations which affect the expression of COLA1, gene which encodes the pr alpha 1 chain of type I collagen. In this study, amplified genomic DNA from 25 affected individuals and 10 controls was scree by denaturing gradient gel electrophoresis for the presence of DNA mismatche Potential mutations were identified in two unrelated families. Amplified DN from each affected individual was cloned and sequenced to determine the natu of the DNA mismatch. Additional clones remain to be evaluated before defini characterization of the mutation can be made. Keywords: #1. Cleft Palate, Retinoic Acid Receptor-`; #2. Osteogenesis imp Collagen

轮换#1：与非综合征性癌症候选基因的关联研究 上颚 畸形导致唇裂或腭裂造成的 环境和遗传因素的结合。 选择的基因是Osteopo 天冬氨酸氨基葡萄糖苷酶和视黄酸受体-α。 多态性检测 在骨桥蛋白和天冬氨酸氨基葡萄糖苷酶基因中不成功。 为 受体α基因，合成了7对寡核苷酸引物， 在RAR-α基因的3'非翻译区内的不同片段。 用PCR扩增100例菲律宾唇腭裂患者的DNA， 对照组、20名爱荷华州对照组和20名爱荷华州唇裂受试者。 扩增的DNA是 SSCP凝胶电泳检测这些人群中的多态性。 一种多态性 在15%的菲律宾唇裂受试者中， 人口。 需要进一步的研究来筛选更多的受试者， 群体，并表征这种多态性，以确定它是否是 有裂缝 旋转#2：I型胶原的COLA 1基因突变的表征 I型成骨细胞 I型成骨细胞（OI）是遗传性脆性的最温和形式， 骨病 受影响个体的成纤维细胞产生大约一半的 预期数量的结构正常的I型胶原蛋白作为一个结果， 合成其组成链之一pro`1。 初步数据显示， I型OI由影响COLA 1表达的突变引起， 编码I型胶原蛋白的pr α 1链的基因。 在本研究中， 从25名患者和10名对照的基因组DNA中筛选扩增产物， 通过变性梯度凝胶电泳检测DNA错配的存在 在两个不相关的家庭中发现了潜在的突变。 放大DN 对每个受影响个体的DNA进行克隆和测序， DNA错配的证据 在定义之前，仍需评估其他克隆 可以进行突变的表征。 关键词：#1. 腭裂，视黄酸受体-#2。 成骨障碍 胶原