GENETIC STUDIES OF ODDD

奇数的遗传学研究

• 批准号: 6380010
• 负责人: Ethylin Wang Jabs
• 金额: $ 20.85万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6380010
• 关键词: artificial chromosomes; autosomal dominant trait; bone disorder; clinical research; congenital oral /facial /cranial defect; dental disorder; eye disorder; family genetics; gene expression; gene mutation; genetic disorder; genetic library; genetic markers; genotype; human subject; limbs; linkage mapping; mitochondrial disease /disorder; neural degeneration; nucleic acid sequence; phenotype; polymerase chain reaction; single strand conformation polymorphism; southern blotting; syndrome

DESCRIPTION (Adapted from the Investigator's Abstract): Oculodentodigital dysplasia (ODDD) is a syndrome with an autosomal dominant pattern of inheritance. The phenotype includes dental, craniofacial, ocular, hand, foot, and long bone abnormalities. Central nervous system signs and symptoms related to white matter degeneration can occur in some ODDD patients. These neurological manifestations and some dysmorphic features may be more severe or occur at an earlier age in successive generations of ODDD kindreds, suggestive of a phenomenon known as "genetic anticipation." The Principal Investigator has confirmed linkage of this condition to chromosome 6 and narrowed the candidate region to a 1.01 to 2.87 cM region between DNA markers D6S266 and D6S1639. This candidate region physically maps within two overlapping YAC clones. The overall goal of this project is to identify the gene associated with ODDD. The specific aims of the proposal are to 1.) Ascertain additional ODDD families and sporadic cases, refine the ODDD genetic map location by linkage and haplotype analyses, and refine the ODDD physical map location by constructing YAC, PAC, BAC, and cosmid contigs; 2.) Isolate candidate cDNAs in the critical region; 3.) Identify the disease gene by detecting mutations; and 4.) Perform phenotype/genotype correlations. Isolations of the gene will be important for accurate diagnosis and identification of genetic factors involved in dental, craniofacial, ocular, limb, bone, and brain development. Knowledge of the ODDD gene increases our understanding of the normal process of craniofacial development, as well as of other development pathways.

描述（改编自研究者的摘要）：Oculodentodigital 发育不良 (ODDD) 是一种具有常染色体显性遗传模式的综合征 遗产。表型包括牙齿、颅面、眼、手、足、 和长骨异常。中枢神经系统相关体征和症状 一些 ODDD 患者可能会出现白质变性。这些 神经系统表现和一些畸形特征可能更严重或 ODDD 家族的连续几代中都出现在较早的年龄，这表明 一种被称为“遗传预期”的现象。首席研究员有 证实了这种情况与 6 号染色体的联系并缩小了候选范围 区域至 DNA 标记 D6S266 和 D6S1639 之间的 1.01 至 2.87 cM 区域。这 候选区域物理映射在两个重叠的 YAC 克隆内。整体 该项目的目标是鉴定与 ODDD 相关的基因。具体的 该提案的目的是 1.) 确定额外的 ODDD 系列和零星的 案例，通过连锁和单倍型分析细化 ODDD 遗传图定位， 通过构造YAC、PAC、BAC和 粘粒重叠群； 2.) 分离关键区域的候选cDNA； 3.) 通过检测突变来识别疾病基因； 4.) 执行 表型/基因型相关性。基因的分离对于 准确诊断和识别涉及牙齿的遗传因素， 颅面、眼部、四肢、骨骼和大脑发育。 ODDD 知识 基因增加了我们对颅面部正常过程的理解 发展以及其他发展途径。