GENETIC STUDIES OF ODDD

奇数的遗传学研究

• 批准号: 6516632
• 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 2004-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6516632
• 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（改编自调查员的摘要）：oculodentodigital 发育不良（ODDD）是一种具有常染色体显性模式的综合征 遗产。表型包括牙齿，颅面，眼，手，脚， 和长骨异常。中枢神经系统的体征和症状相关 一些奇数患者可能会发生白质变性。这些 神经系统表现和某些畸形特征可能更严重或 在连续几代人的奇怪亲戚中发生的年龄较早，暗示性 一种被称为“遗传预期”的现象。首席调查员有 确认这种情况与6染色体的联系并缩小了候选者 DNA标记D6S266和D6S1639之间的1.01至2.87 cm区域。这 候选区域在两个重叠的YAC克隆中进行物理地图。总体 该项目的目标是确定与ODDD相关的基因。具体 该提案的目的为1。）确定其他奇数家庭和零星 案例，通过链接和单倍型分析来完善奇数遗传图位置， 并通过构建YAC，PAC，BAC和 宇宙重叠群； 2.）在关键区域分离候选cDNA； 3.） 通过检测突变来识别疾病基因；和4.）表演 表型/基因型相关性。基因的隔离对于 准确诊断和鉴定牙齿中涉及的遗传因素， 颅面，眼，肢体，骨骼和脑发育。对奇数的了解 基因增加了我们对颅面正常过程的理解 发展以及其他发展途径。