MOLECULAR ANALYSIS OF LANGER-GIEDION SYNDROME

Langer-Giedio 综合征的分子分析

• 批准号: 2673650
• 负责人: DAN E WELLS
• 金额: $ 19.8万
• 依托单位: UNIVERSITY OF HOUSTON
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-09-01 至 2000-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2673650
• 关键词: Mus musculus; achondroplasia; bone development; carcinogenesis; chromosome deletion; congenital skeletal disorder; cytogenetics; developmental genetics; family genetics; gene expression; gene rearrangement; gene targeting; genetic polymorphism; genetically modified animals; human genetic material tag; human tissue; in situ hybridization; linkage mapping; molecular pathology; northern blottings; nucleic acid sequence; phenotype; polymerase chain reaction; pulsed field gel electrophoresis; southern blotting

DESCRIPTION (Adapted from the Investigator's Abstract): Langer-Giedion syndrome is characterized by cone-shaped epiphyses in the hand, multiple cartilaginous exostoses, shortness of stature, and characteristic craniofacial abnormalities, and mental retardation. The clinical features of Langer-Giedion syndrome are essentially identical to those of trichorhinophalangeal syndrome type I except that the latter does not include multiple exostoses and rarely includes mental retardation. The exostoses found in LGS are essentially identical to those seen in hereditary multiple exostoses, an autosomal dominant disorder characterized by multiple, cartilage-capped exostoses (benign tumors) on the juxtaepiphyseal regions of enchondral bones. The long term goal of this research project is the complete characterization at the molecular level of the genes which are responsible for the phenotypes associated with the Langer-Giedion syndrome and the related syndromes hereditary multiple exostoses and trichorhinophalangeal syndrome type 1. This application encompasses the following three specific aims which are directed at our long term goal. First is to isolate and characterize the genes located in the LGS region including TRPSI and any genes that may be involved in normal mental function. Second, isolate and characterize the gene for EXT2 present on chromosome 11 and look for clues as to how its function is related to EXT1. Third, use the mouse as a model system to analyze the role of EXT1 in bone development and tumorigenesis. Characterize the temporal and spatial pattern of EXT1 expression in the mouse using both RNA blot and in situ hybridization techniques determine the role this gene plays in vivo by analyzing mice with a null mutation in the EXT1 gene. The genes involved in the pathology of Langer-Giedion syndrome are likely to be involved in the normal development of bone and connective tissues and of normal mental capabilities. Understanding the functions of these genes may give us insights into these important developmental processes as well as tumor suppression. Molecular analysis of the Langer-Giedion genes will be an essential step towards a detailed understanding of their functions.

描述（改编自调查员的摘要）：Langer-Giedion 综合征的特征是手中的锥形epiphyses，多个 软骨外的遗体，身材矮小和特征性 颅面异常和智力低下。 临床特征 Langer-Giedion综合征的 trichorhinophanophangeal综合征I类型，除了后者没有 包括多个遗体，很少包括智力障碍。 这 LGS中发现的遗传性与遗传中的遗传性相同 多个外遗体，一种常染色体显性疾病，其特征是 多发性软骨限制的外骨（良性肿瘤） 魔力区域。 该研究项目的长期目标是 在基因的分子水平上的完整表征 负责与Langer-Giedion综合征相关的表型 以及相关综合征遗传多个遗体和 Trichorhinophanopolhangeal综合征1型。此应用程序包括 遵循针对我们长期目标的三个具体目标。 首先是分离并表征位于LGS区域的基因 包括trpsi和任何可能涉及正常精神的基因 功能。 其次，分离物并表征存在于Ext2的基因 染色体11，并寻找有关其功能与EXT1如何相关的线索。 第三，将鼠标用作模型系统来分析ext1在骨骼中的作用 发育和肿瘤发生。 特征时间和空间 使用RNA印迹和原位，在小鼠中表达Ext1表达的模式 杂交技术决定了该基因在体内的作用 用Ext1基因中的无效突变分析小鼠。 涉及的基因 Langer-Giedion综合征的病理可能参与 骨骼和结缔组织的正常发育以及正常的精神 功能。 了解这些基因的功能可能会给我们 洞悉这些重要的发展过程以及肿瘤 抑制。 Langer-Giedion基因的分子分析将是 迈向详细了解其功能的基本步骤。

项目成果

Alignment of physical and genetic maps of human 8q23-qter using somatic cell hybrid mapping panel.

使用体细胞混合作图面板对人类 8q23-qter 的物理和遗传图谱进行比对。

• DOI: 10.1007/bf02290684
• 发表时间: 1994
• 期刊: Somatic cell and molecular genetics
• 作者: Parrish,JE;Wang,Y;Wagner,MJ;Wells,DE
• 通讯作者: Wells,DE

Assignment of fragile site 8E (FRA8E) to human chromosome band 8q24.11 adjacent to the hereditary multiple exostoses 1 gene and two overlapping Langer-Giedion syndrome deletion endpoints.

将脆弱位点 8E (FRA8E) 分配给人类染色体带 8q24.11，邻近遗传性多发性外生骨疣 1 基因和两个重叠的 Langer-Giedion 综合征缺失端点。

• DOI: 10.1159/000134628
• 发表时间: 1997
• 期刊: Cytogenetics and cell genetics
• 作者: Hill,A;Harada,Y;Takahashi,E;Hou,J;Wagner,MJ;Wells,DE
• 通讯作者: Wells,DE

Identification of the Xenopus laevis cDNA for EXT1: a phylogenetic perspective.

非洲爪蟾 EXT1 cDNA 的鉴定：系统发育的角度。

• DOI: 10.1080/10425170290029990
• 发表时间: 2002
• 期刊: DNA sequence : the journal of DNA sequencing and mapping
• 作者: Hill,AL;Brown,N;Hill,MS;Wells,DE
• 通讯作者: Wells,DE

An integrated physical map of 8q22-q24: use in positional cloning and deletion analysis of Langer-Giedion syndrome.

8q22-q24 的综合物理图谱：用于 Langer-Giedion 综合征的位置克隆和缺失分析。

• DOI: 10.1006/geno.2000.6438
• 发表时间: 2001
• 期刊: Genomics.
• 作者: Hilton,MJ;Gutierrez,L;Zhang,L;Moreno,PA;Reddy,M;Brown,N;Tan,Y;Hill,A;Wells,DE
• 通讯作者: Wells,DE

Localization of the human H3F3A histone gene to 1q41, outside of the normal histone gene clusters.

人类 H3F3A 组蛋白基因定位于 1q41，位于正常组蛋白基因簇之外。

• DOI: 10.1006/geno.1997.5037
• 发表时间: 1997
• 期刊: Genomics.
• 作者: Lin,X;Wells,DE
• 通讯作者: Wells,DE