MOLECULAR GENETICS OF HUMAN SKELETAL DYSPLASIAS

人类骨骼发育不良的分子遗传学

• 批准号: 5203398
• 负责人: C A FRANCOMANO
• 金额: --
• 依托单位: NATIONAL HUMAN GENOME RESEARCH INSTITUTE
• 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/5203398
• 关键词: congenital skeletal disorder; family genetics; gene expression; genetic disorder; genetic markers; genetic polymorphism; genotype; human genetic material tag; human tissue; linkage mapping; molecular genetics; phenotype

This study is designed to identify disease genes causing a variety of human skeletal dysplasias, including but not limited to the Ellis-van Creveld syndrome, proximal and distal symphalangism, and the nail-patella syndrome. Progress since April 1994 has included: 1) Ellis van Creveld (EvC) syndrome: A total of 110 markers spanning the human genome has been tested for linkage to the EvC phenotype in a large Amish pedigree from Lancaster County, Pennsylvania. To date, no definitive evidence for linkage has been achieved. These studies are continuing with additional markers placed more closely along the human gene map. It may be that the number of DNA samples of available to us for study is inadequate for the identification of linkage at the present time if this turns out to be the case, a major effort will be devoted to the identification and ascertainment of additional cases and families. 2) Proximal symphalangism. Linkage was found between PS phenotype and markers on chromosome 17q in a large Virginia family originally reported by Harvey Cushing in 1901. We have extended the pedigree from the original reports and from a follow-up study performed in 1964. An anonymous genome search was initiated resulting in the identification of markers on chromosome 17q linked to the PS phenotype with a maximum lod score of 5.94 at theta=0.2. 3) Nail-patella syndrome. Previous studies in our laboratory have shown that AK1, the gene encoding adenylate kinase-1 on chromosome 9q34, is the most closely linked marker to NPS in a large Mormon family segregating the disease. Linkage to AK1 has been recognized for three decades, as a result of linkage studies employing protein polymorphisms in the mid 1960s.

这项研究旨在识别引起各种各样的疾病基因 人类骨骼发育不良，包括但不限于Ellis-Van 克里夫尔德综合征，近端和远端交响乐以及指甲蛋白 综合征。 自1994年4月以来的进展包括： 1）Ellis Van Creveld（EVC）综合征：总共110个标记 人类基因组已被测试，以与A中的EVC表型联系 来自宾夕法尼亚州兰开斯特县的大型阿米什人血统。 迄今为止，没有 已经实现了确定的联系证据。 这些研究是 继续沿着人类更紧密地放置其他标记 基因图。 可能是我们可用的DNA样品数量 为了研究目前的联系不足以识别 如果事实证明是这样的，那将是一项重大努力 识别和确定其他案件和家庭。 2）近端交响乐。 在PS表型和 最初报道的弗吉尼亚大家庭中染色体17q的标记 由Harvey Cushing于1901年。我们从 原始报告和1964年进行的后续研究。 启动了匿名基因组搜索，导致识别 染色体17q上的标记与PS表型相关，并具有最大LOD theta = 0.2的得分为5.94。 3）指甲帕特拉综合征。 我们实验室的先前研究表明 AK1是9q34染色体上编码腺苷酸激酶1的基因，是 大型摩门教徒家族中最紧密的标记与NP 隔离疾病。 与AK1的联系已被确认为三个 几十年来，由于使用蛋白质多态性的连锁研究 在1960年代中期。