MOLECULAR GENETICS OF HUMAN SKELETAL DYSPLASIAS

这项研究旨在确定导致各种疾病的疾病基因， 人类骨骼发育不良，包括但不限于 Creveld综合征、近端和远端指关节粘连与甲-髌骨 综合征 自1994年4月以来取得的进展包括： 1)Ellis货车Creveld（EvC）综合征：共有110个标志物， 人类基因组已被测试为与EvC表型的连锁， 来自宾夕法尼亚州兰开斯特县的大型阿米什人血统。 至今没有 已经取得了确定的证据。 这些研究 继续沿着人体更紧密地放置附加标记 基因图谱 可能是因为我们能得到的DNA样本数量 研究是不够的，以确定目前的联系 如果情况果真如此，将作出重大努力， 查明和查明其他案件和家庭。 2)近端指关节粘连。 在PS表型和 最初报道的弗吉尼亚州一个大家庭中染色体17 q上的标记 由哈维库欣于1901年创作。 我们已经从 原始报告和1964年进行的后续研究。 一个 启动了匿名基因组搜索， 染色体17 q上的标记与PS表型连锁，具有最大lod θ =0.2时的得分为5.94。 3)指甲-髌骨综合征 我们实验室以前的研究表明， 染色体9 q34上编码腺苷酸激酶-1的基因AK 1， 在一个摩门教大家庭中， 隔离疾病。 与AK 1的联系已被确认为三个 几十年来，由于连锁研究采用蛋白质多态性 在60年代中期。

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.